Exam 2: q1-q24
CD4 and CD25 of the thymus do what?
"Hassal's Corpuscle"; instruct DC to Induce Reg T-cells
Indicate whether each of the following statements is true or false. If you believe a statement is false, explain why: A) Cytokines can regulate which branch of the immune system is activated. B) Both CTLs and NK cells release perforin after interacting with target cells. C) Activation of naïve CTL-Ps requires a co-stimulatory signal delivered by interaction of CD28 and CD80/86 D) CTLs use a single mechanism to kill target cells. E) CD4+ T cells are absolutely require for the activation of naïve CD8+ T cells F) The ability of an NK cell to kill a target cell is determined by signals received through both activating and inhibiting receptors G) Human NK cells express functional Ly49 receptors H) NK cells must express inhibitory receptors for self-MHC class I proteins in order to develop the capacity to kill altered-self cells.
(A) True. (B) True. (C) True. (D) False. There are two pathways by which cytotoxic T cells kill target cells. One pathway is perforin (E) False. Naïve CD8 T cells can be activated in the absence of CD4 T-cell help. T-cell help, however, is required for optimal proliferation and memory generation. (F) True. (G) False. Ly49 receptors are found on murine cells. Human NK cells express KIR receptors
Multiple choice: One form of anemia results when individuals have a deficiency in the enzyme phosphatidylinositol glycan A (PIGA). This enzyme is required for the membrane attachment of proteins anchored by glycolipids to the plasma membrane, using what is called a 'GPI-linkage.' Included in the group of GPI-linked cell surface proteins is DAF/CD55. These individuals become anemic because: A. DAF/CD55 prevents the lysis of red blood cells by infecting pathogens. B. DAF/CD55 normally prevents the spleen from clearing healthy red blood cells from the circulation. C. In the absence of PIGA, the red blood cell membrane is bare of proteins allowing increased access of complement activating proteins to attach to the cell membrane. D. DAF/CD55 is a complement inhibitory protein that inactivates any C3 convertase that may form on host cell surfaces. E. In the absence of PIGA, red blood cells are unable to synthesize high levels of hemoglobin.
D. DAF/CD55 is a complement inhibitory protein that inactivates any C3 convertase that may form on host cell surfaces.
Multiple choice: In patients with lymphomas, the cancer cells invade the bone marrow and destroy the environment required for normal hematopoiesis. This leads to bone marrow failure, which disrupts the production of hematopoietic cell lineages. All of the following cell types would be affected by this EXCEPT: A. Red blood cells B. Macrophages C. Lymphocytes D. Endothelial cells E. Granulocytes
D. Endothelial cells
Multiple choice: One striking feature of TCR interactions with peptide:MHC complexes is that amino acid residues in the MHC protein are as important to the TCR binding strength as are amino acid residues in the pathogen-derived peptide. This feature is in contrast to antigen recognition by antibodies, which is a direct interaction that is independent of other host proteins. Based on the different functions of T cells versus antibodies in the adaptive immune response, the fact that TCRs recognize components of both the MHC and the bound peptide exists to: A. Prevent TCRs from binding only to surface exposed epitopes of native pathogens B. Prevent immune evasion by a pathogen that has mutated the sequences required for antibody recognition C. Put constraints on T cell recognition, due to the potentially damaging effector molecules made by activated T cells D. Ensure that TCRs are focused on recognizing antigens associated with host cells, and not those that are free in solution E. Ensure that the pathogen has already been destroyed by the host cell before the T cell will recognize it
D. Ensure that TCRs are focused on recognizing antigens associated with host cells, and not those that are free in solution
Multiple choice: The adaptive immune system uses multiple strategies to generate diversity in our ability to mount responses to a wide array of infectious microorganisms. These strategies include the generation of diverse repertoires of B-cell and T-cell antigen receptors, as well as polymorphism of MHC genes. The polymorphism of MHC genes differs from the diversity of lymphocyte antigen receptors in that: A. It involves DNA rearrangements at multiple gene segments in the MHC locus. B. It requires different enzymes than the RAG1/RAG2 recombinase required for antigen receptor rearrangements. C. It results in a diverse repertoire of clonally distributed receptors on dendritic cells, rather than on lymphocytes. D. It creates diversity between individuals in the population rather than within a single individual. E. It does not contribute to the transplant rejection responses that occur after organ transplantation between unrelated individuals.
D. It creates diversity between individuals in the population rather than within a single individual.
Infection of mice with the bacterial pathogen, Citrobacter rodentium, elicits a protective immune response in the gastrointestinal tract. This protective response is characterized by two sequential waves of IL-22 production, both induced by IL-23. The early wave of IL-22 production (<day 8 post-infection) is likely produced by: A. Lamina propria dendritic cells responding to PAMPs of the bacterial pathogen B. Lamina propria macrophages responding to PAMPs of the bacterial pathogen C. Naive CD4 T cells induced to differentiate into TH17 cells in the mesenteric lymphnode D. Lamina propria ILC3 cells stimulated by dendritic cell-produced IL-23 E. IgA immune complexes transporting bacterial antigens and stimulating lamina propria dendritic cells to produce IL-22
D. Lamina propria ILC3 cells stimulated by dendritic cell-produced IL-23
It is well documented that antibody affinities for an immunizing antigen continue to increase upon successive rounds of immunization (i.e., secondary, tertiary, etc.). This is due to the fact that: A. At each round of immunization, new naive B cells are recruited into the response. B. At each round of immunization, the expression of AID increases, leading to higher rates of somatic hypermutation. C. Memory B cells express higher levels of AID than naive B cells, leading to higher rates of somatic hypermutation. D. Memory B cells can re-enter germinal centers and undergo additional somatic hypermutation. E. At each round of immunization, germinal centers become larger and have increased numbers of B cells in them
D. Memory B cells can re-enter germinal centers and undergo additional somatic hypermutation.
It is well documented that antibody affinities for an immunizing antigen continue to increase upon successive rounds of immunization (i.e., secondary, tertiary, etc.). This is due to the fact that: A. At each round of immunization, new naive B cells are recruited into the response. B. At each round of immunization, the expression of AID increases, leading to higher rates of somatic hypermutation. C. Memory B cells express higher levels of AID than naive B cells, leading to higher rates of somatic hypermutation. D. Memory B cells can re-enter germinal centers and undergo additional somatic hypermutation. E. At each round of immunization, germinal centers become larger and have increased numbers of B cells in them
D. Memory B cells can re-enter germinal centers and undergo additional somatic hypermutation.
Multiple choice: The mucosal tissues of the body have their own unique set of immune structures that function as sites for initiating adaptive immune responses. The necessity for mucosa-associated lymphoid tissues to have unique cell types (M cells) and structures is because: A. The mucous layer lining mucosal surfaces makes it difficult for normal antigen- presenting cells to function. B. The epithelial surfaces that line the gut, lungs, and nasal passages prevent antigen-presenting cells from accessing microbes and microbial products. C. The epithelial cells found in mucosal tissues are distinct from those that provide barrier functions to the skin. D. Mucosal sites, where most pathogens access the body, are exposed to vast numbers of diverse microbes. E. Mucosal tissues lack innate sensor cells that can respond to PAMPs and provide short-term innate immune protection.
D. Mucosal sites, where most pathogens access the body, are exposed to vast numbers of diverse microbes.
9.11 Multiple choice: Many virus infections induce robust production of type I interferons, IFN-alpha and IFN-beta. One example is the herpes simplex virus-1 (HSV-2), one of the most common sexually transmitted diseases in the US. Experiments that investigated the immune response to HSV-2 using a mouse model demonstrated essential roles for the DNA sensing Toll-like receptor, TLR9, and its downstream signaling adapter, MyD88, in the production of type I interferons following HSV-2 immunization. The type I interferon response to HSV-2 would be restored in Tlr9-/- mice by transferring into these mice wildtype: A. Macrophages B. Conventional dendritic cells C. Mast cells D. Plasmacytoid dendritic cells E. Neutrophils
D. Plasmacytoid dendritic cells
Many virus infections induce robust production of type I interferons, IFN- and IFN-. One example is the herpes simplex virus-1 (HSV-2), one of the most common sexually transmitted diseases in the US. Experiments that investigated the immune response to HSV-2 using a mouse model demonstrated essential roles for the DNA sensing Toll-like receptor, TLR9, and its downstream signaling adapter, MyD88, in the production of type I interferons following HSV-2 immunization. The type I interferon response to HSV-2 would be restored in Tlr9-/- mice by transferring into these mice wild-type: A. Macrophages B. Conventional dendritic cells C. Mast cells D. Plasmacytoid dendritic cells E. Neutrophils
D. Plasmacytoid dendritic cells
Wild-type mice infected with one strain of Influenza A virus (PR8) by intranasal inoculation are protected from intranasal infection by a related Influenza A virus (Beijing), a phenomenon known as cross-protection. These infections are generallylocalized to the upper respiratory tract. Mice with a homozygous single gene defect in 'gene X' have greatly impaired cross-protection to Influenza A-Beijing following immunization with Influenza A-PR8 by the intranasal route. Gene X likely encodes: A.Fc receptor, FcRIIa B.Complement receptor, CR1 C. TLR adapter protein, MyD88 D. Poly Ig receptor E. AID
D. Poly Ig receptor
Multiple choice: Mycobacteria are intracellular pathogens that have adapted to life inside phagocytic cells, such as macrophages. These intracellular bacteria are taken up by phagocytosis, similar to other pathogens, but the bacteria are not killed. One possible mechanism that could account for this immune evasion by mycobacteria is their ability to: A. Prevent induction of nitric oxide production in the phagosome B. Prevent the acidification of phagosomes C. Prevent the expression of antimicrobial peptides in the phagosome D. Prevent fusion of phagosomes with lysosomes E. Kill the macrophage before it kills them
D. Prevent fusion of phagosomes with lysosomes
4.15 Multiple choice: The innate immune response together with antibodies are generally not effective at clearing infections established by pathogens that replicate inside host cells. The evolution of T cells has provided a means for the immune response to 'see' intracellular infections based on the ability of T cells to: A. Secrete cytokines that diffuse into the infected tissue B. Activate type I interferon production by macrophages and dendritic cells C. Activate macrophages to induce inflammation D. Recognize pathogen-derived peptides on host MHC surface molecules E. Express cytoplasmic sensors for detecting pathogen-derived nucleic acids
D. Recognize pathogen-derived peptides on host MHC surface molecules
Multiple choice: The innate immune response together with antibodies are generally not effective at clearing infections established by pathogens that replicate inside host cells. The evolution of T cells has provided a means for the immune response to 'see' intracellular infections based on the ability of T cells to: A. Secrete cytokines that diffuse into the infected tissue B. Activate type I interferon production by macrophages and dendritic cells C. Activate macrophages to induce inflammation D. Recognize pathogen-derived peptides on host MHC surface molecules E. Express cytoplasmic sensors for detecting pathogen-derived nucleic acids
D. Recognize pathogen-derived peptides on host MHC surface molecules
9.21 Multiple choice: The compound LE135 is an inhibitor of the retinoic acid receptor, and blocks signaling through this receptor. In a mouse model of inflammatory bowel disease (IBD), inflammation in the gastrointestinal (GI) epithelium is significantly exacerbated if animals are treated with LE135. Analysis of the CD4 T cell subsets found in the GI epithelium of LE135-treated mice compared to controls with IBD would likely show: A. Reduced numbers of CD4 T cells of all subsets in the LE135-treated mice B. Increased numbers of TGF- and IL-10-producing CD4 cells in the LE135-treated mice C. Reduced numbers of IL-17 and IL-22-producing CD4 cells in the LE135-treated mice D. Reduced numbers of iTregs in the LE135-treated mice E. Increased numbers of naive CD4 T cells in the LE135-treated mice
D. Reduced numbers of iTregs in the LE135-treated mice
The compound LE135 is an inhibitor of the retinoic acid receptor, and blocks signaling through this receptor. In a mouse model of inflammatory bowel disease (IBD), inflammation in the gastrointestinal (GI) epithelium is significantly exacerbated if animals are treated with LE135. Analysis of the CD4 T cell subsets found in the GI epithelium of LE135-treated mice compared to controls with IBD would likely show: A. Reduced numbers of CD4 T cells of all subsets in the LE135-treated mice B. Increased numbers of TGF- and IL-10-producing CD4 cells in the LE135-treatedmice C. Reduced numbers of IL-17 and IL-22-producing CD4 cells in the LE135-treated mice D. Reduced numbers of iTregs in the LE135-treated mice E. Increased numbers of naive CD4 T cells in the LE135-treated mice22.
D. Reduced numbers of iTregs in the LE135-treated mice
Multiple choice: For alpha:beta T-cell receptors, sequence diversity is heavily concentrated at the junctions formed by the rearrangement of gene segments during the generation of the expressed V and V regions. The result of this organization is to position the most variable part of the T-cell receptor over a certain region of the ligand recognized by this receptor. Which region (outlined in red in Figure Q5.15) indicates this part of the ligand recognized by the T-cell receptor? (SEE IMAGE)
D. SEE IMAGE
Multiple choice: Antibody heavy and light chain polypeptides consist of repeated domains, each of which is ~110 amino acids and folds up into a compact three- dimensional structure known as an 'immunoglobulin domain.' These immunoglobulin domains are: A. Mixed and matched between different antibody heavy and light chains to produce variability B. Always identical to each other within a single antibody heavy chain or light chain polypeptide C. Always differ in amino acid sequence between different light chain polypeptides in both of the two light chain immunoglobulin domains D. Similar but not identical in amino acid sequence when comparing the domains in a single heavy chain polypeptide E. Identical in amino acid sequence for every domain when comparing different antibody heavy chain polypeptides to each other
D. Similar but not identical in amino acid sequence when comparing the domains in a single heavy chain polypeptide
Multiple choice: In recent years, several new vaccines have been developed that are made from purified viral surface proteins, rather than intact or live viruses. They are referred to as subunit vaccines. In order to generate a protective adaptive immune response to a subunit vaccine, the viral protein(s) must be mixed with an adjuvant. The adjuvant functions to: A. Mimic the process of normal virus entry by binding to the host receptor and inducing receptor-mediated endocytosis B. Induce vascular permeability to promote the accumulation of fluid and serum proteins at the vaccine injection site C. Induce the production of chemotactic proteins that recruit neutrophils and then monocytes to the site of vaccine injection D. Stimulate dendritic cells to up-regulate co-stimulatory molecules and migrate to the regional lymph node E. Promote the activation of the complement cascade to induce complement deposition on the viral subunit proteins
D. Stimulate dendritic cells to up-regulate co-stimulatory molecules and migrate to the regional lymph node
9.26 Multiple choice: Wiskott-Aldrich syndrome is an immunodeficiency disease that causes a defect in antibody responses. The most severe defects are in antibody responses to protein antigens, which are dependent on CD4 effector TFH cells providing cytokines to the B cell. The protein defective in individuals with the disease, known as WASp, functions in cytoskeletal reorganization and polarization through its role in promoting actin polymerization. This immune defect could be fixed by a gene therapy approach that restored WASp expression in: A. Antigen-presenting cells such as dendritic cells B. B cells C. B cells and T cells D. T cells E. T cells and antigen-presenting cells
D. T cells
Wiskott-Aldrich syndrome is an immunodeficiency disease that causesa defect in antibody responses. The most severe defects are in antibody responses to protein antigens, which are dependent on CD4 effector TFH cells providing cytokines to the B cell. The protein defective in individuals with the disease, known as WASp, functions in cytoskeletal reorganization and polarization through its role in promoting actin polymerization. This immune defect could be fixed by a gene therapy approach thatrestored WASp expression in: A. Antigen-presenting cells such as dendritic cells B. B cells C. B cells and T cells D. T cells E. T cells and antigen-presenting cells
D. T cells
Multiple choice: The experiment shown in Figure Q6.19 uses two strains of mice that differ in their MHC genes. Strain A is H-2a and Strain B is H-2b. Mice of each strain are infected with the virus LCMV, and T cells are isolated at day 8 post-infection. These T cells are mixed with target cells that express either H-2a or H-2b; in each case, the target cells are either uninfected or infected with LCMV. After a four-hour incubation of T cells with target cells, the percentage of target cells lysed by the T cells is shown in the graph. (SEE IMAGE) The explanation for the results of this experiment is: A. Mice of strain B do not make a T cell response to LCMV. B. Mice of strain A make a more robust T cell response to LCMV than mice of strain C. Target cells that express H-2b cannot be infected with LCMV. D. T cells from mice of strain A only recognize viral peptides on target cells expressing H-2a. E. LCMV peptides do not bind to MHC class I molecules from H-2b mice.
D. T cells from mice of strain A only recognize viral peptides on target cells expressing H-2a.
1.26 Multiple choice: An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure to a pathogen, the organisms have proliferated to dangerous levels requiring immediate systemic antibiotic treatment. It is unlikely that this infant has a defect in B or T lymphocyte responses to the infection because: A. Bacteria and fungi do not require B cell or T cell responses for their clearance. B. Bacteria and fungi are not efficiently transported to draining lymph nodes to initiate adaptive immune responses. C. Systemic infections of bacteria and fungi are usually cleared by the spleen. D. The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses. E. Adaptive immune responses require dendritic cells to take up and degrade pathogens.
D. The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses.
Multiple choice: An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure to a pathogen, the organisms have proliferated to dangerous levels requiring immediate systemic antibiotic treatment. It is unlikely that this infant has a defect in B or T lymphocyte responses to the infection because: A. Bacteria and fungi do not require B cell or T cell responses for their clearance. B. Bacteria and fungi are not efficiently transported to draining lymph nodes to initiate adaptive immune responses. C. Systemic infections of bacteria and fungi are usually cleared by the spleen. D. The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses. E. Adaptive immune responses require dendritic cells to take up and degrade pathogens.
D. The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses.
A healthy intestinal mucosa is one in which induced adaptive immune responses to pathogenic infections are balanced by the lack of responses to innocuous food antigens and commensal microbes. This balance is maintained by an array of different subsets of effector T cells and regulatory T cells that reside in the intestinal epithelium and lamina propria. Although these different T cell subsets have diverse patterns of cytokine production and other effector functions, they share: A. The ability to live for months to years in the intestinal epithelium B. The ability to secrete immunosuppressive cytokines C. The ability to inactivate dendritic cells that have received signals through pattern recognition receptors D. The expression of gut-homing chemokine receptor, CCR9 E. The ability to bind to E-cadherin on the intestinal epithelial cells
D. The expression of gut-homing chemokine receptor, CCR9
In the cases of some infections, such as mice infected with adenovirus,the generation of effector cytotoxic CD8 T cell responses needed to clear the infection is dependent on the antigen-presenting dendritic cells receiving stimulation through the CD40 receptor on their surface, a process known as dendritic cell 'licensing'. In this infection system, the dendritic cell would likely receive CD40 receptor stimulation from: A. The activation of a TLR expressed in the dendritic cell B. The up-regulation of CD40 ligand by virus-infected host cells C. The activation of cytosolic nucleic acid sensors in the dendritic cell D. The interaction with a CD4 effector cell expressing CD40 ligand E. The phagocytosis of apoptotic cell debris resulting from the virus infection
D. The interaction with a CD4 effector cell expressing CD40 ligand
9.1 Multiple choice: Secondary lymphoid organs, such as the lymph nodes, spleen, and mucosa-associated lymphoid tissues, each have distinct features that are important for their role in initiating immune responses focused on different anatomical compartments (i.e., the peripheral tissues, the blood, or the gastrointestinal tract, respectively). Yet these organs share some overall structural features, such as distinct T-cell and B-cell zones. One major difference between these organs is: A. The presence versus the absence of macrophages and dendritic cells B. Their function in bringing rare naive lymphocytes into contact with their specific antigen C. The ability of lymphocytes to enter the organ from the blood D. The mechanism by which antigens or pathogens enter the organ E. The ability of naïve T cells to be activated and proliferate in the organ
D. The mechanism by which antigens or pathogens enter the organ
Secondary lymphoid organs, such as the lymph nodes, spleen, and mucosa-associated lymphoid tissues, each have distinct features that are important for their role in initiating immune responses focused on different anatomical compartments (i.e., the peripheral tissues, the blood, or the gastrointestinal tract, respectively). Yet these organs share some overall structural features, such as distinct T-cell and B-cell zones. One major difference between these organs is: A. The presence versus the absence of macrophages and dendritic cells B. Their function in bringing rare naive lymphocytes into contact with their specific antigen C. The ability of lymphocytes to enter the organ from the blood D. The mechanism by which antigens or pathogens enter the organ E. The ability of naïve T cells to be activated and proliferate in the organ
D. The mechanism by which antigens or pathogens enter the organ
Multiple choice: Different individuals can have different numbers of functional V gene segments as well as different numbers of constant region genes. This type of genetic polymorphism between individuals indicates that: A. The antibody heavy and light chain loci undergo more frequent mutation than other genes in the genome. B. The recombination machinery is active in germ cells. C. Individuals only need K or upside-down y light chains, but not both. D. The precise number of antibody gene segments in an individual is not important. E. Antibody gene segments underwent more frequent duplication during evolution than other genes in the genome.
D. The precise number of antibody gene segments in an individual is not important.
Multiple choice: Some species, like camels, alpacas, and llamas, have evolved variant forms of immunoglobulin proteins that retain the ability to bind to antigens. While overall the antibodies made by these animals are simpler than human or mouse antibodies, an important feature conserved among all of these antibodies is: A. The presence of both heavy and light chain polypeptides B. Antigen-binding sites comprised of VH and VL sequences C. The presence of exactly three constant region domains D. The presence of two antigen-binding sites per antibody E. The presence of multiple disulfide bonds linking antibody light chains to heavy chains
D. The presence of two antigen-binding sites per antibody
Multiple choice: Virus infections induce production of interferons that act on infected cells to enhance their recognition by CD8 cytotoxic T cells. To counter these mechanisms, viruses often encode proteins that interfere with antigen processing and presentation. In an experiment, cells infected with Virus X are treated with interferon and compared with uninfected cells treated with interferon. Proteasomes are isolated from the two cell populations and their enzymatic activities are compared. The data in Figure Q6.4 show the amino acid preferences for cleavage of peptides by the two samples of proteasomes. (SEE IMAGE) Based on these data, Virus X most likely encodes a protein that interferes with: A. The expression of MHC class I on the surface of the infected cell B. The rate at which peptides are produced from intact proteins in the infected cell C. The transport of peptides from the cytosol to the endoplasmic reticulum in the infected cell D. The replacement of constitutive proteasome subunits with immunoproteasome subunits in the infected cell E. The development of CD8 T cells in the thymus by inhibiting the thymoproteasome
D. The replacement of constitutive proteasome subunits with immunoproteasome subunits in the infected cell
6.4 Multiple choice: Virus infections induce production of interferons that act on infected cells to enhance their recognition by CD8 cytotoxic T cells. To counter these mechanisms, viruses often encode proteins that interfere with antigen processing and presentation. In an experiment, cells infected with Virus X are treated with interferon and compared with uninfected cells treated with interferon. Proteasomes are isolated from the two cell populations and their enzymatic activities are compared. The data in Figure Q6.4 show the amino acid preferences for cleavage of peptides by the two samples of proteasomes. Based on these data, Virus X most likely encodes a protein that interferes with: A. The expression of MHC class I on the surface of the infected cell B. The rate at which peptides are produced from intact proteins in the infected cell C. The transport of peptides from the cytosol to the endoplasmic reticulum in the infected cell D. The replacement of constitutive proteasome subunits with immunoproteasome subunits in the infected cell E. The development of CD8 T cells in the thymus by inhibiting the thymoproteasome
D. The replacement of constitutive proteasome subunits with immunoproteasome subunits in the infected cell
In response to an intracellular bacterial or viral infection, effector TH1 cells, macrophages, NK cells, and CD8 cytotoxic effector cells are all recruited to the siteof infection. The coordinated recruitment of all of these cell types is orchestrated by: A. The secretion of the inflammatory cytokine IFN- in the tissue B. The action of TNF- on the endothelial cells, leading to fluid leakage into the tissue C. The up-regulation of integrin ligands such as VLA-4 on the blood vessel endothelial cells D. The shared expression of chemokine receptors on these different cell types E. The shared expression of S1PR1 on these cells, recruiting them out of lymphoid tissues
D. The shared expression of chemokine receptors on these different cell types
In response to an intracellular bacterial or viral infection, effector TH1 cells, macrophages, NK cells, and CD8 cytotoxic effector cells are all recruited to the site of infection. The coordinated recruitment of all of these cell types is orchestrated by: A. The secretion of the inflammatory cytokine IFN-γ in the tissue B. The action of TNF-α on the endothelial cells, leading to fluid leakage into the tissue C. The up-regulation of integrin ligands such as VLA-4 on the blood vessel endothelial cells D. The shared expression of chemokine receptors on these different cell types E. The shared expression of S1PR1 on these cells, recruiting them out of lymphoid tissues
D. The shared expression of chemokine receptors on these different cell types.
A mouse is immunized with the tetanus toxoid protein (inactivated toxin) in adjuvant. One week later, the entire population of splenic B cells are isolated from the mouse and mixed with tetanus toxoid-specific CD4 TFH cells plus the purified tetanus toxoid protein. Four days later, the total number of B cells in the culture and the number of tetanus toxoid-specific B cells are determined and compared to the starting population on the day of isolation. The results are shown in Figure Q10.1.The tetanus-specific B cells preferentially survive and proliferate because: A. They are the only B cells that express CD40. B. They are the only B cells that express the receptor for IL-21. C. They are the only B cells that proliferate in response to their antigen. D. They are the only B cells presenting the tetanus peptide to the TFH cells. E.They are the only B cells that received a TLR stimulus during priming
D. They are the only B cells presenting the tetanus peptide to the TFH cells.
Studies in mice have shown that resident memory cells (TRM) most often take up permanent residence in the tissue where the initial infection that produced those memory cells occurred. In this location, they are poised to respond rapidly should that infection re-occur in that same location. In contrast, central memory cells (TCM) are primarily found in secondary lymphoid organs, where they can be activated to proliferate and differentiate into effector cells when stimulated by antigen-bearing dendritic cells following re-infection. The third subset of memory cells, effector memory cells (TEM), are recirculating cells that can readily enter tissues at sites of inflammation or infection and are poised to rapidly respond to re-infection. The subset of TEM cells provides an important component of protective immunity to re-infection by the same pathogen because: A. They are the only memory cell subset that can produce effector cytokines within a few hours of antigen re-encounter. B. They are able to respond to S1PR1 and enter the blood circulation rapidly upon re-infection. C. They express the integrin E7 that binds to integrin ligands expressed on epithelial cells. D. They can protect against re-infection that occurs in a different site in the body than the primary infection. E. They can simultaneously express cytokines associated with all three effector T cell lineages.
D. They can protect against re-infection that occurs in a different site in the body than the primary infection.
2.13 Multiple choice: Mannose binding lectins (MBL) and ficolins are the two classes of proteins that can initiate the lectin pathway of complement activation. These proteins are selective for activating complement on the surfaces of microbial pathogens rather than host cells because: A. Their higher-order oligomeric structure can be assembled only after the monomers first bind to pathogen membranes. B. They only recruit MASP (MBL-associated serine proteases) proteins when bound to pathogen surfaces and not when bound to host cells. C. They only undergo the conformational change needed to activate MASP proteins when bound to a pathogen and not when bound to a host cell. D. They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes. E. The activated MASP proteins are rapidly inactivated by hydrolysis when present on the surface of a host cell.
D. They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes.
Multiple choice: Mannose binding lectins (MBL) and ficolins are the two classes of proteins that can initiate the lectin pathway of complement activation. These proteins are selective for activating complement on the surfaces of microbial pathogens rather than host cells because: A. Their higher-order oligomeric structure can be assembled only after the monomers first bind to pathogen membranes. B. They only recruit MASP (MBL-associated serine proteases) proteins when bound to pathogen surfaces and not when bound to host cells. C. They only undergo the conformational change needed to activate MASP proteins when bound to a pathogen and not when bound to a host cell. D. They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes. E. The activated MASP proteins are rapidly inactivated by hydrolysis when present on the surface of a host cell.
D. They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes.
Multiple choice: The variable lymphocyte receptors (VLRs) of lampreys represent a highly diverse set of proteins with structural similarity to the mammalian Toll-like receptors. Yet the VLRs and the lymphocytes that produce them are thought to be components of the lamprey's adaptive immune system. This is because: A. The VLRs are highly diverse and have been shown to bind to pathogens. B. Both membrane-bound and secreted forms of VLRs are found in the lampreys. C. VLR coding genes are formed by DNA rearrangement events. D. VLRs are clonally distributed such that each lymphocyte expresses only one form of VLR. E. VLR gene rearrangements occur by a process similar to gene conversion.
D. VLRs are clonally distributed such that each lymphocyte expresses only one form of VLR.
Naive T cells are isolated and left untreated or treated with 'compound X' for 1 hour. Following this, the T cells are incubated with a range of concentrations of asoluble form of ICAM-1 that has been conjugated to a fluorescent dye (soluble-ICAM-1-FITC). Fifteen minutes later, the cells are washed, and the relative amount of fluorescence bound to the cells is measured. The results of this assay are shown in Figure Q9.6.The most likely identity of compound X is: A.The adhesion molecule, LFA-1 B.The adhesion molecule, L-selectin C. The sulfated carbohydrate structure, sulfated sialyl-LewisX D.The chemokine ligand for CCR7 E.The immunoglobulin superfamily member, CD2
D.The chemokine ligand for CCR7
The upper respiratory tract of many individuals is colonized by Streptococcus pneumoniae bacteria. Infections caused by these bacteria, including pneumonia, meningitis, otitis media (ear infections), and sinusitis, are thought to occur inindividuals lacking protective antibodies. For many years, IgG was thought to be the major antibody class responsible for protective immunity to S. pneumoniae, due to the ability of anti-bacterial capsule IgG antibodies to opsonize the bacteria and promote phagocytosis. However, in addition to IgG, pneumococcal polysaccharides elicit robust IgA antibody responses. It was traditionally thought that these IgA antibodies functioned in neutralization, by blocking bacterial attachment to mucosal epithelial cells. It is now known that IgA antibodies, like IgG, can function as opsonins, to induce phagocytosis and killing of IgA-coated pathogens. This function of IgA antibodies depends on: A.The production of high affinity anti-bacterial IgA antibodies B.The dimeric form of IgA antibodies to bind to multivalent sites on the bacteria C.The ability of dimeric IgA binding to recruit and activate the complement cascade D.The presence of IgA-specific Fc receptors on neutrophils and macrophages E.The ability of IgA antibodies to efficiently cross the epithelial surface and enter the airways
D.The presence of IgA-specific Fc receptors on neutrophils and macrophages
In humans, IgA is produced in copious amounts, estimated to be a rateof 3 g/day. Nearly all of the IgA secreting plasma cells are found in the gastrointestinal (GI) tract where the secreted IgA is transported across the GI epithelium into the lumen of the gut. There, this antibody protects the GI epithelium against intestinal pathogens. Incontrast, none of the GI resident long-lived antibody secreting cells produce antibodies of the IgG class. The differential localization of long-lived antibody secreting cells producing IgA compared to those producing IgG is likely due to: A.Their interactions with TFH cells specific for pathogens that infect the gut B.The lack of germinal centers in the mucosal lymphoid organs C.The absence of S1PR1 expression on IgA-secreting plasma cells D.Their priming and differentiation in mucosal lymphoid organs E.Their inability to access the bone marrow compartment
D.Their priming and differentiation in mucosal lymphoid organs
The W/Wvmouse strain is heterozygous for two different alleles of the gene encoding the growth factor receptor, c-kit, an important receptor expressed on hematopoietic progenitor cells in the bone marrow. The major defect in these mice is theabsence of single lineage of hematopoietic cells. When these mice are challenged with larval Haemaphysalis longicornis ticks, they fail to become resistant to the ticks, in spite of generating high titers of anti-tick IgE antibodies. The cell type missing in the W/Wvmice is most likely:Natural Killer (NK) cells A.Eosinophils B.Tissue-resident dendritic cells C.Tissue-resident macrophages D.Tissue-resident mast cells
D.Tissue-resident mast cells
what are three antigen presenting cells
DC marophages BC
Lymphocytes exit the blood and enter the lymph node by extravasating at the high-endothelial venules (HEVs) present in the lymph node cortex. Extravasation does NOT require which of the following?
DCs
Which of the following does NOT occur during dendritic cell maturation?
DCs activate T cells by trafficking from lymph nodes to sites of infection.
Which of the following represents the earliest stage in T-cell development?
DN
somatic recombination
DNA recombination that occurs between gene segments in the immunoglobulin loci and T cell receptor loci in developing B and T cells. -it generates a complete exon composed of a v gene segment and a j gene segment (and a D gene segment at the heavy chain loci) that encodes the variable region of an immunoglobulin or T cell receptor polypeptide chain -selected at random -L chain- one recombination event- V-j -H chain- two recombination events- D-J (H) then V-DJ (H) -brings gene promoter and enhancer into juxtaposition- permits transcription
broken ends of DNA in the RAG complex are rejoined by what?
DNA repair enzymes and non homologous end joining
Migration Out of the Lymph Nodes
Days after initial activation, activated and memory T cells move from node to other body sites, especially those exposed to pathogens. Migration is mediated by cell surface molecules: ¤CD62L (L-‐Selectin or MEL-‐14) is down-‐regulated (this is the homing receptor for naïve T cells to enter lymphnode) ¤CD49dCD29 (VLA-‐4 integrin) and CD44 are upregulated. They have receptors outside the node in tissues of skin and inflammation site.
Lack of appropriate survival signal:s
Death by neglect refers to which of the following?
dendritic cell migration
Dendritic cells, the key antigen presenting cells of the immune system, are generated from progenitors in the bone marrow that migrate into peripheral tissues through the blood stream. There the immature dendritic cells lie in wait for pathogens entering the body, through sites of injury, for example. Dendritic cells express various pattern recognition receptors that can recognize common features of many bacterial and fungal pathogens. Through these receptors they are able to bind to and phagocytose pathogens. When these receptors bind pathogens, they activate the dendritic cells, which then start to mature. In this process they migrate from the tissues and change their behavior to stop phagocytosis and to start expressing immune stimulatory molecules. The activated dendritic cells migrate from the tissues into lymphatic vessels, where lymphatic fluid drains through lymph nodes, carrying the dendritic cells with it. T cells, migrating through the lymph nodes, inspect the dendritic cells for the presence of antigen. T cells that fail to recognize antigen on one dendritic cell carry on to inspect others and eventually return again to the circulation. T cells that do recognize their specific antigen become activated, and both proliferate and differentiate into effector cells.
Indicate whether each of the following statements is true or false. If you believe a statement is false, explain why: A) Cytokines can regulate which branch of the immune system is activated. B) Both CTLs and NK cells release perforin after interacting with target cells. C) Activation of naïve CTL-Ps requires a co-stimulatory signal delivered by interaction of CD28 and CD80/86 D) CTLs use a single mechanism to kill target cells. E) CD4+ T cells are absolutely require for the activation of naïve CD8+ T cells F) The ability of an NK cell to kill a target cell is determined by signals received through both activating and inhibiting receptors G) Human NK cells express functional Ly49 receptors H) NK cells must express inhibitory receptors for self-MHC class I proteins in order to develop the capacity to kill altered-self cells.
(A) True. (B) True. (C) TRUE (D) False. Th ere are two pathways by which cytotoxic T cells kill target cells. One pathway is perforin (E) False. Naïve CD8 T cells can be activated in the absence of CD4 T-cell help. T-cell help, however, is required for optimal proliferation and memory generation. (F) True. (G) False. Ly49 receptors are found on murine cells. Human NK cells express KIR receptors
Indicate whether each of the properties listed below is exhibited by either NK cells, CTLs, NKT cells, All (of these cell populations), or None (of these cell populations). Note, not all cells in the population have to have the property to list them in your answer. A. Can make IFN B. Can make IL-2 C. MHC Class I restricted D. Express CD8 E. Cytotoxic capability F. Express NK1.1 G. Express CD4 H. Express CD3 I.Recognize lipids J.Can express the IL-2 receptor K. Express T cell receptor L. Respond only to soluble antigens M. Produce perforin N. Express FasL
(a) All. (b) All. (c) CTL. (d) CTL. (e) All. (f) Some NK and NKT. (g) Some NKT. (h) CTL and NKT. (i) NKT. (j) All. (k) CTL and NKT. (l) None. (m) All. (n) Some CTLs.
Indicate whether each of the properties listed below is exhibited by either NK cells, CTLs, NKT cells, All (of these cell populations), or None (of these cell populations). Note, not all cells in the population have to have the property to list them in your answer. A. Can make IFN B. Can make IL-2 C. MHC Class I restricted D. Express CD8 E. Cytotoxic capability F. Express NK1.1 G. Express CD4 H. Express CD3 I.Recognize lipids J.Can express the IL-2 receptor K. Express T cell receptor L. Respond only to soluble antigens M. Produce perforin N. Express FasL
(a) All. (b) All. (c) CTL. (d) CTL. (e) All. (f) Some NK and NKT. (g) Some NKT. (h) CTL and NKT. (i) NKT. (j) All. (l) CTL and NKT. (l) None. (m) All. (n) Some CTLs.
The following sentences are all false. Identify the error(s) in each sentence and correct the sentences to be true. A) Macrophages activate naïve T cells better than dendritic cells B) ICOS enhances T-cell activation and is called a co-inhibitory C) Virtually all cells in the body express co-stimulatory ligands D) CD28 is the only co-stimulatory receptor that binds to B7 family members E) Signal 3 is provided by negative co-stimulatory receptors. F) CD4+ T cells interact with MHC class I on CD8+ T cells G) Naïve T cells produce IFN- H) T-Bet and GATA-3 are effector cytokines I)Polarizing cytokines are produced only by APCs J) Bcl-6 is involved in the delivery of co-stimulatory signals K) TH17 and TFH cells subsets are the major sources of B-cell help L) pTREG cells enhance inflammatory disease M) Effector cytokines act exclusively on T cells N) Central memory T cells tend to reside at the site of infection O) Like naïve T cells, effector memory cells express CCR7
(a) Dendritic cells are best at activating naïve T cells— they express a high density of co-stimulatory ligands and MHC molecules. (b) ICOS is a positive co-stimulatory receptor (it is expressed on some effector T cells, including TFH cells). (c) Most cells do not express co-stimulatory ligands. Professional APCs (and thymic epithelial cells) are among the only cells that do. (d) ICOS and CTLA-4 also bind B7 family members (CD80 and CD86). PD1 also binds a B7 like molecule, PD-L1. (e) Signal 3 is provided by cytokines, which include the polarizing cytokines that induce helper T-cell lineage differentiation. (f) They do not have any receptor forMHC class I and do not interact directly with CD8 T cells via their TCRs, which bind to MHC class II. (g). Naïve T cells produce IFN-gamma. (h) They are master transcriptional regulators ofT helper cell lineage differentiation. (i) APCs can make some polarizing cytokines, but many of these cytokines originate from other cells, including other T cells, B cells, mast cells, and NK cells. (j) T-bet is a master transcriptional regulator of TFH lineage differentiation. (k) TFH and TH2 are classically the major sources of B-cell help, although all helper subsets can interact with B cells and influence Ig class switching. (l) They inhibit T-cell activation. (m) Effector cytokines have many different cellular targets, including B cells, endothelial cells, stromal cells in tissues, innate immune cells, and so on, as well as other T cells. (n) Central memory cells tend to reside in secondary lymphoid organs. (o) CCR7 attracts cells to secondary lymphoid tissue, and effector cells tend to rove the periphery. They typically downregulate CCR7.
The following sentences are all false. Identify the error(s) in each sentence and correct the sentences to be true. A) Macrophages activate naïve T cells better than dendritic cells B) ICOS enhances T-cell activation and is called a coinhibitory C) Virtually all cells in the body express costimulatory ligands D) CD28 is the only costimulatory receptor that binds to B7 family members E) Signal 3 is provided by negative costimulatory receptors. F) CD4+ T cells interact with MHC class I on CD8+ T cells G) Naïve T cells produce IFN- H) T-Bet and GATA-3 are effector cytokines I)Polarizing cytokines are produced only by APCs J) Bcl-6 is involved in the delivery of costimulatory signals K) TH17 and TFH cells subsets are the major sources of B-cell help L) pTREG cells enhance inflammatory disease M) Effector cytokines act exclusively on T cells N) Central memory T cells tend to reside at the site of infection O) Like naïve T cells, effector memory cells express CCR7
(a) Dendritic cells are best at activating naïve T cells— they express a high density of costimulatory ligands and MHC molecules. (b) ICOS is a positive costimulatory receptor (it is expressed on some effector T cells, including TFH cells). (c) Most cells do not express costimulatory ligands. Professional APCs (and thymic epithelial cells) are among the only cells that do. (d) ICOS and CTLA-4 also bind B7 family members (CD80 and CD86). PD1 also binds a B7 like molecule, PD-L1. (e) Signal 3 is provided by cytokines, which include the polarizing cytokines that induce helper T-cell lineage differentiation. (f) They do not have any receptor for MHC class I and do not interact directly with CD8 T cells via their TCRs, which bind to MHC class II. (g). Naïve T cells produce IFN-gamma. (h) They are master transcriptional regulators of T helper cell lineage differentiation. (i) APCs can make some polarizing cytokines, but many of these cytokines originate from other cells, including other T cells, B cells, mast cells, and NK cells. (j) T-bet is a master transcriptional regulator of TFH lineage differentiation. (k) TFH and TH2 are classically the major sources of B-cell help, although all helper subsets can interact with B cells and influence Ig class switching. (l) They inhibit T-cell activation. (m) Effector cytokines have many different cellular targets, including B cells, endothelial cells, stromal cells in tissues, innate immune cells, and so on, as well as other T cells. (n) Central memory cells tend to reside in secondary lymphoid organs. (q) CCR7 attracts cells to secondary lymphoid tissue, and effector cells tend to rove the periphery. They typically downregulate CCR7.
Indicate whether each of the following statements regarding Fas-mediated, or perforin-mediated programmed cell death is true of false. If you believe a statement is false, explain why. A) Both mechanisms induce apoptosis in target cells B) Target cells must express FasL to be killed via the Fas-mediated pathway C) Only the perforin mediated pathway stimulates a caspase cascade. D) Both pathways require granzyme to induce apoptosis E) Both pathways lead to the activation of caspase-3 F) Granzyme is responsible for the assembly of membrane pores
(a) True. (b) False. They need to express Fas, which transmits the pro-apoptotic signal. (c) False. Both mechanisms induce caspase activation. (d) False. Only the perforin-mediated pathway depends on granzyme activity. (e) True. (f) False. Perforin is responsible for the development of surface membrane and endocytic membrane pores.
Indicate whether each of the following statements regarding Fas-mediated, or perforin-mediated programmed cell death is true of false. If you believe a statement is false, explain why. A) Both mechanisms induce apoptosis in target cells B) Target cells must express FasL to be killed via the Fas-mediated pathway C) Only the perforin mediated pathway stimulates a caspase cascade. D) Both pathways require granzyme to induce apoptosis E) Both pathways lead to the activation of caspase-3 F) Granzyme is responsible for the assembly of membrane pores
(a) True. (b) False. They need to express Fas, which transmits the pro-apoptotic signal. (c) False. Both mechanisms induce caspase activation. (d) False. Only the perforin-mediated pathway depends on granzyme activity. (e) True. (f) False. Perforin is responsible for the development of surface membrane and endocytic membrane pores.
Like TH1 and TH2 cells, TH17 cells and TREG cells cross-regulate each other. Which of these two statements about this cross-regulation is/are true? Correct the statement, if false. A. TGF- is a polarizing cytokine that stimulates up-regulation of each of the master transcriptional regulators that polarize T cells to the TH17 and TREG lineages B. IL-6 inhibits polarization to the TREG lineage by inhibiting expression of RORT
(a) True. It stimulates production of both FoxP3 and ROR gamma. (b) False. IL-6 in combination with TGF-beta polarizes cells to the TH17 lineage, an event that requires ROR gamma. IL-6 acts in part by inhibiting expression of FoxP3.
Like TH1 and TH2 cells, TH17 cells and TREG cells cross-regulate each other. Which of these two statements about this cross-regulation is/are true? Correct the statement, if false. A. TGF- is a polarizing cytokine that stimulates up-regulation of each of the master transcriptional regulators that polarize T cells to the TH17 and TREG lineages B. IL-6 inhibits polarization to the TREG lineage by inhibiting expression of RORT
(a) True. It stimulates production of both FoxP3 and ROR gamma. (b) False. IL-6 in combination with TGF-beta polarizes cells to the TH17 lineage, an event that requires ROR gamma. IL-6 acts in part by inhibiting expression of FoxP3.
A virus enters a cut in the skin of a mouse and infects dendritic cells, stimulating a variety of PRRs both on and within the dendritic cells that induce them to produce IL-12. The mouse subsequently mounts an immune response that successfully clears the infection. Which of the following statements are likely to be true about the immune response that occurred? Correct any statements that are false to make them true. A) The infected dendritic cells up-regulated CD80/CD86 and MHC Class II B) The dendritic cells encountered and activated naïve T cells in the skin of the mouse C) Naïve T cells activated by these dendritic cells generated signals that release internal Ca2+ stores D) Naïve T cells activated these dendritic cells were polarized to the TH2 lineage. E) Only effector memory T cells were made in this mouse
(a) Very likely. Any activated professional APC, like a dendritic cell, up-regulates MHC molecules and co-stimulatory ligands, making them ideal activators of T cells. (b) Very unlikely. Activated dendritic cells travel to the draining lymph nodes (or spleen) and encounter naïve T cells there, not in peripheral tissues. Naïve T cells travel among secondary lymphoid organs, not peripheral tissues. However, effector T cells and some memory T cells, do travel to peripheral tissues and can be activated by dendritic cells there. (c) Very likely. TCR stimulation rapidly induces Ca2+ mobilization. (d) Very unlikely. The virus induced dendritic cells to make IL-12, one of the central polarizing cytokines for the TH1 lineage. (e) Very unlikely. Central memory cells were certainly generated, too.
A virus enters a cut in the skin of a mouse and infects dendritic cells, stimulating a variety of PRRs both on and within the dendritic cells that induce them to produce IL-12. The mouse subsequently mounts an immune response that successfully clears the infection. Which of the following statements are likely to be true about the immune response that occurred? Correct any statements that are false to make them true. A) The infected dendritic cells up-regulated CD80/CD86 and MHC Class II B) The dendritic cells encountered and activated naïve T cells in the skin of the mouse C) Naïve T cells activated by these dendritic cells generated signals that release internal Ca2+ stores D) Naïve T cells activated these dendritic cells were polarized to the TH2 lineage. E) Only effector memory T cells were made in this mouse
(a) Very likely. Any activated professional APC, like a dendritic cell, up-regulates MHC molecules and costimulatory ligands, making them ideal activators of T cells. (b) Very unlikely. Activated dendritic cells travel to the draining lymph nodes (or spleen) and encounter naïve T cells there, not in peripheral tissues. Naïve T cells travel among secondary lymphoid organs, not peripheral tissues. However, eff ector T cells and some memory T cells, do travel to peripheral tissues and can be activated by dendritic cells there. (c) Very likely. TCR stimulation rapidly induces Ca2+ mobilization. (d) Very unlikely. The virus induced dendritic cells to make IL-12, one of the central polarizing cytokines for the TH1 lineage. (e) Very unlikely. Central memory cells were certainly generated, too.
AID
(activation-induced cytidine deaminase) enzyme that deaminates DNA at cytosine resides, converting them to uracil. The activity of this enzyme and consequent repair of the damaged DNA is the basis of somatic hypermutation and isotope switching in activated B cells -expressed only by B cells initiate the process - somatic mutation takes place in the V region of an antibody - SH in B cells requires T cell help (he per T cells) - can help B cells make diff hyper mutation
Superantigens bind by
*In the case of a superantigen the intact protein binds to class II MHC molecules and to one or more Vβ regions of the TCR *The antigen is not bound to the peptide binding groove of the MHC molecule or to the antigen binding site of the TCR *Any T cell that uses a particular Vβ in its TCR will be activated by a superantigen, resulting in the activation of a large numbers of T cells *Each superantigen will bind to a different set of Vβregions.
The C region of an antibody
- Constant region - Determines the fate of the antigen - Less variation in amino acid sequence between -antibodies in the C region
Antibodies
- Five chemically and physically distinct classes of antibodies (IgG, IgA, IgM, IgD, IgE) - Bind with high specificity and affinity - Produced by the B lymphocytes in response to infection - Circulate as a major component of the plasma in blood and lymph - Bind to pathogenic microorganism and their toxins in the extracellular spaces of the body - Antibody repertoire might be as high as 1016
How do Naïve T lymphocytes home to lymph nodes
- Mediated by CD62L on the surface of naïve T cells - Binds to addressins on vascular endothelium on boundary of lymph nodes - Interaction triggers the naïve T cells to leave circulation by entering the node
plasmacytoid dendritic cells
- very effective at producing IFNs in response to viral infections - protect cells from viral infections - also express chemokine receptors from class I and II - also have ICAMs
Parts of an antibody
-4 polypeptide chains -peptides with variable and constant regions: -2 heavy chains, 2 light chains, N terminal L and H chains
Dendritic Cells
-Found all of the body and act as sentinel cells beneath the barriers of epithelial cells -In normal uninfected cells,act as tasters of the environmentCan take up 4 times their volume in extracellular fluid per hour -Resting state dendritic cells have minimal B7 and MHC molecules on surface -Not effective at presenting antigen in resting state
Explain the route when antigens enter the body through the bloodstream
-It is carried throughout the circulatory system to the spleen where they interact with APC (DCs and macrophages). -The APCs take up, process and then present components of the antigen to the T cells that express the appropriate antigen-specific TCR. -This reaction together with the other co-stimulatory signals derived from cell-cell interaction, activates the T cells. -Splenic B cells expressing antigen-specific BCRs are also activated following exposure to antigen, a process facilitated by the cytokines produced by antigen-activated T cells.
During Ig VH recombination, the processes that contribute to additional diversity at the third complementarity-determining region include
-N nucleotide addition -P nucleotide addition -exonuclease cleavage of the ends of the gene segments -introduction of the D gene segments into the heavy-chain V gene
Explain the route when antigens lodge in the epidermal, dermal, or subcutaneous tissues
-Once they are lodged into the epidermal, dermal or subcutaneous tissues, the antigen (free or trapped by APCs) is transported through the afferent lymphatic channels into the regional draining lymph node. -In the lymph node, the antigen, macrophages, DCs, T cells, and B cells interact to generate an immune response -The antigen-specific T cells and antibodies (synthesized in the lymph node) enter the circulation and are transported to the various tissues -Antigen-specific T and B cells, and antibodies also enter the circulation via the thoracic duct
The formation of a DNA coding sequence for the variable region of Ig involves
-Recombination of signal sequences -the 12/23 rule -DNA rearrangements
First and second hypervariable region of light-chain (CDR1, 2) are encoded by _______________________, the third CDR is determined by the ____ junction
Different V segments; V/J
First and second hypervariable region of heavy-chain (CDR1, 2) are encoded by ____________________, the third CDR is determined by the ____________________________ and the _____ and _____ junctions
Different V segments; different D sections; V/J and D/J
___________________________ to the same antigen ______ considerably in their ______ for an _________
Different antibodies; vary; affinity; epitope
Genetic Polymorphism
Different individuals have different forms of their MHC class I or class II genes Basis for rapid graft rejection between genetically different individuals
antibodies
-form of immunoglobulin produced by effector B cells that clears extracellular pathogens and their toxins
IgA
-monomeric IgA secreted into blood, lymph -dimeric IgA (with J chain) made in GALT/MALT, secreted across mucosae -most abundant immunoglobulin in secretions, more made overall than other isotypes
IgM
-pentamer form increases avidity- 10 binding sites available -other isotope monomeric- 2 antigen binding site -binding to antigen exposes complement binding site in C region
V region encoded by 2-3 gene segments
-requires gene rearrangement to produce an exon that can be transcribed
IgG2
-second most abundant -additional disulfide bonds = decreased flexibility, proteolysis, complement activation -preferentially made against highly repetitive carbohydrate antigens -deficiency of IgG2- poor control of encapsulated bacteria
Recombinational signal sequences (RSSs)
-short stretch of DNA flanking each of the gene segments that are rearranged to generate V-region exons -sites at which somatic recombination occurs -recombination only between different types of RSS (12/23 RULE)- ensures correct ordering of gene segments -provide recognition sites for enzymes, ensure correct ordering of gene segments
mechanism of class switching
-transcription of new C-region gene initiated -AID targets Sm and Sg1, leads to base excisions -Nicked strand of DNA recombine, new gene transcribed
_____________ segments encode __________ peptide (L), _____________ region (V) and __________ regions (C).
Different; leader; variable; constant
Antibody heavy and light chain polypeptides consist of repeated domains, each of which is ~110 amino acids and folds up into a compact three-dimensional structure known as an 'immunoglobulin domain.' These immunoglobulin domains are:
...
Hypervariable Regions
...
Which of the following statements about pattern-recognition receptors on innate immune cells is/are true? 1. pattern-recognition receptors trigger cells to coordinate killing of pathogens. 2. pattern-recognition receptors trigger cells to alert the adaptive immune system of an infection. 3. pattern-recognition receptors each recognize a specific pathogen 4. pattern-recognition receptors are only expressed on APCs
1 and 2
Which of the following statements about pattern-recognition receptors on innate immune cells is/are true? 1. pattern-recognition receptors trigger cells to coordinate killing of pathogens. 2. pattern-recognition receptors trigger cells to alert the adaptive immune system of an infection. 3. pattern-recognition receptors each recognize a specific pathogen 4. pattern-recognition receptors are only expressed on APCs
1 and 2 only
Critical Events in T Cell Activation
1) Binding of MHC and T cell receptor 2) CD45 removes a phosphate from LCK 3) LCK phosphates ITAMs (CD3) 4) FYN associates with phosphorylated CD3s and activates ZAP70 5) ZAP70 docks with zeta chains and activates LAT and SLP 6) This complex activates PLCγ 7) PLCγ activates transcription factors NFAT, NFκB, AP1 8) Expression of cytokines and cell surface receptors
______________ IgA is made in lymphoid tissue underlying mucosal surfaces and is the antibody secreted into the lumen of the gut
Dimeric
Non-lymphoid cells of thymus provide
1) Critical surface interactions required for development of T cells 2) Produce cytokine interleukin 7- Induces proliferation of cells in early T and B cell development
Two different kinds of signals activate dendritic cells
1) First type comes from other immune system cells that are engaged in battle or dying- TNF released by neutrophils and macrophages can activate dendritic cells 2) Second type of signal involves receptors that recognize molecular patterns that are characteristic of a broad class of microbes Ex: TLRs
Upon activation, the dendritic cell
1) Leaves the tissues and migrates through the lymphatic system to the lymph node 2) Has increased expression of B7 on surface 3) Has increased expression of MHC class II molecules on the surface (or if infected with viruses, MHC class I molecules) 4) Synthesizes high levels of chemokines (pro-‐inflammatory cytokines) 5) In the lymph node, dendritic cells present antigen to naïve T cells
Life of a T-cell
1) Lymphoid precursor cell 2) Double Negative Cell 3) Pre-T-cell 4) Double Positive Cell 5) Naive T-Cell 6) Memory T-Cell or Effector Cells
MHC Association with Resistance and Susceptibility to Disease
1) Polymorphism of MHC genes and molecules • Problematic for transplantation, Highly unlikely that two individuals will have same MHC 2) Variability is mechanism for protection against variety of pathogens • The more variability in the MHC, the more peptides that will be presented 3) Expression of specific HLA alleles has been associated with susceptibility or resistance to infectious diseases such as: • Human T lymphotropic virus 1, hepatitis B, leprosy, malaria, tuberculosis, and rapid progression to AIDS
List the similarities between B cell receptors and T cell receptors
1) TCR is clonally selected like BCR 2) TCR is part of immunoglobulin superfamily 3) T cell receptor (TCR) comprised of α & β chains 4) Transmembrane glycoproteins linked by disulfide bond 5) Made up of variable (V) and constant (C) regions 6) V regions contain complementarity determining regions that make up the antigen binding pocket
List the differences between B cell receptors and T cell receptors
1) Valence and conformation -TCR is 2-chain structure that has a single antigen binding site -Ig is 4-chain structure that has 2 antigen binding sites 2) Antigen recognition -Ig binds to many types of antigens and can respond to linear and conformational epitopes -TCR interacts with small linear protein fragments expressed on the surface of the host cell that is presented on MHC molecule -Interacts with MHC molecule and small portion of peptide -Vα & Vβ CD3 interacts with 2-3 amino acids of peptide sequence 3) Secretion of the receptor -TCR does not exist in a secreted form and is not secreted in response to activation by antigen -Ig is secreted in response to activation by antigen 4) No change in the TCR during the response to antigen -Ig molecules undergo somatic hypermutation and class switching -TCR does not change during response to antigen
What are the 2 ways that CD8+ kill
1) use of cytotoxic granules to kill 2) use FasL to interact with Fas to activate the FasDD
Steps in MHC Class I Pathway Endogenous Antigens: Generation of MHC Class I-peptide Complexes
1)Endogenous Antigens Proteins are fragmented in the cytosol by proteosomes (a complex of proteins having proteolytic activity) or by other proteases. 2)The fragments are then transported across the membrane of the endoplasmic reticulum by transporter proteins (TAP1 and TAP2) 3)Synthesis and assembly of class I heavy chain (alpha) 4) Calnexin helps further fold alpha chain 5) Calnexin transfers the chain to calreticulin which aids further folding and the association of β2-microglobulin 6) Erp57 and Tapasin further stabilize the complex 7) Short peptides are then loaded via peptide editing to find the best binding peptide, causes final folding and disassociation of other chaparones. 8)Transported through the golgi apparatus to the cell surface
Steps in MHC Class II Pathway Processing and Presenting of Exogenous Antigen
1)Exogenous antigen is internalized into phagosome 2)Phagosome fuses with endosome or lysosome 3)Exogenous proteins taken in by endocytosis are fragmented by proteases in an endosome 4)The alpha and beta chains of MHC class II, along with an invariant chain, are synthesized and assembled in the endoplasmic reticulum. 5)The invariant chain prevents endogenous peptides from the cytosol from associating with class II MHC molecules 6)The class II MHC molecules with the associated invariant chain are transported through the Golgi and trans-Golgi apparatus to reach the endosome 7)Nearly all of the invariant chain is digested, except for a remaining fragment referred to as CLIP 8)The peptide fragments from the exogenous protein are able to associate with the class II MHC molecules this association is mediated by HLA-DM, which removes CLIP 9) Transported to the cell surface
how many subclasses of IgG?
1,2,3,4 each have different and complementary functions -flexibility of hinge region offset by increased susceptibility to proteolytic cleavage -evolution of four isotypes of IgG differ in C region of heavy chains (mainly hinge region)
Describe the properties of IgE
1. Able to move into extravascular space.
3.33 Short answer: Individuals with natural killer (NK) cell deficiencies have susceptibilities to infections with herpesviruses and other DNA viruses, as well as with intracellular bacteria such as the mycobacteria that cause tuberculosis. Mycobacterium tuberculosis is a pathogen that infects macrophages and replicates in their phagocytic vesicles. Which effector function of NK cells is likely most important in promoting immunity to M. tuberculosis?
1. Activated NK cells secrete large amounts of IFN-. 2. IFN- directly activates macrophages to enhance their phagocytosis 3. IFN- promotes the differentiation of TH1 CD4 T cells 4. NK cells also produce cytokines and chemokines to recruit macrophages
What is IgM responsible for?
1. Activation of complement (it is very effective at this). 2. It is the first AB made in the immune response.
Explain the process of expressing IgM and IgD.
1. All B cells (even before an antigen encounter) will express the constant region for IgM and IgD. 2. When the time comes, the constant region for IgD will be left out and the the constant region for IdM will remain. 3. The same occurs for IgD except the IgM region will be left out.
Describe the properties of IgG.
1. Can cross placenta. 2. They diffuse into extravascular sites.
TLR signaling in immature dendritic cells in induce what two things
1. Dendritic cell expresses CCR7 which allows chemokine CCL21 to bind to it, changing the behavior of the dendritic cell and now the dendritic cell is program to activate T cells. 2. The processing of antigen take up into phagosomes
Describe the 5 types of constant heavy chains of an antibody and the 2 types of constant light chains.
1. Heavy chains- gamma, alpha, epsilon, mu, delta. 2. Light chains- kappa, lambda. +
When an effector TH1 cell specific for a bacterial peptide contacts an infected macrophage, the T cell is induced to secrete two signals to activate it, what are the two signals
1. IFN-γ: 2. CD40 ligand:
What are the five types of antibodies?
1. IgG 2. IgM 3. IgD 4. IgA 5. IgE
What does RAG-2 do?
1. It recognizes and binds the 12 nucleotide spacer between the V and the J region (light chains). In the heavy chain it is between the V and the D region. 2. Working with RAG-1, it works to cut out the portion between V and J.
What does RAG-1 do?
1. It recognizes and binds the 23 nucleotide spacer between the V and the J region (light chains). In the heavy chain it is between the V and the D region. 2. Working with RAG-2, it works to cut out the portion between V and J.
What is an activation induced cytidine deaminase (AID)?
1. It removes an amine group from cytidine which converts it to uridine. 2. Other enzymes then change the uridine into one of the other four nucleotide bases. 3. This allows immunoglobulins to change forms. For example, IgM can change to IgG, etc.
What are the gene segments that are used to encode the v region of an antibody?
1. Lambda light chain locus. 2. kappa light chain locus 3. heavy chain locus. 4. Only one of the light chains is expressed at a time (allelic exclusion)
Describe the structure of antibodies (light chain and heavy chain).
1. Light chain is shorter and is connected to heavy chain via disulfide bonds. 2. Heavy chains are long and connected to each other and to the light chain via disulfide bonds. 3. The N-terminus has the antigen bind site.
What is a linear epitope? Discontinuous epitope?
1. Linear epitope- The anitgen binds to the antibody sequentially. 2. Discontinuous- Antigen binds to antibody in a non sequential way.
What is IgA responsible for?
1. Neutralization of pathogens.
What is IgG responsible for?
1. Neutralization. 2. Opsonization. 3. Sensitization (for NK). 4. Activation of complement.
Descibe how the D and J regions become connected.
1. RAG complex will cleave the recombinant signaling sequence from the ends of both J and D. 2. Now the ends of the nucleotides are exposed and they covalently bond to the nucleotide on the opposite strand within the same DNA molecule. 3. RAG breaks this covalent bond and extends the DNA molecule. 4. New nucleotides are added to the ends of these strands and J and D nucleotides bond together. 5. Correctly bonded nucleotides will stay in place, whereas incorrectly bonded will be excised. 6. New nucleotides are added to fix the rest of the DNA sequence.
Describe the different states that a B cell undergoes.
1. Resting- has membrane bound Ig's which can bind to antigens. 2. Antigen bound- has bacteria bound and which start to producing antibody producing plasma cells. 3. Plasma cell- secretes antibodies into the interstitium which can bind to specific antigens.
What is IgE responsible for?
1. Sensitizing mast cells (allergies)
What two signals are required to activate T cells?
1. T cell expression of peptide (epitope)- specific TCRs 2. Ligation of T-cell expressed co-stimulatory molecules with Complimentary membrane molecules expressed by APCs
major components of cell-mediated immunity
1. T cell-mediated cytotoxicity, 2. macrophage activation by effector T cells, 3. help B cells to trigger antibody production.
What determines the isotype of an antibody?
1. The heavy chain is the only factor that will what isotype is expressed.
How does the heavy chain rearrange to form a gentically distinct antibody sequence?
1. The intron between D region and J region is spliced. 2. Then region between V and newly formed DJ region is spliced. 3. Both of these are somatic recombinations.
How does the light chain rearrange to form a genetically distinct antibody sequence?
1. The intron between the V region and the J region is spliced out and the V and J region are bound together. 2. This is called somatic recombination. 3. There are multiple V and J regions but only one of each are combined to for the variable region of the light chain. (This is done for each of the V regions on the light chain because there are multiple V sections.) 4. The constant region of the light chain is encoded by one C region on the loci.
What does isotype switching do to AB in terms of antigen specificity?
1. The new Immunoglobulin will have a different C region, but the antigen binding region will be the same.
Describe the difference, in terms of genetic makeup, between a secreted Imunoglobulin and a transmembrane Imunoglobulin.
1. They are basically the same makeup 2. The major difference between them are that the transmembrane (hydrophobic) portion of the DNA is expressed in transmembrane Imunoglobulins. This occurs at the carboxy terminus of the immunoglobulin. 3. This portion is left off for secreted Imunoglobulins and replaced with a hydrophilic carboxy terminus.
Two major functions of the secondary lymphoid organs
1. They are highly efficient in trapping and concentrating foreign substances 2. They are the main sites of production of antibodies and the induction of antigen-specific T lymphocytes
Describe the properties of IgM
1. They can move across the epithelium. 2. They can somewhat move into extravascular sites.
What are the different regions of the light and heavy chains alleles called?
1. V- variable 2. J- joining 3. D- diversity 4. C- constant
Describe the structure of antibodies (variable and constant regions).
1. Variable regions are on the ends and they are where the antigen can bind. The variable region is on both the light and the heavy chains. 2. The constant region is unchanged throughout antibodies. It is on both the heavy and the light chains.
Describe the properties of IgA.
1. Very good at moving across the epithelium (as a dimer) 2. Good at moving into extravascular space (as a monomer).
What do DNA ligase-4 and DNA-depedent protein kinase do? (Blue hot dog)
1. Works to affix the V to J bond. 2. It also introduces new nucleotides that are not sequenced in the genome.
signal 1, 2, 3 are what
1. activation 2. survival 3. differentiation
what are the three different types of signals involved in activation of naive T cells by APC
1. antigen specific signals 2. costimulatory signals 3. signals for t-cells differentiation
pathogen and their products must be transported to lymphoid tissues to be picked up by APCs, what are they three different kind of ways
1. antigens in the bloodstream are picked up by APCs in the spleen 2. pathogen infected sites like the skin wound are transported in the lymph and trapped in the lymph node nearest to the infection (as intact antigen or antigen-MHC complex on DC) 3. pathogen infecting muscosul surfaces are transported directly across the muscosa to lymphoid tissues such as peyer's patches or tonsils.
naive T cells recognizing self peptides can not become activated instead they become what three things
1. clonal deletion 2. angery 3. regulatory T cells
Dendritic cells, macrophages, and B cells are the main cell types that present foreign antigens to T cells. But their reasons for antigen presentation are different in what ways
1. dendritic cells is primarly to active naive T cells for expansion and differentiation 2. M and B cells present antigen primary to receive help from effector T cells in the from of cytokines or surface molecules
Two outcomes are possible for circulating naive T cells:
1. if they do not encounter their specific antigen, they exit from the lymphoid tissue via the efferent lymphatics, eventually reenter the bloodstream and continue recirculating. 2. when a naive T cell recognizes its specific antigen on a mature dendritic cell, it stops mirgration, profilerates (clonal expansion) and differentiates into effector T cells and memory T cells of identical antigen specificity
Because the effector actions of cytotoxic T cells are so destructive, naive CD8 T cells require more co-stimulatory activity than do naive CD4 T cells. more co-stimulatory activity can be provided in what two ways?
1. in some viral infection DCs become sufficiently activated to have high intrinsic co-stimulatory activity that directly activate naive CD 8 t cells. 2. in Majorcity of viral infections naive CD 8 activation requires additional help provided by effector cd 4 T cell (th17)
how does CD 4 T cells help naive CD 8 become activated
1. inducing increased levels of co-stimulatory active ( of two types: CD 80.86 and 4-IBBL) on APC 2. producing abudant IL-2
what are two main groups of regulatory T cells
1. natural regulatory t cells 2. induced regulatory T cells
Cytotoxic granules are modified lysosomes that contain distinct classes of cytotoxic effector proteins that are expressed specifically in cytotoxic T cells, what are those 4 distinct classes
1. perforin 2. grandzymes 3. granulysin 4. Serglycin
The main classes of adhesion molecules involved in lymphocyte interaction are
1. selectins 2. vascular addressins 3. integrins 4. immunoglobulin superfamily
naive T cells recognizing self peptides are normally not activated,because
1. self peptide can be presented by MHC class 1 molecules expressed on pheripheral tissues, but pherpheral tisssues do not express co stimulatory molecules thus no activation 2. self peptide can be presented by MHC molecules expressed on DCS but without infection DC molecules express very low levels of co-stimulatory molecules
what three effects does CCL21 signaling through CCR7 have on dendritic cells other than migration
1. they can no longer phagocytosis or macropinocytosis of antigens. 2. they express high levels of long-lived MHC class 1 and III molecues 3. they also have high levels of co stimulatory molecules
Monoclonal Antibody Humanization
1. to prevent anti-antibody immune response 2. to engage the human effector cells through Fc region therapy uses antibody that are made in a lab. once given, antibodies may recruit immune system to destroy the targeted antigen (ex: cancer cells)
how are effector T cell different from naive T cells
1. when effector T cells encounter with its specific target, they act on it without need for CD 80 co stimulation 2. effector T cells change the cell-adhesion molecules and receptors on the celll surface
___________ rule ensures that gene segments are joined in the correct order
12/23
How many peptides can MHC class II bind and why
13-25 peptides because it is open
Heavy-chain locus on chromosome
14
1-5. Match the immunosuppressive drugs with their working mechanisms 1. Corticosteroids 2. Cytotoxic drugs such as azathioprine and cyclophosphamide 3. Cyclosporin A and tacrolimus (FK506) 4. Rapamycin (sirolimus) 5. Fingolimod, a S1P analog A. Retention of effector lymphocytes in lymphoid organs B. Alteration of gene transcription profile C. Inhibition of cell growth and proliferation by inhibiting mTOR activity D. Interference with DNA synthesis E. Inhibition of calcineurin activity, NFAT activation, and IL-2 production
1: B 2: D 3: E 4: C 5: A
Three major routes followed by an antigen after it has penetrated the interior of the body
1: Enter through the bloodstream 2: Lodge in the epidermal, dermal, or subcutaneous tissues 3: Enter the gastrointestinal or respiratory tract where it lodges in the MALT and BALT.
H chain of antibody
1VH domain, 3-4 CH domains -the larger of the two types of polypeptides in an immunoglobulin molecule -come in a variety of heavy chain isotypes, each of which confers a distinctive effector function on the antibody molecule
L chain of antibody
1Vl domain, 1 CL domain disulfide-bonded to a heavy chain in the immunoglobulin molecule -k and lambda -the smaller of the two types of polypeptide chains in immunoglobulin molecules.
kinetics of handling viral infection
1st 3 days: in lung dealing with initial infection - infiltration of neutrophils and natural killers- in tissues introducing IFNs viral production leveling off (not growing) - T cells come from lymph node to fight infection. but take 1 week to produce T cells. unless memory response = shorter interval of time
k Light-chain on chromosome
2
Which of the following occurs when macrophages become activated after phagocytosing a pathogen? 1. Presentation of peptides from the pathogen on MHC class I molecules 2. Secretion of inflammatory mediators to recruit and activate T cells and neutrophils 3. Direct activation of B cells by macrophages 4. An increase in co-stimulatory molecules for interacting with T cells
2 and 4 only
Which of the following occurs when macrophages become activated after phagocytosing a pathogen? 1. Presentation of peptides from the pathogen on MHC class I molecules 2. Secretion of inflammatory mediators to recruit and activate T cells and neutrophils 3. Direct activation of B cells by macrophages 4. An increase in co-stimulatory molecules for interacting with T cells
2 and 4 only
Light-chain on chromosome
22
A RAG complex binds to the __________________ (2-turn RSS) and another to the 1_________________ (1-turn-rss)
23-bp spacer; 12-bp spacer
end of slide 28
28
One RSS is located ___ to each V gene segment and ___ to each J gene segment, and on ________________ of each D gene segment.
3'; 5'; both sides
switch regions
5' to each C gene transcription of new C region gene initiated -AID targets switch regions (old and new) -nicked DNA strands combine
About _______% of the spleen cells are B lymphocytes. _____% are T lymphocytes
50; 30-40%
Using only random VDJ recombination, from 40V, 23 D, and 6J gene segments, what are the number of possible variable regions of an antigen receptor molecule?
5520 (40x23x6)
In a heterozygous individual, what is the maximum number of different MHC molecules that an epithelial cell normally expresses at its surface?
6
Every cell within one person expresses up to how many HLA class I molecules
6 different HLA class I molucules- Three from each chromosome Some individuals may be homozygous and express fewer than 6 different molecules
7-10. Match each allergic reaction with the corresponding immune process 7. Arthus reaction 8. Poison ivy rash 9. Serum sickness 10. Nickel allergy A. Formation of local immune complexes caused by IgG antibodies acting against an antigen in previously sensitized individuals B. Systemic reaction to injection of large quantities of foreign antigen, primarily IgG-mediated C. Type of allergic contact dermatitis caused by lipid-soluble chemicals that alter intracellular proteins, primarily CD8 T cell-driven D. Cellular hypersensitivity, primarily T-cell driven; can also invoke inflammatory response by binding to TLR4.
7:A 8:C 9:B 10:D
Antigen-presenting cells are distributed by type in specific areas of the lymph node: (9- 45: ) are found throughout the cortex of the lymph node in the T-cell areas. (9-46: ) are distributed throughout the lymph node, But (9-46: ) are concentrated mainly in the marginal sinus where the afferent lymph collects before percolating through the lymphoid tissue, and also in the medullary cords, where the efferent lymph collects before passing via the efferent lymphatics into the blood. (9-47) are found mainly in the follicles and can contributes to neutralizing soluble antigens such as toxins. A. Dendritic cells (DCs), B. T-cells, C. Natural killer cells, D. Macrophages, E. B-cells.
9- 45: DCs 9-46:Macrophages 9-47: B cells
Mature recirculating T cells that have not yet encountered their specific antigens is called (9-1:______). (9-1: ) must meet its specific antigen, presented to it as a peptide:MHC complex on the surface of an antigen-presenting cell. Subsequently, (9-1) should be induced to proliferate and differentiate into progeny (9-2: ____) with new activities that contribute to removal of antigen. (9-2:) performs their functions as soon as they encounter their specific antigen on other cells (generally without requirement for further differentiation) A. Immature T cell, B. Mature T cell, C. Progenitor T cell, D. Naïve T cell, E. Effector T cell,
9-1) Naive T-cell (9-2) Effector T cell
explain the priming of naive T cells by pathogen-activated dendritic cells
9-10: cell-adhesion molecules mediate the initial interaction - naive T cells in cortical region of lymph node bind to each APC they encounter. mature dendritic cells bind naive T cells efficiently through LFA-1 and CD2 T cell interactions, and ICAM-1, 2 and CD58 on dendritic cell - transient binding of naive T cells to APCs is crucial in providing time for T cells to sample large numbers of MHC molecules on each APC for the presence of a specific peptide - when naive T recognizes a peptide:MHC ligand, signalin through T-cell receptor induces conformational change in LFA-1 that increases its affinity for ICAM-1 and 2 9.17. cell-surface molecules of immunoglobulin superfamily are important in interactions of lymphocytes with APCs 9-11: APCs deliver 3 kinds of signals for clonal expansion and differentiation of naive T cells 9.18. transient adhesive interactions between T cells and APCs are stabilized by specific Ag recognition - integrins bind ICAMs - T cells exp. LFA, but MPs exp MAC-1 9.19. 3 kinds of signals involved in activation of naive T cells by APCs: 1. activation 2. survival 3. differentiation 9-12: CD28-dependent co-stimulation of activated T cells induces expression of T-cell growth factor Il-2 and receptor 9.20. High-affinity IL-2 receptors are 3-chain structures present only on activated T cells: IL-2, gamma and beta chains = moderate affinity of naive/resting T cell. +alpha chain = IL-2 receptor of activated T cell - CD25 really important in thymus and bone marrow to get 1st cell division - mitogen / IL-2 receptor - gamma chain shared by many other cytokines 9-13: Signal 2 can be modified by additional co-stimulatory pathways 9.21. activated T cells secrete and respond to IL-2: 1. resting T cells express only a moderate affinity IL-2 receptor 2. activated T cells express a high-affinity IL-2 receptor and secrete IL-2 3. binding of IL-2 to its receptor signals T cell to enter cell cycle 4. IL-2 incudes T-cell proliferation - activation of naive T cells in presence of co-stimulation through CD28 signaling induces expression and secretion of IL-2 and exp of IL-2 receptors. IL-2 binds to receptors to promote autocrine T-cell growth 9-14: Ag recognition in absence of co-stimulation leads to functional inactivation or clonal deletion of peripheral T cells 9.22. CTLA-4 is an inhibitory receptor for B7 molecules - binds more avidly than CD28 and delivers inhibitory signals to activated T cells - interaction between TCR and MHC with no B7 or B7+CD28 with no TCR won't get activation 9-15: proliferating T cells differentiate into effector T cells that don't require co-stimulation to act 9.24. effector T cells can respond to their target cells without co-stimulation - once naive T cell recognizes antigen on surface of APC and receives required 2 signals and becomes activated and secretes/repsonds to IL-2, (autocrine) IL-2 driven clonal expansion is followed by differentiation of T cells to effector cell status (leaves LN looking for Ag, circulates in endothelium, go to alveoli where flu is replicating), and Ag triggers effector actions without co-stimulation. so cytotoxic T can kill virus target cell with only peptide:MHC complex and not co-stimulatory signals - T cell finds APC and right peptide expressed on class I MHC, CD8 interacts with domain of MHC and have activation and cytokines made - 7-10 days recovery, Ab made 2 weeks later (virally infected cells are gone) 9-16: CD8 T cells can be activated to become cytotoxic effector cells 9.25. activation of T cells changes expression of several cell-surface molecules - resting express L-selectin, S1P1 - activated express VLA-4 - both express TCR, and LFA-1, CD2, and CD44, but activated exp the last 3 more strongly! 9.26. CD8 cytotoxic T cells are specialized to kill cells with intracellular pathogens - display peptide fragments of cytosolic pathogens (viruses) bound to MHC class I molecules at cell surface 9-17: CD4 T cells differentiate into several subsets of functional different effector cells - CD4 T cells help B cells produce Ab 9.27. Most CD8 T cell responses require CD4 T cells - APC has both class I and II molecules on surface - present many peptides to TCRs in different cells that are capable of seeing those peptides - T cell will be activated through recognition of B7 - CD4 and MHC and CD40 (another signal) - cell will make lots of cytokines- some activate CD8, induce expression of more B7, which interacts with CD28 - induce expression of 4-IBBL - ligand for 4-IBB - all these signals and additional cytokines get CD8 cell activated by APC 9.28. subsets of CD4 effector T cells specialized to provide help for different classes of pathogens - also CD4 TH1 cells are CTLs 9-18: various forms of signal 3 induce differentiation of naive CD4 T cells down distinct effector pathway 9.29. variation in signal 3 causes naive CD4 T cells to acquire several distinct types of effector functions - some characteristic TFs used to ID different classes of T cells - every Treg expresses FoxP3
9-11 & 9-12: Fill-in-the-Blank: Peyer's patches are the mucosa-associated lymphoid tissue (MALT) in the small intestines. Microbes and antigens enter through specialized (9-11: ____) called (9-12: ____). A. Epithelial cells, B. Endothelial cells, C. Macrofold (M) cells, D. Microfold (M) cells,
9-11: Epithelial cells 9-12:Microfold (M) cells
Follicular dendritic cells (FDCs) are specialized for the capture of antigen in the form of immune complexes made up of (9-13: ____). In this way, FDCs present native antigens to potential memory B cells, of which only B cells with high affinity B cell receptors (BCR) can bind. A. Antigen, Antibody, and Complement, B. T cell Receptor and Peptide:MHC Class I molecule, C. T cell receptor and Peptide:MHC Class II molecule, D. Antigen and B cell receptor, E. Antigen, B cell receptor, and Complement.
9-13: antigen, antibody, and complement
(9-16: ) circulate from the bloodstream into lymph nodes, spleen, and mucosa-associated lymphoid tissues and back to the blood. Such circulation allows (9-16:) to contact thousands of (9-17: ) every day and sample the peptide:MHC complexes on the surfaces of these cells. In T cell zone of the lymphoid tissue, incoming (9-17) dwell and high rate of T cells exist. Then, each T cell has a high probability of encountering antigens. When (9-16: ) recognize its specific antigen on the surface of an activated (9-17: ), T cells ceases to migrate and remains in the T-cell zone. In T cell zone, the T cell proliferates for several days, undergoing clonal expansion and differentiation to give rise to (9-18: ) and memory cells. (9-18:) exit the lymphoid organ and reenter the bloodstream, through which they migrate to the site of infection. However, some (9-18: ) having the fate to interact with B cells migrate to B- cell zone, generating the germinal center. A. Macrophages, B. Dendritic cells, DCs, C. Mature T cells, D. Naïve T cells, E. Effector T cells.
9-16: Naïve T cells 9-17: dendritic cells, DCs 9-18: effector T cells
Migration of naïve T cells into secondary lymphoid tissues depends on their binding to (9-19:___) through cell-cell interaction governed by cell-adhesion molecules and chemokines. Entry of lymphocytes into lymph nodes occurs in distinct stages (1st) (9-20: ___) along the endothelial surface of (9-19), (2nd)(9-21: ___), (3rd)(9-22: ___), (4th) (9-23: ____) across the endothelial layer in the paracortical area, the T-cell zones. A. Activation of integrins, B. Rolling of lymphocytes, C. Diapedesis, D. Firm adhesion, E. High-endothelial venules, HEVs
9-19: high-endothelial venules, HEVs 9-20: Rolling of lymphocytes 9-21: Activation of integrins 9-22: Firm adhesion 9-23: Diapedesis
explain entry of naive T cells and APCs into peripheral lymphoid organs
9-1: naive T cells migrate through peripheral lymphoid tissues, sampling peptide:MHC complexes on dendritic cell surfaces 9-2: lymphocyte entry into lymphoid tissues depends on chemokines and adhesion molecules 9.2 naive T cells encounter antigen during recirculation through peripheral lymphoid organs 1. T cells enter lymph node cortex from blood via high endothelial venules (HEVs) 2. T cells not activated by antigen presented by dendritic cells exit from lymph node via cortical sinuses 3. T cells activated by antigen presented by dendritic cells start to proliferate and lose ability to exit from lymph node 4. activated T cells differentiate to effector cells and exit lymph node - skin scratch- bacteria gets in- activate tissue dendritic (Langerhans) cell - takes bacteria as it's going from skin to draining lymph node- processing and presenting bacterial antigens - comes in through lymph, presents in T-cell rich regions - turn on T cells specific for bacterial antigens - some become TFH, others engage B cells also specific for that bacteria and turn it on and produce specific Ab - cells that aggregate around dendritic cell look to see if right antigen- if isn't, go away and wait more - if it is, divide and differentiate - leave and go into circulation to site of inflammation - afferent/efferent lymphatic circulation 9-3: activation of integrins by chemokines is responsible for entry of naive T cells into lymph nodes 9.4. 1. rolling: selectins (L-selectin), 2. activation: chemokines (CCL21), 3. adhesion: integrins (LFA-1), 4. diapedesis: chemokines (CCL21, CXL12) - roll along blood vessel walls all day unless something happens, in which case activate endothelium - changes what it expresses on surface- presentation of chemokines - causes cell to stop, gets activated, infiltration, diapedesis (enters tissue). 9.5 L-selectin binds to mucin-like vascular addressins 9.6 Integrins important in T-lymphocyte adhesion 9.7 Immunoglobulin superfamily adhesion omlecules involved in leukocyte interactions 9.8 lymphocytes in blood enter lymphoid tissue by crossing HEV walls 9-4: T-cell responses initiated in peripheral lymphoid organs by activated dendritic cells - move from peripheral tissues to lymphoid circulation to lymphoid tissues 9.10. dendritic cells found in T cell-rich regions of lymph node, MPs found everywhere, B cells found in follicles, blood, lymph node and spleen (not skin or tissue) 9.11. cell surface molecules of conventional and plasmacytoid dendritic cell - really effective at Ag processing and presentation. have cell adhesion molecules, chemokine receptors, dendritic cell-specific surface markers, and MHC I and II cells. better than MPs! - B7 interacts with CD28 or CTLA-4 - has ITIM (inactivating) instead of ITAM (activating) - 9.13. Langerhans cells take up antigen in skin, migrate to peripheral lymphoid organs, and present foreign antigens to T cells 9-6 pathogen-induced TLR signaling in immature dendritic cells induces their migration to lymphoid organs and enhances antigen processing 9.14. 1. Immature dendritic cells in peripheral tissues encounter pathogens and are activated by PAMPS 2. TLR signaling induces CCR7 and enhances processing of pathogen-derived antigens 3. CCR7 directs migration into lymphoid tissues and augments expression of co-stimulatory molecules and MHC molecules 4. Mature dendritic cell in T-cell zone primes naive T cells - in skin, different set of molecules presented - waiting for Ag - has lots of PAMPs - takes up Ag, activated, leaves skin, finds draining lymphatics, goes to lymph node where it already has bacterial peptide on surface and expresses more molecules needed on T cells - MHC -> bacterial peptide -> TCR + CD4 -> B7 + CD28 - ICAM binds LFA and vice versa - cytokines activate native T cells to divide and differentiate in lymph node 9.15. B cells can use their surface Ig to present specific antigen very efficiently to T cells - B cells are lousy APCs when not for specific Ag - B cell brings Ag in, processes and presents it, then it will be on its surface 9-7 Plasmacytoid dendritic cells produce abundant type I interferons and may act as helper cells for antigen presentation by conventional dendritic cells
list general properties of effector T cells and their cytokines
9-20: effector T-cell interactions with target cells are initiated by antigen-nonspecific cell-adhesion molecules 9.30. interactions of T cells with their targets initially involve nonspecific adhesion molecules - effector T cell released from lymph node or spleen - programmed to recognize viral antigen and MHC - goes into tissue and engages velcro, no viral peptide there - T cell recognizes viral peptide, delivers lethal hit, leaves, cell undergoes apoptosis, effector T cell goes on to bind many more - NO bystander damage! (doesn't kill unaffected cells) 1. initial interaction of CD8 cell with target made by nonspecific adhesion molecules 2. no antigen-specific interaction: cells separate 3. antigen-specific recognition: stable pairing and focused release of effector molecules 4. death of target and release of CD8 T cell 9-21: an immunological synapse forms between effector T cells and their targets to regulate signaling and direct release of effector molecules - when binding to their specific antigenic peptide:self-MHC complexes or to self-peptide:self-MHC complexes, the T-cell receptors and their associated co-receptors cluster at the site of cell-cell contact, forming the supramolecular activation complex (SMAC) or immunological synapse 9.31. area of contact between effector R cell and its contact forms immunological synapse - different tight junctions between cells that velcro (LFA or ICAM interactions) control - MHC in center, in TCR either CD4 or CD8, and CD28 - where interactions 9-22: effector functions of T cells are determined by effector molecules they produce 9.33. CD8 and CD4 cells also have membrane attack complex from complement like perforin - TH1 - macrophage-activating effector molecules: IFN-gamma, GM-CSF, TNF-alpha, CD40 ligand, Fas ligand - TH2 - involved in cytokines - IL-4 and 5- IgE production - IL-10 - anti-inflammatory cytokine- prevents APCs from presenting Ag- another way to shut down immune response - TGF-B- important for Treg, TH17, and TFH 9-23: cytokines can act locally or at a distance 9-24: T cells express several TNF-family cytokines as trimeric proteins that are usually associated with the cell surface
9-24 to 27: Fill-in-the-Blank: The main classes of adhesion molecules involved in lymphocyte interactions are: (9-24:), (9-25: ), (9-26: ), and (9-27:). Indications for 9-24 to 9-27: A. Selectins, B. Integrins, C. Immunoglobulin superfamily, D. Mucin-like molecules, E. Immunoglobulin.
9-24: Selectins 9-25: Integrins 9-26: Immunoglobulin superfamily 9-27: Mucin-like molecules
explain T cell-mediated cytotoxicity
9-25: cytotoxic T cells can induce target cells to undergo programmed cell death 9-26: cytotoxic effector proteins that trigger apoptosis are contained in the granules of CD8 cytotoxic T cells 9.36. cytotoxic effector proteins released by cytotoxic T cells 9. 37. perforin, granzymes, and serglycin are released from cytotoxic granules and deliver granzymes into cytosol of target cells to induce apoptosis - CTL vesicles release at tight junctions - granzymes get in, activate apoptosis, release cytochrom c to cytoplasm, activates CAD (nuclease-clips DNA btwn nucleotides) 1. engagement of TCR by peptide:MHC complex causes direct release of perforin and granzymes complexed with serglycin 2. granzyme is delivered into cytosol of infected cell and targets BID and pro-caspase 3 3. truncated BID disrupts mitochondrial outer membrane, and activated caspase 3 cleaves ICAD, released caspase-activated DNAse (CAD) 4. release of cytochrome c into cytosol activates apoptosis, and CAD induces DNA fragmentation 9-27: cytotoxic T cells are selective and serial killers of targets expressing a specific antigen 9-28: cytotoxic T cells also act by releasing cytokines 9.39. cytotoxic T cells kill target cells bearing specific antigen while sparing neighboring uninfected cells
(9-24: Selectins) bind to the carbohydrate moiety (sulfated sialyl-Lewis-X) of (9-27: mucin-like molecules) expressed on the surface of vascular-endothelial cells. (9-27: mucin-like molecules) is also known as (9-28: ): Examples of (9-28) are (9-29: ) expressed on high endothelial venules in lymph nodes, and (9-30: ) is expressed on endothelium in mucosae, and guides lymphocyte entry into mucosal lymphoid tissue such as the Peyer's patches in the gut. A. Vascular aresstins, B. Vascular addressins, C. CD35 & GlyCAM-1, D. MAdCAM-1, E. CD34 & GlyCAM-1,
9-28: Vascular addressins 9-29: CD34 & GlyCAM-1 9-30: MAdCAM-1
describe macrophage activation by TH1 cells
9-29: TH1 cells have a central role in macrophage activation 9.40. T cells activate macrophages to become highly microbicidial- when effector TH1 cell specific for a bacterial peptide contacts an infected MP, T cell induced to secrete MP-activating factor IFN-gamma and express CD40 ligand, and TH1 cells activate MP 9-30: activation of macrophages by TH1 cells promotes microbial killing and must be tightly regulated to avoid tissue damage 9-31: TH1 cells coordinate host response to intracellular pathogens 9.41. activated MPs undergo changes that increase antimicrobial effectiveness and amplify the immune response - activated MPs increase expression of CD40 and TNF receptors, and are stimulated to secrete TNF-a. this autocrine stimulus synergizes with IFN-gamma secreted by TH1 cells to increse antimicrobial action of MP by inducing production of NO and O2-. MP also upregulates its B7 molecules in response to binding to CD40 ligand on T cell, and increases expression of MHC class II molecules allowing further activation of resting CD4 T cells 9.42. immune response to intracellular bacteria is coordinated by activated TH1 cells - IFN-gamma- lethal hit- not punching hole, triggering through signal transdution cascade - secrete lymphotoxin, Fas - if lots of death domain signals, undergoes apoptosis - IL-2 - help CD8 cells divide and differentiate - produces IL-3 and GM-CSF - TNF-a - activate blood vessels and promote local infection - recruit all other TH1 cells- get reaction - 1 cell activated- divide and differentiate - make memory cells - Next time - exposed to less, get worse reaction (poison ivy) - extreme localization 9.43. granulomas form when an intracellular pathogen or its constituents cannot be totally eliminated - granuloma- wall of extracellular bacterial infections - seen as cyst in skin - requires T cells - if activated, can get rid of mycobacterium exposed to cells
Activation of (9-25: integrins) by chemokines is responsible for the entry of naïve T cells into lymph nodes. (9-25: Integrins) bind to a group of (9-31: ) which is the member of (9-26: immunoglobulin superfamily), (9-25: integrin) molecule consists of a large chain and a smaller ( 2 in leukocytes) chain. All T cells express the integrin L: 2 (CD11a:CD18) which is also known as (9-30: ). LFA-1 enables migration of both naïve and effector T cells out of the blood. A. ICAM, B. ICBM, C. ICEM, C. leukotriene functional antigen-1, LFA-1, D. leukocyte functional antigen-1, LFA-1
9-31: ICAM 9-30: leukocyte functional antigen-1, LFA-1
The exit of T cells from lymph nodes is controlled by a chemotactic lipid, (9-38:). (9-38) can induce cellular signaling by binding to the receptor S1PR1, and induce T cell exiting from a lymph node via the cortical sinuses medullary sinus (9-39: ). A. Sphingosine 1-phospholipid, B. Sphingosine 1-phosphate, C. Afferent lymphatic vessel, D. Efferent lymphatic vessel, E. High endothelial venule.
9-38: Sphingosine 1-phosphate, S1P 9-39: efferent lymphatic vessel
T cell activation by antigen in lymphoid organs induces (9-40: ) expression. (9-40: ) causes the internalization of S1PR1. Thus, T cell activation results in reduction of S1PR1 on the T-cell surface. During the T cell activation, therefore, T-cells cannot respond to the S1P and do not exit the lymphoid organ After several days of proliferation, as T-cell activation wanes, (9-40: ) expression decreases and S1PR1 reappears on the surface of effector T-cells. Allowing effector T-cells to migrate out of the lymphoid tissue in response to the (9-38: S1P) gradient. A. CD65, B. CD66, C. CD67, D. CD68, E. CD69.
9-40: CD69
(9-41: ) is a new immunosuppressive drug. (9-41:) binds to (9-42:), leading to ligand-induced internalization of (9-42: ). Thus, (9-41:) causes the inactivation and down-regulation of (9-42: ). In addition, (9-41: ) increases the tight junction formation and close exit portals on the endothelium In this way, (9-41: ) prevents lymphocytes from returning to the circulation, thereby sequestering them in lymphoid tissues, and causing rapid onset of (9-43: ) which is a lack of lymphocytes in the blood. A. FTY720, fingolimod, B. FTY740, fingolimod, C. S1P receptor, D. lymphomegia, E. lymphopenia.
9-41: FTY720, fingolimod 9-42: S1P receptor 9-43: lymphopenia
In the lymph node, T and B cells enter the lymph node via (9-4:____) in T-cell zones, and then diverge into T-cell and B-cell zones. Antigen is delivered in lymph either free or as cargo of (9-5:____) that have taken up the antigen in the tissues drained by the lymph node. The antigen is delivered via (9-6: _____) to (9-7: ____), from which it is delivered to T-cell zones. Then, in T-cell zones, T cells can recognize the antigen on the surface of Dendritic cells. B-cells detect the antigen as a free antigen at the border of the T-cell zone and B-cell follicles. A. High endothelial venules, HEVs, B. Dendritic cells, DCs, C. Afferent lymphatics, D. Subcapsular sinus, E. Efferent lymphatics
9-4: high endothelial venules, HEVs 9-5: Dendritic cells, DCs 9-6: afferent lymphatics 9-7: subcapsular sinus
The receptor for (9-53:) consists of(9-54: ) and (9-55:) chains. In naïve T cells, the receptor for (9-53) is composed of and chains, which as only moderate affinity for (9-53:) binding. Activated T cells upregulate the expression of (9-54:) chain, creating the complete (9-54) heteromeric complex, which has a much higher affinity for (9-53: ). allowing the T cell to respond to very low concentrations of (9-53:). A. γ and δ , B. β and γ , C. α, CD25, D. α , CD40, E. ε, CD45
9-53: Interleukin 2 9-54: α, CD25 9-55: β and γ
(9-56:) constitutively express (9-54: ), and form the high-affinity, trimeric receptor for (9-53: ). With the high-affinity form of the receptor, (9-56: ) can outcompete T cells that express only the low-affinity form of the receptor for binding of the limited quantity of (9-53: ). In this way, (9-56:) act as a 'sink' for (9-53: ) to limit its availability to other cells. Once activated, naïve T cells have upregulated (9-54: ) to form the high-affinity receptor and compete with (9-56: ) for (9-53:). A. TH1 cells, B. TH2 cells, C. A. TFH cells, D. Dendritic cells, E. Regulatory T (Treg) cells,
9-56: Regulatory T cells, Treg 9-54: CD25 9-53: IL2
(9-65: ) is made by T cells in soluble and membrane-associated forms and assembles into a homotrimers. Lymphotoxins (LTs): secreted LT- is a homotrimer. LT- in a membrane-bound form is linked to LT- (a transmembrane member of this family) to form herotrimers. .
9-65: TNF
(9-66:) binds to the transmembrane protein (9-67:) on target cells. (9- 67: ) contains a 'death' domain in its cytoplasmic tail. Thus, the interaction between (9-66) and (9-67) induces cell death by apoptosis.
9-66: Fas Ligand, FasL, CD178 9-67: Fas, CD95
Cytotoxic T cells target the infected host cells for death. There are two different forms of cell death: -Physical or chemical injury (9-68:). (9-68) is caused by the deprivation of (9-69: ) that occurs in heart muscle during a heart attack or membrane damage with antibody and complement leads to cell (9-68: ). -Programmed cell death: Programmed cell death can occur by (9-70: ) or (9-71: ). (9-70:) is a regulated process that is induced either by specific extracellular signals or by the lack of signals required for survival. (9-71: ) is the process of degrading senescent or abnormal proteins and organelles A. apoptosis, B. Autophagy, C. Necrosis, D. Reactive oxygen species, E. Oxygen.
9-68: necrosis 9-69: oxygen 9-70: apoptosis 9-71: autophagy
what happens when bacteria gets into skin?
9.13. 1. dendritic/Langerhans cell activated, process and presents antigen, goes into T cell-rich region of lymph node, activates T cells through interaction with velcro (mature dendritic cells enter lymph node from infected tissues and can transfer some antigens to resident dendritic cells) 2. B7 gives second signal - B7-positive dendritic cells stimulate naive T cells - 3rd signal - through cytokines released- dendritic cell
what happens if virus gets in through receptor-mediated endocytosis?
9.14. make viral proteins in cell using ribosomes (obligate intracellular parasites), viral proteins presented on class I MHC, go to TAP, pore, to ER, bind to nascent class I molecules, get out to cell surface CD8 - if virus - infected cell undergoes apoptosis and has proteins inside, it could come into cell and be expressed on class I or II molecules - transfer from incoming dendritic cell to resident dendritic cell - cell can also burp and peptides can go on as MHC molecule
what 3 signals are involved in activation of naive T cells by antigen-presenting cells?
9.19. binding of foreign-peptide:self-MHC complex by TCR and a CD4 co-receptor transmits signal 1 to T cell that Ag has been found. effective activation of naive T cells requires a second signal (co-stimulatory_ to be delivered by same APC. CD28 on T cell encountering B7 molecules on APC delivers signal 2, which increases survival and proliferation of T cell that received signal 1. ICOS and other TNFs may also give co-stimulatory signals. For CD4 T cells, different paths of differentiation produce effector T cells subsets that carry out different effector responses, depending on nature of 3rd signal delivered by APC - cytokines commonly involved in directing this differentiation - some B cells have Ab that can recognize DNA - B cell can present self proteins - If host developed non-specifically, some clones capable of recognizing other molecules, could have autoimmune disease (lupus) - but thymus got rid of almost all clones that recognize self proteins because had AER expressed - velcro holding cells together so T cell can sample CD4 / class II - need specific recognition of MHC by TCR, or nothing else happens! - CD28 recognition of B7 gives survival signal - if were CTLA4 instead of CD28, would be an off signal with an ITIM, because CTLA4 binds more avidly than CD28 - APC can make many types of cytokines depending on how it was activated- bidn to cyutokine receptors - on surface of T cell and determine its path of differentiation
6.11 Peptide editing is an important component of antigen presentation for both MHC class I and MHC class II pathways, as it drives the preferential presentation of high-affinity binding peptides. For MHC class II peptide editing, HLA-DM plays a key role. In the absence of HLA-DM: A. MHC class II molecules traffic to the cell surface with CLIP in their binding sites. B. No MHC class II molecules are released to traffic to the cell surface. C. MHC class II molecules bind to HLA-DO and are inhibited from binding peptides. D. Pathogens can evade the immune system by blocking peptide exchange on MHC class II. E. HLA-DO competes for high-affinity binding peptides with MHC class II molecules and blocks antigen presentation.
A
A mouse is immunized with a single 9 amino acid peptide derived from the influenza virus. This peptide binds to MHC class I and produces an epitope (peptide:MHC complex) recognized by a small number of naive CD8 T cells in the mouse. The peptide is mixed with CpG oligonucleotides that are ligands for TLR-9. Surprisingly, this immunization regimen generates a very poor cytotoxic CD8 effector response to targets coated with this peptide compared to immunization with a preparation of intact heat-killed influenza virus mixed with CpG oligonucleotides. The enhanced cytotoxic T cell response to the peptide observed following immunization with intact viral particles compared to the peptide alone is due to: A. The presence of CD4 T cell epitopes in the intact virus B. The increased production of type I interferon elicited by the intact virus C. The presence of additional CD8 epitopes in the intact virus D. Presentation of peptides by macrophages instead of dendritic cells E. Up-regulation of MHC class I molecules by the intact virus
A
A mouse is infected with staphylococcal bacteria through a laceration in the skin of its paw. Dendritic cells are isolated from the tissue at the site of infection, and are incubated together with naïve staphylococcal-specific CD4 T cells. Seventy-two hours later, the proliferation of the CD4 T cells is measured as a readout for T cell activation. Surprisingly, the T cell response is quite poor compared to the response observed when the same T cells are mixed with a comparable number of dendritic cells isolated from the draining lymph node of the infected mouse. A comparison of the dendritic cells isolated from the two different sites would reveal: A. Much higher levels of MHC and B7 molecules on the lymph node dendritic cells than those from the infected tissue B. Much higher expression of all TLRs in the lymph node dendritic cells than those from the infected tissue C. An increased number of MHC class II molecules bearing bacterial peptides on the surface of dendritic cells from the infected tissue than on those from the lymph node D. Increased phagocytic activity of the lymph node dendritic cells than those from the infected tissue E. Increased expression of Dectin-1, DEC205, and DC-SIGN on the lymph node dendritic cells than on those from the infected tissue
A
An immunodeficient mouse strain is identified, that has a single gene defect causing its disease. Mice with this defect have greatly impaired responses to protein antigens following subcutaneous immunization and also exhibit severely delays in the kinetics of their antibody responses. Analysis of their lymph nodes revealed profound alterations in the normal architecture, with a lack of organization of distinct T-cell and B-cell zones. A likely candidate for the defect in these mice is: A. The chemokine receptor CCR7, which recruits B cells, T cells, and dendritic cells to lymph nodes. B. The TNF family member LT-β, which is made by Lti cells. C. The chemokine receptor CXCR5 that recruits B cells to the lymph node follicles. D. Prox1, the transcription factor required for the development of lymphatic vessels. TNF-α, which is required for the development of FDCs.
A
BCR signaling on B cells is initiated by antigen binding, leading to mTOR activation. This occurs, for instance, when the antigen is a live microbe that binds to the BCR on the B cells. Which one of the forms of antigen shown below the graph would correctly account for the data shown in Figure Q7.40. Figure Q7.40
A
Cytotoxic T cells are rapid killers of infected target cells. Within minutes of the interaction of a cytotoxic T cell with a target cell, the program of apoptosis in the target cell is initiated. This rapid activity is a consequence of: A. The expression and packaging of perforin and granzymes in cytotoxic granules prior to target cell encounter B. The extremely rapid production of granzymes and perforin by cytotoxic effector cells upon encountering a target cell C. The extremely potent activity of perforins in poking holes in target cell membranes allowing entry of granzymes D. The efficient activity of granzymes in cleaving effector caspases leading to direct activation of apoptosis E. The large number of cytotoxic granules made and secreted by a single effector cytotoxic T cell
A
Effector caspases are activated downstream of both extrinsic and intrinsic pathways of apoptosis. Consequently, cells lacking one or more of these enzymes show defects in apoptosis. An alternative means of eliminating the activity of an effector caspase would be to: A. Generate a form of the pro-caspase with a mutation in the initiator caspase cleavage site B. Express a mutant form the caspase that lacked the pro-domain C. Express a constitutively active form of the initiator caspase D. Generate a knockout mutation that prevented expression of the Fas receptor E. Generate a mutation in the proteins required for autophagy
A
Hepatitis C is a virus that infects hepatocytes, which are non-immune cells of the liver. Currently, patients with chronic Hepatitis C infections are treated with repeated administration of type I interferon, predominantly interferon . One aspect of this treatment that might aid the patient's immune system in clearing this virus infection is: (Hint: HCV replicates in the cytosol of hepatocytes) A. Upregulation of MHC class I expression levels on hepatocytes B. Activation of macrophages to produce noxious compounds that might kill the virus C. Induction of an inflammatory response to promote neutrophil trafficking to the liver D. Production of TNF- in response to type I interferons leading to vasodilation in the liver E. Induction of IL-1 and IL-6 leading to the acute phase response
A
MHC class II molecules expressed on the surface of thymic cortical epithelial cells normally have a wide repertoire of different peptides bound to them. By engineering a construct that fuses the MHC class II protein to a single peptide sequence, and expressing this construct in thymic cortical epithelial cells that have their endogenous MHC class II genes knocked out, it is possible to generate a mouse line where all MHC class II proteins expressed on all thymic cortical epithelial cells are bound to the same peptide. These mice are often referred to as 'single-peptide' mice. Examination of the T cell developing in these single peptide mice would likely show: A. A significant reduction in the numbers of mature CD4 T cells B. No change in the numbers of mature CD4 T cells C. A block in T cell development at the CD4+CD8+ double-positive stage D. A repertoire of T-cell receptors on mature CD4 T cells restricted to a single Vβ A block in T cell development at the CD4-CD8- double-negative stage
A
Most effector T cells migrate out of secondary lymphoid organs and into tissues to exert their function. In which of the cases shown in Figure Q9.25 will the TH1 effector cell undergo long-lived interactions with its target cell, an infected macrophage? Assume all of the target cells shown below are infected with the pathogen recognized by the specific TH1 cells. Figure Q9.25
A
Multiple choice: Most effector T cells migrate out of secondary lymphoid organs and into tissues to exert their function. In which of the cases shown in Figure Q9.25 will the TH1 effector cell undergo long-lived interactions with its target cell, an infected macrophage? Assume all of the target cells shown below are infected with the pathogen recognized by the specific TH1 cells.
A
Second messengers, such as calcium ions (Ca2+), are chemical mediators commonly used in intracellular signaling pathways. Despite its common usage in many different cell types in the body, Ca2+ has specific effects in lymphocytes following antigen receptor stimulation. The specific responses of lymphocytes to increased concentrations of intracellular Ca2+ are determined by: A. The expression of a specific subset of Ca2+-responsive enzymes in lymphocytes compared to other cell types B. The increased expression of calmodulin in lymphocytes compared to other cell types C. The presence of enzymes that bind calmodulin in lymphocytes but not other cell types D. The high levels of Ca2+ in the endoplasmic reticulum of lymphocytes compared to other cell types E. The ability of Ca2+ to amplify signaling pathways in lymphocytes but not other cell types
A
Self-reactive B cells can be eliminated from the repertoire at several stages of B cell maturation, including immature B cells that have already emigrated from the bone marrow into the circulation. This latter stage of tolerance induction is critical because: A. Not all self-antigens are expressed or present in the bone marrow during B cell development. B. Immature circulating B cells are more sensitive to antigen stimulation than the developing B cells in the bone marrow. C. Receptor editing is not a perfect process and some self-reactive B cells may fail to be eliminated in the bone marrow. D. Circulating immature B cells do not encounter tissue-specific antigens in peripheral organs and tissues. E. Immature B cells are trapped in the bone marrow by strong B-cell receptor cross-linking.
A
Several types of pathogens encode proteins that function as superantigens, which activate massive numbers of T cells in an individual. One example is the staphylococcal enterotoxins that cause food poisoning. These superantigens are the exception to the general rule that T cells only recognize specific peptide:MHC complexes, because they: A. Induce activation of any T cell whose T-cell receptor uses a particular Vβ region bound by that superantigen B. Simultaneously stimulate all of the T-cell receptors on a given T cell C. Cover up the peptide-binding site, preventing MHC molecules from binding peptides D. Activate a large number of T cells that are specifically recognizing peptides derived from the superantigen protein E. Induce anti-microbial cytokine production that aids the immune system in clearing the pathogen
A
Some CD1 molecules bind to glycosphingolipids, and are recognized by a subset of T cells known as invariant NKT (iNKT) cells. The ability of these T cells to recognize different glycolipid constituents from microorganisms when they are bound to CD1d places these cells in the 'innate immune' category. While iNKT cells do express a fully rearranged α:β T-cell receptor, one key feature of the T-cell receptors expressed on iNKT cells also places them in the 'innate immune' category. This feature is: A. iNKT cells have a highly restricted T-cell receptor repertoire, with the majority of cells utilizing the same Vα and Jα rearrangement. B. iNKT cells express receptors that are also expressed on NK cells. C. iNKT cells express T-cell receptors that induce inhibitory, rather than activating D. iNKT cells do not generally express CD4 or CD8. E. The T-cell receptors expressed on iNKT cells recognize both MHC class I and MHC class II molecules.
A
TNF-receptor signaling commonly includes several steps that are regulated by ubiquitination. One important step following TNF-receptor stimulation is the: A. K48-linked ubiquitination and degradation of a TRAF protein, itself a ubiquitin-ligase B. K48-linked ubiquitination of the TNF-receptor cytoplasmic tail, leading to its degradation C. K63-linked ubiquitination of the TNF-receptor, providing a docking site for TRAF protein binding D. K48-linked ubiquitination of NIK, the NFκB-inducing kinase E. K63-linked ubiquitination of cIAP, leading to its binding to NIK, the NFκB-inducing kinase
A
The TCR signaling module leading to transcription factor activation is dependent on the enzyme phospholipase-C-γ (PLC-γ). The mechanism by which PLC-γ activates multiple transcription factors is by: A. Generating two small second messengers that act on multiple target proteins in the T cell B. Directly cleaving inhibitory subunits of multiple transcription factors, thereby releasing the active transcription factors C. Generating two small second messengers that diffuse to the nucleus and activate transcription factors present there D. Generating two small second messengers that act as chaperones to promote nuclear localization of transcription factors E. Directly cleaving the lipid binding domain from membrane-tethered transcription factors, allowing them to migrate to the nucleus
A
The adaptive immune system developed a strategy for monitoring the proteins synthesized in virtually any cell in the body, thereby preventing pathogens from 'hiding out' by adopting an intracellular lifestyle. To accomplish this, the immune system: A. Co-opted the ubiquitin-proteasome system used by cell for protein turnover B. Created a novel pathway using the immunoproteasome for generating peptides C. Created a novel pathway to express foreign proteins on the cell surface D. Took advantage of proteolytic enzymes present in endocytic vesicles E. Engineered an immune-specific ubiquitin molecule for tagging foreign proteins
A
The immunosuppressive drug rapamycin acts by inhibiting mTOR. When activated T cells are treated with rapamycin in a cell culture assay, they show greatly diminished proliferation, and accumulate to much lower numbers than control-treated cells. This is because: A. Rapamycin inhibits cells from increasing their synthesis of lipids and proteins. B. Rapamycin inhibits cells from activating the pro-survival protein, Bcl-2. C. Rapamycin inhibits DNA synthesis in activated T cells. D. Rapamycin inhibits cell cycle progression in activated T cells. E. Rapamycin inhibits the T cell's production of the growth factor, IL-2.
A
The pre-B-cell receptor provides an important signal that induces transition of pro-B cells to pre-B cells. An important characteristic of this receptor is that: A. It signals without binding to an extracellular ligand. B. It is composed of immunoglobulin heavy chains and the VJ region of a rearranged λ light chain. C. It is expressed at very high levels on the surface of the pro-B cell. D. It signals without requiring association with B-cell receptor signaling subunits, Igα and Igβ. E. It signals without requiring the B-cell receptor signaling kinase, BTK.
A
Unlike α:β T cells, γ:δ T cells are considered to be components of the innate immune system. One feature of γ:δ T cells that leads to their classification as innate cells is: A. That they migrate from the thymus directly to barrier surfaces such as mucosa and epithelia B. Their ability to produce pro-inflammatory cytokines C. That their T-cell receptors are germline encoded rather than a product of VD-J recombination D. Their rapid turnover in the tissue, with an average survival time of 3-4 days E. Their ability to make growth factors that act on epithelial cells rather than other hematopoietic cells
A
Matching: The diagram in Figure Q6.1 shows a pathogen (in red) that is present in different cellular compartments of each of the cell types shown. In each case, a specific T cell subset will recognize peptides of that pathogen presented on MHC molecules on the surface of the cell, and will execute its effector function. From the list below, match the appropriate T cell effector response to the cell type and location of the pathogen. (SEE IMAGE)
A = ii B= v C = iii
In mice that lack both MHC class I and class II in the thymus, T cell development will show
A block in T-cell development at the CD4+CD8+ double positive stage
CXCR5 is the receptor for the chemokine CXCL13, secreted by follicular stromal cells and follicular dendritic cells in the B cell zones (i.e., lymphoid follicles) of secondary lymphoid organs. A conditional knockout mouse in which CXCR5 was specifically deleted only in T cells would have ___
A defect in T cell-dependent antibody responses
CXCR5 is the receptor for the chemokine CXCL13, secreted by follicular stromal cells and follicular dendritic cells in the B cell zones (i.e., lymphoid follicles) of secondary lymphoid organs. A conditional knockout mouse in which CXCR5 was specifically deleted only in T cells would have:
A defect in T cell-dependent antibody responses
CXCR5 is the receptor for the chemokine CXCL13, secreted by follicular stromal cells and follicular dendritic cells in the B cell zones (i.e., lymphoid follicles) of secondary lymphoid organs. If the CXCR5 gene is disrupted in all T cells but remains fully functional in all other cell types, the individual would have:
A defect in T-cell dependent antibody response
Patients with the disease X-linked lymphoproliferative syndrome (XLP) lack expression of the small adapter protein SAP, which associates with receptors of the SLAM family. One characteristic of this disease is an inability of cytotoxic T cells to control infections with a virus, Epstein-Barr virus (EBV), that replicates in B cells. This defect in control of EBV results from:
A defect in adhesion of cytotoxic T cells to EBV-infected B cells
Lipid rafts
A dense part of the cell membrane containing sphingolipids, cholesterol, and sometimes receptors is/are known as:
Histocompatibility antigens
A family of proteins that determines the ability of one individual in a specie to accept (or reject) tissue or cell grafts from another individual are known as:
Endocytic (phagocytic) pathway
A metabolic pathway in which extracellular antigen is internalized and moves from compartment to compartment encountering phagolysosome in:
Allergic airway inflammation can be induced in mice by immunizing them with an allergen that produces a TH2 effector response, and then challenging the immunized mice with an inhaled form of that allergen. In this disease model, the TH2 effector cells present in the lung respond to the inhaled allergen challenge by producing type 2 cytokines that recruit eosinophils and induce airway inflammation. In addition, a component of this TH2 response is antigen-independent, as shown by the effects of administering a neutralizing antibody along with the allergen challenge. This neutralizing antibody (anti-'X' IgG) has the effects shown in Figure Q11.14. In this experiment, the anti-'X' antibody was shown to inhibit the response of the TH2 cells, and therefore is likely to be:
A neutralizing antibody to TSLP
CD3 complex molecules , TCR ( PT α and B chains )
A pre T cell complex consists of:
MHC class II molecules expressed on the surface of thymic cortical epithelial cells normally have a wide repertoire of different peptides bound to them. By engineering a construct that fuses the MHC class II protein to a single peptide sequence, and expressing this construct in thymic cortical epithelial cells that have their endogenous MHC class II genes knocked out, it is possible to generate a mouse line where all MHC class II proteins expressed on all thymic cortical epithelial cells are bound to the same peptide. These mice are often referred to as 'single-peptide' mice. Examination of the T cell developing in these single peptide mice would likely show:
A significant reduction in the numbers of mature CD4 T cells
Leprosy is a disease caused by the intracellular bacterium Mycobacterium leprae, which infects macrophages and replicates in their phagosomes. Human patients with leprosy have a persistent infection of the mycobacteria, as their immune systems are unable to complete eradicate the pathogen. Furthermore, two different forms of the disease have been identified. Some patients have many skin lesions containing a large number of bacteria with little inflammatory response. This is the very disfiguring form of the disease, and is known as lepromatous leprosy. In other patients, few skin lesions and only occasional bacteria are observed, and the skin lesions are accompanied by a robust inflammatory response. These patients have the form of the disease known as tuberculoid leprosy. If one examined a skin biopsy from a patient with tuberculoid leprosy, one would expect to see:
A substantial number of granulomas
How do self-antigens that are specific to tissues away from the thymus (like insulin or keratin for example) get in the thymus so that developing T cells that react to them can be deleted?
A transcription factor, AIRE is expressed in thymic medullary epithelial cells, which allows these cells to express proteins normally found in other tissues.
T cells
A transplant patient began to show signs of rejection 8 days after receipt of the transplanted organ. What immune elements might be found in the rejected organ?
In an MLR, the uptake of 3H-thymidine is often used to assess cell proliferation. A) Which cell type (responders or stimulators) proliferates in an MLR? Why? B) Explain why IL-2 production can also be used to assess cell proliferation in an MLR.
A) T cells (CD4+ and CD8+) as long as both MHC class I and class II differ. B) To demonstrate the identity of the proliferating cells, you could incubate them with distinct fluorochrome conjugated antibodies (e.g., fluorescein-labeled anti-CD4 monoclonal antibody and phycoerythrin-labeled anti-CD8 monoclonal antibody). The proliferating cells will be stained only with the anti-CD4 reagent.
In an MLR, the uptake of 3H-thymidine is often used to assess cell proliferation. A) Which cell type (responders or stimulators) proliferates in an MLR? Why? B) Explain why IL-2 production can also be used to assess cell proliferation in an MLR.
A) T cells (CD4+ and CD8+) as long as both MHC class I and class II differ. B) To demonstrate the identity of the proliferating cells, you could incubate them with distinct fluorochrome conjugated antibodies (e.g., fluorescein-labeled anti-CD4 monoclonal antibody and phycoerythrin-labeled anti-CD8 monoclonal antibody). The proliferating cells will be stained only with the anti-CD4 reagent.
Among the following indications, choose the appropriate description when it comes to describing the spleen? 1.The spleen is specialized for the capture of antigens that enter the blood stream. 2.In the spleen, the lymphoid tissue component is called the white pulp. 3.Circulating T-cells and B-cells are delivered to the marginal sinus. 4.Marginal sinus is rich in M and contains the marginal zone B cells which do not recirculate. 5.Marginal sinus is specialized for the capture of blood-borne antigens or intact microbes (viruses and bacteria). 6.Antigen is delivered via arterioles to the marginal sinus, which is the boundary between the white pulp and red pulp. A. All of the above, B. (1)+(3)+(4)+(5)+(6), C. (2)+(3)+(4)+(5)+(6), D. (1)+(4)+(5)+(6), A-E. None of the above,
A-all of the above
Patients receiving hematopoietic stem cell transplants often suffer fromgraft-versus-host disease (GVHD), involving immune-mediated damage to the gastrointestinal (GI) tract. The symptoms of GVHD include nausea, vomiting, diarrhea, and abdominal cramping due to epithelial cell apoptosis and inflammatory leukocyte infiltration into the GI epithelium. One proposed treatment has been tested in mouse models of GVHD for potential therapeutic benefit. This treatment is: A. Administration of IL-22 B. Administration of anti-microbial peptides C. Administration of mucosal (M2) macrophages D. Administration of TGF- E. Administration of IL-1 + IL-6
A. Administration of IL-22
4.8 Multiple choice: In Figure Q4.8, which close-up view of these two V domains has the amino acid sequences most important for antigen-binding highlighted correctly in red? LOOK AT PIC
A. All three hypervariable loops of both the heavy chain and light chain V regions are important for antigen-binding.
The vaccine to Haemophilus influenzae type b is called a conjugate vaccine. It is composed of the tetanus toxoid protein conjugated to the capsular polysaccharide of the H. influenzae type b bacteria. When used to vaccinate infants, the antibody response generated by this vaccine would include: A. Antibodies to the bacterial polysaccharide and the tetanus toxoid B. Antibodies to the tetanus toxoid only C. Antibodies to the bacterial polysaccharide only D. Antibodies that only bind to the protein-polysaccharide conjugate in the vaccine E. Antibodies that recognize the polysaccharide capsule when shed by the bacteria
A. Antibodies to the bacterial polysaccharide and the tetanus toxoid
Which of the following is a molecule that is NOT targeted for checkpoint blockade? A. CD28 B. CTLA-4 C. PD-1 D. PD-L1
A. CD28
Multiple choice: The adaptive immune system developed a strategy for monitoring the proteins synthesized in virtually any cell in the body, thereby preventing pathogens from 'hiding out' by adopting an intracellular lifestyle. To accomplish this, the immune system: A. Co-opted the ubiquitin-proteasome system used by cell for protein turnover B. Created a novel pathway using the immunoproteasome for generating peptides C. Created a novel pathway to express foreign proteins on the cell surface D. Took advantage of proteolytic enzymes present in endocytic vesicles E. Engineered an immune-specific ubiquitin molecule for tagging foreign proteins
A. Co-opted the ubiquitin-proteasome system used by cell for protein turnover
Multiple choice: B cells express a complement receptor that binds to C3b cleavage products, such as iC3b and C3dg. When a B cell with an antigen receptor that specifically recognizes that pathogen also has its complement receptor stimulated because the pathogen is opsonized with these C3 fragments, B cell activation is greatly enhanced. Due to this mechanism, B cells can be activated by much lower concentrations of antigen (in this case, the pathogen) than if the antigen is devoid of complement components. This mechanism functions to: A. Ensure that pathogens are readily detected by the adaptive immune system before they replicate to high levels in the host B. Prevent B cells from being activated in response to antigens that are not pathogens C. Allow B cells to phagocytose the pathogen and help destroy it D. Induce increased rounds of B cell replication to make more pathogen-specific B cells E. Allow the B cell to block pathogen replication by interfering with multiple pathogen surface functions
A. Ensure that pathogens are readily detected by the adaptive immune system before they replicate to high levels in the host
Secretory IgA produced in the epithelium of mucosal surfaces has several functions in protective immunity. Among these are neutralization of pathogens ortoxins in the gastrointestinal tract lumen or in epithelial cell endosomes, neutralization of pathogens or toxins that cross the epithelial barrier, and transport of pathogens or toxins across M cells for delivery to lamina propria dendritic cells. All of these functions share the common feature that they: A. Fail to induce local inflammation in the gastrointestinal epithelium B. Are efficient at inducing opsonization of pathogens for uptake by phagocytes C. Are efficient at inducing complement activation D. Fail to completely protect the epithelium from cytotoxic effects of pathogens E. Induce IgA-secreting plasma cells to produce increased amounts of secretory IgA
A. Fail to induce local inflammation in the gastrointestinal epithelium
9.30 Multiple choice: Effector caspases are activated downstream of both extrinsic and intrinsic pathways of apoptosis. Consequently, cells lacking one or more of these enzymes show defects in apoptosis. An alternative means of eliminating the activity of an effector caspase would be to: A. Generate a form of the pro-caspase with a mutation in the initiator caspase cleavage site B. Express a mutant form the caspase that lacked the pro-domain C. Express a constitutively active form of the initiator caspase D. Generate a knockout mutation that prevented expression of the Fas receptor E. Generate a mutation in the proteins required for autophagy
A. Generate a form of the pro-caspase with a mutation in the initiator caspase cleavage site
Effector caspases are activated downstream of both extrinsic and intrinsic pathways of apoptosis. Consequently, cells lacking one or more of these enzymes show defects in apoptosis. An alternative means of eliminating the activity of an effector caspase would be to: A. Generate a form of the pro-caspase with a mutation in the initiator caspase cleavage site B. Express a mutant form the caspase that lacked the pro-domain C. Express a constitutively active form of the initiator caspase D. Generate a knockout mutation that prevented expression of the Fas receptor E. Generate a mutation in the proteins required for autophagy
A. Generate a form of the pro-caspase with a mutation in the initiator caspase cleavage site
Toxoplasma gondii is a single-celled parasitic protozoan that infects and replicates in macrophages. It is common in the environment, and is transmitted to humans by the ingestion of undercooked meat or by accidental ingestion of the parasite's oocytes from contaminated water or cat litter. Infected individuals with healthy immune systems are generally asymptomatic, and rapidly clear the infection. However, in AIDS patients, infections of Toxoplasma gondii can lead to severe disease and even death. To investigate the immune mechanisms important in controlling Toxoplasma gondii, a mouse model of the infection was developed. Mice were infected with the protozoa at a dose where the majority of the mice survive the infection, and at the same time, were injected with a neutralizing antibody to a cytokine made by T cells (anti-'X' IgG). A second group of mice received the protozoa plus a control IgG antibody, as shown in Figure Q11.10 The most likely candidate for cytokine 'X' is: A. IFN- B. IL-2 C. IL-4 D. IL-17 E. GM-CSF
A. IFN-
Salmonella typhimurium is a Gram-negative bacterial pathogen that infects its host via the gastrointestinal (GI) tract. Early in infection, the bacteria enter and replicate in gut epithelial cells, where the infection provokes a type 3 response, includingthe development of TH17 cells, in the GI tract. However, this type 3 response in the GI tract does not eradicate the pathogen, as S. typhimurium has evolved strategies to evade the TH17 response and to spread systemically by infecting and replicating in macrophages. Therefore, a second phase of the immune response is required to completely eliminate the pathogen from the body, as has been demonstrated in mouse models of S. typhimurium infection. These experiments in mouse models likely showed that: A. IFN- is required to clear S. typhimurium from the body. B. IL-17 is required to clear S. typhimurium from the body. C. IL-22 is required to clear S. typhimurium from the body. D. IL-13 is required to clear S. typhimurium from the body E. IL-4 is required to clear S. typhimurium from the body
A. IFN- is required to clear S. typhimurium from the body.
Following an acute virus infection in which the host clears the virus by approximately one week post-infection, a population of virus-specific memory CD8 T cells is maintained and can be detected for months to years post-infection. In mice with aknockout of a single cytokine, virus-specific memory CD8 T cells cannot be maintained, and disappear over time as shown in Figure Q11.23 The most likely identity of the cytokine that is missing in these knockout mice is: A. IL-15 B. IL-2 C. IL-21 D. IL-23 E. IL-4
A. IL-15
1.10 Multiple choice: When macrophages in a tissue encounter bacteria, they release cytokines that induce an inflammatory response. These cytokines act on other immune cells, to recruit them to the site of infection and to enhance their activities. In addition, these cytokines act on the endothelial cells of the blood vessel wall to: A. Increase their permeability, allowing fluid and proteins to leak into the tissue B. Solidify the tight junctions to prevent the bacteria from entering the blood C. Proliferate, allowing the blood vessel to enlarge D. Up-regulate microbicidal mechanisms, so they can kill bacteria E. Secrete anti-microbial peptides
A. Increase their permeability, allowing fluid and proteins to leak into the tissue
Multiple choice: When macrophages in a tissue encounter bacteria, they release cytokines that induce an inflammatory response. These cytokines act on other immune cells, to recruit them to the site of infection and to enhance their activities. In addition, these cytokines act on the endothelial cells of the blood vessel wall to: A. Increase their permeability, allowing fluid and proteins to leak into the tissue B. Solidify the tight junctions to prevent the bacteria from entering the blood C. Proliferate, allowing the blood vessel to enlarge D. Up-regulate microbicidal mechanisms, so they can kill bacteria E. Secrete anti-microbial peptides
A. Increase their permeability, allowing fluid and proteins to leak into the tissue
Infections of intracellular pathogens (e.g., mycobacteria, listeria, toxoplasma, viruses, etc.) cause a rise in the numbers of monocytes in the blood, a symptom known as monocytosis. In the cases of these infections, monocytosis is likely caused by: A. Increased production of monocytes in the bone marrow induced by TH1 cytokines B. Loss of monocytes into tissues due to inflammation, leading to increased production in the bone marrow C. Differentiation of blood monocytes into macrophages, inducing bone marrow production of new monocytes D. Sticking of blood monocytes to vessel walls due to integrin binding, reducing the numbers of monocytes in the circulation E. Apoptosis of monocytes caused by the toxic effects of the infecting pathogen
A. Increased production of monocytes in the bone marrow induced by TH1 cytokines
Multiple choice: Several types of pathogens encode proteins that function as superantigens, which activate massive numbers of T cells in an individual. One example is the staphylococcal enterotoxins that cause food poisoning. These superantigens are the exception to the general rule that T cells only recognize specific peptide:MHC complexes, because they: A. Induce activation of any T cell whose T-cell receptor uses a particular Vβ region bound by that superantigen B. Simultaneously stimulate all of the T-cell receptors on a given T cell C. Cover up the peptide-binding site, preventing MHC molecules from binding peptides D. Activate a large number of T cells that are specifically recognizing peptides derived from the superantigen protein E. Induce anti-microbial cytokine production that aids the immune system in clearing the pathogen
A. Induce activation of any T cell whose T-cell receptor uses a particular Vβ region bound by that superantigen
Multiple choice: Chemokines such as CXCL8 have a key role in the rapid recruitment of neutrophils to the site in the tissue containing the focus of an infection. In this response, CXCL8 has two different functions. In addition to inducing integrin activation on the neutrophil, CXCL8 also functions to: A. Induce directional migration of the neutrophil in the tissue B. Induce increased expression of P-selectin and E-selectin on the endothelium C. Induce increased expression of integrins on the neutrophil surface D. Induce blood vessel dilation and fluid leakage into the infected tissue E. Induce increased phagocytic activity by the neutrophil
A. Induce directional migration of the neutrophil in the tissue
Multiple choice: Secondary (or peripheral) lymphoid organs are sites for initiation of adaptive immune responses. Given the rarity of lymphocytes specific for any given antigen and the vast amount of body tissue that must be protected, the system of secondary lymphoid tissues is efficient because: A. It concentrates antigens in centralized locations for rare lymphocytes to encounter B. It provides the optimal environment for the rapid proliferation of lymphocytes C. It traps the pathogens and antigens in a contained environment so they cannot spread to other tissues in the body D. It helps the innate immune cells eliminate the infection by using lymphatic fluid to drain pathogens from the infected tissue E. It filters the lymph fluid and removes pathogenic organisms before they can enter the bloodstream
A. It concentrates antigens in centralized locations for rare lymphocytes to encounter
Multiple choice: When stimulated by binding to bacterial products, the fMet-Leu-Phe (fMLF) receptor triggers multiple responses by phagocytes, including migration and induction of antimicrobial activities. Most of these responses are activated by small GTPases of the Rac and Rho families that are indirectly activated by fMLF receptor stimulation. The fMLF receptor can initiate multiple downstream signaling pathways because: A. It couples to a heterotrimeric G protein that has alpha and beta-gamma subunits with independent activities. B. It couples directly to two different guanine nucleotide exchange factors (GEFs). C. It binds to Rac, Rho, and cdc42 directly. D. It promotes fusion of phagosomes with lysosomes, initiating multiple signals. E. It induces assembly of multiple enzymes from individual cytosolic components.
A. It couples to a heterotrimeric G protein that has alpha and beta-gamma subunits with independent activities.
Multiple choice: Once expressed on the surface of host cells, an MHC protein remains stably associated with its bound peptide for several days. This highly stable peptide binding behavior is important because: A. It prevents peptide exchanges on the cell surface, ensuring that peptide:MHC complexes are reliable indicators of the proteins present inside that host cell. B. If the MHC protein lost its peptide it would become unstable, and would be rapidly internalized and degraded. C. Pathogens would otherwise evade the immune response by making decoy peptides that mimic host cell peptides. D. Pathogens would be able to evade the T cell response by making proteases that cleave MHC proteins inducing peptide release. E. Immune responses to infection often induce noxious chemicals that damage surface MHC proteins, and might result in peptide loss.
A. It prevents peptide exchanges on the cell surface, ensuring that peptide:MHC
4.19 Multiple choice: Once expressed on the surface of host cells, an MHC protein remains stably associated with its bound peptide for several days. This highly stable peptide binding behavior is important because: A. It prevents peptide exchanges on the cell surface, ensuring that peptide:MHC complexes are reliable indicators of the proteins present inside that host cell. B. If the MHC protein lost its peptide it would become unstable, and would be rapidly internalized and degraded. C. Pathogens would otherwise evade the immune response by making decoy peptides that mimic host cell peptides. D. Pathogens would be able to evade the T cell response by making proteases that cleave MHC proteins inducing peptide release. E. Immune responses to infection often induce noxious chemicals that damage surface MHC proteins, and might result in peptide loss.
A. It prevents peptide exchanges on the cell surface, ensuring that peptide:MHC complexes are reliable indicators of the proteins present inside that host cell.
Multiple choice: Opsonization of pathogens by both antibodies and complement proteins (C3b) leads to uptake and destruction of the pathogen by phagocytic cells that express both Fc receptors and complement receptors. Which of the following in Figure Q2.16 is the most efficient form of dual opsonization of the pathogen by antibody and C3b to maximize phagocytosis? (LOOK AT PICTURE)
A. Look at picture (one with words)
Multiple choice: Peptide editing is an important component of antigen presentation for both MHC class I and MHC class II pathways, as it drives the preferential presentation of high-affinity binding peptides. For MHC class II peptide editing, HLA-DM plays a key role. In the absence of HLA-DM: A. MHC class II molecules traffic to the cell surface with CLIP in their binding sites. B. No MHC class II molecules are released to traffic to the cell surface. C. MHC class II molecules bind to HLA-DO and are inhibited from binding peptides. D. Pathogens can evade the immune system by blocking peptide exchange on MHC class II. E. HLA-DO competes for high-affinity binding peptides with MHC class II molecules and blocks antigen presentation.
A. MHC class II molecules traffic to the cell surface with CLIP in their binding sites.
Multiple choice: NK cells can be activated following recognition of a virus-infected cell, if that cell has down-regulated expression of MHC class I proteins on its surface. However, NK cells can also recognize infected cells or tumor cells, even if they still express MHC class I proteins. In this latter case, activating receptors on NK cells are recognizing: A. Molecules on the target cell up-regulated by cellular or metabolic stress B. Cytokines secreted by the virus-infected or tumor cell C. MHC class I-like decoy molecules encoded by the virus D. Mutated self-proteins expressed by the tumor cell E. Double-stranded DNA in the cytoplasm of the infected or tumor cell
A. Molecules on the target cell up-regulated by cellular or metabolic stress
9.10 Multiple choice: A mouse is infected with staphylococcal bacteria through a laceration in the skin of its paw. Dendritic cells are isolated from the tissue at the site of infection, and are incubated together with naïve staphylococcal-specific CD4 T cells. Seventy-two hours later, the proliferation of the CD4 T cells is measured as a readout for T cell activation. Surprisingly, the T cell response is quite poor compared to the response observed when the same T cells are mixed with a comparable number of dendritic cells isolated from the draining lymph node of the infected mouse. A comparison of the dendritic cells isolated from the two different sites would reveal: A. Much higher levels of MHC and B7 molecules on the lymph node dendritic cells than those from the infected tissue B. Much higher expression of all TLRs in the lymph node dendritic cells than those from the infected tissue C. An increased number of MHC class II molecules bearing bacterial peptides on the surface of dendritic cells from the infected tissue than on those from the lymph node D. Increased phagocytic activity of the lymph node dendritic cells than those from the infected tissue E. Increased expression of Dectin-1, DEC205, and DC-SIGN on the lymph node dendritic cells than on those from the infected tissue
A. Much higher levels of MHC and B7 molecules on the lymph node dendritic cells than those from the infected tissue
A mouse is infected with staphylococcal bacteria through a laceration in the skin of its paw. Dendritic cells are isolated from the tissue at the site of infection, and are incubated together with naïve staphylococcal-specific CD4 T cells. Seventy-two hours later, the proliferation of the CD4 T cells is measured as a readout for T cell activation. Surprisingly, the T cell response is quite poor compared to the response observed when the same T cells are mixed with a comparable number of dendritic cells isolated from the draining lymph node of the infected mouse. A comparison of the dendritic cells isolated from the two different sites would reveal: A. Much higher levels of MHC and B7 molecules on the lymph node dendritic cells than those from the infected tissue B. Much higher expression of all TLRs in the lymph node dendritic cells than those from the infected tissue C. An increased number of MHC class II molecules bearing bacterial peptides on the surface of dendritic cells from the infected tissue than on those from the lymph node D. Increased phagocytic activity of the lymph node dendritic cells than those from the infected tissue E. Increased expression of Dectin-1, DEC205, and DC-SIGN on the lymph node dendritic cells than on those from the infected tissue
A. Much higher levels of MHC and B7 molecules on the lymph node dendritic cells than those from the infected tissue
Multiple choice: Some pathogenic microorganisms encode proteins, such as the Staphylococcus Protein A, that bind to immunoglobulin constant region domains with high affinity. These microbial proteins provide a benefit to the microorganism by: A. Preventing antibodies bound to the microbe from binding to Fc receptors on phagocytes B. Blocking the binding of anti-microbial antibodies to the pathogen surface C. Cleaving the antibody into fragments that separate the antigen-binding region from the effector function D. Inducing aggregation of the anti-microbial antibodies by multivalent binding to the pathogen-derived protein E. Preventing the antibody from neutralizing the pathogen
A. Preventing antibodies bound to the microbe from binding to Fc receptors on phagocytes
Salmonella typhimurium is the causative agent of typhoid fever, and infects the host by translocating across the intestinal epithelium. Recent studies have shown that S. typhimurium produces an effector protein called SopB that induces intestinal enterocytes to differentiate into M cells. This is beneficial to the bacteria because: A. S. typhimurium gains access to the host by crossing the intestinal epithelium inside M cells. B. M cells are unable to secrete antimicrobial peptides as do the enterocytes. C. M cells are unable to secrete mucus as do the enterocytes. D. S. typhimurium utilizes the M cell metabolic machinery for its proliferation. E. M cells lack the pattern recognition receptors that induce innate responses to pathogens
A. S. typhimurium gains access to the host by crossing the intestinal epithelium inside M cells.
Multiple choice: Early studies analyzing the antibody protein fragments generated after proteolytic cleavage revealed important information about the overall structure of the antibody molecule. Which cleavage pattern (indicated by the red triangles in Figure Q4.5) yields a fragment that has the same antigen-binding avidity as the intact antibody, but is unable to activate complement after binding to a pathogen? (SEE IMAGE)
A. SEE IMAGE
Multiple choice: In Figure Q4.8, which close-up view of these two V domains has the amino acid sequences most important for antigen-binding highlighted correctly in red? (SEE IMAGE)
A. SEE IMAGE
Multiple choice: The pattern recognition receptors on cells of the innate immune system are genetically encoded, meaning that their sequences and specificities are determined prior to the development of the individual. In contrast, the antigen receptors of B and T lymphocytes arise from a random rearrangement process that occurs differently in each lymphocyte as it develops. One potential problem entailed by the random process that generates lymphocyte antigen receptors is the possibility that: A. Some antigen receptors might recognize the individuals own cells or antigens B. Many lymphocytes might generate antigen receptors that don't recognize anything C. Many lymphocytes might generate antigen receptors that recognize multiple different pathogens D. Some antigen receptors might recognize foreign tissues and lead to graft rejection during organ transplantation E. Some lymphocytes might not generate functional antigen receptor proteins
A. Some antigen receptors might recognize the individuals own cells or antigens
When mice are born, their intestinal lamina propria lacks TH17 effector cells. These cells develop after birth due to: A. Stimulation by antigens derived from commensal microbes that populate the gastrointestinal tract after birth B. Stimulation by retinoic acid from dietary sources C. Stimulation by IL-10 produced from FoxP3+ regulatory T cells D. Stimulation by short-chain fatty acids derived from commensal microbes that populate the gastrointestinal tract after birth E. Stimulation by antimicrobial peptides produced by intestinal epithelial cells
A. Stimulation by antigens derived from commensal microbes that populate the gastrointestinal tract after birth
Multiple choice: Septic shock is a serious, often fatal response to an infection in the bloodstream. This response can be elicited in mice by intravenous injection of bacterial LPS. However, it was found that one strain of mice, C3H/HeJ, is resistant to LPS- induced shock. This fact was used to clone the gene for TLR-4 based on positional cloning from C3H/HeJ mice. Another example of a strain of mice that is resistant to LPS- induced septic shock is: A. TNF-receptor-deficient mice B. TLR-2-deficient mice. C. LFA-1-deficient mice D. Neutrophil-deficient mice E. Complement receptor-deficient mice
A. TNF-receptor-deficient mice
Multiple choice: Signaling through the Drosophila Toll pathway is initiated when pathogen recognition receptors (PRRs) bind to microbial products, such as bacterial peptidoglycan. Aspects of this pathway share similarity to the mammalian complement cascade as well as to the innate recognition system based on TLRs. One feature of Toll signaling that resembles the complement pathway is: A. The activation of an extracellular proteolytic cascade involving cleavage of self-proteins B. The deposition of Toll signaling proteins onto the microbial surface C. The release of soluble fragments of Toll that induce inflammation D. The assembly of a membrane attack complex in the microbial membrane following Toll activation E. The presence of receptors for Toll cleavage products on phagocytic cells to promote pathogen ingestion
A. The activation of an extracellular proteolytic cascade involving cleavage of self-proteins
Multiple choice: Stimulation of the nucleic acid sensing TLRs that reside in endosomal membranes induces the production of a different cytokine response than is produced by stimulation of the plasma membrane TLRs. In part, this distinction is based on the different adapter proteins used by the nucleic acid sensing TLRs, leading to the activation of IRF factors. The cytokine response following stimulation of nucleic acid-sensing TLRs is characterized by production of: A. The antiviral cytokine, type I interferon B. TNF-alpha, which induces increased vascular permeability C. Antimicrobial peptides by macrophages D. Chemokines that recruit neutrophils E. The inflammatory complement fragments, C3a and C5a
A. The antiviral cytokine, type I interferon
9.3 Multiple choice: An immunodeficient mouse strain is identified, that has a single gene defect causing its disease. Mice with this defect have greatly impaired responses to protein antigens following subcutaneous immunization and also exhibit severely delays in the kinetics of their antibody responses. Analysis of their lymph nodes revealed profound alterations in the normal architecture, with a lack of organization of distinct T-cell and B-cell zones. A likely candidate for the defect in these mice is: A. The chemokine receptor CCR7, which recruits B cells, T cells, and dendritic cells to lymph nodes. B. The TNF family member LT-, which is made by Lti cells. C. The chemokine receptor CXCR5 that recruits B cells to the lymph node follicles. D. Prox1, the transcription factor required for the development of lymphatic vessels. E. TNF-, which is required for the development of FDCs.
A. The chemokine receptor CCR7, which recruits B cells, T cells, and dendritic cells to lymph nodes.
An immunodeficient mouse strain is identified, that has a single gene defect causing its disease. Mice with this defect have greatly impaired responses to protein antigens following subcutaneous immunization and also exhibit severely delays in the kinetics of their antibody responses. Analysis of their lymph nodes revealed profound alterations in the normal architecture, with a lack of organization of distinct T-cell and B-cell zones.A likely candidate for the defect in these mice is: A. The chemokine receptor CCR7, which recruits B cells, T cells, and dendritic cells to lymph nodes. B. The TNF family member LT-, which is made by Lti cells. C. The chemokine receptor CXCR5 that recruits B cells to the lymph node follicles. D. Prox1, the transcription factor required for the development of lymphatic vessels. E. TNF-, which is required for the development of FDCs
A. The chemokine receptor CCR7, which recruits B cells, T cells, and dendritic cells to lymph nodes.
Multiple choice: Classical MHC molecules function as peptide-binding receptors that present these peptides to alpha:beta T cells for recognition by alpha:beta T-cell receptors. MHC molecules can be detected as far back in evolution as sharks, the same time at which T- cell receptors can be identified. Examination of shark MHC proteins indicates that these molecules likely function identically to human MHC molecules. This conclusion is based on: A. The conservation of amino acid residues important in peptide binding in both shark and human MHC proteins B. The observation that MHC genes are highly polymorphic in sharks as well as humans C. The fact that sharks have both MHC class I and MHC class II molecules D. The finding that sharks have both classical and nonclassical MHC molecules, like humans E. The ability to trace the evolution of MHC protein sequences from the earliest vertebrates to humans
A. The conservation of amino acid residues important in peptide binding in both shark and human MHC proteins
Multiple choice: Antibody diversity is generated by multiple mechanisms, each of which contributes to the generation of antibodies with up to 1011 different amino acid sequences in their antigen-binding sites. Several of these mechanisms involve changes in the DNA sequences encoding the antibody heavy and light chain proteins. One mechanism that does not rely on changes to the DNA within the immunoglobulin heavy and light chain gene loci is, instead, dependent on: A. The contributions of amino acids from both the heavy chain and the light chain to form the antigen-binding site B. The random usage of V, D, and J gene segments to form the heavy chain V region sequence C. The random usage of light chains versus light chains to pair with the heavy chain D. The activity of TdT to add random nucleotides at the junctions between the V, J, and D region sequences E. The fact that heavy chain V regions contain an extra gene segment encoded by the D region compared to light chain V regions
A. The contributions of amino acids from both the heavy chain and the light chain to form the antigen-binding site
2.29 Multiple choice: The importance of complement activation as an innate immune defense against infections is illustrated by: A. The evolution of complement avoidance strategies by many pathogens B. The large number of proteins involved in the complement pathway C. The large number of complement regulatory pathways expressed by the host D. The existence of three different mechanisms for initiating complement activation E. The ability of the membrane attack complex to lyse some pathogens
A. The evolution of complement avoidance strategies by many pathogens
Multiple choice: The importance of complement activation as an innate immune defense against infections is illustrated by: A. The evolution of complement avoidance strategies by many pathogens B. The large number of proteins involved in the complement pathway C. The large number of complement regulatory pathways expressed by the host D. The existence of three different mechanisms for initiating complement activation E. The ability of the membrane attack complex to lyse some pathogens
A. The evolution of complement avoidance strategies by many pathogens
1.40 Multiple choice: One surprising aspect of the immune system is that individuals make responses to human tissues from a different individual, causing serious problems for organ and tissue transplantation. The basis for this immune response is: A. The extensive polymorphism of MHC genes in the human population B. The fact that transplanted tissues often carry infectious microbes into the recipient C. The fact that individuals may differ in their blood group antigens (i.e., their blood type) D. The presence of many antigen-presenting-cells in the transplanted tissue E. The presence of many B and T lymphocytes in the transplanted tissue
A. The extensive polymorphism of MHC genes in the human population
Multiple choice: One surprising aspect of the immune system is that individuals make responses to human tissues from a different individual, causing serious problems for organ and tissue transplantation. The basis for this immune response is: A. The extensive polymorphism of MHC genes in the human population B. The fact that transplanted tissues often carry infectious microbes into the recipient C. The fact that individuals may differ in their blood group antigens (i.e., their blood type) D. The presence of many antigen-presenting-cells in the transplanted tissue E. The presence of many B and T lymphocytes in the transplanted tissue
A. The extensive polymorphism of MHC genes in the human population
Vibrio cholerae causes an acute diarrheal illness that can be fatal if nottreated. Several vaccines have been developed in an effort to prevent this disease. The oral cholera vaccine is a mixture of killed Vibrio cholerae bacteria plus additional inactivated cholera toxin protein. Efficacy studies of this vaccine indicate that it prevents 50-60% of the cases of cholera infection observed in non-vaccinated individuals. In contrast, injectable vaccines made from killed bacteria or purified bacterial subunits are substantially less effective at preventing infections. This is likely due to the fact that: A. The injectable vaccine fails to elicit gut-homing immune responses. B. The oral vaccine lasts substantially longer in the body than the injectable vaccine. C. The oral vaccine has a higher concentration of bacterial antigens than the injectable vaccine. D. The oral vaccine contains the inactivated cholera toxin. E. The injectable vaccine does not contain protein epitopes to elicit CD4 helper T cells
A. The injectable vaccine fails to elicit gut-homing immune responses.
9.19 Multiple choice: A mouse is immunized with a single 9 amino acid peptide derived from the influenza virus. This peptide binds to MHC class I and produces an epitope (peptide:MHC complex) recognized by a small number of naive CD8 T cells in the mouse. The peptide is mixed with CpG oligonucleotides that are ligands for TLR-9. Surprisingly, this immunization regimen generates a very poor cytotoxic CD8 effector response to targets coated with this peptide compared to immunization with a preparation of intact heat-killed influenza virus mixed with CpG oligonucleotides. The enhanced cytotoxic T cell response to the peptide observed following immunization with intact viral particles compared to the peptide alone is due to: A. The presence of CD4 T cell epitopes in the intact virus B. The increased production of type I interferon elicited by the intact virus C. The presence of additional CD8 epitopes in the intact virus D. Presentation of peptides by macrophages instead of dendritic cells E. Up-regulation of MHC class I molecules by the intact virus
A. The presence of CD4 T cell epitopes in the intact virus
A mouse is immunized with a single 9 amino acid peptide derived fromthe influenza virus. This peptide binds to MHC class I and produces an epitope (peptide:MHC complex) recognized by a small number of naive CD8 T cells in the mouse. The peptide is mixed with CpG oligonucleotides that are ligands for TLR-9. Surprisingly, this immunization regimen generates a very poor cytotoxic CD8 effector response to targets coated with this peptide compared to immunization with a preparation of intact heat-killed influenza virus mixed with CpG oligonucleotides. The enhanced cytotoxic T cell response to the peptide observed following immunization with intact viral particles compared to the peptide alone is due to: A. The presence of CD4 T cell epitopes in the intact virus B. The increased production of type I interferon elicited by the intact virus C. The presence of additional CD8 epitopes in the intact virus D. Presentation of peptides by macrophages instead of dendritic cells E. Up-regulation of MHC class I molecules by the intact virus
A. The presence of CD4 T cell epitopes in the intact virus
Multiple choice: Some T cells express gamma:delta T-cell receptors rather than alpha:beta T-cell receptors. The organization of the alpha locus and the delta locus helps to ensure that each T cell cannot express both types of T-cell receptors. The mechanism involved is that: A. The rearrangement of a T-cell receptor alpha gene deletes the delta locus on that allele. B. The rearrangement of a T-cell receptor delta gene deletes the alpha locus on that allele. C. The RAG recombinase enzymes are down-regulated immediately after the first T-cell receptor genes rearrange. D. The alpha:beta T-cell receptor signals the T cell to delete the delta locus. E. The gamma:delta T-cell receptor signals the T cell to delete the alpha locus.
A. The rearrangement of a T-cell receptor alpha gene deletes the delta locus on that allele.
5.17 Multiple choice: Some T cells express : T-cell receptors rather than : T-cell receptors. The organization of the locus and the locus helps to ensure that each T cell cannot express both types of T-cell receptors. The mechanism involved is that: A. The rearrangement of a T-cell receptor gene deletes the locus on that allele. B. The rearrangement of a T-cell receptor gene deletes the locus on that allele. C. The RAG recombinase enzymes are down-regulated immediately after the first T-cell receptor genes rearrange. D. The : T-cell receptor signals the T cell to delete the locus. E. The : T-cell receptor signals the T cell to delete the locus. LOOK AT PIC
A. The rearrangement of a T-cell receptor gene deletes the locus on that allele.
In humans, IgA is produced in copious amounts, estimated to be a rate of 3 g/day. Nearly all of the IgA secreting plasma cells are found in the gastrointestinal (GI) tract where the secreted IgA is transported across the GI epithelium into the lumen of the gut. There, this antibody protects the GI epithelium against intestinal pathogens. In contrast, none of the GI resident long-lived antibody secreting cells produce antibodies of the IgG class. The differential localization of long-lived antibody secreting cells producing IgA compared to those producing IgG is likely due to:
A. Their priming and differentiation in mucosal lymphoid organs
Multiple choice: The majority of vaccines work by eliciting pathogen-specific antibodies that circulate in our bodies and protect us in the event that we are later exposed to that specific pathogen. For most viruses and bacterial toxins that we are vaccinated against, these pre-existing antibodies are protective because: A. They neutralize the virus or toxin, preventing it from attaching to and entering our cells. B. They bind to the virus or toxin and carry it to the liver where it can be degraded. C. They bind to the virus or toxin and directly induce lysis. D. They induce mucus production that helps flush the toxin or virus out of the body. E. They bind to epithelial cells and induce the production of antimicrobial peptides.
A. They neutralize the virus or toxin, preventing it from attaching to and entering our cells.
Multiple choice: Recombination signal sequences are conserved heptamer and nonamer sequences that flank the V, J, and D gene segments which undergo recombination to generate the final V region coding exon. Some of these have 12- nucleotide spacers between the heptamer and nonamer, and others have 23-nucleotide spacers. The reason recombination signal sequences come in these two forms is: A. To ensure the correct assembly of gene segments so that a VH recombines to a DH and not to another VH, for instance B. To ensure that the heptamer and nonamer are found on the same face of the DNA double helix C. To ensure that K, upside-down Y, and heavy chains recombine within a locus and not between loci D. To ensure that K, upside-down Y, and heavy chain gene segments do not undergo recombination with non-immunoglobulin genes E. To ensure that the RAG recombinase cuts the DNA between the last nucleotide of the heptamer and the coding sequence
A. To ensure the correct assembly of gene segments so that a VH recombines to a DH and not to another VH, for instance
Multiple choice: Although the complement cascade can be initiated by antibodies bound to the surface of a pathogen, complement activation is generally considered to be an innate immune response. This is because: A. Two of the three pathways for complement activation are initiated by constitutively produced recognition molecules that directly interact with microbial surfaces. B. When the complement cascade leads to the formation of a membrane-attack complex, the pathogen is killed. C. Several of the soluble products generated by complement activation lead promote the inflammatory response. D. Complement proteins bound to the pathogen promote uptake and destruction by phagocytic cells. E. The C3 convertase is only produced when complement activation is initiated by antibody binding to a pathogen.
A. Two of the three pathways for complement activation are initiated by constitutively produced recognition molecules that directly interact with microbial surfaces.
Multiple choice: Hepatitis C is a virus that infects hepatocytes, which are non-immune cells of the liver. Currently, patients with chronic Hepatitis C infections are treated with repeated administration of type I interferon, predominantly interferon . One aspect of this treatment that might aid the patient's immune system in clearing this virus infection is: A. Up-regulation of MHC class I expression levels on hepatocytes B. Activation of macrophages to produce noxious compounds that might kill the virus C. Induction of an inflammatory response to promote neutrophil trafficking to the liver D. Production of TNF- in response to type I interferon leading to vasodilation in the liver E. Induction of IL-1 and IL-6 leading to the acute phase response
A. Up-regulation of MHC class I expression levels on hepatocytes
Multiple choice: Adaptive immune responses are slow to develop, taking days to weeks after exposure to reach their peak. However, these responses are more specific than innate responses, and also generate immunological memory. These latter features, which provide enhanced protection upon re-infection with the same pathogen, are the basis of: A. Vaccines B. Antibiotics C. Systemic shock D. Complement activation E. Phagocytosis
A. Vaccines
Multiple choice: Vaccination against many infectious diseases has provided enormous benefit in developed countries, leading to the virtual eradication of diseases such as polio, measles, smallpox, and others. However, efforts to create long-lasting vaccines against some viral infections, like Influenza and HIV, have not been successful to date because: A. Viruses like HIV and Influenza undergo antigenic variation to evade previous immune responses. B. Viruses like HIV and Influenza spread too rapidly in the population for a vaccine to be effective. C. Viruses like HIV and Influenza have RNA, rather than DNA genomes, and are resistant to current vaccine strategies. D. Viruses like HIV and Influenza infect via mucosal surfaces, a route that is not well protected by current vaccine strategies. E. Viruses like HIV and Influenza are transmitted vertically (from mother to child) during fetal development, so babies are infected before they can be vaccinated.
A. Viruses like HIV and Influenza undergo antigenic variation to evade previous immune responses.
The germinal center is a region within the secondary B cell follicle where sustained B cell proliferation and differentiation take place. The processes of B cell proliferation and differentiation, including affinity maturation and class switching, require periodic interactions of the germinal center B cells with CD4 TFH cells. These periodic interactions between the B cells and TFH cells can occur: A. When B cells cycle between the dark zone and the light zone of the germinal center B. When B cells leave the germinal center and migrate through the T-cell zone on their way to the blood C. When B cells migrate and form a primary focus of antibody-secreting plasmablasts in the medullary cords of the lymph node D. When B cells migrate to the border between the T-cell zone and the B-cell zone of the lymph node E. When B cells up-regulate CXCR4 and migrate into the dark zone of the germinal center
A. When B cells cycle between the dark zone and the light zone of the germinal center
Multiple choice: Some CD1 molecules bind to glycosphingolipids, and are recognized by a subset of T cells known as invariant NKT (iNKT) cells. The ability of these T cells to recognize different glycolipid constituents from microorganisms when they are bound to CD1d places these cells in the 'innate immune' category. While iNKT cells do express a fully rearranged alpha:beta T-cell receptor, one key feature of the T-cell receptors expressed on iNKT cells also places them in the 'innate immune' category. This feature is: A. iNKT cells have a highly restricted T-cell receptor repertoire, with the majority of cells utilizing the same V-alpha and J-alpha rearrangement. B. iNKT cells express receptors that are also expressed on NK cells. C. iNKT cells express T-cell receptors that induce inhibitory, rather than activating signals. D. iNKT cells do not generally express CD4 or CD8. E. The T-cell receptors expressed on iNKT cells recognize both MHC class I and MHC class II molecules.
A. iNKT cells have a highly restricted T-cell receptor repertoire, with the majority of cells utilizing the same V-alpha and J-alpha rearrangement.
Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important effector mechanism in immunity to virus infections. This immune pathway has also been exploited for clinical applications. For instance, patients with various disorders, including rheumatoid arthritis and some B cell lymphomas, are treated with an antibody directed atCD20, a surface receptor expressed on all B cells. This antibody leads to the depletion of B cells from the patients by the actions of: A.Natural killer (NK) cells B.Cytotoxic CD8 T cells C.Cytotoxic CD4 T cells D.Activated macrophages E.The complement cascade membrane attack complex
A.Natural killer (NK) cells
Infants born with the immunodeficiency disease X-linked agammaglobulinemia (XLA) have a block in B cell development, and fail to produce mature B cells. As a result, these infants lack the ability to produce antibodies. After birth, babies with XLA first begin to show symptoms of recurrent and persistent extracellular bacterial infections due to common environmental pathogens when they are4-6 months of age. The reason these infants are healthy for the first 4-6 months after birth is because:Newborn infants have high circulating levels of maternal IgG at birth. A.Newborn infants are not exposed to bacterial pathogens for the first 4-6 months of life. B.Newborn infants are born with high circulating levels of complement proteins to protect them. C.Newborn infants are born with high circulating levels of antimicrobial peptides to protect them. D.Newborn infants are vaccinated against these common bacterial pathogens.
A.Newborn infants are not exposed to bacterial pathogens for the first 4-6 months of life.
Unlike somatic hypermutation, class switching occurs in discrete sequence regions upstream of the immunoglobulin heavy chain coding sequences (called switch regions). One key element in directing the enzyme AID to a specific switchregion is the opening of the DNA duplex combined with polymerase stalling during active transcription in that region. A second key feature of directing AID to a specific switch region is: A.The processed RNA from the switch region guides AID to this site in the DNA B.The binding of DNA-PK's to the switch region sequence in the DNA C.The presence of double-stranded breaks in the DNA in this region D.The binding of AID to the RNA polymerase that is transcribing the switch region E.The predominance of G:C base pairs in the switch sequence
A.The processed RNA from the switch region guides AID to this site in the DNA
1.41 Multiple choice: Vaccination against many infectious diseases has provided enormous benefit in developed countries, leading to the virtual eradication of diseases such as polio, measles, smallpox, and others. However, efforts to create long-lasting vaccines against some viral infections, like Influenza and HIV, have not been successful to date because: A. Viruses like HIV and Influenza undergo antigenic variation to evade previous immune responses. B. Viruses like HIV and Influenza spread too rapidly in the population for a vaccine to be effective. C. Viruses like HIV and Influenza have RNA, rather than DNA genomes, and are resistant to current vaccine strategies. D. Viruses like HIV and Influenza infect via mucosal surfaces, a route that is not well protected by current vaccine strategies. E. Viruses like HIV and Influenza are transmitted vertically (from mother to child) during fetal development, so babies are infected before they can be vaccinated.
A.Viruses like HIV and Influenza undergo antigenic variation to evade previous immune responses.
6.1 Matching: The diagram in Figure Q6.1 shows a pathogen (in red) that is present in different cellular compartments of each of the cell types shown. In each case, a specific T cell subset will recognize peptides of that pathogen presented on MHC molecules on the surface of the cell, and will execute its effector function. From the list below, match the appropriate T cell effector response to the cell type and location of the pathogen. i. CD4 T cell killing of target cell ii. CD8 T cell killing of target cell iii. CD4 T cell activation of target cell's antibody production iv. CD8 T cell activation of target cell's antibody production v. CD4 T cell activation of target cell's ability to kill intracellular pathogen vi. CD8 T cell activation of target cell's ability to kill intracellular pathogen LOOK AT PIC
A: ii B: v C: iii
Adaptive immune responses develop
AFTER exposure to or immunization with a given substance or antigen
Which of the following do you expect would be actively functioning in a B cell that had migrated to a germinal center?
AID
Defects in which of the following proteins do NOT result in severe combined immunodeficiency (SCID)?
AID The ones that do result in SCID are.. Artemis IL2-Ry RAG1/2 WASp
A(n) ____ is a molecule that is used by immune cells for communication. Interleukin chemoattractant chemokine cytokine ALL OF THE ABOVE
ALL OF THE ABOVE Interleukin chemoattractant chemokine cytokine
D Segment
Diversity
Plasma cells secrete
Ab with same specificity as the membrane-bound Igs
The mucosal immune system provides protection for a vast area of the body and contains three-quarters of all the lymphocytes in the body. A key feature of the mucosal immune system is its:
Ability to avoid responding to the large numbers and differing species of commensal microbes
CD3 and ζ chains
Do not bind antigen Act as signal transduction molecules Have immunoreceptor tyrosine-based activation motifs
Which of the following statements about NK-T cells is TRUE?
Activated NK-T cells can act as both TH and TC cells.
Strep throat is commonly caused by group A Streptococcus bacteria. A common symptom of strep throat is the presence of swollen lymph nodes in the neck. This symptom usually peaks about 2-4 days after the onset of the infection, and is due to:
Activation and proliferation of antigen-specific lymphocytes in the lymph nodes of the neck
Which event occurs first in T-cell signaling?
Activation of Lck
What function are macrophages unable to carry out?
Activation of naive T-cells
B7 molecules attaching to CD28 at the same time peptide:MHC complex binds to T cell receptors
Activation of naïve T cell requires
AICD
Activation-‐induced cell death (AICD) is used to induce apoptosis in previously activated T cells (both CD4+ and CD8+). ¤Fas-‐FasL interaction is the basis of AICD ¤T cells express Fas, and when activated also make FasL (both on the surface and secreted). ¤After CTLs have killed their targets, they interact with each other (either directly or thru released FasL) and induce apoptosis.
False
Acute Lymphoblastic Leukemia originates from a cancer of the plasma cell
Patients receiving hematopoietic stem cell transplants often suffer from graft-versus-host disease (GVHD), involving immune-mediated damage to the gastrointestinal (GI) tract. The symptoms of GVHD include nausea, vomiting, diarrhea, and abdominal cramping due to epithelial cell apoptosis and inflammatory leukocyte infiltration into the GI epithelium. One proposed treatment has been tested in mouse models of GVHD for potential therapeutic benefit. This treatment is:
Administration of IL-22
. Studies in mice have revealed important features about some chronic infections. In the case of mice infected with a persistent strain of lymphocytic choriomeningitis virus (LCMV), these studies showed that a majority of the virus-specific T cells were eliminated from the mice over time; however, some virus-specific CD8 T cells persisted but were unable to eradicate the viral infection. These remaining cells expressed high levels of several inhibitory receptors, including PD-1. One possible treatment for these mice to promote their ability to clear this chronic infection would be:
Administration of anti-PD-1 antibody
Cross-regulation of various members of a subset of T cells is frequently observed with:
All TH cells
Among the following description about follicular dendritic cells (FDCs), choose the appropriate description about FDCs? 1-FDCs are residing in the B-cell zone, which are concentrated mainly in the area of the follicle. 2-FDCs are in contact with B cells. 3-FDCs are not leukocytes and not derived from bone-barrow precursors. 4-FDCs are not phagocytic and do not express MHC class II proteins. 5-The immune complexes are not internalized, but remain intact on the surface of the FDC for prolonged periods of time, where the antigen can be recognized by B cells. A. All of the above, B. (1)+(2)+(3), C. (1)+(2)+(4)+(5), D. (2)+(3)+(4)+(5) E. None of the above,
All of the above
: CD28 is the co-stimulatory receptor of activated T cells. Which of the following are the ways that co- stimulation through CD28 contributes to the production of IL-2? A. CD28 signaling activates PI3-kinase, which increases production of the transcription factor AP-1 and NF B, resulting in increased transcription of IL-2 mRNA. B. CD28 signaling prolongs the lifetime of an IL-2 mRNA molecule by inducing the expression of proteins that block the activity of the instability sequence (AUUUAUUUA), resulting in increased translation and more IL-2 protein. C .PI3-Kinase helps activate the protein kinase Akt, which promotes cell growth and survival, increasing the total production of IL-2 by activated T cells.
All the above
Regarding the interaction of antigen-presenting cell with naïve T cells, which of the following is NOT correct? A.Cell-adhesion molecules mediate the initial interaction of naïve T cells with antigen-presenting cells. B.As activated DCs migrate through the cortical region of the lymph node, naïve T cells bind to each APC that they encounter. C.The transient binding of activated DCs to naïve T cells is achieved by the interaction between LFA-1 and CD2 on the T cells and ICAM-1, ICAM-2, and CD58 on DCs (Fig. 9.20). D.Transient binding of naïve T cells to APCs is providing time for a T cell to sample large numbers of MHC molecule for the presence of its cognate antigenic peptide. E. Specific antigen recognition stabilizes the transient interaction between T cells and APCs
All the above are correct
False
Alloreactivity refers to the ability of T cells to respond to allelic polymorphisms in MHC molecules when mixed with antigen-presenting cells from a genetically different individual. The T-cell receptors involved in alloreactive responses are recognizing amino acid sequences on foreign MHC molecules and do not interact at all with the peptides bound to these MHC molecules.
Malaria is caused by Plasmodium falciparum and Plasmodium vivax. These pathogens are transmitted when an individual is bitten by a Plasmodium infected mosquito. This route of transmission:
Allows the parasite to avoid the normal mechanisms blocking infections at barrier surfaces
non-professional APCs
Almost all others cells are capable of expressing MHC class II if have right TFs and are stimulated by IFN-gamma
Most normal tissues contain resident macrophages, and connective tissue sites in the gastrointestinal tract and the lung contain large numbers of these cells. Yet the blood also contains a high number of circulating 'classical' monocytes that can differentiate into macrophages after entering tissues. These circulating monocytes function to:
Amplify the local innate immune response by entering tissues that are infected
IL-2R aßy
An IL-2R (recpetor) that has a high affinity for IL-2 is
Multivalent
An antigen that contains more than one epitope
False
An individual bears 90 % similarity of MHC genes with either parent.
are not activated in the presence of a pathogen
Anergic B cells
You isolate naïve T cells from your own blood and want to polarize them to the TH1 lineage. You can use any of the following reagents to do this. Which would you choose?
Anti-TCR antibody IL-12 Anti-CD28 antibody
You isolate naïve T cells from your own blood and want to polarize them to the TH1 lineage. You can use any of the following reagents to do this. Which would you choose?
Anti-TCR antibody Anti-CD28 antibody IL-12
You isolate naïve T cells from your own blood and want to polarize them to the TH1 lineage. You can use any of the following reagents to do this. Which would you choose?
Anti-TCR antibody IL-12 Anti-CD28 antibody
What is the effector molecule of humoral immunity?
Antibodies
The vaccine to Haemophilus influenzae type b is called a conjugate vaccine. It is composed of the tetanus toxoid protein conjugated to the capsular polysaccharide of the H. influenzae type b bacteria. When used to vaccinate infants, the antibody response generated by this vaccine would include:
Antibodies to the bacterial polysaccharide and the tetanus toxoid
_______________ produced by a _____________ have ____________ than those in a _______ response
Antibodies; memory response; higher affinity; primary
False
Antigen receptor signaling pathways are initiated by the action of a Src-family kinase ( Fyn, Lyn, Blk) in T cells.
IgD functions primarily as an _____________________ on __________
Antigen receptor; B cells
Which of the following is required for T-cell activation?
Antigen-specific TCR binding to MHC peptide AND interaction with CD80, CD86, or ICOS-L
In influenza infections BLANK cause(s) milder and limited disease, whereas BLANK causes more severe disease and higher mortality
Antigenic drift; Antigenic shift
Exogenous antigens
Antigens taken into cells by endocytosis or phagocytosis Derived from viruses and bacteria Presented to Th cells by MHC Class II molecules
Stimulation of the nucleic acid sensing TLRs that reside in endosomal membranes induces the production of a different cytokine response than is produced by stimulation of the plasma membrane TLRs. The cytokine response following stimulation of nucleic acid-sensing TLRs is characterized by production of:
Antiviral type I interferons
Stimulation of the nucleic acid sensing TLRs that reside in endosomal membranes induces the production of a different cytokine response than is produced by stimulation of the plasma membrane TLRs. The cytokine response following stimulation of nucleic acid-sensing TLRs is characterized by production of:
Antiviral type I interferons NOTE: Yes. Microbial nucleic acids typically only become detectable in the cytoplasm when cells are infected with a virus so the receptors that detect viral nucleic acids lead to the induction of antiviral cytokines (type I interferons).
ICAD
Apoptosis occurs when which of the following molecules is destroyed by activated caspase 3?
False
Apoptotic program is absent in some cells
Antigens
Are bound by antibodies and are biological macromolecules - Proteins and carbohydrates most common antigens
In addition to Peyer's patches that resemble systemic lymph nodes, the intestinal epithelium also contains several thousand isolated lymphoid follicles. Unlike the organized secondary lymphoid tissues in the mucosal immune system, these lymphoid follicles:
Are found only in the intestinal epithelium, and not in other mucosal epithelia
The structure of MHC class II molecules are?
Are transmembrane glycoproteins Have cytoplasmic and extracellular domains
Receptors that are multivalent tend to bind to their ligands more strongly than receptors with a single binding site. What is the term used to describe this phenomenon?
Avidity
: Immunoreceptor signaling proteins, such as the TCR ζ chain and CD3 subunits, have conserved ITAM motifs in their cytoplasmic tails. When fully phosphorylated, the ITAM recruits a tyrosine kinase with a tandem SH2 domain structure at the amino-terminal end of the protein. Tandem SH2 domain-containing kinases do not bind to sequences in other proteins, even if they contain a phosphorylated tyrosine because: A. The amino acid sequence adjacent to the phosphorylated tyrosines in the ITAM motif is unique, and not found in any other proteins. B. The affinity of a single SH2 domain within these kinases for a tyrosine phosphorylated sequence is too low for efficient binding. C. The amino-terminal SH2 domain of the kinase has very high affinity for both of the phosphorylated tyrosines in the ITAM motif, so will not bind to other proteins. D. The amino-terminal SH2 domain of the kinase is in an autoinhibited conformation and can only bind to a phosphorylated ITAM. E. The tandem SH2 domain-containing kinase phosphorylates the tyrosines in the ITAM itself, so can only bind to these sequences.
B
B-1 B cells are considered a component of the innate rather than the adaptive immune response. The antibodies produced by B-1 B cells generally recognize capsular polysaccharide antigens found on many bacteria and viruses. These antibodies are considered part of the innate immune response because: A. They recognize pathogens rather than innocuous harmless antigens. B. They are produced prior to the exposure to the pathogen. C. They are specific for carbohydrate rather than protein antigens. D. They are secreted by B-1 B cells starting at 48 hour post-infection. E. They are not generated by the process of VD-J recombination of immunoglobulin genes.
B
Cytotoxic effector T cells also produce inflammatory cytokines such as IFN-γ and TNF-α when their T-cell receptor recognizes peptide:MHC on a target cell. One effect of this cytokine secretion is to enhance the ability of CD8 effector T cells to recognize and kill other infected cells in the nearby vicinity. This enhanced activity is due to: A. The increased production of perforin and granzymes by CD8 cells B. The up-regulation of MHC class I protein expression by IFN-γ C. The ability of TNF-α to induce vascular leakage D. The effect of cytokines on promoting target cell apoptosis E. The effect of IFN-γ to enhance viral replication leading to increased viral antigen presentation
B
Eosinophils are a subset of granulocytes that normally reside in the circulation. When activated, these cells secrete toxic compounds that are a key component in the eradication of helminthic parasite infections. Eosinophils are recruited to sites of parasite infections by: A. Interferon-γ produced by TH1 cells B. CCL11 produced by TH2 cells C. Interferon-γ produced by CD8 cytotoxic T cells D. CCL20 produced by TH17 cells E. GM-CSF produced by TH1, TH2, and TH17 cells
B
Experimental mouse models have been developed to study the mechanisms leading to the breakdown of self-tolerance and the onset of autoimmunity. One strategy is to express a foreign antigen, such as a viral protein, in a single defined cell type in a peripheral organ. For instance, the lymphocytic choriomeningitis virus (LCMV) glycoprotein has been expressed in β-islet cells of the pancreas by making a line of mice that is transgenic for a construct linking the LCMV-glycoprotein gene to the insulin promoter. In these transgenic mice, the LCMV protein is expressed only in pancreatic β-islet cells. Thymocytes with T-cell receptors specific for a peptide of LCMV-glycoprotein bound to MHC class I develop normally in the thymus, and do not undergo negative selection. The fate of these T cells once they emigrate from the thymus would likely be: A. They would be activated in the periphery and attach and kill the pancreatic β-islet cells. B. They would either be deleted in the periphery or would become unresponsive. C. They would induce an inflammatory response in the pancreas that would up-regulate co-stimulatory molecules on antigen-presenting cells. D. They would secrete cytokines that promote T cell proliferation. E. They would differentiate into virus-specific memory T cells that would protect mice upon infection with LCMV.
B
Following their activation, naive CD4 T cells differentiate into one of several subsets of effector T cells. This developmental choice is determined by which specific cytokines the T cells are exposed to during their activation; in turn, the cytokines that are produced will reflect the nature of the infecting pathogen. In order for this system to be flexible enough to produce all five effector CD4 subsets (TH1, TH2, TH17, TFH, and iTreg): A. Each naive CD4 T cell must already express one of the lineage-specific transcription factors (i.e., T-bet, GATA-3, etc.). B. Each naive CD4 T cell must express all of the STAT proteins. C. Each naive CD4 T cell must express only a single STAT protein (i.e., STAT1 or STAT6 or STAT3, etc.). D. Each naive CD4 T cell must already express low levels of the subset specific cytokines (i.e., IFNγ, IL-4, IL-17, etc.). E. Each naive CD4 T cell must express all of the lineage-specific transcription factors (i.e., T-bet, GATA-3, etc.).
B
Human patients with genetic defects that result in a failure to produce the calcium channel protein ORAI1, or the ER calcium sensor protein STIM1, have severe immunodeficiency diseases. An immunosuppressive drug that would most closely mimic these primary immunodeficiencies is: A. Rituximab, a drug that depletes B cells B. Cyclosporin A, a calcineurin inhibitor C. Rapamycin, an mTOR inhibitor D. Tysabri, an inhibitor of integrin binding E. Enbrel or Humira that inhibit TNF
B
In a second experiment, the isolated splenic and lamina propria macrophages were treated with LPS and then incubated with the protein antigen, chicken ovalbumin. CD4 T cells specific for a peptide of ovalbumin (OVA) bound to MHC class II where then incubated with each population of macrophages, and three days later, the culture supernatants were analyzed for IL-2 and IFN-y production. Which of the graphs most likely represent the results of this experiment?
B
In patients with 'CD40 ligand deficiency', T cell-dependent B cell activation is impaired, leading to poor antibody responses to protein antigens. The signaling pathway missing in these patients' B cells is important for: A. Inducing integrin activation to promote adhesion B. Inducing NFκB activation by the noncanonical pathway C. Inducing WASp activation and actin polymerization D. Inducing Ca2+ influx leading to NFAT activation E. Inducing Ras activation and Erk Map-kinase signaling
B
Lymphocyte activation leads to robust proliferation and effector cell differentiation. The metabolic demands of these processes are met, in part, by up-regulation of glycolytic enzymes and nutrient transporters on the activated cell membrane. A key intermediate in the signaling pathway leading to enhanced glucose metabolism following antigen receptor stimulation is: A. The lipid mediator diacyl-glycerol (DAG) B. The phosphoinositide, PIP3 C. Increases in cytoplasmic Ca2+ D. Cleavage of the membrane phospholipid, PIP2 The mitochondrial protein, Bcl-2
B
Some viruses have mechanisms to down-regulate MHC class I protein expression on the surface of cells in which the virus is replicating. This immune evasion strategy might prevent effector CD8 cytotoxic T cells from recognizing and killing the virus-infected cells. Would this immune evasion strategy also prevent the initial activation of virus-specific CD8 T cells? A. Yes, because no viral peptide:MHC class I complexes would form to activate CD8 T cells. B. No, because dendritic cells would take up infected cells and cross-present viral peptides to activate CD8 T cells. C. No, because some presentation of MHC class I complexes with viral peptides would occur before the virus could down-regulate all the surface MHC class I protein. D. Yes, because this immune evasion strategy would also function in dendritic cells, even if the virus doesn't replicate in dendritic cells. E. No, because the type I interferon response induced by the virus infection will up-regulate MHC class I expression and override the immune evasion mechanism.
B
T cells expressing γ:δ T-cell receptors have been found to recognize a diversity of ligands, including pathogen-derived proteins, self-peptides, and stress-induced molecules. This pattern of antigen recognition shows similarity to that of iNKT cells and MAIT cells, suggesting that γ:δ T cells: 1. Do not play an important role in immunity, but likely have a non-immune function 2. Share features of both innate and adaptive immune cells 3. Are only able to respond when the host is infected with a virus such as herpes simplex virus 4. Are involved in maintaining the integrity of endothelial cells in the host 5. Are most important in responses to tumor cells that show stress responses
B
The MARCH-1 E3-ubiquitin ligase is expressed in B cells, dendritic cells, and macrophages. The pathway regulated by MARCH-1 is targeted by some pathogens in an immune evasion strategy. In this strategy, the pathogens encode: A. A protein that induces degradation of MARCH-1 B. A protein that mimics MARCH-1 and functions similarly C. A protein that binds to MARCH-1 and inhibits its function D. A protein that is induced by IL-10 in macrophages and dendritic cells E. A protein that induces degradation of CD86
B
Two distinct lineages of T cells can be identified based on their expression of α:β versus γ:δ T-cell receptors. A deficiency in the signaling receptor Notch1 would result in: A. A loss of α:β but not γ:δ T cells B. A loss of both of α:β and γ:δ T cells C. A loss of α:β T cells and a massive expansion of γ:δ T cells D. An increased number of both of α:β and γ:δ T cells E. A normal number of both of α:β and γ:δ T cells
B
Two mutant lines of mice have been identified, each of which has a defect in T cell development. The subsets of thymocytes found in each mutant mouse line are shown in Figure Q8.26A. Figure Q8.26A To narrow down the possible defects in each mutant line, a series of bone marrow chimeras are made in which bone marrow from one strain of mice (the 'donor' strain) is used to reconstitute a second strain (the 'recipient' strain), immediately following the irradiation of the recipient strain to eliminate its own hematopoietic cells. In this procedure, the resulting chimeras have hematopoietic cells that are 100% derived from the donor strain, and all other cells and tissues are derived from the recipient strain. The thymocyte profiles of the series of bone marrow chimeras is shown in Figure 8.26B in each case the label at the top of each FACS plot refers to 'donor bone marrow → recipient': Figure Q8.26B 8.26 Multiple choice: A potential candidate molecule for the gene that is defective in Mutant-1 is: A. CD4 B. MHC class II C. Th-POK D. MHC class I E. Runx3
B
Using an antibody that recognizes the phosphorylated, but not the non-phosphorylated form of the transcription factor, NFAT, T cells are permeabilized, stained with this antibody, and analyzed by flow cytometry. Which of the data in Figure Q7.15 represent the expected pattern of staining from wild-type T cells before and after TCR stimulation.
B
T cell killing
Degradation of virus within the cell allows viral peptides to be displayed at the cell surface bound to MHC class I molecules. CD8 T cells that recognize these MHC:peptide complexes are activated and kill the infected cell. Having killed one cell, the T cell can move to a new target, kill that cell, and move on again. The killing process is initiated when the T cell receptor and CD8 together bind to an MHC class I molecule bearing a viral peptide, producing signals that activate the T cell. Cytotoxic T cells contain membrane vesicles called cytotoxic granules, which package the proteins that kill target cells. The most important of these are a protein called perforin, and a set of proteases called granzymes. These proteins are complexed with a scaffolding protein called serglycin. Activation of the T cell causes the release of the content of these vesicles, delivering the proteins directly onto the surface of the target cell. Perforin facilitates delivery of the granzymes into the cytosol. At this point the target cell is destined for death, and the T cell can migrate onwards to find a new target cell. The granzymes target various cellular proteins that regulate apoptosis, such as BID and pro-caspase-3. The granzymes cleave BID, which in its truncated form, causes cytochrome c to release from the mitochondria into the cytosol. Simultaneously, granzyme B activates pro-caspase-3, which in turn cleaves I-CAD, the inhibitor of the caspase-activated DNAse. The active DNAse migrates into the nucleus where it degrades the DNA, ensuring the death of the cell.
CCL 19
Dendrictic cells secrete which of the following cytokines to attract B and T cells to the developing lymph nodes
9.9
Dendritic
Main APCs for initiating primary response of naïve T cells is?
Dendritic Cells
While CD28 co-stimulation is important for the initial activation of naive T cells, other co-stimulatory molecules function at later stages of the T cell response. Several of these other co-stimulatory molecules are members of the TNF-receptor family, and function by activating the transcription factor, NFκB. Therefore, stimulation of these co-stimulatory TNF-receptors on activated T cells is likely to: A. Induce programmed cell death in the T cell B. Enhance T cell survival C. Increase T cell proliferation D. Promote T cell migration into tissues E. Inhibit T cell activation and differentiation
B
Which of the following did represent the antigen presenting cells (APCs)? (1) Dendritic cells (DCs); (2) T-cells; (3) Natural killer cells; (4) Macrophages; (5) B-cells. A. (1)+(2)+(3), B. (1)+(4)+(5), C. (2)+(3)+(5), D. (3)+(4)+(5),
B DCs, Macrophages, and B-cells are APCs
Two components of the recombinase - RAG-1 and RAG-2 are only made in
B and T Lymphocytes
Cells that secrete antibodies are called:
B cell derived plasma cells
The failure of the pro-B cell to make a complete immunoglobulin heavy chain protein.
B cell development in the bone marrow is an inherently wasteful process. Nearly half of the pro-B cells produced will die without progressing on to the next stage of B cell development. This massive loss of pro-B cells is due to
The lose their immunogenecity when a protein antigen is denatured by heat
B cell epitope
Their immunogenecity may depend on the three-dimensional structure of the antigen
B cell epitope
They are generally located on the surface of a protein antigen
B cell epitope
antigen binding w B cell induces proliferation/differentiation of what?
B cells
While B cells and T cells differ markedly in their functions during an immune response, the two lymphocyte subsets share the enzymatic machinery and overall scheme for generating antigen receptor diversity. This is because:
B cells and T cells both need enormous antigen receptor diversity to provide protection against the diversity of pathogens.
What cells are dependent on what other cells for optimal antibody responses to most antigens?
B cells are dependent on T cells. Often referred to T-cell-dependent antigens
Allelic Exclusion
B cells are diploid and contain both maternal and paternal chromosomes; Rearranged heavy chain or light is expressed from only one chromosome
Humoral Immunity is when
B cells expressing antigen-specific B-cell receptors (BCRs) synthesize and secrete antibody into the bloodstream
In germinal centers, proliferating B cells undergo a process called somatic hypermutation, in which mutations are introduced into the V regions of the antibody heavy and light chain genes. When this process is complete after several weeks, the overall affinities of the antibodies produced are greatly increased compared to those present early in the primary response. The somatic hypermutation process leads to increased antibody affinity because:
B cells making higher affinity antibodies receive more help from TFH cells.
In germinal centers, proliferating B cells undergo a process called somatic hypermutation, in which mutations are introduced into the V regions of the antibody heavy and light chain genes. When this process is complete after several weeks, the overall affinities of the antibodies produced are greatly increased compared to those present early in the primary response. The somatic hypermutation process leads to increased antibody affinity because:
B cells making higher affinity antibodies receive more help from Tfh cells
have a short life span
B cells that fail to recirculate through the lymphoid follicle
5Anergy
B cells that have af respond to it
All of the following are true regarding B-cell development EXCEPT:
B cells, like T cells, are MHC class restricted.
A set of mice are each immunized with one of the following as shown in Figure Q11.20. Mouse A is immunized with tetanus toxoid protein. Mouse B is immunized with the Haemophilus influenzae type b polysaccharide antigen. Mouse C is immunized with a conjugate of the diphtheria toxoid protein linked to H. influenzae type b polysaccharide. Mouse D is left unimmunized (naive). Four weeks later the spleen cells from each mouse are isolated, and B lymphocytes and T lymphocytes from each spleen cell population are purified. When mixed together in culture together with a conjugate antigen of the tetanus toxoid protein linked to the to H. influenzae type b polysaccharide, which combination of spleen cells would generate a memory B cell response?
B lymphocytes from mouse C plus T lymphocytes from mouse A
Borrelia hermsii is a spirochete bacterium, transmitted by tick bites, that causes an illness characterized by a relapsing fever. The bacteria enter the host bloodstream and replicate there. Studies in mice show that episodes of bacteremia (bacteria in the blood) are efficiently controlled by anti-bacterial antibodies, but interestingly, follicular B cells are not required for this response, nor is the response impaired by splenectomizing the mice (i.e., removing the spleen). Which B cells are most likely responsible for this antibody response?
B-1 B cells
They are produced prior to the exposure to the pathogen.
B-1 B cells are considered a component of the innate rather than the adaptive immune response. The antibodies in body cavities. These antibodies are considered part of the polysaccharide antigens found on many bacteria and viruses produced by B-1 B cells generally recognize capsular innate immune response because:
They are produces prior to the exposure to the pathogen.
B-1 B cells are considered a component of the innate rather than the adaptive immune response. The antibodies in body cavities. These antibodies are considered part of the polysaccharide antigens found on many bacteria and viruses produced by B-1 B cells generally recognize capsular innate immune response because:
TFH cells
B-cell help, Isotype switching, Ab production. pathogens: all - architecture in spleen at interface between B- and T-cell rich regions of lymph node and spleen - provide signals to B cells to make specific Ab
Patients with the disease X-linked lymphoproliferative syndrome (XLP) lack expression of the small adapter protein SAP, which associates with receptors of the SLAM family. One characteristic of this disease is an inability of cytotoxic T cells to control infections with a virus, Epstein-Barr virus (EBV), that replicates in B cells. This defect in control of EBV results from: A. A defect in antibody responses to EBV due to impaired T cell help for B cells B. A defect in adhesion of cytotoxic T cells to EBV-infected B cells C. Impaired migration of activated B cells to the germinal center D. Impaired survival of activated B cells, normally induced by CD40 stimulation E. A defect in TFH differentiation, normally induced by ICOS on B cells binding to ICOS-ligand on TFH cells
B. A defect in adhesion of cytotoxic T cells to EBV-infected B cells
Multiple choice: The MARCH-1 E3-ubiquitin ligase is expressed in B cells, dendritic cells, and macrophages. The pathway regulated by MARCH-1 is targeted by some pathogens in an immune evasion strategy. In this strategy, the pathogens encode: A. A protein that induces degradation of MARCH-1 B. A protein that mimics MARCH-1 and functions similarly C. A protein that binds to MARCH-1 and inhibits its function D. A protein that is induced by IL-10 in macrophages and dendritic cells E. A protein that induces degradation of CD86
B. A protein that mimics MARCH-1 and functions similarly
In germinal centers, proliferating B cells undergo a process called somatic hypermutation, in which mutations are introduced into the V regions of the antibody heavy and light chain genes. When this process is complete after several weeks, the overall affinities of the antibodies produced are greatly increased compared to those present early in the primary response. The somatic hypermutation process leads to increased antibody affinity because: A. Mutations that decrease the antibody affinity lead to an arrest of B cell proliferation. B. B cells making higher affinity antibodies receive more help from TFH cells. C. Somatic hypermutations only take place in the sequences encoding the CDR1, CDR2, and CDR3 regions. D. Mutations that increase antibody affinity lead to an increased rate of B cell proliferation .E. The majority of nucleotide changes introduced by AID don't change the amino acid coding sequence
B. B cells making higher affinity antibodies receive more help from TFH cells.
9.27 Multiple choice: Eosinophils are a subset of granulocytes that normally reside in the circulation. When activated, these cells secrete toxic compounds that are a key component in the eradication of helminthic parasite infections. Eosinophils are recruited to sites of parasite infections by: A. Interferon- produced by TH1 cells B. CCL11 produced by TH2 cells C. Interferon- produced by CD8 cytotoxic T cells D. CCL20 produced by TH17 cells E. GM-CSF produced by TH1, TH2, and TH17 cells
B. CCL11 produced by TH2 cells
Eosinophils are a subset of granulocytes that normally reside in the circulation. When activated, these cells secrete toxic compounds that are a key component in the eradication of helminthic parasite infections. Eosinophils are recruited to sites of parasite infections by: A. Interferon- produced by TH1 cells B. CCL11 produced by TH2 cells C. Interferon- produced by CD8 cytotoxic T cells D. CCL20 produced by TH17 cells E. GM-CSF produced by TH1, TH2, and TH17 cells
B. CCL11 produced by TH2 cells
4.24 Multiple choice: The cellular distribution of MHC class I versus MHC class II molecules is quite different, with MHC class II molecules generally expressed on a very limited set of cell types. This is because: A. It would be detrimental to have CD8 T cells killing macrophages or B cells. B. CD4 T cells generally secrete cytokines that act on macrophages and B cells. C. Viruses generally do not infect and replicate in macrophages and B cells. D. Dendritic cells are more important in stimulating CD4 than CD8 T cell responses. E. CD4 T cells can only kill macrophages, dendritic cells, and B cells.
B. CD4 T cells generally secrete cytokines that act on macrophages and B cells.
Multiple choice: The cellular distribution of MHC class I versus MHC class II molecules is quite different, with MHC class II molecules generally expressed on a very limited set of cell types. This is because: A. It would be detrimental to have CD8 T cells killing macrophages or B cells. B. CD4 T cells generally secrete cytokines that act on macrophages and B cells. C. Viruses generally do not infect and replicate in macrophages and B cells. D. Dendritic cells are more important in stimulating CD4 than CD8 T cell responses. E. CD4 T cells can only kill macrophages, dendritic cells, and B cells.
B. CD4 T cells generally secrete cytokines that act on macrophages and B cells.
In addition to the CD28-induced signaling for T-cell co-stimulatory pathways, there are additional co- stimulatory pathways involved in T-cell activation. Which of the following does induce the inhibitory signal for T cell activation? A. Inducible co-stimulator (ICOS), B. CTLA-4 (CD152), C. CD70 and CD27 interaction, D. CD40 and CD40 ligand (CD40L) interaction E. CD137 (T cell molecule 4-1BB) and its ligand 4-1BBL interaction
B. CTLA-4
Multiple choice: Many of the inflammatory mediators produced by tissue macrophages at sites of infection act on the endothelial cells lining the blood vessel walls. An exception to this is (are) the: A. Cytokines that induce increased vascular permeability B. Chemokines that induce directed migration of blood monocytes C. Cytokines that induce increased expression of adhesion molecules D. TNF produced by tissue-resident sensor cells E. Bradykinin produced that causes pain
B. Chemokines that induce directed migration of blood monocytes
In addition to Peyer's patches that resemble systemic lymph nodes, the intestinal epithelium also contains several thousand isolated lymphoid follicles. Unlike the organized secondary lymphoid tissues in the mucosal immune system, these lymphoid follicles: A. Contain mostly T cells and very few B cells B. Develop only after birth in response to colonization by commensal microbes C. Are not connected to the lymphatic system that drains to lymph nodes D. Have no M cells to deliver gut antigens to the lymphocytes in the follicles E. Are found only in the intestinal epithelium, and not in other mucosal epithelia
B. Develop only after birth in response to colonization by commensal microbes
Multiple choice: Amino acid sequence analysis of all of the peptides found in a single IgG antibody would reveal unique peptide sequences totaling ~600-700 amino acids. Using this estimate, the predicted molecular weight of an antibody protein would be ~70-75 kDa. Yet, an intact antibody protein has a molecular weight of ~150 kDa. The explanation for this discrepancy is: A. IgG antibodies have many more heavy amino acids in them than most other proteins. B. Each IgG antibody is a complex of two identical light chains and two identical heavy chains. C. IgG antibodies tend to aggregate together during purification, thereby distorting molecular weight estimates. D. Each IgG antibody is a complex of four identical polypeptides. E. IgG antibodies are produced as dimers of two identical IgG monomers.
B. Each IgG antibody is a complex of two identical light chains and two identical heavy chains.
9.22 Multiple choice: Following their activation, naive CD4 T cells differentiate into one of several subsets of effector T cells. This developmental choice is determined by which specific cytokines the T cells are exposed to during their activation; in turn, the cytokines that are produced will reflect the nature of the infecting pathogen. In order for this system to be flexible enough to produce all five effector CD4 subsets (TH1, TH2, TH17, TFH, and iTreg): A. Each naive CD4 T cell must already express one of the lineage-specific transcription factors (i.e., T-bet, GATA-3, etc.). B. Each naive CD4 T cell must express all of the STAT proteins. C. Each naive CD4 T cell must express only a single STAT protein (i.e., STAT1 or STAT6 or STAT3, etc.). D. Each naive CD4 T cell must already express low levels of the subset specific cytokines (i.e., IFN, IL-4, IL-17, etc.). E. Each naive CD4 T cell must express all of the lineage-specific transcription factors (i.e., T-bet, GATA-3, etc.).
B. Each naive CD4 T cell must express all of the STAT proteins.
9.17 Multiple choice: While CD28 co-stimulation is important for the initial activation of naive T cells, other co-stimulatory molecules function at later stages of the T cell response. Several of these other co-stimulatory molecules are members of the TNF-receptor family, and function by activating the transcription factor, NFB. Therefore, stimulation of these co-stimulatory TNF-receptors on activated T cells is likely to: A. Induce programmed cell death in the T cell B. Enhance T cell survival C. Increase T cell proliferation D. Promote T cell migration into tissues E. Inhibit T cell activation and differentiation
B. Enhance T cell survival
While CD28 co-stimulation is important for the initial activation of naiveT cells, other co-stimulatory molecules function at later stages of the T cell response. Several of these other co-stimulatory molecules are members of the TNF-receptor family, and function by activating the transcription factor, NFB. Therefore, stimulation ofthese co-stimulatory TNF-receptors on activated T cells is likely to: A. Induce programmed cell death in the T cell B. Enhance T cell survival C. Increase T cell proliferation D. Promote T cell migration into tissues E. Inhibit T cell activation and differentiation
B. Enhance T cell survival
Macrophages were isolated from the spleen or the intestinal lamina propria, and stimulated in vitro with the indicated TLR ligands. Twenty-four hours later, the culture supernatants were tested for the amounts of IL-10, the IL-12p40 subunit (shared between IL-12 and IL-23), and for IL-12, and the results are shown in Figure Q12.9. These data indicate that the lamina propria macrophages: A. Make robust responses to a variety of MAMPs B. Function as anti-inflammatory cells C. Are unable to respond to TLR stimulation D. Are less efficient at cytokine production than splenic macrophages E. Function to promote epithelial cell repair in case of disruptions in the intestinal barrier
B. Function as anti-inflammatory cells
Reovirus is an enteric virus that infects mice by adhering to intestinal M cells and then using M cell transport to enter Peyer's patches. Mice that were orally inoculated with reovirus cleared the primary infection, and upon secondary challenge 21 days later, had no detectable virus in their Peyer's patches. In contrast, naive controls that did not receive the primary inoculation had >103 PFU of virus/mg of tissue following oral challenge with virus. The protective response induced by the primary oral inoculation would also be eliminated in: A. FcRn-deficient mice B. IgA-deficient mice C. IgM-deficient mice D. FcRI-deficient mice E. IgG-deficient mice
B. IgA-deficient mice
(9-53: ) is required for the activation, proliferation, and differentiation of naïve T cells. The binding of (9-53:) by activated naïve T cells triggers signaling that supports their activation and differentiation and proliferation. Thus, activated T cells can divide up to four times a day for several days, allowing one precursor cell to give rise to thousands of clonal progeny. A. Interleukin 1, IL-1, B. Interleukin 2, IL-2, C. Interleukin 6, IL-6, D. Interferon- , E. Interferon-
B. Interleukin IL-2
Multiple choice: The antigen receptor on a T cell recognizes a degraded fragment of a protein (i.e., a peptide) bound to a specialized cell surface peptide-binding receptor called an MHC molecule. One key aspect of this system is that the peptides displayed on MHC molecules can be derived from intracellular proteins. This mode of antigen recognition is particularly important in allowing the adaptive immune response to detect infections by: A. Large helminthic parasites in the gastrointestinal tract B. Intracellular pathogens, such as viruses and some protozoa C. Extracellular bacteria that colonize the lungs D. Fungi that form hyphae in the bronchial airways E. Fungal infections in the skin epithelium
B. Intracellular pathogens, such as viruses and some protozoa
Multiple choice: In spite of their low affinity for binding to their antigen, IgM antibodies can be quite effective at promoting the elimination of extracellular bacterial infections. This is due to: A. The ability of IgM antibodies to traffic across epithelial surfaces B. Multivalent binding of IgM pentamers to repetitive epitopes on bacterial surfaces C. The high concentration of IgM antibodies in the serum and in all tissues D. The early production of IgM antibodies during an immune response E. The high rate of somatic hypermutation in the genes encoding IgM antibodies
B. Multivalent binding of IgM pentamers to repetitive epitopes on bacterial surfaces
Multiple choice: Two strains of mice were infected with 5x10^4 PFU of Influenza A virus, and the survival data shown in Figure Q3.31 were obtained. (FIGURE) Next, both strains were infected again with Influenza A, and levels of type I interferons were measured and found to be similar between the two strains. Likewise, cells from both strains expressed similar levels of the IFN-alpha/beta receptor (IFNAR). Which of the following proteins might be more highly expressed in strain B than in strain A following Influenza A infection? A. MHC class I B. Mx-1 C. TLR4 D. Complement C3 E. ICAM-1
B. Mx-1
Multiple choice: The classical complement pathway is initiated by C1q binding to the surface of a pathogen. In some cases, C1q can directly bind the pathogen, for instance by recognizing proteins of bacterial cell walls, but in most cases C1q binds to IgM antibodies that are bound to the pathogen surface. How does this IgM-binding feature of C1q contribute to rapid, innate immune responses rather than to slow, adaptive responses? A. C1q induces B lymphocytes to begin secreting antibody within hours of pathogen exposure. B. Natural antibody that binds to many microbial pathogens is produced prior to pathogen exposure. C. C1q binds to C-reactive protein which then binds to IgM on the pathogen surface. D. C1q directly induces inflammation, recruiting phagocytes and antibodies from the blood into the infected tissue. E. C1q binds to dendritic cells in the infected tissue, inducing them to secrete inflammatory cytokines.
B. Natural antibody that binds to many microbial pathogens is produced prior to pathogen exposure.
Multiple choice: Some viruses have mechanisms to down-regulate MHC class I protein expression on the surface of cells in which the virus is replicating. This immune evasion strategy might prevent effector CD8 cytotoxic T cells from recognizing and killing the virus-infected cells. Would this immune evasion strategy also prevent the initial activation of virus-specific CD8 T cells? A. Yes, because no viral peptide:MHC class I complexes would form to activate CD8 T cells. B. No, because dendritic cells would take up infected cells and cross-present viral peptides to activate CD8 T cells. C. No, because some presentation of MHC class I complexes with viral peptides would occur before the virus could down-regulate all the surface MHC class I protein. D. Yes, because this immune evasion strategy would also function in dendritic cells, even if the virus doesn't replicate in dendritic cells. E. No, because the type I interferon response induced by the virus infection will up- regulate MHC class I expression and override the immune evasion mechanism.
B. No, because dendritic cells would take up infected cells and cross-present viral peptides to activate CD8 T cells.
Multiple choice: In rare instances, B cells can be found that have two immunoglobulin light chain alleles, both of which are rearranged in frame, and can encode functional light chain proteins. Yet, on the surface of the B cell, only one of the two light chain proteins is detected in the membrane-bound immunoglobulin receptor. The reason these rare cells have two functional light chain rearrangements but only express one of the two light chains as part of the B-cell receptor is: A. One of the two light chains is formed from rearrangement of a V gene segment that is a pseudogene. B. One of the two light chain proteins doesn't form a stable complex with the heavy chain expressed in this cell. C. One of the two light chain alleles is not transcribed efficiently, and produces only low levels of protein. D. One of the two light chain alleles uses a V gene segment that is not targeted very often by the RAG recombinase. E. One of the two light chains is rapidly degraded after synthesis due to improper folding.
B. One of the two light chain proteins doesn't form a stable complex with the heavy chain expressed in this cell.
Mice deficient in the enzyme MMP7, that cleaves prepro--defensin to the active -defensin, show an increased susceptibility to the enteric pathogen, Salmonella typhimurium. The cell type in the gastrointestinal (GI) epithelium most likely to express the highest levels of MMP7 is: A. Goblet cells B. Paneth cells C. M cells D. GI-resident macrophages E. Intraepithelial lymphocytes
B. Paneth cells
Helicobacter pylori is a human gastrointestinal (GI) pathogen that can lead to a state of chronic GI inflammation in some individuals, and has been linked to gastric ulcers and other diseases. Studies have shown that human mucosal gastric biopsies of infected individuals have dendritic cells producing IL-23, and that human monocytes isolated and cultured from healthy individuals produce IL-23, but not IL-12, inresponse to stimulation with live H. pylori. Given these findings, which of the following responses would be enhanced in the GI tract of H. pylori-infected individuals compared to uninfected individuals? A. Mucus production by goblet cells B. Recruitment of neutrophils C. Recruitment of eosinophils D. Production of nitric oxide and superoxide E. Production of IL-13
B. Recruitment of neutrophils
Multiple choice: Epithelial surfaces provide the first line of defense against infection by the use of several types of mechanisms. One of the chemical mechanisms used by epithelia is: A. Joining of epithelial cells by tight junctions B. Secretion of antimicrobial peptides by epithelial cells C. Production of mucus, tears, or saliva in the nose, eyes, and oral cavity D. Movement of mucus by cilia E. Peristalsis in the gastrointestinal tract
B. Secretion of antimicrobial peptides by epithelial cells
Multiple choice: T cells expressing delta:gamma T-cell receptors have been found to recognize a diversity of ligands, including pathogen-derived proteins, self-peptides, and stress- induced molecules. This pattern of antigen recognition shows similarity to that of iNKT cells and MAIT cells, suggesting that delta:gamma T cells: A. Do not play an important role in immunity, but likely have a non-immune function B. Share features of both innate and adaptive immune cells C. Are only able to respond when the host is infected with a virus such as herpes simplex virus D. Are involved in maintaining the integrity of endothelial cells in the host E. Are most important in responses to tumor cells that show stress responses
B. Share features of both innate and adaptive immune cells
IL-23 is a cytokine made by macrophages and dendritic cells in response to extracellular bacterial and fungal infections. Mice with a genetic defect in theproduction of IL-23 are highly susceptible to the gastrointestinal bacterial pathogen, Citrobacter rodentium. Thus, unlike wild-type mice which clear the infection, mice that fail to produce IL-23 succumb to the bacteria and die 1-2 weeks post-infection. Yet, this cytokine does not directly act on the bacteria nor does it function to recruit the granulocytes that are needed to eliminate the pathogen. Instead, IL-23: A. Functions as a chemoattractant for eosinophils and basophils B. Stimulates IL-17 and IL-22 production by ILC3 cells C. Activates tissue-resident ILC2 cells to produce IL-5 and IL-13 D. Induces the differentiation of naive CD8 T cells into cytotoxic T cells E. Stimulates gastrointestinal epithelial cells to produce antimicrobial peptides
B. Stimulates IL-17 and IL-22 production by ILC3 cells
Individuals with the HIV-induced immunodeficiency disease AIDS havea progressive loss in the number of CD4 T cells in their bodies. These patients have a greatly increased rate of life-threatening disease caused by the inability of their immune system to control infections of the intracellular bacterium, Mycobacterium tuberculosis (Mtb). Mtb infects macrophages and then replicates in the cell's phagosomes. The most important immune mechanism lacking in these patients that leads to their increased susceptibility to Mtb is a defect in: A. CD4 T cell help for cytotoxic effector CD8 T cells B. The activation of macrophages by TH1 effector cells C. The production of opsonizing antibodies that requires TFH cell help for B cells D. The production of TNF- by the infected macrophages E. The recruitment of neutrophils to the site of infection
B. The activation of macrophages by TH1 effector cells
Multiple choice: Several subsets of innate lymphoid cells (ILCs) have been identified that share their patterns of cytokine production with the known subsets of T cells. The combined activity of related ILC and T cell subsets is effective in eradicating pathogenic infections because: A. ILCs cannot kill the pathogen, whereas the antigen-specific T cells can kill the pathogen. B. The early response of ILCs that reside at the site of infection is followed by the later more robust response of pathogen-specific T cells that migrate to the site of infection. C. The ILCs activate B cells to induce antibody responses whereas the T cells are able to directly eliminate the pathogen. D. The ILCs are induced to migrate from the site of infection to the draining lymph nodes where they activate the antigen-specific T cells. E. The ILCs are activated to secrete antimicrobial compounds which cause them to lyse, releasing RNA and DNA that act on T cells to stimulate T cell cytotoxic activities.
B. The early response of ILCs that reside at the site of infection is followed by the later more robust response of pathogen-specific T cells that migrate to the site of infection.
Multiple choice: Inherited immunodeficiency diseases result from a single gene defect in one component of the immune system. By identifying the class of microbial pathogens a given immunodeficient individual becomes susceptible to, studies of these diseases indicate: A. Which type of antibiotics each patient should be given B. The essential immune mechanism required for resistance to each category of pathogen C. Whether the disease is a genetically inherited or an acquired form of immunodeficiency D. Whether the immunodeficiency disease is likely to be transmitted to another individual E. Whether the disease is likely to be life-threatening or not
B. The essential immune mechanism required for resistance to each category of pathogen
Cytotoxic T cells are rapid killers of infected target cells. Within minutes of the interaction of a cytotoxic T cell with a target cell, the program of apoptosisin the target cell is initiated. This rapid activity is a consequence of: A. The expression and packaging of perforin and granzymes in cytotoxic granules prior to target cell encounter B. The extremely rapid production of granzymes and perforin by cytotoxic effector cells upon encountering a target cell C. The extremely potent activity of perforins in poking holes in target cell membranes allowing entry of granzymes D. The efficient activity of granzymes in cleaving effector caspases leading to direct activation of apoptosis E. The large number of cytotoxic granules made and secreted by a single effector cytotoxic T cell
B. The extremely rapid production of granzymes and perforin by cytotoxic effector cells upon encountering a target cell
Multiple choice: Some Pattern Recognition Receptors (PRRs) recognize nucleic acids, like RNA or DNA. Since our own cells contain human RNA and DNA, the activation of innate immune pathways by these PRRs must rely on additional criteria to discriminate self from nonself. Additional criteria include everything EXCEPT: A. The subcellular location of the RNA B. The presence of adenosine residues in viral RNA C. The methylation state of the DNA D. Unique structures found on viral RNA E. The subcellular location of the DNA
B. The presence of adenosine residues in viral RNA
Immunological memory in humans has been examined by assessing responses in individuals who were given the vaccinia virus to induce immunity against smallpox. Antiviral CD4 and CD8 T cell responses could be detected many years after the vaccinia immunization, but declined with an estimated half-time of about 10 years. In contrast, antiviral antibody responses were maintained at a relatively constant level, witha barely detectable decline over decades. The persistence of antiviral antibodies for years after immunization is likely due to: A. The presence of CD4 T cell help for memory B cells B. The presence of long-lived antibody secreting plasma cells C. The periodic reactivation of memory B cells by low levels of antigen exposure D. The persistence of the virus in the immunized host E. The presence of pro-survival cytokines, such as IL-7 and IL-15
B. The presence of long-lived antibody secreting plasma cells
Cytotoxic effector T cells also produce inflammatory cytokines such as IFN- and TNF- when their T-cell receptor recognizes peptide:MHC on a target cell. One effect of this cytokine secretion is to enhance the ability of CD8 effector T cells to recognize and kill other infected cells in the nearby vicinity. This enhanced activity is dueto: A. The increased production of perforin and granzymes by CD8 cells B. The up-regulation of MHC class I protein expression by IFN- C. The ability of TNF- to induce vascular leakage D. The effect of cytokines on promoting target cell apoptosis E. The effect of IFN- to enhance viral replication leading to increased viral antigen presentation
B. The up-regulation of MHC class I protein expression by IFN-
5.1 Multiple choice: The exon encoding the V region of an immunoglobulin protein is generated by a process of somatic recombination. This recombination event brings V gene and J gene segments together: A. In all cells of the body to encode a V region sequence B. To generate maximum diversity in the CDR3 sequence of the V region C. By alternative RNA splicing to encode a V region sequence D. By a precise mechanism that never adds or loses nucleotides at the junction E. To generate a single exon encoding the entire immunoglobulin protein
B. To generate maximum diversity in the CDR3 sequence of the V region
Multiple choice: The exon encoding the V region of an immunoglobulin protein is generated by a process of somatic recombination. This recombination event brings V gene and J gene segments together: A. In all cells of the body to encode a V region sequence B. To generate maximum diversity in the CDR3 sequence of the V region C. By alternative RNA splicing to encode a V region sequence D. By a precise mechanism that never adds or loses nucleotides at the junction E. To generate a single exon encoding the entire immunoglobulin protein
B. To generate maximum diversity in the CDR3 sequence of the V region
Multiple choice: Multiple pathways for regulating complement activation limit the potential damage caused by complement deposition on host cells or caused by the spontaneous activation of complement proteins in the plasma. Genetic deficiencies in these mechanisms often lead to chronic inflammatory diseases, but in some cases can paradoxically lead to increased susceptibility to bacterial infections. This latter outcome may occur because: A. Complement regulatory proteins have dual functions in inhibiting and promoting complement activation. B. Uncontrolled complement activation leads to the depletion of serum complement proteins. C. The inhibition of the membrane attack complex by complement regulatory proteins normally leads to enhanced activation of the early steps of the complement pathway. D. Complement regulatory proteins normally cause the rapid depletion of plasma complement factors. E. Uncontrolled complement activation recruits the majority of phagocytic cells, leaving few remaining to fight infections in the tissues.
B. Uncontrolled complement activation leads to the depletion of serum complement proteins.
Multiple choice: Individuals or mice with defects in the biochemical pathways needed for loading peptides onto MHC molecules show greatly increased susceptibility to virus infections. Experiments examining the MHC molecules present on the surface of host cells in these individuals would show: A. Normal numbers of MHC molecules expressed on host cells, but no peptides bound to them. B. Very low levels of total MHC proteins expressed on the cell surface. C. Normal numbers of MHC proteins on the surface but all of them bound to self- peptides not pathogen peptides. D. Very high levels of total MHC proteins expressed on the cell surface. E. Only virus-infected cells expressing high levels of MHC proteins on the cell surface.
B. Very low levels of total MHC proteins expressed on the cell surface.
Multiple choice: Antibodies, complement proteins, and phagocytic cells provide effective protection against all of the following types of infections in Figure Q2.1, except (SEE FIGURE): A. Fungi B. Virus-infected cell C. Worms D. Bacteria E. Viruses
B. Virus-infected cell
Multiple choice: To identify genes encoding the receptors for the cytokines IL-2, IL-4, and IL-7, an siRNA screen is performed using purified T lymphocytes. To identify siRNAs that knock-down cytokine receptor expression, the T cells have been transfected with a construct that produces green fluorescent protein (GFP) when any one of these three cytokines is used to stimulate the cells. When the screen is completed, several different siRNAs have been identified that substantially reduce the T cells ability to respond to these cytokines as shown in Figure Q3.22. A correct statement regarding these data is: A. siRNA-1 and siRNA-3 target subunits of the IL-2 receptor but siRNA-2 does not. B. siRNA-2 targets a shared subunit of all three receptors, whereas siRNA-1 and siRNA-3 do not. C. siRNA-3 targets a subunit of the IL-7 receptor, but the other two siRNAs do not. D. siRNA-2 and siRNA-3 do not target a subunit of the IL-2 receptor. E. siRNA-2 targets a subunit shared by all receptors in the hematopoietin receptor superfamily.
B. siRNA-2 targets a shared subunit of all three receptors, whereas siRNA-1 and siRNA-3 do not.
Neutralizing antibodies are effective at preventing infection or toxicity mediated by pathogens or their toxic products. In fact, nearly all vaccines currently in use function by eliciting neutralizing antibodies. One example is the tetanus vaccine, in which neutralizing antibodies are generated against an inactivated form of the tetanus toxin (i.e., the tetanus toxoid). The most important feature of a neutralizing antibody is: A.Having a high degree of multi-valency, such as being a pentamer or hexamer of immunoglobulin monomers B.Having high affinity for the antigen C.Being present at a high concentration in the circulation D.Being efficient at activating the complement cascade E.Having a long half-life in the body
B.Having high affinity for the antigen
When a naive T cell recognizes peptide:MHC complex on an APC, the T cell shows activation responses, including the up-regulation of multiple genes. For the T cell to undergo robust proliferation, which of the following signals are required
B7 family ligands for CD28
Purified naive T cells isolated from a T-cell receptor transgenic mouse represent a homogeneous population of cells with specificity for a single known peptide:MHC complex. This specific peptide:MHC complex can be purified and formed into multivalent complexes, such as peptide:MHC tetramers. When the naive T cells are stimulated with their 'antigen' in the form of these peptide:MHC tetramers, the T cells show activation responses, including the up-regulation of genes that are induced within several hours after T-cell receptor stimulation. However, these activated T cells fail to undergo robust proliferation, and the majority of cells die after 3-4 days in culture. T cell proliferation and survival could be greatly augmented by addition of:
B7 ligands for CD28
What cell interaction is thought not to be needed in activation of memory T cells
B7-CD28
Bronchus-associated lymphoid tissue
BALT; those tissues associated with the bronchial tree
Multiple different epitopes may occur in the same antigen
BOTH
Which of the following mechanisms of mutagenesis mediated by AID activity is possible? Select all that apply.
Base excision repair, followed by error-prone DNA polymerase fill-in of the gap created. Mismatch repair, followed by error-prone DNA polymerase fill-in of the gap created. The lesion is not repaired prior to replication, resulting in a CG→TA transition.
Describe a multivalent antigen with different epitopes.
Basically, the antigen will have multiple distinct sites for antibody binding. These means that multiple antibodies can be activated.
Where are single-stranded cuts made in the DNA backbone during the cleavage step of somatic recombination?
Between each coding segment and its RSS
The major function of the Human Leukocyte Antigen is to:
Bind antigen peptide fragments for presentation to T cells
First step in gene rearrangement is the _____________ of the ______ complex to the _______
Binding; RAG; RSS
While many cell types in the thymus are able to induce negative selection of developing self-reactive thymocytes, bone marrow-derived antigen-presenting cells, such as macrophages and dendritic cells, appear to be the most important for this process. One likely reason for the prominent role of bone marrow-derived antigen-presenting cells in inducing negative selection of developing thymocytes is:
Bone marrow-derived antigen-presenting cells are highly phagocytic and have specialized mechanisms for presenting peptides on both MHC class I and class II.
Cell mediated immunity includes ________________
Both TC and TH cells.
Which of the following statements is TRUE about B-1 B cells and MZB cells? Select all that apply.
Both are self-renewing in the periphery, not requiring replacement from bone marrow. Both can respond to TI antigens Both predominantly produce IgM
Members of type I and type III interferon are responsible for controlling:
Both proliferation of infected host cells AND viral replication within host cells
Bruton's X-linked agammaglobulinemia (XLA) results from a mutation in:
Btk (Bruton's tyrosine kinase)
'Checkpoint blockade' is a therapeutic strategy based on enhancing T cell responses by inhibiting the function of inhibitory receptors, such as CTLA-4, and PD-1. Patients being treated with these protein-based therapeutics would likely be suffering from: A. An autoimmune disease B. An immunodeficiency disease C. Cancer D. Inflammatory bowel disease E. A neurodegenerative disease
C
. Some viruses have mechanisms to down-regulate MHC class I protein expression on the surface of cells in which the virus is replicating. This immune evasion strategy might prevent effector CD8 cytotoxic T cells from recognizing and killing the virus-infected cells. Would this immune evasion strategy also prevent the initial activation of virus-specific CD8 T cells? A. Yes, because no viral peptide:MHC class I complexes would form to activate CD8 T cells. B. Yes, because this immune evasion strategy would also function in dendritic cells, even if the virus doesn't replicate in dendritic cells. C. No, because dendritic cells would take up infected cells and cross-present viral peptides to activate CD8 T cells. D. No, because some presentation of MHC class I complexes with viral peptides would occur before the virus could down-regulate all the surface MHC class I protein. E. No, because the type I interferon response induced by the virus infection will up-regulate MHC class I expression and override the immune evasion mechanism.
C
5.5 Figure Q5.5 shows the germ-line configuration of three V gene segments (#1, 2, 3), and two J gene segments (#4, 5). Which of the choices below represents a DNA configuration that would result from V-to-J recombination? LOOK AT PIC
C
8.14The thymic cortex has a substantial population of macrophages in addition to the developing T cells (i.e., thymocytes). These macrophages are extremely useful in: A. Eliminating bacterial infections in the thymus B. Producing cytokines that promote T cell maturation C. Engulfing apoptotic thymocytes D. Maintaining the structural integrity of the thymic organ E. Inducing inflammatory signals to increase blood flow to the thymus
C
A T cell line growing in culture is subjected to a chemical mutagen, and individual mutant lines are derived from this population. The individual mutant cell lines are each screened for their ability to proliferate in response to stimulation with antibodies to the T-cell receptor plus CD28 (anti-CD3 + anti-CD28). In addition, the cells are treated with varying doses of added IL-2, and three days later, T cell proliferation is measured by 3H-thymidine incorporation (cpm). The data for one mutant line and the wild-type control are shown in Figure Q9.16. Figure Q9.16 The gene that is defective in this mutant T cell line most likely encodes: A. The CD3 epsilon subunit of the T-cell receptor complex B. The co-stimulatory molecule CD28 C. CD25, also known as the IL-2 receptor α chain D. The IL-2 receptor β chain E. The cytokine IL-2
C
A key step in the development of B cells is the expression of the RAG-1 and RAG-2 recombinase proteins. The up-regulation of RAG-1 and RAG-2 in early pro-B cells is induced by: A. The cytokine IL-7, which is made by bone marrow stromal cells B. The chemokine CXCL12, which is made by bone marrow stromal cells C. The B cell-specific transcription factors E2A and EBF D. Signaling through the Igα subunit of the B-cell receptor complex E. Signaling through the FLT3 receptor tyrosine kinase binding to membrane-bound FLT3
C
Approximately one in every three α:β T cells expresses two different rearranged TCRα chain proteins. Yet T cells are still considered to have 'clonal specificity' for recognizing antigen. The reason for asserting that each T cell has a single functional specificity for recognizing antigen is that: A. Only one of the two TCRα chains expressed by a T cell will pair with its TCRβ chain. B. T cells expressing two different TCRα chains will die by apoptosis when they are activated. C. Only one T-cell receptor expressed by each T cell will recognize peptide presented by self-MHC molecules. D. The majority of T cells in an individual will never encounter their specific peptide-MHC ligand and so will not be part of an immune response. E. The majority of T cells are self-reactive and therefore eliminated during their development in the thymus.
C
At early timepoints following an infection, examination of lymph node CD4 T cells responding to the pathogen would show a heterogeneous population of cells representing several different effector lineages. Likewise, the cytokines produced by these cells would include IFNγ, IL-4, and possibly others. However, approximately one week later at the peak of the T cell response, the pathogen-specific CD4 T cell population would be largely homogeneous in their production of a single effector subset cytokine profile. This change comes about due to: A. Death of the CD4 T cells making the non-protective cytokines B. Increased proliferation of CD4 T cells making protective cytokines C. Enhanced differentiation of newly activated CD4 T cells into one effector subset D. Inhibition of antigen-presenting cells by CD4 T cell-derived cytokines E. Impaired proliferation of effector CD4 T cells by IFNγ
C
Autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are characterized by high levels of circulating autoreactive antibodies in the patient's circulation. An analysis of developing B cells in the bone marrow of these individuals might reveal that in some cases: A. Developing B cells become anergic in response to strong B-cell receptor cross-linking by multivalent self-antigens. B. Developing B cells are excluded from the B-cell follicles in the bone marrow and undergo rapid cell death. C. sIgM-positive developing B cells show premature down-regulation of RAG recombinase proteins prior to the onset of receptor editing. D. Hyperactive B-cell receptor signaling leads to rapid turnover of self-reactive developing B cells. E. Developing B cells have defects in allelic exclusion and express two different B-cell receptors on their surface.
C
Inbred strains of mice often generate highly polarized CD4 T cell responses to specific infections that are dominated by one subset of effector cells. In the case of Balb/c mice infected with the intracellular protozoan Leishmania major, a robust CD4 T cell response is elicited, generating large numbers of L. major-specific T cells; however, this response does not eliminate the pathogen, and instead the mice succumb to the infection. One likely explanation for this finding is: A. L. major produces immune evasion molecules that prevent pathogen clearance. B. The antibody response to L. major is too weak to eradicate the pathogen. C. The CD4 T cell response produces effector cytokines that do not activate macrophages. D. The CD4 T cells have differentiated into TH1 instead of TH2 effector cells. The TFH cells specific for L. major induce a non-protective class of immunoglobulins.
C
MHC polymorphism at individual MHC genes appears to have been strongly selected by evolutionary pressures. In other words, there appears to be selection for maintaining hundreds to thousands of different alleles of each MHC gene in the population. This notion is based on the observation that nucleotide differences between alleles that lead to amino acid substitutions are more frequent than those that are silent substitutions (i.e., not changing the amino acid sequence of the protein). In addition, the positions within the MHC protein where most of the allelic sequence variation occurs are not randomly distributed, but are concentrated in certain regions of the MHC protein. This latter point indicates: A. That some nucleotide sequences within the MHC genes are hot-spots for mutation B. That MHC genes are more susceptible to point mutations than to larger nucleotide deletions C. That MHC allelic polymorphism has been driven by selection for diversity in peptide binding specificity D. That MHC genes are more susceptible to all types of mutations than are other genes in the genome E. That MHC polymorphism has evolved to prevent pathogens that infect non-human primates from infecting humans
C
NKG2D is an activating receptor expressed on NK cells, γ:δ T cells, and some cytotoxic α:β T cells. When stressed or infected cells up-regulate receptors that bind to and activate NKG2D molecules, the stressed or infected cells will be killed. This pathway relies on the fact that stressed or infected cells up-regulate: A. All classical MHC class I molecules B. HLA-C molecules that bind KIRs C. MHC class Ib genes such as MICA, MICB, and RAET1 D. Qa-1 and HLA-E molecules that bind leader peptides of other HLA class I molecules HLA-G molecules just like those expressed on the fetal-derived cells in the placenta
C
Proteins found in the circulation travel throughout the body, including the thymus. One example is serum albumin. Developing T cells with T-cell receptors specific for peptides of human serum albumin bound to MHC class II molecules would likely be: A. Positively selected and would mature into CD4 T cells B. Positively selected and would mature into CD8 T cells C. Negatively selected in the thymus and deleted from the mature repertoire D. Targeted for peripheral mechanisms of self-tolerance after emigrating from the thymus E. Excluded from the T cell zones of the spleen after emigrating from the thymus
C
Small GTPases, such as Ras, Rho, and cdc42, are activated when they exchange their bound GDP for GTP. In the GTP-bound state, these proteins contribute to signaling by: A. Hydrolyzing the bound GTP back to GDP B. Interacting with GTPase-activating proteins (GAPs) C. Interacting with target proteins and altering their activity D. Diffusing from the membrane and entering the nucleus E. Inducing calcium release from the endoplasmic reticulum
C
Strep throat is commonly caused by group A Streptococcus bacteria. A common symptom of strep throat is the presence of swollen lymph nodes in the neck. This symptom usually peaks about 2-4 days after the onset of the infection, and is due to: 1. Damage to the pharyngeal epithelium by the bacteria 2. Release of bacterial PAMPs leading to inflammatory cytokine production 3. Trapping and activation of antigen-specific lymphocytes in the lymph nodes of the neck 4. Recruitment of neutrophils to the lymph nodes of the neck 5. Recruitment of circulating macrophages to the lymph nodes of the neck
C
T cells with defective TCR signaling are discovered, and found to have an inactivating mutation in a key TCR signaling protein. Using an antibody that recognizes the phosphorylated (activated) form of the Erk Map-kinase, stimulated T cells are permeabilized, stained with this antibody, and analyzed on the flow cytometer. These data are shown in Figure Q7.21. Figure Q7.21 Additional experiments examining Ca2+ influx into T cells following TCR stimulation show a normal response in the mutant T cells. One likely candidate gene that could be mutated in the defective cells is: A. PLC-γ B. ITK C. RasGRP D. Calcineurin E. WASp
C
TCR and CD28 signaling together lead to maximal production of IL-2 by the activated T cell. Experiments investigating the mechanism underlying the CD28 co-stimulation-mediated increase in IL-2 production show that T cells stimulated through the TCR plus CD28 have increased levels of IL-2 mRNA compared to cells stimulated through the TCR alone. One important component contributing to increased IL-2 mRNA levels is: A. Increased protein synthesis due to increased production of ribosomes B. Increased glucose metabolism due to increased production of glycolytic enzymes C. Increased mRNA stability after transcription and splicing D. Enhanced mRNA transport from the nucleus to the cytoplasm E. Increased levels of splicing enzymes that increase IL-2 mRNA splicing efficiency
C
The B cell co-receptor, composed of CD19/CD21/CD81, is a receptor that binds to complement fragments such as C3dg. When an antigen bound by the BCR on a B cell has also been tagged with C3dg, the B cell co-receptor is stimulated together with the BCR. Signaling through the co-receptor: A. Inhibits BCR signaling by leading to ITAM dephosphorylation B. Inhibits BCR signaling by leading to PIP3 dephosphorylation C. Enhances BCR signaling by recruiting and activating PI 3-kinase D. Enhances BCR signaling by bringing the Src-kinase together with Ig-α and Ig-β. E. Inhibits BCR signaling by sequestering the antigen away from the BCR.
C
The Bcl-2 protein was first identified based on its overexpression in a subset of B cell lymphomas, where it was shown to promote the resistance of the tumor cells to apoptosis. Subcellular localization experiments would show that Bcl-2 is present: A. In the nucleus, where it blocks DNA fragmentation B. In the cytotoxic granules where it inactivates granzymes C. In the mitochondria where it blocks cytochrome c release D. In the cytosol where it blocks caspase activation E. In the plasma membrane where it blocks death receptor signaling
C
The TCR and BCR are multi-subunit receptor complexes. Experiments examining the synthesis and transport of these receptors to the lymphocyte cell surface have shown that the signaling subunits of each receptor complex are required for transport of the ligand-binding receptor subunits to the cell surface. One possible reason for this stringent control on cell surface expression is:A. To ensure that very few complete TCRs or BCRs are expressed on the lymphocyte surfaceB. To ensure that each lymphocyte expresses only a single specificity of antigen receptorC. To prevent surface expression of receptors that will bind ligand but fail to induce signalsD. To prevent lymphocytes from triggering antigen receptor signaling pathways from intracellular forms of the receptorsE. To ensure that equimolar amounts of all antigen receptor signaling subunits are produced
C
The TNF family of cytokines and their receptors are critical for the development of secondary lymphoid organs, such as the lymph nodes and Peyer's patches. As a consequence, knockout mice lacking expression of LT-β fail to develop most of these structures. Reconstitution of irradiated LT-β-deficient mice with bone marrow stem cells from wild-type mice (e.g., LT-β-sufficient) would: A. Restore all missing lymphoid structures in the recipient mice B. Restore the missing lymphoid structures but not the missing follicular dendritic cells in the recipient mice C. Restore the missing follicular dendritic cells but not the missing lymphoid structures in the recipient mice D. Have no effect on any lymphoid structures in the recipient mice E. Only restore the proper organization of B cell follicles in the recipient mice
C
The extensive polymorphism of MHC genes in the population is thought to represent an evolutionary response to outflank the evasive strategies of pathogens. This polymorphism makes it difficult for pathogens to eliminate all potential MHC binding epitopes from their proteins. Based on this reasoning, it would seem advantageous for each individual to encode more than three different MHC class I and three different MHC class II genes per chromosome copy. If some individuals in the population had MHC loci that encoded 10 different MHC class I and 10 different MHC class II genes, the T cell repertoire in those individuals would likely be: A. Much more diverse than in the rest of the individuals of that population B. Much better at recognizing rare pathogens not encountered by most individuals in that population C. Much less diverse than the rest of the individuals in that population D. Much more alloreactive than the T cells found in the other individuals of that population E. Very reactive to bacterial and viral superantigens
C
The integrin LFA-1 is constitutively expressed on the surface of resting T cells. Yet, integrin-dependent T cell adhesion to antigen-presenting cells increases substantially following TCR stimulation. This increased integrin-dependent adhesion is mediated in part by: A. Increased synthesis of the LFA-1 protein B. Increased transport of intracellular pools of LFA-1 to the cell surface C. LFA-1 conversion to a high affinity binding state D. Increased phosphorylation of the LFA-1 cytoplasmic tail Activation of cdc42 and WASp
C
The mechanism of cross-presentation by dendritic cells is an essential pathway for generating CD8 T cell responses to some intracellular pathogens. If this pathway did not exist, we would be highly susceptible to: A. Intracellular pathogens that can survive inside macrophage endocytic vesicles B. Intracellular pathogens that are able to evade antibody responses C. Intracellular pathogens that do not infect and replicate in dendritic cells D. Intracellular pathogens that can spread from cell to cell by inducing cell fusion E. Intracellular pathogens that infect and replicate in red blood cells
C
The virus shown in the diagram below is only able to infect and replicate in epithelial cells. In order for the cross-presenting dendritic cell to display viral peptides, rather than self peptides on its surface MHC class I proteins, which of the following procedures could be utilized, starting with the components shown in Figure Q6.8? Figure Q6.8 A. Mix epithelial cells with heat-killed virus, wait 24 hrs, wash away any virus particles outside the epithelial cells, then add epithelial cells to dendritic cells. B. Mix epithelial cells with viral peptides, wait 24 hrs, wash away any viral peptides not bound to the epithelial cells, then add epithelial cells to dendritic cells. C. Mix epithelial cells with live virus particles, wait 24 hrs, wash away any virus particles outside the epithelial cells, then add epithelial cells to dendritic cells. D. Mix dendritic cells with viral nucleic acids and epithelial cells for 24 hrs. E. MIx epithelial cells will viral nucleic acids, wait 24 hrs, wash away any viral nucleic acid remaining outside the epithelial cells, then add epithelial cells to dendritic cells.
C
Three major cell types, dendritic cells, macrophages, and B cells, present peptides bound to MHC class II molecules for recognition by CD4 T cells. In general, these peptides are derived from proteins or pathogens taken up by the cell by endocytosis, phagocytosis, or macropinocytosis. Based on these pathways of antigen uptake, some of the enzymes that degrade proteins to generate peptides for MHC class II presentation are: A. Ubiquitin ligases that tag proteins for degradation by the proteasome B. ATP transporter proteins that deliver endocytic proteins into the cytosol for degradation C. Cysteine proteases like cathepsins that function at acidic pH D. The lysosomal thiol reductase found in the endosomes E. The lysosome-associated membrane trafficking protein, LAMP-2
C
To generate a vaccine to pertussis toxin, a heat-killed preparation of Bordetella pertussis (the bacteria that produce pertussis toxin) is mixed with a purified preparation of the inactivated toxin protein. The mixture is then injected subcutaneously into mice. In an effort to enhance the antibody response to the toxin, a group of test mice is depleted of all their dendritic cells immediately prior to immunization. However, instead of enhancing the antibody response, the dendritic cell depletion nearly eliminated the anti-toxin antibody response because: A. All of the toxin-specific B cells underwent apoptosis in the absence of dendritic cells. B. The heat-killed Bordetella pertussis could not be ingested by macrophages in the mice. C. Dendritic cells are needed to activate naive CD4 T cells, which can then help the B cells produce anti-toxin antibody. D. The macrophages in the mice did not express the appropriate pattern recognition receptors to recognize Bordetella pertussis. E. The toxin-specific B cells did not up-regulate their MHC class II molecules after encountering the Bordetella pertussis.
C
Two mutant lines of mice have been identified, each of which has a defect in T cell development. The subsets of thymocytes found in each mutant mouse line are shown in Figure Q8.26A. Figure Q8.26A To narrow down the possible defects in each mutant line, a series of bone marrow chimeras are made in which bone marrow from one strain of mice (the 'donor' strain) is used to reconstitute a second strain (the 'recipient' strain), immediately following the irradiation of the recipient strain to eliminate its own hematopoietic cells. In this procedure, the resulting chimeras have hematopoietic cells that are 100% derived from the donor strain, and all other cells and tissues are derived from the recipient strain. The thymocyte profiles of the series of bone marrow chimeras is shown in Figure 8.26B in each case the label at the top of each FACS plot refers to 'donor bone marrow → recipient': Figure Q8.26B 8.27 Multiple choice: A potential candidate molecule for the gene that is defective in Mutant-2 is: A. CD4 B. MHC class II C. Th-POK D. MHC class I E. Runx3
C
While many cell types in the thymus are able to induce negative selection of developing self-reactive thymocytes, bone marrow-derived antigen-presenting cells, such as macrophages and dendritic cells, appear to be the most important for this process. One likely reason for the prominent role of bone marrow-derived antigen-presenting cells in inducing negative selection of developing thymocytes is: A. Bone marrow-derived antigen-presenting cells are the most abundant stromal cells in the thymus. B. Bone marrow-derived antigen-presenting cells are very good at inducing mature T cell activation. C. Bone marrow-derived antigen-presenting cells are highly phagocytic and have specialized mechanisms for presenting peptides on both MHC class I and class II. D. Bone marrow-derived antigen-presenting cells are concentrated in the thymic medulla where negative selection is most prominent. Bone marrow-derived antigen-presenting cells are hematopoietic in origin, so share the same genetic make-up as the developing thymocytes
C
Heavy-chain locus contains ____________ for _____ isotypes
C genes; all
"stem" of antibody
C-terminal parts of two H chains covalently linked
3.11 Multiple choice: As a family, TLRs can recognize PAMPs associated with a broad array of different pathogens, including bacteria, viruses, and fungi. Patients with a specific susceptibility to herpesvirus infections have a defect in their ability to respond to viral nucleic acids using TLR-3, TLR-7, or TLR-9, even though these proteins are expressed in the patients' cells. Analysis of the TLRs in macrophages and dendritic cells from these patients would likely show which of the arrangements in Figure Q3.11? LOOK AT PICTURE
C. TLR3, TLR7, TLR9 reside in the membranes of endosomes, not the plasma membrane.
To generate a vaccine to pertussis toxin, a heat-killed preparation of Bordetella pertussis (the bacteria that produce pertussis toxin) is mixed with a purified preparation of the inactivated toxin protein. The mixture is then injected subcutaneously into mice. In an effort to enhance the antibody response to the toxin, a group of test mice is depleted of all their dendritic cells immediately prior to immunization. However, instead of enhancing the antibody response, the dendritic cell depletion nearly eliminated the anti-toxin antibody response because:
Dendritic cells are needed to activate naive CD4 T cells, which can then help the B cells produce anti-toxin antibody.
Antigen-presenting cells deliver three kinds of signals to naïve T cells for the T cell activation. From the following description for that, choose the right ones. (i)The signal from the interaction of a peptide:MHC complex with the T-cell receptor (ii)Co-stimulatory signals to promote the survival and expansion of the T cell. (iii) Cytokines that direct T-cell differentiation into one of the different subsets of effector T cells. (iv) Immunoglobulin production to recognize antigenic pathogens. A. (ii)+(iii)+(iv), B. (i)+(ii)+(iv), C. (i)+(ii)+(iii), D. (i)+(iii)+(iv)
C. (i)The signal from the interaction of a peptide:MHC complex with the T-cell receptor (ii)Co-stimulatory signals to promote the survival and expansion of the T cell. (iii) Cytokines that direct T-cell differentiation into one of the different subsets of effector T cells.
Allergic airway inflammation can be induced in mice by immunizing them with an allergen that produces a TH2 effector response, and then challenging the immunized mice with an inhaled form of that allergen. In this disease model, the TH2 effector cells present in the lung respond to the inhaled allergen challenge by producing type 2 cytokines that recruit eosinophils and induce airway inflammation. In addition, a component of this TH2 response is antigen-independent, as shown by the effects of administering a neutralizing antibody along with the allergen challenge. This neutralizing antibody (anti-'X' IgG) has the effects shown in Figure Q11.14 In this experiment, the anti-'X' antibody was shown to inhibit the response of the TH2 cells, and therefore is likely to be: A. A neutralizing antibody to IL-12 B. A neutralizing antibody to IL-4 C. A neutralizing antibody to TSLP D. A neutralizing antibody to STAT4 E. A neutralizing antibody to IL-13
C. A neutralizing antibody to TSLP
Leprosy is a disease caused by the intracellular bacterium Mycobacterium leprae, which infects macrophages and replicates in their phagosomes. Human patients with leprosy have a persistent infection of the mycobacteria, as their immune systems are unable to complete eradicate the pathogen. Furthermore, two different forms of the disease have been identified. Some patients have many skin lesions containing a large number of bacteria with little inflammatory response. This is the very disfiguring form of the disease, and is known as lepromatous leprosy. In other patients, few skin lesions and only occasional bacteria are observed, and the skin lesions are accompanied by a robust inflammatory response. These patients have the form of the disease known as tuberculoid leprosy. If one examined a skin biopsy from a patient with tuberculoid leprosy, one would expect to see: A. A large influx of neutrophils and other granulocytes B. A widespread occurrence of tissue necrosis C. A substantial number of granulomas D. Evidence of large numbers of dead or dying mycobacteria E. A large number of skin epithelial cells with intracellular bacteria
C. A substantial number of granulomas
The mucosal immune system provides protection for a vast area of thebody and contains three-quarters of all the lymphocytes in the body. A key feature of the mucosal immune system is its: A. Ability to respond to thousands of different bacterial species B. Inability to provide adequate protection, leading to millions of deaths per year dueto mucosal infections C. Ability to avoid responding to the large numbers and differing species of commensal microbes D. Use of the identical mechanisms and response features compared to the systemic immune system E. Inability to produce antibodies that cross epithelial barriers
C. Ability to avoid responding to the large numbers and differing species of commensal microbes
Multiple choice: While B cells and T cells differ markedly in their functions during an immune response, the two lymphocyte subsets share the enzymatic machinery and overall scheme for generating antigen receptor diversity. This is because: A. B cells and T cells recognize the same form of antigen expressed by an infecting pathogen. B. Animals with B cells developed first, and later evolving species then developed T cells. C. B cells and T cells both need enormous antigen receptor diversity to provide protection against the diversity of pathogens. D. Antibody and T-cell receptor gene segments are both flanked by similar recombination signal sequences. E. B cells and T cells both secrete their antigen receptor proteins after they are activated by antigen-binding.
C. B cells and T cells both need enormous antigen receptor diversity to provide protection against the diversity of pathogens.
5.13 Multiple choice: While B cells and T cells differ markedly in their functions during an immune response, the two lymphocyte subsets share the enzymatic machinery and overall scheme for generating antigen receptor diversity. This is because: A. B cells and T cells recognize the same form of antigen expressed by an infecting pathogen. B. Animals with B cells developed first, and later evolving species then developed T cells. C. B cells and T cells both need enormous antigen receptor diversity to provide protection against the diversity of pathogens. D. Antibody and T-cell receptor gene segments are both flanked by similar recombination signal sequences. E. B cells and T cells both secrete their antigen receptor proteins after they are activated by antigen-binding.
C. B cells and T cells both need enormous antigen receptor diversity to provide protection against the diversity of pathogens.
A set of mice are each immunized with one of the following as shown in Figure Q11.20. Mouse A is immunized with tetanus toxoid protein. Mouse B is immunized with the Haemophilus influenzae type b polysaccharide antigen. Mouse C is immunized with a conjugate of the diphtheria toxoid protein linked to H. influenzae type b polysaccharide. Mouse D is left unimmunized (naive). Four weeks later the spleen cells from each mouse are isolated, and B lymphocytes and T lymphocytes from each spleen cell population are purified. When mixed together in culture together with a conjugate antigen of the tetanus toxoid protein linked to the to H. influenzae type b polysaccharide,which combination of spleen cells would generate a memory B cell response? A. B lymphocytes from mouse B plus T lymphocytes from mouse B B. B lymphocytes from mouse A plus T lymphocytes from mouse A C. B lymphocytes from mouse C plus T lymphocytes from mouse A D. B lymphocytes from mouse C plus T lymphocytes from mouse D E. B lymphocytes from mouse B plus T lymphocytes from mouse D
C. B lymphocytes from mouse C plus T lymphocytes from mouse A
A T cell line growing in culture is subjected to a chemical mutagen, andindividual mutant lines are derived from this population. The individual mutant cell lines are each screened for their ability to proliferate in response to stimulation with antibodiesto the T-cell receptor plus CD28 (anti-CD3 + anti-CD28). In addition, the cells are treatedwith varying doses of added IL-2, and three days later, T cell proliferation is measured by 3H-thymidine incorporation (cpm). The data for one mutant line and the wild-type control are shown in Figure Q9.16.The gene that is defective in this mutant T cell line most likely encodes: A. The CD3 epsilon subunit of the T-cell receptor complex B. The co-stimulatory molecule CD28 C. CD25, also known as the IL-2 receptor chain D. The IL-2 receptor chain E. The cytokine IL-2
C. CD25, also known as the IL-2 receptor chain
Immune responses to tumors have been studied extensively in mice, using transplantable tumors injected into syngeneic mice. The basis for many of these studies is the assumption that the process of tumorigenesis generates mutations in genes encoding self-antigens that would allow the immune system to see these mutant proteins as 'foreign'. In this scenario, the dominant immune response targeting the tumor cells would be mediated by: A. Antibodies B. CD4 TH1 cells C. CD8 T cells D. NK cells E. FcR+ phagocytic cells
C. CD8 T-cells
Multiple choice: Three major cell types, dendritic cells, macrophages, and B cells, present peptides bound to MHC class II molecules for recognition by CD4 T cells. In general, these peptides are derived from proteins or pathogens taken up by the cell by endocytosis, phagocytosis, or macropinocytosis. Based on these pathways of antigen uptake, some of the enzymes that degrade proteins to generate peptides for MHC class II presentation are: A. Ubiquitin ligases that tag proteins for degradation by the proteasome B. ATP transporter proteins that deliver endocytic proteins into the cytosol for degradation C. Cysteine proteases like cathepsins that function at acidic pH D. The lysosomal thiol reductase found in the endosomes E. The lysosome-associated membrane trafficking protein, LAMP-2
C. Cysteine proteases like cathepsins that function at acidic pH
9.13 Multiple choice: To generate a vaccine to pertussis toxin, a heat-killed preparation of Bordetella pertussis (the bacteria that produce pertussis toxin) is mixed with a purified preparation of the inactivated toxin protein. The mixture is then injected subcutaneously into mice. In an effort to enhance the antibody response to the toxin, a group of test mice is depleted of all their dendritic cells immediately prior to immunization. However, instead of enhancing the antibody response, the dendritic cell depletion nearly eliminated the anti-toxin antibody response because: A. All of the toxin-specific B cells underwent apoptosis in the absence of dendritic cells. B. The heat-killed Bordetella pertussis could not be ingested by macrophages in the mice. C. Dendritic cells are needed to activate naive CD4 T cells, which can then help the B cells produce anti-toxin antibody. D. The macrophages in the mice did not express the appropriate pattern recognition receptors to recognize Bordetella pertussis. E. The toxin-specific B cells did not up-regulate their MHC class II molecules after encountering the Bordetella pertussis.
C. Dendritic cells are needed to activate naive CD4 T cells, which can then help the B cells produce anti-toxin antibody.
To generate a vaccine to pertussis toxin, a heat-killed preparation of Bordetella pertussis (the bacteria that produce pertussis toxin) is mixed with a purified preparation of the inactivated toxin protein. The mixture is then injected subcutaneously into mice. In an effort to enhance the antibody response to the toxin, a group of test miceis depleted of all their dendritic cells immediately prior to immunization. However, insteadof enhancing the antibody response, the dendritic cell depletion nearly eliminated the anti-toxin antibody response because: A. All of the toxin-specific B cells underwent apoptosis in the absence of dendritic cells. B. The heat-killed Bordetella pertussis could not be ingested by macrophages in themice. C. Dendritic cells are needed to activate naive CD4 T cells, which can then help the B cells produce anti-toxin antibody. D. The macrophages in the mice did not express the appropriate pattern recognitionreceptors to recognize Bordetella pertussis. E. The toxin-specific B cells did not up-regulate their MHC class II molecules after encountering the Bordetella pertussis.
C. Dendritic cells are needed to activate naive CD4 T cells, which can then help the B cells produce anti-toxin antibody.
Which of the following options incorrectly describes a mechanism used to prevent fetal rejection? A. High expression of 2,3-dioxygenase (IDO), which starves T cells of tryptophan B. Absence of MHC class II expression and low levels of MHC class I expression by the trophoblast C. Downregulation of HLA-G expression by the trophoblast D. Secretion of TGF-β and IL-10 by the uterine epithelium and the trophoblast
C. Downregulation of HLA-G expression by the trophoblast
Multiple choice: NK cells express receptors from several families, each of which has multiple members. Some of these receptors are activating and others are inhibitory, and NK cell activation is dependent on the balance of signaling overall. The individual NK cells in an individual: A. Always express a majority of activating versus inhibitory receptors B. Are more potent effectors of cytotoxicity than of cytokine-production C. Each express only a subset of all possible NK receptors D. Are not considered members of the innate lymphoid cell lineage E. Undergo massive proliferation in response to infection, similar to T lymphocytes
C. Each express only a subset of all possible NK receptors
Multiple choice: Pathogenic infections induce damage to the host by a variety of mechanisms. While many mechanisms are direct effects of the pathogen, some damaging mechanisms result from the immune response to the infection, as illustrated in Figure Q2.2. Examples of damage caused by the host immune response are: (SEE FIGURE) A. Exotoxin production, Endotoxin B. Cell-mediated immunity, Direct cytopathic effect C. Endotoxin, Immune Complexes D. Direct cytopathic effect, Endotoxin E. Cell-mediated immunity, Immune complexes
C. Endotoxin, Immune Complexes
Multiple choice: Even when the complement cascade fails to proceed beyond generating the C3 convertase, complement activation is effective at inducing pathogen uptake and destruction. This process of immune protection is mediated by: A. Activation of complement inhibitory receptors on phagocytes that promote pathogen uptake B. Activation of soluble proteases in the serum that disrupt pathogen membranes C. Engagement of complement receptors on phagocytes by C3b and its cleavage products which promotes phagocytosis D. Engagement of complement receptors on B cells that promotes antibody production E. Stimulation of antimicrobial peptide secretion by phagocytes
C. Engagement of complement receptors on phagocytes by C3b and its cleavage products which promotes phagocytosis
9.23 Multiple choice: At early timepoints following an infection, examination of lymph node CD4 T cells responding to the pathogen would show a heterogeneous population of cells representing several different effector lineages. Likewise, the cytokines produced by these cells would include IFN, IL-4, and possibly others. However, approximately one week later at the peak of the T cell response, the pathogen-specific CD4 T cell population would be largely homogeneous in their production of a single effector subset cytokine profile. This change comes about due to: A. Death of the CD4 T cells making the non-protective cytokines B. Increased proliferation of CD4 T cells making protective cytokines C. Enhanced differentiation of newly activated CD4 T cells into one effector subset D. Inhibition of antigen-presenting cells by CD4 T cell-derived cytokines E. Impaired proliferation of effector CD4 T cells by IFN
C. Enhanced differentiation of newly activated CD4 T cells into one effector subset
At early timepoints following an infection, examination of lymph node CD4 T cells responding to the pathogen would show a heterogeneous population of cellsrepresenting several different effector lineages. Likewise, the cytokines produced by these cells would include IFN, IL-4, and possibly others. However, approximately one week later at the peak of the T cell response, the pathogen-specific CD4 T cell population would be largely homogeneous in their production of a single effector subset cytokine profile. This change comes about due to: A. Death of the CD4 T cells making the non-protective cytokines B. Increased proliferation of CD4 T cells making protective cytokines C. Enhanced differentiation of newly activated CD4 T cells into one effector subset D. Inhibition of antigen-presenting cells by CD4 T cell-derived cytokines E. Impaired proliferation of effector CD4 T cells by IFN
C. Enhanced differentiation of newly activated CD4 T cells into one effector subset
2.19 Multiple choice: Patients with recurrent infections of Neisseria meningitidis, an extracellular bacterial pathogen that causes meningitis, were examined to determine the underlying cause of their immunodeficiency. A subset of these patients were found to have defects in complement activation on the bacterial surface, a process that for this bacterium is dominated by alternative complement activation leading to C3b deposition on the pathogen surface. When neutrophils from these patients were examined in vitro, the results in Figure Q2.19 were obtained. Based on these data, the identity of the green neutrophil mediator in Figure Q2.19 is likely to be: A. Complement factor B B. The C3 convertase C. Factor P (properdin) D. C3b E. Mannose-binding lectin (MBL) LOOK AT PIC
C. Factor P (properdin)
Multiple choice: Patients with recurrent infections of Neisseria meningitidis, an extracellular bacterial pathogen that causes meningitis, were examined to determine the underlying cause of their immunodeficiency. A subset of these patients were found to have defects in complement activation on the bacterial surface, a process that for this bacterium is dominated by alternative complement activation leading to C3b deposition on the pathogen surface. When neutrophils from these patients were examined in vitro, the results in Figure Q2.19 were obtained. Based on these data, the identity of the green neutrophil mediator in Figure Q2.19 is likely to be: A. Complement factor B B. The C3 convertase C. Factor P (properdin) D. C3b E. Mannose-binding lectin (MBL)
C. Factor P (properdin)
Multiple choice: Lymph nodes function as meeting points between antigen-bearing dendritic cells arriving from the tissue and recirculating B and T lymphocytes. Whereas the dendritic cells coming from the tissue enter the lymph node via the afferent lymphatic vessels, the recirculating lymphocytes enter the lymph node: A. Also from the lymph fluid draining the tissue B. Directly from their primary lymphoid organ where they develop C. From the blood by crossing the high endothelial venules D. By being trapped in the lymphoid follicle by resident macrophages E. By being carried there by dendritic cells
C. From the blood by crossing the high endothelial venues
9.31 Multiple choice: The Bcl-2 protein was first identified based on its overexpression in a subset of B cell lymphomas, where it was shown to promote the resistance of the tumor cells to apoptosis. Subcellular localization experiments would show that Bcl-2 is present: A. In the nucleus, where it blocks DNA fragmentation B. In the cytotoxic granules where it inactivates granzymes C. In the mitochondria where it blocks cytochrome c release D. In the cytosol where it blocks caspase activation E. In the plasma membrane where it blocks death receptor signaling
C. In the mitochondria where it blocks cytochrome c release
The Bcl-2 protein was first identified based on its overexpression in a subset of B cell lymphomas, where it was shown to promote the resistance of the tumor cells to apoptosis. Subcellular localization experiments would show that Bcl-2 is present: A. In the nucleus, where it blocks DNA fragmentation B. In the cytotoxic granules where it inactivates granzymes C. In the mitochondria where it blocks cytochrome c release D. In the cytosol where it blocks caspase activation E. In the plasma membrane where it blocks death receptor signaling
C. In the mitochondria where it blocks cytochrome c release
Multiple choice: Unlike B lymphocytes, T lymphocytes do not generate a secreted form of their antigen receptor after they are activated and proliferate. This is because the effector functions of T cells are restricted to: A. Responses important in protozoan infections, but not other types of infections B. Interactions with large helminthic parasites, which cannot be phagocytosed C. Interactions with other cells, such as virus-infected cells or other immune cells D. Responses important in mucosal surfaces (e.g., the lung), where antibodies cannot go E. Stimulating B cells and not any other types of cells
C. Interactions with other cells, such as virus-infected cells or other immune cells
Multiple choice: The mechanism of cross-presentation by dendritic cells is an essential pathway for generating CD8 T cell responses to some intracellular pathogens. If this pathway did not exist, we would be highly susceptible to: A. Intracellular pathogens that can survive inside macrophage endocytic vesicles B. Intracellular pathogens that are able to evade antibody responses C. Intracellular pathogens that do not infect and replicate in dendritic cells D. Intracellular pathogens that can spread from cell to cell by inducing cell fusion E. Intracellular pathogens that infect and replicate in red blood cells
C. Intracellular pathogens that do not infect and replicate in dendritic cells
Multiple choice: NKG2D is an activating receptor expressed on NK cells, gamma:delta T cells, and some cytotoxic alpha:beta T cells. When stressed or infected cells up-regulate receptors that bind to and activate NKG2D molecules, the stressed or infected cells will be killed. This pathway relies on the fact that stressed or infected cells up-regulate: A. All classical MHC class I molecules B. HLA-C molecules that bind KIRs C. MHC class Ib genes such as MICA, MICB, and RAET1 D. Qa-1 and HLA-E molecules that bind leader peptides of other HLA class I molecules E. HLA-G molecules just like those expressed on the fetal-derived cells in the placenta
C. MHC class Ib genes such as MICA, MICB, and RAET1
Multiple choice: The virus shown in the diagram below is only able to infect and replicate in epithelial cells. In order for the cross-presenting dendritic cell to display viral peptides, rather than self peptides on its surface MHC class I proteins, which of the following procedures could be utilized, starting with the components shown in Figure Q6.8? (SEE IMAGE) A. Mix epithelial cells with heat-killed virus, wait 24 hrs, wash away any virus particles outside the epithelial cells, then add epithelial cells to dendritic cells. B. Mix epithelial cells with viral peptides, wait 24 hrs, wash away any viral peptides not bound to the epithelial cells, then add epithelial cells to dendritic cells. C. Mix epithelial cells with live virus particles, wait 24 hrs, wash away any virus particles outside the epithelial cells, then add epithelial cells to dendritic cells. D. Mix dendritic cells with viral nucleic acids and epithelial cells for 24 hrs. E. MIx epithelial cells will viral nucleic acids, wait 24 hrs, wash away any viral nucleic acid remaining outside the epithelial cells, then add epithelial cells to dendritic cells.
C. Mix epithelial cells with live virus particles, wait 24 hrs, wash away any virus particles outside the epithelial cells, then add epithelial cells to dendritic cells.
Multiple choice: The extensive polymorphism of MHC genes in the population is thought to represent an evolutionary response to outflank the evasive strategies of pathogens. This polymorphism makes it difficult for pathogens to eliminate all potential MHC binding epitopes from their proteins. Based on this reasoning, it would seem advantageous for each individual to encode more than three different MHC class I and three different MHC class II genes per chromosome copy. If some individuals in the population had MHC loci that encoded 10 different MHC class I and 10 different MHC class II genes, the T cell repertoire in those individuals would likely be: A. Much more diverse than in the rest of the individuals of that population B. Much better at recognizing rare pathogens not encountered by most individuals in that population C. Much less diverse than the rest of the individuals in that population D. Much more alloreactive than the T cells found in the other individuals of that population E. Very reactive to bacterial and viral superantigens
C. Much less diverse than the rest of the individuals in that population
Multiple choice: The skin and bodily secretions provide the first line of defense against infection. One response in this category that is common during upper respiratory virus infections is: A. Production of antibodies B. Infiltration by white blood cells C. Mucus production D. Increased saliva production E. Fever
C. Mucus production
9.2 Multiple choice: The TNF family of cytokines and their receptors are critical for the development of secondary lymphoid organs, such as the lymph nodes and Peyer's patches. As a consequence, knockout mice lacking expression of LT-beta fail to develop most of these structures. Reconstitution of irradiated LT-beta-deficient mice with bone marrow stem cells from wild-type mice (e.g., LT-beta-sufficient) would: A. Restore all missing lymphoid structures in the recipient mice B. Restore the missing lymphoid structures but not the missing follicular dendritic cells in the recipient mice C. Restore the missing follicular dendritic cells but not the missing lymphoid structures in the recipient mice D. Have no effect on any lymphoid structures in the recipient mice E. Only restore the proper organization of B cell follicles in the recipient mice
C. Restore the missing follicular dendritic cells but not the missing lymphoid structures in the recipient mice
The TNF family of cytokines and their receptors are critical for the development of secondary lymphoid organs, such as the lymph nodes and Peyer's patches. As a consequence, knockout mice lacking expression of LT- fail to develop most of these structures. Reconstitution of irradiated LT--deficient mice with bone marrow stem cells from wild-type mice (e.g., LT--sufficient) would: A. Restore all missing lymphoid structures in the recipient mice B. Restore the missing lymphoid structures but not the missing follicular dendritic cells in the recipient mice C. Restore the missing follicular dendritic cells but not the missing lymphoid structures in the recipient mice D. Have no effect on any lymphoid structures in the recipient mice E. Only restore the proper organization of B cell follicles in the recipient mice
C. Restore the missing follicular dendritic cells but not the missing lymphoid structures in the recipient mice
Figure Q5.5 shows the germ-line configuration of three V gene segments (#1, 2, 3), and two J gene segments (#4, 5). Which of the choices below represents a DNA configuration that would result from V-to-J recombination? (SEE IMAGE)
C. SEE IMAGE
Multiple choice: Both MHC class I and MHC class II molecules are highly polymorphic genes in the human population, with tens to hundreds of different alleles co-existing in the population. This means that a comparison of the MHC protein sequences between two individuals would reveal amino acid differences between one individual and the next. However, these amino acid differences are not randomly distributed along the entire protein, but are clustered in certain locations. The diagram in Figure Q4.16 that most correctly indicates the regions of greatest variability between different MHC proteins (shown by the red highlights) is: (SEE IMAGE)
C. SEE IMAGE
Multiple choice: The drawing in Figure Q4.12 shows antibodies bound to repetitive epitopes on the surface of a bacterial pathogen. Even though all of these epitopes are identical, not all of them have antibodies bound to them. (SEE IMAGE) The most likely explanation for this failure of antibodies to bind to every possible epitope on the surface of the pathogen is: A. There is an insufficient amount of antibody to saturate all the epitopes. B. The pathogen has an immune evasion strategy to avoid antibody binding to all epitopes. C. Some of the epitopes cannot bind antibody due to steric hindrance. D. The antibodies are only able to bind when both antigen-binding sites are engaged on the pathogen surface. E. The epitopes on the pathogen are not all in the same conformation, so not all will bind the same antibody.
C. Some of the epitopes cannot bind antibody due to steric hindrance.
Multiple choice: Streptococcus pneumoniae is a Gram-positive bacterium that colonizes the mucosal surface of the upper respiratory tract in humans. The presence of this bacterium in the nose and throat is widespread in the population, and in most people, colonization with Strep. pneumoniae is asymptomatic. Figure Q2.7 shows a comparison of in vitro growth curves of the wild-type strain of Strep. pneumoniae, as well as a Strep. pneumoniae mutant strain with a defect in one bacterial gene. The graph on the right shows the growth curve following addition of lysozyme during the logarithmic phase of bacterial growth. Which statement could account for the data in these graphs? (IMAGE) A. Strain B is wild-type Strep. pneumoniae, and strain A is a mutant that cannot modify its peptidoglycan to be lysozyme-resistant. B. Strain B is wild-type Strep. pneumoniae, and strain A is a mutant that that expresses increased levels of LPS. C. Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that cannot modify its peptidoglycan to be lysozyme-resistant. D. Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that secretes an enzyme that inactivates lysozyme. E. Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that cannot grow well in vitro.
C. Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that cannot modify its peptidoglycan to be lysozyme-resistant.
Multiple choice: MHC polymorphism at individual MHC genes appears to have been strongly selected by evolutionary pressures. In other words, there appears to be selection for maintaining hundreds to thousands of different alleles of each MHC gene in the population. This notion is based on the observation that nucleotide differences between alleles that lead to amino acid substitutions are more frequent than those that are silent substitutions (i.e., not changing the amino acid sequence of the protein). In addition, the positions within the MHC protein where most of the allelic sequence variation occurs are not randomly distributed, but are concentrated in certain regions of the MHC protein. This latter point indicates: A. That some nucleotide sequences within the MHC genes are hot-spots for mutation B. That MHC genes are more susceptible to point mutations than to larger nucleotide deletions C. That MHC allelic polymorphism has been driven by selection for diversity in peptide binding specificity D. That MHC genes are more susceptible to all types of mutations than are other genes in the genome E. That MHC polymorphism has evolved to prevent pathogens that infect non- human primates from infecting humans
C. That MHC allelic polymorphism has been driven by selection for diversity in peptide binding specificity
9.20 Multiple choice: Inbred strains of mice often generate highly polarized CD4 T cell responses to specific infections that are dominated by one subset of effector cells. In the case of Balb/c mice infected with the intracellular protozoan Leishmania major, a robust CD4 T cell response is elicited, generating large numbers of L. major-specific T cells; however, this response does not eliminate the pathogen, and instead the mice succumb to the infection. One likely explanation for this finding is: A. L. major produces immune evasion molecules that prevent pathogen clearance. B. The antibody response to L. major is too weak to eradicate the pathogen. C. The CD4 T cell response produces effector cytokines that do not activate macrophages. D. The CD4 T cells have differentiated into TH1 instead of TH2 effector cells. E. The TFH cells specific for L. major induce a non-protective class of immunoglobulins.
C. The CD4 T cell response produces effector cytokines that do not activate macrophages.
Inbred strains of mice often generate highly polarized CD4 T cell responses to specific infections that are dominated by one subset of effector cells. In thecase of Balb/c mice infected with the intracellular protozoan Leishmania major, a robust CD4 T cell response is elicited, generating large numbers of L. major-specific T cells; however, this response does not eliminate the pathogen, and instead the mice succumb to the infection. One likely explanation for this finding is: A. L. major produces immune evasion molecules that prevent pathogen clearance. B. The antibody response to L. major is too weak to eradicate the pathogen. C. The CD4 T cell response produces effector cytokines that do not activate macrophages. D. The CD4 T cells have differentiated into TH1 instead of TH2 effector cells. E. The TFH cells specific for L. major induce a non-protective class of immunoglobulins.
C. The CD4 T cell response produces effector cytokines that do not activate macrophages.
Multiple choice: The antibody surface involved in antigen binding varies depending on the size and nature of the antigen. This surface can be concave or flat, and sometimes, can have extended protrusions. This is accomplished by: A. Flexibility in the hinge regions of the antibody allowing rotation of the antigen-binding sites B. Some antibodies using V region framework sequences instead of the CDRs to bind antigen C. The ability of different CDR sequences to form many structurally distinct shapes and surfaces D. The ability of the same heavy chain to pair with different light chains E. The differential usage of κ versus λ light chains, as κ chains form concave binding sites whereas λ chains make flatter surfaces
C. The ability of different CDR sequences to form many structurally distinct shapes and surfaces
Mice lacking the poly Ig receptor (pIgR) have an immunodeficiency disease characterized by increased susceptibility to mucosal infections and an increase in the penetration of commensal microbes into the body's tissues. Yet, a genetic deficiency in the production of IgA antibodies is the most common form of human immunodeficiency, and is generally a mild disease and often even asymptomatic. This dichotomy can be explained by: A. The difference in the immune system between mice and humans B. The different types of commensal microbes found in mice and humans C. The ability of pIgR to transport IgM across the gut epithelium D. The reduced exposure of humans compared to mice to pathogens that infect via the gastrointestinal epithelium E. The development of improved human hygiene, including pasteurization
C. The ability of pIgR to transport IgM across the gut epithelium
Multiple choice: Cytokine receptors of the hematopoietin superfamily engage signaling pathways that begin with JAK kinases and lead to activation of STAT-family transcription factors. Each receptor subunit in this superfamily binds a specific JAK kinase (one of four members) and each receptor complex usually activates one major STAT homodimer (one of seven). The specificity for activation of one STAT homodimer by each cytokine is determined by: A. The specificity of each JAK kinase for only phosphorylating one or two out of the seven possible STAT members B. The specificity of each cytokine receptor complex to only activate one of the four Jak kinase members, which then homodimerizes C. The amino acid sequence surrounding the phosphorylated tyrosine on each cytokine receptor subunit's cytoplasmic tail D. The expression of only one STAT member in each type of immune cell, depending on which cytokine receptors are expressed E. The inhibition of all but one STAT protein by the inhibitor SOCS proteins expressed in each cell type
C. The amino acid sequence surrounding the phosphorylated tyrosine on each cytokine receptor subunit's cytoplasmic tail
Multiple choice: A mutagenesis screen performed on mice identified a gene with an important function in B cells. Analysis of B cells from the spleens of these mutant mice showed the results shown in Figure Q5.23A. However, when the C coding sequences were determined, no mutations in these DNA sequences were found. To study this further, genetic crosses were set-up with another mouse strain carrying an allelic variant of the immunoglobulin heavy chain locus. The original mutant mouse strain (strain A) carries IgMa and IgDa alleles of these heavy chain genes. The second mouse strain (strain B) carries the IgMb and IgDb alleles of the heavy chain genes. These two parental strains were crossed together, generating progeny that were all heterozygous for IgM and IgD alleles (i.e., all progeny are IgMa/b and IgDa/b). These heterozygous progeny represent the F1 generation. Brother/sister matings of F1 mice generate F2 progeny. These F2 mice were genotyped by PCR analysis using primers that allow discrimination of the two alleles of the heavy chain locus. As expected 50% of the F2 mice were heterozygous for IgMa/IgDa and IgMb/IgDb, 25% were homozygous for IgMa/IgDa, and the final 25% homozygous for IgMb/IgDb. Further analysis was performed on the F2 progeny mice homozygous for either IgMa/IgDa or for IgMb/IgDb. The B cells from these mice were stained with antibodies to IgM and IgD, and the results shown in Figure Q5.23B were obtained. (SEE IMAGE) Based on these data, the mutation in the original mutant mouse strain most likely inactivates: A. The gene for a transcription factor required for IgD gene transcription B. A regulatory region in the immunoglobulin heavy chain gene locus required for IgD gene transcription C. The gene for a factor required for alternative mRNA splicing of the immunoglobulin heavy chain primary mRNA transcript D. The gene encoding the RAG-1 or RAG-2 recombinase E. The gene for a factor that is required for IgD surface expression
C. The gene for a factor required for alternative mRNA splicing of the immunoglobulin heavy chain primary mRNA transcript
Multiple choice: The best evidence supporting the concept of immunological memory is: A. The increased numbers of antigen receptors expressed by lymphocytes after primary exposure to an antigen B. The increased levels of cytokines made by lymphocytes after primary exposure to an antigen C. The increased rapidity and magnitude of the secondary response to the same antigen D. The increased swelling of lymph nodes during the secondary response to the same antigen E. The long lifespan of vertebrates, which would be impossible without immunological memory
C. The increased rapidity and magnitude of the secondary response to the same antigen
Antigen are brought into the deep cortical area by
Dendritic cells which present antigen fragments (peptides) to T cells. These events result in activation of the T cells.
Multiple choice: Dendritic cells in the skin, known as Langerhans cells, express very high levels of the NOD-like receptor, NLRP3. Previous studies showed that treatment of these cells with the Staphylococcus aureus pore-forming toxin causes K+ efflux from the cells. To investigate whether this signal could induce IL-1 (an inflammatory cytokine) secretion by the cells, the following study (Figure Q3.16) was performed: The explanation for these results is: A. NLRP3 is not activated by K+ efflux from the cells. B. The S. aureus toxin does not kill the Langerhans cells. C. The live S. aureus bacteria activate a TLR and NLRP3. D. The S. aureus membrane prep does not contain a TLR ligand. E. TLR activation by S. aureus membranes induces interferon production.
C. The live S. aureus bacteria activate a TLR and NLRP3.
Multiple choice: For immunoglobulin heavy and light chain genes, and for T-cell receptor beta chain genes, there are a large number of V gene segments, and relatively few J and/or D segments that rearrange to form the final coding sequence for each gene. The TCR alpha locus is different in this regard, and this difference is thought to reflect the fact that nearly all alpha:beta T-cell receptors recognize a peptide bound to an MHC molecule. This unique feature of the T-cell receptor locus is: A. The presence of only five different V-alpha gene segments B. The presence of two different C-alpha coding sequences C. The presence of over sixty different J-alpha gene segments D. The absence of D gene segments E. The large sequence distance separating the V-alpha gene segments from the J-alpha gene segments
C. The presence of over sixty different J-alpha gene segments
Multiple choice: The first pattern recognition receptor (PRR) important in innate immune responses was discovered in the fruit fly Drosophila melanogaster. Stimulation of this receptor, called Toll, induces: A. The synthesis of prostaglandins and leukotrienes B. The inflammatory response in Drosophila hemolymph vessels C. The production of antimicrobial peptides D. The recruitment of phagocytic cells to the site of infection E. The activation of Drosophila complement
C. The production of antimicrobial peptides
Multiple choice: The formation of the C3 convertase is a key step in complement activation that occurs in all three complement pathways. This enzyme cleaves C3 in blood plasma, leading to a conformational change in the C3b fragment that exposes its reactive thioester group. The activated C3b is potentially harmful to the host, if it becomes covalently attached to a host cell, rather than to the surface of a pathogen. This deleterious outcome is largely avoided by: A. The inability of active C3b to diffuse away in the blood plasma. B. The inability of active C3b to covalently attach to the membranes of eukaryotic cells. C. The rapid hydrolysis of active C3b in solution, rendering it inactive. D. The tight binding of active C3b to the C3 convertase. E. The ability of active C3b to recruit phagocytic cells.
C. The rapid hydrolysis of active C3b in solution, rendering it inactive.
Analysis of human milk from lactating mothers shows that it contains IgA antibodies against infections that were recent (<3 weeks earlier) and those from the distant past (>1 year). These antibodies are directed against a host of organisms, including viruses, such as enteroviruses, herpes simplex viruses, respiratory syncytial virus, rubella, reovirus, and rotavirus. In addition, IgA antibodies against many bacteria are found in human milk, including those reactive to E. coli, Shigella, Salmonella, Campylobacter, Vibrio cholerae, H. influenzae, S. pneumoniae, Clostridium difficile, C. botulinum, and Klebsiella pneumoniae. IgA antibodies to the parasite Giardia and the fungus, Candida albicans, are also seen in human milk. Since most of these infections were localized in the gastrointestinal tract of the mother, these IgA antibodies ended up in breast milk by: A. Being transported from the lymph fluid in the breast tissue into across the breast epithelium into the secretory glands. B. The trafficking of germinal center B cells from the mother's mesenteric lymph nodes to the breast epithelium. C. The trafficking of gut-primed activated B cells from the mother's circulation into the lactating milk gland. D. The ability of gut-primed activated B cells to traffic to all secondary lymphoid tissues in the mother. E. The ability of activated B cells primed in the spleen to switch to IgA secretion after entering the mother's lactating milk gland
C. The trafficking of gut-primed activated B cells from the mother's circulation into the lactating milk gland.
The process of somatic hypermutation of antibody V regions sequences is initiated by the enzyme AID. This enzyme targets cytidine residues in the DNA sequence that are normally part of a G:C pair in the double-stranded DNA. Yet the hypermutation process generates mutations at both G:C and A:T base pairs of the original sequence because: A. Following AID action, a double-stranded DNA break plus chewing back of the ends occurs before re-ligation of the sequence. B. The error-prone polymerase repairs the sequence by inserting random nucleotides. C. There are two different pathways of repair target, one targeting G:C and one targeting A:T base pairs. D. B cells are the only cells to express the enzyme uracil-DNA glycoslyase (UNG). E. During active transcription both A:T and G:C base pairs are temporarily single-stranded
C. There are two different pathways of repair target, one targeting G:C and one targeting A:T base pairs.
9.4 Multiple choice: Strep throat is commonly caused by group A Streptococcus bacteria. A common symptom of strep throat is the presence of swollen lymph nodes in the neck. This symptom usually peaks about 2-4 days after the onset of the infection, and is due to: A. Damage to the pharyngeal epithelium by the bacteria B. Release of bacterial PAMPs leading to inflammatory cytokine production C. Trapping and activation of antigen-specific lymphocytes in the lymph nodes of the neck D. Recruitment of neutrophils to the lymph nodes of the neck E. Recruitment of circulating macrophages to the lymph nodes of the neck
C. Trapping and activation of antigen-specific lymphocytes in the lymph nodes of the neck
Strep throat is commonly caused by group A Streptococcus bacteria. Acommon symptom of strep throat is the presence of swollen lymph nodes in the neck. This symptom usually peaks about 2-4 days after the onset of the infection, and is due to: A. Damage to the pharyngeal epithelium by the bacteria B. Release of bacterial PAMPs leading to inflammatory cytokine production C. Trapping and activation of antigen-specific lymphocytes in the lymph nodes of the neck D. Recruitment of neutrophils to the lymph nodes of the neck E. Recruitment of circulating macrophages to the lymph nodes of the neck
C. Trapping and activation of antigen-specific lymphocytes in the lymph nodes of the neck
Multiple choice: Naive B and T lymphocytes are small, quiescent cells with little cytoplasm and low metabolic activity. Yet within hours after being activated following encounter with their antigen, these cells enlarge and up-regulate many biosynthetic and metabolic pathways. Approximately one day later, the cells begin dividing, and for several days they are the most rapidly dividing cells in the body, undergoing 2-4 rounds of cell division every day. In order to maintain this phenomenal rate of cell division, lymphoblasts must: A. Use the large energy stores accumulated by them when they were naive quiescent cells prior to their activation B. Engulf their neighboring small quiescent lymphocytes in order to take their lipids and proteins for raw material C. Up-regulate synthesis of mRNA and proteins, some of which encode for glucose transporters and enzymes used for glycolysis D. Phagocytose extracellular proteins and lipids and degrade them for energy production E. Macropinocytose metabolites and sugars from the blood for use in glycolysis
C. Up-regulate synthesis of mRNA and proteins, some of which encode for glucose transporters and enzymes used for glycolysis
Multiple choice: As a family, TLRs can recognize PAMPs associated with a broad array of different pathogens, including bacteria, viruses, and fungi. Patients with a specific susceptibility to herpesvirus infections have a defect in their ability to respond to viral nucleic acids using TLR-3, TLR-7, or TLR-9, even though these proteins are expressed in the patients' cells. Analysis of the TLRs in macrophages and dendritic cells from these patients would likely show which of the arrangements in Figure Q3.11? (LOOK AT FIGURE)
C. all on outside of ring
Some individuals with repetitive exposure to high doses of Schistosoma mansoni develop resistance to re-infection by this helminthic parasite. In contrast, other individuals remain highly susceptible. Population studies showed that resistant individuals had increased numbers of circulating eosinophils in their blood compared to susceptible individuals, and further, that these eosinophils had increased levels of: A.Complement receptor, CR1 B.Mannose binding lectin C.FcRII, the low affinity IgE receptor D.FcRII-B, the inhibitor IgG receptor E. Anti-microbial ficolins
C.FcRII, the low affinity IgE receptor
Individuals with a genetic polymorphism in the Fc receptor, FcRIIa (CD32), have an increased susceptibility to bacterial meningitis (inflammation of the membranes (meninges) surrounding the brain and spinal cord) caused by the encapsulated bacterium, Neisseria meningitidis. This polymorphism reduces the efficiency with which the phagocytes expressing FcRIIa bind to the constant region of this receptor's target antibody. The reason this FcRIIa-dependent response it the majorform of protection against Neisseria meningitidis is because: A.T cells are unable to enter the brain and spinal cord. B.Mast cells are unable to localize to the meninges. C.IgG antibodies are the major isotype able to diffuse into tissues. D.IgM antibodies do not have high enough affinity to provide protection. E.Neutrophils are unable to phagocytose encapsulated bacteria.
C.IgG antibodies are the major isotype able to diffuse into tissues.
Two different vaccines have been developed that protect vaccinated individuals against pneumococcal disease, a bacterial infection that causes pneumonia, meningitis and sepsis (blood stream infection). This disease is caused by the bacteria, Streptococcus pneumoniae. One vaccine, PPSV23, is a mixture of polysaccharides isolated from 23 different serotypes of S. pneumoniae. The second vaccine, PCV13, is a conjugate vaccine made from polysaccharides of 13 different serotypes of the bacteria conjugated to diphtheria toxoid (inactivated toxin protein). The PPSV23 vaccine is only given to adults, whereas infants and small children are given PCV13. This is because: A.Adults are likely exposed to more different strains (serotypes) of S. pneumoniaethan infants. B.Adult B cells don't require TFH cells to make antibody responses. C.Infant B cells are immature and don't respond to TI-2 antigens. D.Adult B cells respond more robustly than infant B cells to B-cell mitogens. E.Infant B cells are more dependent on the cytokine BAFF.
C.Infant B cells are immature and don't respond to TI-2 antigens.
Which is not a C3 or C5 convertase?
C1r/C1s
This complement component can be cleaved by a complex it might be part of:
C3
The membrane attack complex consists of:
C5b, 6, 7, 8, 9
The ___ genes are ready to be _________________.
C; transcribed
Eosinophils are a subset of granulocytes that normally reside in the circulation. When activated, these cells secrete toxic compounds that are a key component in the eradication of helminthic parasite infections. Eosinophils are recruited to sites of parasite infections by:
CCL11 produced by TH2 cells
True
CCL19 and CCL21 account for T cells localization in T zones
Gut-homing activated T-cells express which chemokine receptor and adhesion molecule combination?
CCR9 and a4:B7 integrin
what induces expression of the T-cell growth factor IL-2 and the high-affinity IL-2 receptor
CD 28-dependent co-stimulation
CD 9 t cells recognizing antigen weakly may become activated only in the present of _________ recongnizing antigen on the same APC.
CD 4 T cells
The best characterized example of co-stimulatory molecule is
CD 80 (B7) on the surface of the dendritic cells and receptor CD 28 on the T cells
A T cell line growing in culture is subjected to a chemical mutagen, and individual mutant lines are derived from this population. The individual mutant cell lines are each screened for their ability to proliferate in response to stimulation with antibodies to the T-cell receptor plus CD28 (anti-CD3 + anti-CD28). In addition, the cells are treated with varying doses of added IL-2, and three days later, T cell proliferation is measured by 3H-thymidine incorporation (cpm). The data for one mutant line and the wild-type control are shown in the figure below. Based on the data, the gene that is defective in this mutant T cell line most likely encodes
CD25
A T cell line growing in culture is subjected to a chemical mutagen, and individual mutant lines are derived from this population. The individual mutant cell lines are each screened for their ability to proliferate in response to stimulation with antibodies to the T-cell receptor plus CD28 (anti-CD3 + anti-CD28). In addition, the cells are treated with varying doses of added IL-2, and three days later, T cell proliferation is measured by 3H-thymidine incorporation (cpm). The data for one mutant line and the wild-type control are shown in Figure Q9.16.
CD25, also known as the IL-2 receptor alpha chain
A T cell line growing in culture is subjected to a chemical mutagen, and individual mutant lines are derived from this population. The individual mutant cell lines are each screened for their ability to proliferate in response to stimulation with antibodies to the T-cell receptor plus CD28 (anti-CD3 + anti-CD28). In addition, the cells are treated with varying doses of added IL-2, and three days later, T cell proliferation is measured by 3H-thymidine incorporation (cpm). The data for one mutant line and the wild-type control are shown in the figure below. Based on the data, the gene that is defective in this mutant T cell line most likely encodes _____________________.
CD25, also known as the IL-2 receptor alpha chain
A T cell line growing in culture is subjected to a chemical mutagen, and individual mutant lines are derived from this population. The individual mutant cell lines are each screened for their ability to proliferate in response to stimulation with antibodies to the T-cell receptor plus CD28 (anti-CD3 + anti-CD28). In addition, the cells are treated with varying doses of added IL-2, and three days later, T cell proliferation is measured by 3H-thymidine incorporation (cpm). The data for one mutant line and the wild-type control are shown in the figure below. Based on the data, the gene that is defective in this mutant T cell line most likely encodes _____________________. IMAGE ON PHONE
CD25, also known as the IL-2 receptor alpha chain
CD19/CD21/CD81
CD28
What is the receptor on T-cell surface that binds to B7 family molecules?
CD28
normally, co-stimulation through ______ signaling prevents the induction of GRAIL, so that no bloackade in T-cell pathway occurs in these circumstances
CD28
targets of monoclonal antibodies
CD3 (Transplantation), CD20 (lymphoma) IgE (asthma), TNF (rheumatoid arthritis)
Iga or Igb
CD3 complex
At least some NK-T cells (NKTs) express
CD4
At least some NK-T cells (NKTs) express ________
CD4
What allows HIV to infect immune cells
CD4
Which of the following molecules would double-negative T cells never express?
CD4
_______ is expressed by T cells whose function is to activate other cells.
CD4
Individuals with the HIV-induced immunodeficiency disease AIDS have a progressive loss in the number of CD4 T cells in their bodies. These patients have a greatly increased rate of life-threatening disease caused by the inability of their immune system to control infections of the intracellular bacterium, Mycobacterium tuberculosis (Mtb). Mtb infects macrophages and then replicates in the cell's phagosomes. The most important immune mechanism lacking in these patients that leads to their increased susceptibility to Mtb is a defect in:
CD4 T cell help for cytotoxic effector CD8 T cells
The cellular distribution of MHC class I versus MHC class II molecules is quite different, with MHC class II molecules generally expressed on a very limited set of cell types. This is because:
CD4 T cells generally secrete cytokines that act on macrophages and B cells.
The cellular distribution of MHC class I versus MHC class II molecules is quite different, with MHC class II molecules generally expressed on a very limited set of cell types. This is because:
CD4 T cells generally secrete cytokines that act on macrophages and B cells. NOTE: Correct. The major function of CD4 T cells that recognize MHC class II molecules is to activate other effector cells of the immune system so MHC class II molecules are normally found on dendritic cells, B lymphocytes, and macrophages (as these are antigen-presenting cells that participate in immune responses), but not on other tissue cells. The peptides presented by MHC class II molecules expressed by dendritic cells can function to activate naive CD4 T cells. When previously activated CD4 T cells recognize peptides bound to MHC class II molecules on B cells, the T cells secrete cytokines that can influence the isotype of antibody that those B cells will choose to produce. Upon recognizing peptides bound to MHC class II molecules on macrophages, CD4 T cells activate these cells, again in part through cytokines, to destroy the pathogens in their vesicles.
How does CD4 enhance antigen sensitivity?
CD4 enhances sensitivity to antigen, as the T cell is about 100-fold more sensitive to the antigen when CD4 is present. The enhancement process results from the ability of the intracellular portion of CD4 to bind to a cytoplasmic tyrosine kinase called Lck; bringing Lck into proximity with the T-cell receptor complex helps activate the signaling cascade induced by antigen recognition. Like CD4, CD8 binds Lck through the cytoplasmic tail of the α chain, and CD8αβ increases the sensitivity of T cells to antigen presented by MHC class I molecules about 100-fold.
___________ is expressed by cytotoxic T cells.
CD8
The α3 domain interacts with?
CD8 co-receptor
All naive CD8 T cells differentiate into ___________, which kill their target cells (e.g., virus-infected cells) that display viral peptide:MHC class I complexes.
CD8 cytotoxic T cells
To avoid the potential for activating self-reactive T cells that might cause autoimmunity, naive T cell activation has stringent requirements for co-stimulatory signals in addition to the engagement of T-cell receptors with peptide:MHC complexes. Yet this requirement is abandoned once T cells have differentiated into effector cells. Name two effector T cell functions that would fail if effector T cells also required T-cell receptor signals plus co-stimulatory signals through CD28 to elicit their effector responses.
CD8+ Cytotoxic T cells would be unable to target/destroy virally infected cells that do not express co-stim molecules such as CD80/CD86. CD4+ T cells would have attenuated functional capability in release of cytokines (IL-2, etc.) if they were limited to releasing them in presence of mature, professional APCs.
Constant domain of the heavy chain is ______.
CH
The heavy chain of IgG has three domains - ____, _____, _______.
CH1; CH2; CH3
Effector CD8 T cells can respond to their target cells without
CO-STIMULATION
Naïve T cells fall into two large classes, CD8 T cells and CD4 T cells. Naïve T cells differentiate into several subsets of functionally different effector cells, cytotoxic t lymphocytes (CTLs), TH1, TH2, TH17, TFH, and Treg cells. Which of the following is correct? A. CTLs, TFH cells, and Treg cells are CD8 T cells, while TH1, TH2, and TH17 cells are CD4 T -cells B. CTLs and TFH cells are CD4 T cells, while TH1, TH2, TH17, and Treg cells are CD4 T cells. C. CTLSs and Treg cells are CD8 T cells, while TH1, TH2, TH17, and TFH cells are CD4 T cells. D. CTLs are CD8 T cells, while TH1, TH2, TH17, TFH, and Treg cells are CD4 T cells. E. CTLs and TH17 cells are CD8 T cells, while TH1, TH2, , TFH, and Treg cells are CD4 T
CTLs are CD8 T cells, while TH1, TH2, TH17, TFH, and Treg cells are CD4 T cells.
B cells follow which of the following chemotactic signals to migrate to the cortical regions of secondary lymphoid tissue?
CXCL13
What is a coreceptor for HIV
CXCR4
Which of the following are chaperone molecules of the Cytosolic pathway?
Calnexin and calreticulin = both A & C
IgD
Can be only secreted immunoglobulin (cryptic switch region) -producing cells concentrated in upper airways -binds to high-affinity IgD receptor on basophils in absence of antigen
Pre T cell
Can βchain associate with preTα if so then βchain and preTα are turned off and α chain V to J rearrangement. Pre T-cell receptor- preTα, βchain, CD3, Zeta Ends with successful α chain production
Which of the following antigen types could be characterized as TI antigens?
Capsular polysaccharides Bacterial cell wall components
What is measured by the cell-mediated lympholysis (CML) assay?
Cell lysis of target tumor or viral infected host cells
What is measured by the cell-mediated lympholysis (CML) assay?
Cell lysis of target tumor or viral infected host cells .
Cell division cell differenciation Cell death All of the above
Changes due to signaling include:
Neutrophil activation
Chemokine signaling
Mature B cells contain ______________________ that is no longer identical to ________________________.
Chromosomal DNA; germ-line DNA
The α and δ genes are found
Chromosome 14
The β and γ genes are located
Chromosome 7
Constant domain of light chain is _______.
Cl
MHC Class I vs Class II- Peptide Presented to:
Class I- CD8+ T cells Class II- CD4+ T cells
MHC Class I vs Class II- Peptide-Binding Groove
Class I- Closed, binds 8-9 amino acid peptide; formed by α1 and α2 domains Class II- Open, binds 12-17 amino acid peptides; formed by α1 and β1 domains
MHC Class I vs Class II- Peptides Derived From:
Class I- Endogenous antigens, catabolized in cytoplasm Antigens derived from Cross priming Class II- Exogenous antigens, catabolized in acidic compartments such as endosomes
MHC Class I vs Class II- Constitutive Cellular Expression
Class I- Nearly all nucleated cells Class II- APCs (B cells dendritic cells, macrophages)
MHC Class I vs Class II- structure
Class I- α chain + β2 microglobulin Class II- α and β chains
MHC Class I vs Class II- domains
Class I- α1, α2, α3, and β2 microblobulin Class II- α1, α2, β1, β2
Invariant chain
Class Il MHC molecules do not bind Class I peptides during assembly due to the presence of:
Which complement pathway would be most affected by an absence of RAG1 in developing B cells?
Classical
The adaptive immune system developed a strategy for monitoring the proteins synthesized in virtually any cell in the body, thereby preventing pathogens from 'hiding out' by adopting an intracellular lifestyle. To accomplish this, the immune system:
Co-opted the ubiquitin-proteasome system used by cell for protein turnover
Other Important Molecules Expressed on the T Cell Surface
Co-stimulatory Ligands- CD28, CD152 Adhesion Molecules- CD2, CD4, CD8, intregrins
Major Ig present in external secretions - _____________, _________, ___________.
Colostrum; milk; saliva
2.25 Short answer: Recent studies using mouse models of pulmonary inflammation (a model for human asthma) have found that mice deficient in the C3a receptor have greatly reduced disease symptoms when challenged with inhaled preparations containing extracts of the fungal pathogen Aspergillus fumigatus. Specifically, the C3a receptor-deficient mice showed reduced influx of granulocytes and lymphocytes into the lung and reduced fluid in the lung after challenge. What is the explanation for these findings?
Complement activation: C3 convertase generates C3a. C3a induces a local inflammatory response by acting on the vascular endothelial cells: increased vascular permeability, leading to an increase of fluid in the lung, and also acts to up-regulate adhesion molecules on the local vascular endothelium resulting in increased recruitment of leukocytes into the lung.
Stem of the Y
Consists of the paired C-terminal portions of the two-H chains
C Segment
Constant
MHC class II are expressed?
Constitutively only on B cells, dendritic cells, thymic epithelial cells, macrophages, and monocytes Or: Induced by cytokines to be expressed on endothelial cells and fibroblasts B cells express both MHC class I and MHC class II molecules Very few cells express MHC class II without having MHC class I expressed 1st
The integrin LFA-1 is constitutively expressed on the surface of resting T cells. Yet, integrin-dependent T cell adhesion to antigen-presenting cells increases substantially following TCR stimulation. This increased integrin-dependent adhesion is mediated in part by:
Conversion of LFA-1 to a high affinity binding state
Cellular organization of the thymus
Cortex is densely populated with lymphocytes of various sizes, most of which are immature and scattered macrophages (bone marrow origin) involved in clearing apoptotic thymocytes. The Medulla consist of sub-capsular epithelium, cortical epithelial cel (ectodermal origin)l, thymocyte (bone marrow origin) and medullary epithelial cell (endodermal origin)
Positive selection
Cortical Epithelial Cells Determines if CD4+ or CD8+ binds better, which ever binds the strongest, the other is turned off and determines what type of T-cell it becomes.
Important Thymic Cells are
Cortical Epithelial Cells Medullary Dendritic Cells
Which of the following types of bonds would be LEAST likely in a receptor-ligand interaction?
Covalent bond
What does B7 ligands on APC also bind CD152 (CTLA-‐4), which is induced as T cell is activated
Creates a NEGATIVE signal to the activated T cell, turning off IL-‐2 and thus T cell proliferation, limiting the immune response
Antigen-presenting cells present peptides bound to MHC class II molecules for recognition by CD4 T cells. In general, these peptides are derived from proteins or pathogens taken up by the cell by endocytosis, phagocytosis, or macropinocytosis. The enzymes that degrade these proteins to generate peptides for MHC class II presentation are:
Cystein proteases (cethespins)
The expression and packaging of perforin and granzymes in cytotoxic granules prior to target cell encounter
Cytotoxic T cells are rapid killers of infected target cells. Within minutes of the interaction of a cytotoxic T cell with a target cell, the program of apoptosis in the target cell is initiated. This rapid activity is a consequence of
The expression and packaging of perforin and granzymes in cytotoxic granules prior to target cell encounter
Cytotoxic T cells are rapid killers of infected target cells. Within minutes of the interaction of a cytotoxic T cell with a target cell, the program of apoptosis in the target cell is initiated. This rapid activity is a consequence of:
True
Cytotoxic T cells that lack expression of perforin are more defective in killing target cells than those that lack granzymes
6.19 The experiment shown in Figure Q6.19 uses two strains of mice that differ in their MHC genes. Strain A is H-2a and Strain B is H-2b. Mice of each strain are infected with the virus LCMV, and T cells are isolated at day 8 post-infection. These T cells are mixed with target cells that express either H-2a or H-2b; in each case, the target cells are either uninfected or infected with LCMV. After a four-hour incubation of T cells with target cells, the percentage of target cells lysed by the T cells is shown in the graph. Figure Q6.19 The explanation for the results of this experiment is: A. Mice of strain B do not make a T cell response to LCMV. B. Mice of strain A make a more robust T cell response to LCMV than mice of strain B. C. Target cells that express H-2b cannot be infected with LCMV. D. T cells from mice of strain A only recognize viral peptides on target cells expressing H-2a. E. LCMV peptides do not bind to MHC class I molecules from H-2b mice.
D
: Virus infections induce production of interferons that act on infected cells to enhance their recognition by CD8 cytotoxic T cells. To counter these mechanisms, viruses often encode proteins that interfere with antigen processing and presentation. In an experiment, cells infected with Virus X are treated with interferon and compared with uninfected cells treated with interferon. Proteasomes are isolated from the two cell populations and their enzymatic activities are compared. The data in Figure Q6.4 show the amino acid preferences for cleavage of peptides by the two samples of proteasomes. Figure Q6.4 Based on these data, Virus X most likely encodes a protein that interferes with: A. The expression of MHC class I on the surface of the infected cell B. The rate at which peptides are produced from intact proteins in the infected cell C. The transport of peptides from the cytosol to the endoplasmic reticulum in the infected cell D. The replacement of constitutive proteasome subunits with immunoproteasome subunits in the infected cell E. The development of CD8 T cells in the thymus by inhibiting the thymoproteasome
D
: Wiskott-Aldrich syndrome is an immunodeficiency disease that causes a defect in antibody responses. The most severe defects are in antibody responses to protein antigens, which are dependent on CD4 effector TFH cells providing cytokines to the B cell. The protein defective in individuals with the disease, known as WASp, functions in cytoskeletal reorganization and polarization through its role in promoting actin polymerization. This immune defect could be fixed by a gene therapy approach that restored WASp expression in: A. Antigen-presenting cells such as dendritic cells B. B cells C. B cells and T cells D. T cells E. T cells and antigen-presenting cells
D
A mutant B cell line is examined by confocal microscopy after incubation with a microbial pathogen recognized by the BCR on these B cells. The B cells have been stained with antibodies to visualize the localization of polymerized actin and microtubules. As a control, wild-type B cells are examined. The results are shown in Figure Q7.32, with the numbers indicating the proportion of cells examined that show each pattern of staining. Figure Q7.32 To identify the specific signaling defect in these mutant B cells, a reasonable biochemical assay would be to: Determine if BCR stimulation of mutant B cells produces enhanced binding of the B cell to the microbe Determine whether the mutant B cells have reduced levels of the enzyme Protein kinase C-θ Determine whether the mutant B cells are overexpressing the enzyme Vav Determine whether BCR stimulation of mutant B cells promotes exchange of GDP for GTP on cdc42 Determine whether BCR stimulation of mutant B cells produces increased levels of DAG
D
Following TCR stimulation, the small GTPase Ras is activated. Ras activation is induced by the Ras GTP-exchange factor (GEF), RasGRP. Both Ras and RasGRP are constitutively expressed in resting T cells. The reason Ras activation is only induced following TCR stimulation is: A. RasGRP undergoes a Ca2+-dependent conformational change required for its activity. B. RasGRP requires tyrosine phosphorylation for its activity. C. RasGRP is ubiquitinated and degraded in the absence of TCR stimulation. D. RasGRP recruitment to the plasma membrane requires TCR stimulation. E. Ras is only recruited to the activated TCR following assembly of the LAT:Gads:SLP-76 complex.
D
Humans with defective expression of the integrin LFA-1 have an immunodeficiency disease characterized by the failure of lymphocytes and granulocytes to migrate to tissues at sites of infection or inflammation. A similar immunodeficiency would be expected if individuals had mutations disrupting the gene for: A. CD3ζ B. The complement receptor, CD21 C. WASp D. Rap1 E. SLP-76
D
In different mammalian species, the ratio of B cells expressing κ versus λ light chain-containing antibodies is about 65%:35%. In other species, such as mice, this ratio is vastly different, at 95%:5%. If a routine blood test performed on an individual revealed that their κ-expressing versus λ-expressing B cells were seen at a ratio of 95%:5%, this would likely indicate that the individual had: A. An increased number of functional Vκ gene segments compared to the average human in the population B. A defect in allelic exclusion of antibody light chain genes C. A defect in isotypic exclusion of antibody light chains D. A lymphoproliferative disorder E. A genetic defect in one of their two λ light chain alleles
D
Like the γ:δ T cells in other specific mucosal surfaces, the γ:δ T cells that reside in the epithelial surface of the skin: A. Are slow to respond to activation signals, requiring several days of priming and differentiation B. Are able to produce cytokines that simultaneously induce type I, type II, and type III immune responses C. Are primarily responsible for recruiting macrophages and dendritic cells to the tissue D. Are characterized by the homogeneous expression of a single specific Vγ and Vδ in their T-cell receptors E. Are unlikely to play any role in immunity to infection, but are likely important for tissue repair
D
Mannose binding lectins (MBL) and ficolins are the two classes of proteins that can initiate the lectin pathway of complement activation. These proteins are selective for activating complement on the surfaces of microbial pathogens rather than host cells because: A. Their higher-order oligomeric structure can be assembled only after the monomers first bind to pathogen membranes. B. They only recruit MASP (MBL-associated serine proteases) proteins when bound to pathogen surfaces and not when bound to host cells. C. They only undergo the conformational change needed to activate MASP proteins when bound to a pathogen and not when bound to a host cell. D. They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes. E. The activated MASP proteins are rapidly inactivated by hydrolysis when present on the surface of a host cell.
D
Many virus infections induce robust production of type I interferons, IFN-α and IFN-β. One example is the herpes simplex virus-1 (HSV-2), one of the most common sexually transmitted diseases in the US. Experiments that investigated the immune response to HSV-2 using a mouse model demonstrated essential roles for the DNA sensing Toll-like receptor, TLR9, and its downstream signaling adapter, MyD88, in the production of type I interferons following HSV-2 immunization. The type I interferon response to HSV-2 would be restored in Tlr9-/- mice by transferring into these mice wild-type: A. Macrophages B. Conventional dendritic cells C. Mast cells D. Plasmacytoid dendritic cells E. Neutrophils
D
Naive T cells are isolated and left untreated or treated with 'compound X' for 1 hour. Following this, the T cells are incubated with a range of concentrations of a soluble form of ICAM-1 that has been conjugated to a fluorescent dye (soluble-ICAM-1-FITC). Fifteen minutes later, the cells are washed, and the relative amount of fluorescence bound to the cells is measured. The results of this assay are shown in Figure Q9.6. Figure Q9.6 The most likely identity of compound X is: The adhesion molecule, LFA-1 The adhesion molecule, L-selectin The sulfated carbohydrate structure, sulfated sialyl-LewisX The chemokine ligand for CCR7 The immunoglobulin superfamily member, CD2
D
Purified naive T cells isolated from a T-cell receptor transgenic mouse represent a homogeneous population of cells with specificity for a single known peptide:MHC complex. This specific peptide:MHC complex can be purified and formed into multivalent complexes, such as peptide:MHC tetramers. When the naive T cells are stimulated with their 'antigen' in the form of these peptide:MHC tetramers, the T cells show activation responses, including the up-regulation of genes that are induced within several hours after T-cell receptor stimulation. However, these activated T cells fail to undergo robust proliferation, and the majority of cells die after 3-4 days in culture. T cell proliferation and survival could be greatly augmented by addition of: A. Anti-inflammatory cytokines B. Toll-like receptor ligands C. Antibodies to the T-cell receptor D. B7 ligands for CD28 E. The integrin LFA-1
D
Scaffold proteins are often phosphorylated at multiple sites, allowing the recruitment of several different signaling proteins. In antigen receptor signaling pathways, this mechanism is used to bring enzymes in close proximity to their substrates. Termination of this signaling mechanism would be most efficiently accomplished by: A. Ubiquitination of the scaffold protein, leading to its degradation B. Binding of the enzyme to a GTPase activating protein (GAP) C. Depletion of the substrate due to enzyme catalysis D. Dephosphorylation of the scaffold by a phosphatase E. Ubiquitination of the enzyme by K63-linkage of polyubiquitin
D
Secondary lymphoid organs, such as the lymph nodes, spleen, and mucosa-associated lymphoid tissues, each have distinct features that are important for their role in initiating immune responses focused on different anatomical compartments (i.e., the peripheral tissues, the blood, or the gastrointestinal tract, respectively). Yet these organs share some overall structural features, such as distinct T-cell and B-cell zones. One major difference between these organs is: A. The presence versus the absence of macrophages and dendritic cells B. Their function in bringing rare naive lymphocytes into contact with their specific antigen C. The ability of lymphocytes to enter the organ from the blood D. The mechanism by which antigens or pathogens enter the organ E. The ability of naïve T cells to be activated and proliferate in the organ
D
Studies show that about 50-100 different B cells initially seed each germinal center (d7 post-infection). These different B cells are represented by different colored circles in a white oval (germinal center) in Figure Q10.9. Which of the choices shown best represents the B cell population that would be found in the same germinal center approximately two weeks later?
D
The adaptive immune system uses multiple strategies to generate diversity in our ability to mount responses to a wide array of infectious microorganisms. These strategies include the generation of diverse repertoires of B-cell and T-cell antigen receptors, as well as polymorphism of MHC genes. The polymorphism of MHC genes differs from the diversity of lymphocyte antigen receptors in that: A. It involves DNA rearrangements at multiple gene segments in the MHC locus. B. It requires different enzymes than the RAG1/RAG2 recombinase required for antigen receptor rearrangements. C. It results in a diverse repertoire of clonally distributed receptors on dendritic cells, rather than on lymphocytes. D. It creates diversity between individuals in the population rather than within a single individual. E. It does not contribute to the transplant rejection responses that occur after organ transplantation between unrelated individuals.
D
The compound LE135 is an inhibitor of the retinoic acid receptor, and blocks signaling through this receptor. In a mouse model of inflammatory bowel disease (IBD), inflammation in the gastrointestinal (GI) epithelium is significantly exacerbated if animals are treated with LE135. Analysis of the CD4 T cell subsets found in the GI epithelium of LE135-treated mice compared to controls with IBD would likely show: A. Reduced numbers of CD4 T cells of all subsets in the LE135-treated mice B. Increased numbers of TGF-β and IL-10-producing CD4 cells in the LE135-treated mice C. Reduced numbers of IL-17 and IL-22-producing CD4 cells in the LE135-treated mice D. Reduced numbers of iTregs in the LE135-treated mice E. Increased numbers of naive CD4 T cells in the LE135-treated mice
D
The final stages of T cell development occur in the thymic medulla, after the developing cells become CD4 or CD8 single-positive. One important change that occurs during this final maturation is: A. The down-regulation of the pre-T-cell receptor α (pre-Tα) chain protein B. The up-regulation of genes encoding effector cytokines and cytolytic effector proteins C. The increased susceptibility to T-cell receptor-induced apoptosis D. The loss of susceptibility to T-cell receptor-induced apoptosis E. The up-regulation of signaling proteins required for T cell activation
D
Wiskott-Aldrich syndrome is an immunodeficiency disease due to mutations in the gene encoding WASp. Individuals with this disease make poor antibody responses to protein antigens, due to impaired T cell help for B cells. WASp-deficient T cells are likely impaired in providing adequate help to B cells due to: A. Defects in up-regulating expression of genes encoding cytokines required by B cells B. Defects in up-regulating metabolic pathways for T cell macromolecular synthesis C. Defects in up-regulating expression of genes needed for T cell survival D. Defects in cytoskeletal reorganization needed for directed T cell cytokine secretion E. Defects in up-regulating T cell integrin adhesion for stable interactions with B cells
D
Studies show that about 50-100 different B cells initially seed each germinal center (d7 post-infection). These different B cells are represented by different colored circles in a white oval (germinal center) in the figure below. Which of the choices shown best represents the B cell population that would be found in the same germinal center approximately two weeks later? INSERT PICTURE HERE
D (all teal blue)
Studies show that about 50-100 different B cells initially seed each germinal center (d7 post-infection). These different B cells are represented by different colored circles in a white oval (germinal center) in Figure Q10.9. Which of the choices shown best represents the B cell population that would be found in the same germinal center approximately two weeks later?
D (all teal)
Heavy chain also contains _______________ between V and J
D segments
CXCR5 is the receptor for the chemokine CXCL13, secreted by follicular stromal cells and follicular dendritic cells in the B cell zones (i.e., lymphoid follicles) of secondary lymphoid organs. A conditional knockout mouse in which CXCR5 was specifically deleted only in T cells would have: A. No defects in any type of antibody response B. Defects in the initial activation of all B cells C. A lack of discrete B cell and T cell zones in the lymphoid organ D. A defect in T cell-dependent antibody responses E. An increased number and size of germinal centers
D. A defect in T cell-dependent antibody responses
Multiple choice: IgM is the first antibody isotype secreted following activation of a naive B cell. IgM is found at high concentrations in the serum, and is found as a very high molecular weight complex. This high molecular weight complex is composed of: A. A single IgM monomer plus monomers of IgA and IgG B. A single IgM monomer bound to several non-immunoglobulin serum proteins C. A single IgM monomer bound to serum complement components D. A pentamer of IgM monomers E. Two dimers of IgM plus IgD forming a tetrameric complex
D. A pentamer of IgM monomers
Multiple choice: Most normal tissues contain resident macrophages, and connective tissue sites in the gastrointestinal tract and the lung contain large numbers of these cells. Yet the blood also contains a high number of circulating 'classical' monocytes that can differentiate into macrophages after entering tissues. These circulating monocytes function to: A. Phagocytose and kill pathogens in the blood B. Line the endothelial surfaces of the blood vessels with phagocytic cells C. Enter lymph nodes and patrol for infecting microbes in these organs D. Amplify the local innate immune response by entering tissues that are infected E. Differentiate into dendritic cells during an inflammatory response
D. Amplify the local innate immune response by entering tissues that are infected
Multiple choice: Immunodeficiency diseases occur when individuals have defects in leukocyte adhesion to inflamed endothelial cells, thereby impeding the extravasation of phagocytes into infected tissues. When neutrophils from one class of these patients were isolated and tested using in vitro assays for neutrophil-endothelial cell interactions and extravasation, it was found that the neutrophils could slowly roll along the endothelial vessel wall but were unable to arrest and migrate across the endothelium. The most likely protein deficient in these neutrophils is: A. ICAM-1 or ICAM-2 B. P-selectin C. E-selectin D. An integrin E. Sulfated sialyl-LewisX
D. An integrin
9.15 Multiple choice: Purified naive T cells isolated from a T-cell receptor transgenic mouse represent a homogeneous population of cells with specificity for a single known peptide:MHC complex. This specific peptide:MHC complex can be purified and formed into multivalent complexes, such as peptide:MHC tetramers. When the naive T cells are stimulated with their 'antigen' in the form of these peptide:MHC tetramers, the T cells show activation responses, including the up-regulation of genes that are induced within several hours after T-cell receptor stimulation. However, these activated T cells fail to undergo robust proliferation, and the majority of cells die after 3-4 days in culture. T cell proliferation and survival could be greatly augmented by addition of: A. Anti-inflammatory cytokines B. Toll-like receptor ligands C. Antibodies to the T-cell receptor D. B7 ligands for CD28 E. The integrin LFA-1
D. B7 ligands for CD28
Purified naive T cells isolated from a T-cell receptor transgenic mouse represent a homogeneous population of cells with specificity for a single known peptide:MHC complex. This specific peptide:MHC complex can be purified and formed into multivalent complexes, such as peptide:MHC tetramers. When the naive T cells are stimulated with their 'antigen' in the form of these peptide:MHC tetramers, the T cells show activation responses, including the up-regulation of genes that are induced within several hours after T-cell receptor stimulation. However, these activated T cells fail to undergo robust proliferation, and the majority of cells die after 3-4 days in culture. T cell proliferation and survival could be greatly augmented by addition of: A. Anti-inflammatory cytokines B. Toll-like receptor ligands C. Antibodies to the T-cell receptor D. B7 ligands for CD28 E. The integrin LFA-1
D. B7 ligands for CD28
Multiple choice: The clonal selection theory was first proposed in the 1950s, decades before the molecular details of B and T lymphocyte development and lymphocyte antigen recognition responses were elucidated. Nonetheless, Burnet, who proposed this theory, correctly inferred several key aspects of adaptive immune responses. One key postulate that Burnet proposed was that: A. Cells of the innate immune system are distinct from those of the adaptive immune system. B. Cells of the adaptive immune system are generated from a pluripotent hematopoietic stem cell that resides in the bone marrow. C. B and T lymphocytes are closely related cells that have distinct properties from myeloid cells. D. Circulating antibodies are generated by many different antibody-secreting cells, each of which expresses a single type of antibody on its surface as a receptor. E. Antibodies binding to pathogens lead to efficient pathogen clearance by phagocytic cells.
D. Circulating antibodies are generated by many different antibody-secreting cells, each of which expresses a single type of antibody on its surface as a receptor.
Multiple choice: Innate lymphoid cells (ILCs) are effector cells that generally reside in barrier tissues, such as the skin, the gut, and the lung. These cells closely resemble subsets of T lymphocytes, but lack a T cell antigen-receptor. Instead, these cells produce their effector molecules following stimulation by: A. Microbial PAMPs that stimulate pattern recognition receptors on ILCs B. TNF-, which is produced during the inflammatory response C. Acute phase response proteins produced in the liver during an infection D. Cytokines made by other innate cells, such as macrophages or dendritic cells E. Antimicrobial peptides made by epithelial cells in response to infection
D. Cytokines made by other innate cells, such as macrophages or dendritic cells
Prevents surface MHC class I molecules from undergoing peptide exchange at the cell surface
During MHC class I synthesis and folding in the endoplasmic reticulum (ER), a process of peptide editing takes place as the newly synthesized MHC class I protein is held in a 'peptide receptive' state by binding to the calreticulin:ERp57:tapasin complex. Peptide editing ensures that the MHC class I molecules that reach the cell surface have stable, high affinity binding for their peptide cargo. Peptide editing is important to the immune response because it:
Prevents aurface MHC class I molecules from undergoing peptide exchange at the cell surface.
During MHC class I synthesis and folding in the endoplasmic the newly synthesized MHC class I protein is held in place by reticulum (ER), a process of peptide editing takes place as editing ensures that the MHC class I molecules that reach binding to the calreticulin:ERp57:tapasin complex. Peptide the cell surface have stable, high affinity binding for their peptide. Peptide editing is important to the immune response because it:
Where do CD4 and CD8 bind?
During antigen recognition, CD4 or CD8 (depending on the type of T cell) associates with the T-cell receptor on the T-cell surface and binds to invariant sites on the MHC portion of the composite peptide:MHC ligand, away from the peptide-binding site
: Empty MHC class I and MHC class II molecules are rapidly removed from the cell surface. This process prevents: A. The accumulation of empty MHC molecules on the cell surface which would interfere with T cells recognizing pathogen-derived peptide:MHC complexes B. Pathogens from evading the immune response by inducing peptide release from cell surface MHC molecules C. MHC class I molecules from being internalized into endosomes and binding endosome-derived peptides D. HLA-DM from trafficking to the cell surface with MHC class II E. Inappropriate T cell recognition of healthy cells that are not infected, nor have ingested a pathogen
E
A key feature of TLR signaling is the ability to induce inflammatory cytokine gene expression extremely rapidly following TLR stimulation. This is accomplished by signaling pathways using several mechanisms to activate transcription factors that are already present in the cell prior to TLR stimulation, but are kept in an inactive state. These signaling pathways use all of the following mechanisms EXCEPT: A. Induced ubiquitination leading to protein degradation B. Induced ubiquitination inducing protein-protein interactions C. Induced phosphorylation leading to nuclear translocation D. Induced phosphorylation leading to kinase activation E. Induced phosphorylation preventing protein degradation
E
A new strain of immunodeficient mice has been discovered, and found to have T cells that are unresponsive to TCR stimulation. The T cells from these mice have normal levels of the TCR complex on their surface, but when this TCR is stimulated, the cells fail to secrete IL-2. As a first step in determining the signaling defect responsible for this immunodeficiency, the T cells are stimulated with a phorbol ester (PMA) and Ionomycin. It is found that this treatment elicits IL-2 production by the immunodeficient T cells. Based on this information, candidate genes that could be mutated in these T cells include all of the following EXCEPT: A. ZAP-70 B. PLC-γ C. SLP-76 D. ITK E. Calcineurin
E
An important transcription factor activated by antigen receptor signaling in lymphocytes is an NFκB heterodimer of the two subunits, p50 and p65Rel. Defects in the IκB-kinase complex (NEMO) or mutations in IκB that prevent its phosphorylation interfere with NFκB activation and result in severe immunodeficiency diseases. This is due to the important function of: NEMO in targeting p50:p65Rel for ubiquitination and degradation NEMO in ubiquitinating IκB causing its release from NFκB IκB in blocking the DNA binding activity of NFκB IκB as a chaperone to promote NFκB nuclear localization NEMO in phosphorylating IκB inducing its degradation, thereby releasing NFκB
E
Antigen receptor signaling pathways are initiated by the action of a Src-family kinase. In T cells, the predominant Src-kinase is Lck. In resting T cells, Lck is maintained in an inactive state by allosteric interactions involving multiple domains of the enzyme. When T cells are treated with a small molecule inhibitor of the tyrosine kinase Csk, TCR signaling is initiated even in the absence of a ligand to stimulate the TCR. This occurs because: A. Csk phosphorylates Lck in its kinase domain, leading to Lck activation. B. Csk phosphorylates ZAP-70, maintaining ZAP-70 in an auto-inhibited state. C. Csk phosphorylates the ITAM motifs in the TCR ζ chain, leading to ZAP-70 recruitment. D. Csk phosphorylates and activates the membrane tyrosine phosphatase CD45. E. Csk phosphorylates the C-terminal negative regulatory tyrosine in Lck.
E
B cell development in the bone marrow is an inherently wasteful process. Nearly half of the pro-B cells produced will die without progressing on to the next stage of B cell development. This massive loss of pro-B cells is due to: A. The failure of many pro-B cells to up-regulate Pax5 and become committed to the B cell lineage. B. The inability of many pro-B cells to proceed with rearranging a VH to their rearranged DJH sequence. C. Large insertions of untemplated nucleotides into the rearranged gene by TdT. D. Detrimental DJH rearrangements on both alleles of the immunoglobulin heavy chain locus. E. The failure of the pro-B cell to make a complete immunoglobulin heavy chain protein.
E
During MHC class I synthesis and folding in the endoplasmic reticulum (ER), a process of peptide editing takes place as the newly synthesized MHC class I protein is held in a 'peptide receptive' state by binding to the calreticulin:ERp57:tapasin complex. Peptide editing ensures that the MHC class I molecules that reach the cell surface have stable, high affinity binding for their peptide cargo. Peptide editing is important to the immune response because it: A. Maintains high levels of surface MHC class I expression B. Ensures that MHC class I molecules are not degraded in the ER C. Retains the nascent MHC class I molecule in a peptide receptive state D. Allows surface MHC class I molecules to bind new peptides from the extracellular milieu E. Prevents surface MHC class I molecules from undergoing peptide exchange at the cell surface
E
Each subset of effector T cells produces a distinct array of secreted factors known as cytokines. One common feature of nearly all effector T cell responses is the rapid production of increased numbers of macrophages, granulocytes, and dendritic cells from the bone marrow. This response occurs due to: A. Effector T cell trafficking to the bone marrow to activate hematopoietic progenitor cells B. Depletion of peripheral myeloid cells after leaving the blood, leading to increased bone marrow production C. Inflammation-induced blood vessel dilation causing transient reductions in circulating myeloid cells D. Pathogen-induced migration of tissue-resident dendritic cells to lymph nodes inducing new dendritic cell production E. Effector T cell production of GM-CSF that traffics to the bone marrow
E
Experiments performed with T-cell receptor transgenic mice identified the fate of developing thymocytes that failed positive selection. Based on these findings, examination of thymocytes in MHC class I-MHC class II-deficient mice (lacking all MHC class I and class II expression in the thymus) would show: A. A 100-fold decrease in total thymocytes numbers B. A block in T cell development at the CD4-CD8- double-negative stage C. Normal numbers and subsets of thymocytes and peripheral T cells D. Normal numbers of thymocytes, but no peripheral T cells E. A block in T cell development at the CD4+CD8+ double-positive stage
E
Genetically inherited immunodeficiency diseases can result from defects in nearly any component of the immune response. The most severe forms of immunodeficiency occur when T cells are absent or non-functional. An individual with normal B cells, but an absence of T cells might have a defect in: A. RAG-1 or RAG-2 recombinase proteins B. Terminal deoxynucleotidyl transferase (TdT) C. Hematopoietic stem cells D. Bone marrow stromal cells E. Thymic stromal cells
E
In a mixed lymphocyte reaction, T cells from individual A make a robust response to antigen-presenting-cells from individual B, as long as the two individuals express different alleles of MHC molecules. Estimates indicate that up to 10% of the T cells from individual A may contribute to this response. If one performed this assay using responder T cells from a child and antigen-presenting cells from one parent, the result would be: A. A massive proliferative response made by the antigen-presenting cells of the parent B. A very weak response by the child's T cells, involving only 0.1% of their T cells C. The complete absence of any proliferative response by the child's T cells D. A robust cytolytic response that kills all of the parent's antigen-presenting cells E. A robust response by the child's T cells
E
Individuals that overexpress the cytokine BAFF show increased susceptibility to autoimmune diseases such as Sjögren's syndrome, a disease that targets the exocrine glands that produce saliva, tears, and other bodily secretions. If one examined the circulating antibodies in these patients, one would expect to find: A. Increased development of B cells in the bone marrow B. A failure of receptor editing of immunoglobulin light chain genes in the bone marrow C. An increased rate of immature B cell export from the bone marrow D. Reduced B-cell receptor signaling following strong cross-linking of the receptor E. An increased number of circulating mature autoreactive B cells
E
Several effector T cell functions are mediated by cell surface molecules on the effector cell interacting with binding partners on the target cells. In the case of the CD40-CD40 ligand interaction, effector CD4 T cells express CD40 ligand, which binds to CD40 target cells. Individuals with a genetic deficiency in CD40 ligand expression show greatly reduced antibody responses, particularly to protein antigens which require CD4 TFH cell interactions with B cells. Another expected defect in these individuals would be: A. Reduced recruitment of eosinophils by TH2 cells B. Reduced recruitment of neutrophils by TH17 cells C. Reduced production of anti-microbial peptides induced by TH17 cells D. Reduced suppression of dendritic cells by Treg cells E. Reduced activation of macrophages by TH1 cells
E
When T cells are activated by recognizing peptide:MHC complexes on dendritic cells in the lymph node, they up-regulate the receptor CD69. For T cells expressing a given T-cell receptor, the initial strength of the T-cell receptor signal can be modulated by varying the number of peptide:MHC complexes on the dendritic cells, or by varying the affinity with which the T cell-receptor binds to the peptide:MHC complexes. As a result, T cells stimulated with stronger T-cell receptor signals will maintain high expression of CD69 for one or two days longer that if those same T cells were stimulated with weaker T-cell receptor signals. Therefore, T cells stimulated with weaker T-cell receptor signals are likely to: A. Die by apoptosis B. Undergo more rounds of proliferation that T cells stimulated with stronger T-cell receptor signals C. Migrate to the B-cell zones of the lymph node D. Have reduced effector functions, such as cytokine production E. Egress from the lymph node 1-2 days earlier than T cells stimulated with stronger T-cell receptor signals
E
When macrophages in the lung are infected with an intracellular bacterium, such as Mycobacterium tuberculosis, they are activated by the interactions of their pattern recognition receptors with the microbe. These activated macrophages will then: A. Migrate to the marginal sinus of the draining lymph node to activate naive CD4 T cells B. Increase their phagocytic properties to scavenge dead and dying neighboring cells C. Migrate to the liver where they will remove dying cells from the blood D. Migrate to the red pulp of the spleen where they will remove immune complexes from the circulation E. Up-regulate MHC class II and B7 molecules to amplify CD4 T cell responses in the lung
E
Which of the following is not correct about the secondary lymphoid organs? A)Adaptive immune responses are initiated in the secondary lymphoid organs-lymph nodes B)The secondary lymphoid organs include the spleen, the lymph node, or the mucosa-associated lymphoid tissues (MALTs) such as the Peyer's patches in the gut. C)The secondary lymphoid organs provide a crossroads for the interaction of their recirculating T and B cells with their cognate antigens. D)The secondary lymphoid tissues serve as sites that facilitate interaction between lymphocytes and antigens. E)The secondary lymphoid organs provide progenitor lymphocytes for mature T cells.
E
Multiple choice: In a mixed lymphocyte reaction, T cells from individual A make a robust response to antigen-presenting-cells from individual B, as long as the two individuals express different alleles of MHC molecules. Estimates indicate that up to 10% of the T cells from individual A may contribute to this response. If one performed this assay using responder T cells from a child and antigen-presenting cells from one parent, the result would be: A. A massive proliferative response made by the antigen-presenting cells of the parent B. A very weak response by the child's T cells, involving only 0.1% of their T cells C. The complete absence of any proliferative response by the child's T cells D. A robust cytolytic response that kills all of the parent's antigen-presenting cells E. A robust response by the child's T cells
E. A robust response by the child's T cells
Multiple choice: When a mixture of different IgG antibody proteins are treated with the enzyme papain, each antibody is cleaved into three roughly equal size fragments. From each original antibody, two of the three fragments are identical to each other, and represent the 'arms' of the antibody 'Y'. These fragments are known as Fab fragments. The third fragment is known as the Fc region, because this fragment will crystallize when purified. The reason a mixture of Fc fragments will crystallize is because: A. It is the only part of the antibody protein that can easily be purified at the high concentrations needed for crystallization. B. It has no disulfide bonds holding the domains together, as disulfide bonds will inhibit crystallization. C. It is the only fragment of the antibody that still has disulfide bonds, so it remains intact during the crystallization process. D. The Fc fragments of IgG are much more water soluble than the Fab fragments. E. All Fc fragments generated from a mixture of IgG molecules have the identical amino acid sequence.
E. All Fc fragments generated from a mixture of IgG molecules have the identical amino acid sequence.
Multiple choice: In some vertebrates, such as rays and some shark species, immunoglobulin light chain genes consist of multiple units of already rearranged VJ-C genes, of which one is chosen for expression in a developing B cell. This strategy may have evolved in these organisms: A. Prior to the evolution of rearranging gene segments requiring somatic recombination in developing B cells B. Prior to the evolution of the RAG1 and RAG2 enzymes needed for recombination C. As a mechanism to increase light chain diversity beyond that achieved by the use of rearranging gene segments in humans D. As a mechanism to increase light chain diversity beyond that achieved the gene conversion process used in chickens E. As a means to generate a rapid response to common pathogens encountered by these animals
E. As a means to generate a rapid response to common pathogens encountered by these animals
Multiple choice: An infection in the skin, such as a pimple, often produces pus. The major component of pus is: A. Toxic oxygen molecules released by macrophages B. Toxic nitrogen molecules released by macrophages C. NETs released by neutrophils D. Dead epithelial cells killed by lysozyme E. Dead and dying neutrophils
E. Dead and dying neutrophils
3.17 Multiple choice: Many different NOD-like receptors, including several with pyrin domains and several with HIN domains, can function to trigger inflammasome assembly leading to the activation of caspase-1. The reason for many different sensors in this innate response system is that: A. Each NOD-like receptor is expressed in a different set of phagocytic cells, depending on its tissue location. B. Each NOD-like receptor resides in a different intracellular compartment. C. Each NOD-like receptor performs a different step in the multi-step cascade leading to inflammasome activation. D. Each NOD-like receptor binds to a different adapter protein and triggers a different form of the inflammasome. E. Each NOD-like receptor recognizes different PAMPs and is activated by different pathogens.
E. Each NOD-like receptor recognizes different PAMPs and is activated by different pathogens.
Multiple choice: Many different NOD-like receptors, including several with pyrin domains and several with HIN domains, can function to trigger inflammasome assembly leading to the activation of caspase-1. The reason for many different sensors in this innate response system is that: A. Each NOD-like receptor is expressed in a different set of phagocytic cells, depending on its tissue location. B. Each NOD-like receptor resides in a different intracellular compartment. C. Each NOD-like receptor performs a different step in the multi-step cascade leading to inflammasome activation. D. Each NOD-like receptor binds to a different adapter protein and triggers a different form of the inflammasome. E. Each NOD-like receptor recognizes different PAMPs and is activated by different pathogens.
E. Each NOD-like receptor recognizes different PAMPs and is activated by different pathogens.
Multiple choice: The production of antimicrobial peptides is one of the most evolutionarily ancient mechanisms of defense for multicellular organisms, and most eukaryotic species make many different forms of these proteins. For instance, human paneth cells in the gastrointestinal epithelium make 21 different defensins. The reason for this diversity of antimicrobial peptides is: A. Epithelial cells make different forms than those made by neutrophils. B. Neutrophils make many different defensins and store them as inactive proteins in their secretory granules. C. Most of them are produced only in response to infection. D. The production of different peptides is induced following a bacterial infection versus a fungal infection. E. Each one has distinct activities against Gram-negative bacteria, Gram-positive bacteria, or fungi.
E. Each one has distinct activities against Gram-negative bacteria, Gram-positive bacteria, or fungi.
9.28 Multiple choice: Each subset of effector T cells produces a distinct array of secreted factors known as cytokines. One common feature of nearly all effector T cell responses is the rapid production of increased numbers of macrophages, granulocytes, and dendritic cells from the bone marrow. This response occurs due to: A. Effector T cell trafficking to the bone marrow to activate hematopoietic progenitor cells B. Depletion of peripheral myeloid cells after leaving the blood, leading to increased bone marrow production C. Inflammation-induced blood vessel dilation causing transient reductions in circulating myeloid cells D. Pathogen-induced migration of tissue-resident dendritic cells to lymph nodes inducing new dendritic cell production E. Effector T cell production of GM-CSF that traffics to the bone marrow
E. Effector T cell production of GM-CSF that traffics to the bone marrow
Each subset of effector T cells produces a distinct array of secreted factors known as cytokines. One common feature of nearly all effector T cell responses is the rapid production of increased numbers of macrophages, granulocytes, and dendritic cells from the bone marrow. This response occurs due to: A. Effector T cell trafficking to the bone marrow to activate hematopoietic progenitor cells B. Depletion of peripheral myeloid cells after leaving the blood, leading to increased bone marrow production C. Inflammation-induced blood vessel dilation causing transient reductions in circulating myeloid cells D. Pathogen-induced migration of tissue-resident dendritic cells to lymph nodes inducing new dendritic cell production E. Effector T cell production of GM-CSF that traffics to the bone marrow
E. Effector T cell production of GM-CSF that traffics to the bone marrow
9.7 Multiple choice: When T cells are activated by recognizing peptide:MHC complexes on dendritic cells in the lymph node, they up-regulate the receptor CD69. For T cells expressing a given T-cell receptor, the initial strength of the T-cell receptor signal can be modulated by varying the number of peptide:MHC complexes on the dendritic cells, or by varying the affinity with which the T cell-receptor binds to the peptide:MHC complexes. As a result, T cells stimulated with stronger T-cell receptor signals will maintain high expression of CD69 for one or two days longer that if those same T cells were stimulated with weaker T-cell receptor signals. Therefore, T cells stimulated with weaker T-cell receptor signals are likely to: A. Die by apoptosis B. Undergo more rounds of proliferation that T cells stimulated with stronger T-cell receptor signals C. Migrate to the B-cell zones of the lymph node D. Have reduced effector functions, such as cytokine production E. Egress from the lymph node 1-2 days earlier than T cells stimulated with stronger T-cell receptor signals
E. Egress from the lymph node 1-2 days earlier than T cells stimulated with stronger T-cell receptor signals
When T cells are activated by recognizing peptide:MHC complexes on dendritic cells in the lymph node, they up-regulate the receptor CD69. For T cells expressing a given T-cell receptor, the initial strength of the T-cell receptor signal can bemodulated by varying the number of peptide:MHC complexes on the dendritic cells, or by varying the affinity with which the T cell-receptor binds to the peptide:MHC complexes. As a result, T cells stimulated with stronger T-cell receptor signals will maintain high expression of CD69 for one or two days longer that if those same T cells were stimulated with weaker T-cell receptor signals. Therefore, T cells stimulated with weaker T-cell receptor signals are likely to: A. Die by apoptosis B. Undergo more rounds of proliferation that T cells stimulated with stronger T-cell receptor signals C. Migrate to the B-cell zones of the lymph node D. Have reduced effector functions, such as cytokine production E. Egress from the lymph node 1-2 days earlier than T cells stimulated with stronger T-cell receptor signals
E. Egress from the lymph node 1-2 days earlier than T cells stimulated with stronger T-cell receptor signals
The kinetics of a typical CD8 T cell response to an acute virus infectionin mice is shown in Figure Q11.18.In this example, the virus is cleared by ~day 7 post-infection, and starting at ~day 10 post-infection, the majority of the virus-specific CD8 T cells die. The death of these virus-specific CD8 T cells is caused by: A. Lysis from the virus infection B. Engulfment and destruction by phagocytes in the body C. Destruction by cytotoxic T cells D. Natural killer cell lysis E. Fas-induced death or cytokine withdrawal
E. Fas-induced death or cytokine withdrawal
IPEX syndrome is a genetic disease due to mutations that disrupt the function of an important transcription factor expressed in subset of CD4 T cells. Individuals with this disease generally begin showing symptoms shortly after birth. This disease is often fatal. One of the most prominent symptoms of IPEX is severe gastrointestinal inflammation accompanied by severe diarrhea. This transcription factor is most likely: A. RORt B. T-bet C. STAT3 D. NFB E. FoxP3
E. FoxP3
While innate immune responses to all types of infections induce local inflammatory responses due to activation of blood vessel endothelial cells, some components of the innate response differ depending on the nature of the pathogen. In the case of intracellular bacterial or protozoan infections, tissue-resident dendritic cells and macrophages produce a cytokine that stimulates ILC cells to produce: A. IL-13 B. TNF- C. IL17 D. IL22 E. IFN-
E. IFN-
Multiple choice: Empty MHC class I and MHC class II molecules are rapidly removed from the cell surface. This process prevents: A. The accumulation of empty MHC molecules on the cell surface which would interfere with T cells recognizing pathogen-derived peptide:MHC complexes B. Pathogens from evading the immune response by inducing peptide release from cell surface MHC molecules C. MHC class I molecules from being internalized into endosomes and binding endosome-derived peptides D. HLA-DM from trafficking to the cell surface with MHC class II E. Inappropriate T cell recognition of healthy cells that are not infected, nor have ingested a pathogen
E. Inappropriate T cell recognition of healthy cells that are not infected, nor have ingested a pathogen
Multiple choice: A key feature of TLR signaling is the ability to induce inflammatory cytokine gene expression extremely rapidly following TLR stimulation. This is accomplished by signaling pathways using several mechanisms to activate transcription factors that are already present in the cell prior to TLR stimulation, but are kept in an inactive state. These signaling pathways use all of the following mechanisms EXCEPT: A. Induced ubiquitination leading to protein degradation B. Induced ubiquitination inducing protein-protein interactions C. Induced phosphorylation leading to nuclear translocation D. Induced phosphorylation leading to kinase activation E. Induced phosphorylation preventing protein degradation
E. Induced phosphorylation preventing protein degradation
Multiple choice: Many different viruses encode proteins that function to down-regulate MHC class I expression on host cells following infection with the virus. This immune evasion mechanism allows the virus to hide from CD8 T lymphocytes that normally detect virus-infected cells by using their T cell antigen receptor to recognize viral peptides bound to MHC class I proteins on the surface of the infected cell. To counteract this immune evasion strategy, NK cells have: A. Activating receptors that recognize MHC class I proteins B. A mechanism to secrete antiviral peptides C. Inhibitory receptors that recognize viral capsid proteins D. Activating receptors that recognize viral capsid proteins E. Inhibitory receptors that recognize MHC class I proteins
E. Inhibitory receptors that recognize MHC class I proteins
Mice lacking IL-15 or the IL-15R chain have substantially reduced numbers of type b IELs, including both : and : T-cell receptor-positive subsets. Normal numbers of type b IELs can be restored in il15-/- mice by cell-type specific expression of IL-15 in: A. Thymic medullary epithelial cells B. Thymic cortical epithelial cells C. Dendritic cells D. CD8+ T cells E. Intestinal epithelial cells
E. Intestinal epithelial cells
Inflammatory bowel disease (colitis) is a CD4 T-cell mediated disease that can be transferred to naive mice by administration of effector CD4 T cells that home to the gastrointestinal tract and induce inflammation. Simultaneous administration of neutralizing antibodies to IL-12p40 can prevent the disease, as can neutralizing antibodies to IL-23p19. Disease symptoms can be exacerbated by administration of IL-23, but not of IL-12. These data strongly suggest that: A. Both TH1 and TH17 effector cells contribute to disease. B. TH1 cells producing INF- are the major causes of disease C. IL-12p35 is a critical component of disease induction. D. The inducible IL-12R subunit is essential for disease induction. E. Neutralizing antibodies to IL-17 would prevent disease
E. Neutralizing antibodies to IL-17 would prevent disease
Multiple choice: During MHC class I synthesis and folding in the endoplasmic reticulum (ER), a process of peptide editing takes place as the newly synthesized MHC class I protein is held in a 'peptide receptive' state by binding to the calreticulin:ERp57:tapasin complex. Peptide editing ensures that the MHC class I molecules that reach the cell surface have stable, high affinity binding for their peptide cargo. Peptide editing is important to the immune response because it: A. Maintains high levels of surface MHC class I expression B. Ensures that MHC class I molecules are not degraded in the ER C. Retains the nascent MHC class I molecule in a peptide receptive state D. Allows surface MHC class I molecules to bind new peptides from the extracellular milieu E. Prevents surface MHC class I molecules from undergoing peptide exchange at the cell surface
E. Prevents surface MHC class I molecules from undergoing peptide exchange at the cell surface
Multiple choice: When complement proteins are covalently deposited onto the surface of a bacterium, this can sometimes lead to direct lysis of the bacterium. However, more commonly, the deposition of complement proteins onto the bacterial surface does not directly harm the bacterium. Instead, these complement proteins aid in bacterial elimination by: A. Recruiting antibodies to the bacterial surface, leading the antibody-dependent neutralization B. Providing a mechanism for phagocytes to use their Fc receptors to recognize and ingest the bacterium C. Cross-linking carbohydrate structures on the bacterial surface, thereby preventing the bacterium from replicating D. Stimulating B lymphocytes to produce more antibodies against the bacterium E. Providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacterium
E. Providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacterium
9.29 Multiple choice: Several effector T cell functions are mediated by cell surface molecules on the effector cell interacting with binding partners on the target cells. In the case of the CD40-CD40 ligand interaction, effector CD4 T cells express CD40 ligand, which binds to CD40 target cells. Individuals with a genetic deficiency in CD40 ligand expression show greatly reduced antibody responses, particularly to protein antigens which require CD4 TFH cell interactions with B cells. Another expected defect in these individuals would be: A. Reduced recruitment of eosinophils by TH2 cells B. Reduced recruitment of neutrophils by TH17 cells C. Reduced production of anti-microbial peptides induced by TH17 cells D. Reduced suppression of dendritic cells by Treg cells E. Reduced activation of macrophages by TH1 cells
E. Reduced activation of macrophages by TH1 cells
Several effector T cell functions are mediated by cell surface molecules on the effector cell interacting with binding partners on the target cells. In the case of the CD40-CD40 ligand interaction, effector CD4 T cells express CD40 ligand, which binds to CD40 target cells. Individuals with a genetic deficiency in CD40 ligand expression show greatly reduced antibody responses, particularly to protein antigens which require CD4 TFH cell interactions with B cells. Another expected defect in these individuals would be: A. Reduced recruitment of eosinophils by TH2 cells B. Reduced recruitment of neutrophils by TH17 cells C. Reduced production of anti-microbial peptides induced by TH17 cells D. Reduced suppression of dendritic cells by Treg cells E. Reduced activation of macrophages by TH1 cells
E. Reduced activation of macrophages by TH1 cells
IL-10-deficient mice develop spontaneous colitis, a disease due to chronic inflammation in the gastrointestinal (GI) tract. However, when these mice are housed in germ-free conditions, in which they lack all commensal microbes in their GI tract, no colitis was observed. In addition, one would expect germ-free IL-10-deficient mice to also show: A. Evidence of enhanced systemic immune activation compared to conventionally housed il10-/- mice B. Enlarged mesenteric lymph nodes compared to conventionally housed il10-/- mice C. Elevated numbers of FoxP3+ T cells in the lamina propria compared to conventionally housed il10-/- mice D. Increased production of IgG antibodies compared to conventionally housed il10-/-mice E. Reduced production of IgA antibodies compared to conventionally housed il10-/-mice
E. Reduced production of IgA antibodies compared to conventionally housed il10-/-mice
3.30 Multiple choice: In healthy adults, neutrophils represent approximately half of their white blood cells. During a bacterial infection, this number often rises to >80%. One factor contributing to this rise is: A. Recruitment of neutrophils from tissues into the blood B. Proliferation of neutrophils at the site of infection C. Proliferation of neutrophils in the blood D. Differentiation of blood monocytes into neutrophils E. Release of neutrophils into the blood from the bone marrow
E. Release of neutrophils into the blood from the bone marrow
Multiple choice: In healthy adults, neutrophils represent approximately half of their white blood cells. During a bacterial infection, this number often rises to >80%. One factor contributing to this rise is: A. Recruitment of neutrophils from tissues into the blood B. Proliferation of neutrophils at the site of infection C. Proliferation of neutrophils in the blood D. Differentiation of blood monocytes into neutrophils E. Release of neutrophils into the blood from the bone marrow
E. Release of neutrophils into the blood from the bone marrow
Multiple choice: Several invertebrate species, such as some insect and snail species, have mechanisms for increasing the diversity of immune recognition molecules that are expressed in an individual beyond the simple 'one gene encodes one protein' rule that applies to most genes in the genome. One of these mechanisms: A. Uses a pair of enzymes that are related to the RAG recombinase enzymes found in vertebrates B. Creates a library of complement proteins that function like vertebrate complement to promote phagocytosis of microbes by macrophages and neutrophils C. Creates a clonally distributed set of immune recognition molecules by a process involving different DNA rearrangement events in each cell D. Uses a mechanism in which a small number of cells expressing a few different proteins undergo massive proliferation to provide protective immunity E. Resembles the V-D-J recombination process in vertebrates but occurs by differential RNA splicing rather than by DNA rearrangement
E. Resembles the V-D-J recombination process in vertebrates but occurs by differential RNA splicing rather than by DNA rearrangement
Multiple choice: The addition and subtraction of nucleotides at the junctions between V, D, and J gene segments creates antibody proteins with wide variations in the numbers of amino acids in their CDR3 regions. This variability in CDR3 length is important as: A. Overall variability in CDR3 sequence is needed to create a sufficiently diverse antibody repertoire. B. The CDR3 region is more important in binding antigen than the CDR1 and CDR2 regions are. C. Some light chains bind better to heavy chains with longer CDR3 region sequences. D. Longer CDR3 sequences generally create antibodies with higher affinity for the antigen. E. Some antibodies bind relatively flat surfaces and others bind deep clefts in the antigen.
E. Some antibodies bind relatively flat surfaces and others bind deep clefts in the antigen.
Multiple choice: Antibodies that bind with high affinity to some viral surface proteins require heavy chain CDR3 loops of unusual length. Whereas the average human heavy chain CDR3 length is ~15 amino acids, antibodies with VH CDR3 loops of >30 amino acids are readily detected in the repertoire. These antibody heavy chains with CDR3 lengths of >30 amino acids would likely be missing in individuals lacking: A. RAG-1 and RAG-2 B. DNA-dependent protein kinase (DNA-PK) C. The nuclease, Artemis D. The Ku70:Ku80 complex E. Terminal deoxy nucleotidyl transferase (TdT)
E. Terminal deoxy nucleotidyl transferase (TdT)
Multiple choice: The alternative pathway of complement activation has an important role in innate immunity, due to its ability to greatly amplify the amount of C3b deposited onto the pathogen surface. This amplification occurs because: A. The C3 convertase of the alternative pathway is much more active than those of the classical and lectin pathways. B. The C3 convertase of the alternative pathway works as a soluble enzyme in the plasma. C. The C3 convertase of the alternative pathway cannot be inactivated by complement regulatory factors in the host. D. The C3 convertase of the alternative pathway is more efficiently recruited to pathogen surfaces than the C3 convertases of the classical and lectin pathways. E. The C3 convertase of the alternative pathway contains C3b, and can generate more of itself.
E. The C3 convertase of the alternative pathway contains C3b, and can generate more of itself.
Multiple choice: One strategy for vaccine development currently under investigation is the use of pathogen-derived T cell epitopes as a component of the vaccine. For viral pathogens, implementing this strategy involves scanning the predicted amino acid sequences of the viral proteins for likely peptide epitopes that would bind to MHC class I and MHC class II molecules. In addition to the complication of MHC sequence polymorphism in the human population, another complication of this strategy for peptide epitopes that would bind to MHC class II proteins is: A. The importance of viral proteins containing peptides that are cleaved into 8-10 amino acid long fragments. B. The ability of viruses to mutate their proteins to avoid MHC anchor residue sequences. C. The fact that long peptides (>13 amino acids) are rapidly degraded in cells. D. The fact that MHC class II proteins are intrinsically stable, even in the absence of binding to a peptide. E. The absence of defined sequence motifs that predict peptide binding to MHC class II molecules.
E. The absence of defined sequence motifs that predict peptide binding to MHC class II molecules.
Multiple choice: Women with urinary tract infections caused by E. coli are generally treated with a course of antibiotics. A common complication of the antibiotic treatment is the occurrence of a vaginal yeast infection caused by Candida albicans, an organism that is normally present in very low numbers in the human vaginal tract. This complication occurs because: A. The E. coli infection damages the reproductive epithelium, causing a breach in the tight junctions and allowing invasion by the Candida albicans. B. The E. coli infection induces adhesion molecule expression on the reproductive epithelium, allowing attachment of the yeast. C. The antibiotic treatment kills all strains of fungi present in the reproductive tract, except the Candida albicans. D. The E. coli infection causes gastrointestinal distress leading to diarrhea. E. The antibiotics kill many of the commensal organisms in the reproductive tract, allowing overgrowth of the fungus.
E. The antibiotics kill many of the commensal organisms in the reproductive tract, allowing overgrowth of the fungus.
Multiple choice: Macrophages express multiple types of receptors on their surface that stimulate phagocytosis of microbes, leading to pathogen internalization and destruction. Many of these receptors, such as Dectin-1, rely on direct recognition of a PAMP on the pathogen surface. However, some receptors that stimulate phagocytosis rely on soluble factors (not associated with the phagocyte membrane) to identify and mark the pathogen for uptake by the phagocyte. One such receptor is: A. The mannose receptor B. The class A scavenger receptor C. The lipid receptor D. The macrophage C-type lectin receptor E. The complement receptor
E. The complement receptor
Multiple choice: Individuals with defects in T cell development have a severe immunodeficiency disease called SCID (severe combined immunodeficiency disease). In these individuals, the absence of all T cells causes defects in both cell-mediated (T cell- based) and humoral (antibody-based) immune responses. The defect in antibody responses in SCID patients is due to: A. The important role of T cells in regulating B cell development in the bone marrow B. The inter-dependence of T cells and B cells for the normal development of secondary lymphoid organs. C. The absence of phagocytic cells needed for antibody-dependent pathogen clearance in SCID patients D. The poor survival of B cells in patients with defects in their T cells E. The important role of T follicular helper cells in generating protective antibody responses
E. The important role of T follicular helper cells in generating protective antibody responses
1.37 Multiple choice: Individuals with defects in T cell development have a severe immunodeficiency disease called SCID (severe combined immunodeficiency disease). In these individuals, the absence of all T cells causes defects in both cell-mediated (T cell-based) and humoral (antibody-based) immune responses. The defect in antibody responses in SCID patients is due to: A. The important role of T cells in regulating B cell development in the bone marrow B. The inter-dependence of T cells and B cells for the normal development of secondary lymphoid organs. C. The absence of phagocytic cells needed for antibody-dependent pathogen clearance in SCID patients D. The poor survival of B cells in patients with defects in their T cells E. The important role of T follicular helper cells in generating protective antibody responses
E. The important role of T follicular helper cells in generating protective antibody responses
Multiple choice: The terminal components of the complement pathway assemble to form a membrane attack complex that can induce pathogen lysis and death. Yet, evidence indicates that this feature of complement is less important than the earlier steps that promote pathogen opsonization and induce inflammation. This conclusion is based on: A. In vitro experiments showing that very few species of bacteria are susceptible to lysis by the membrane attack complex B. Experiments indicating that only bacteria, but not viruses or fungi, are susceptible to lysis by the membrane attack complex C. The very low levels of terminal complement components in the serum D. The fact that other mammalian species lack the terminal components of the complement pathway needed to form the membrane attack complex E. The limited susceptibility to infections of patients with deficiencies in terminal complement components
E. The limited susceptibility to infections of patients with deficiencies in terminal complement components
Multiple choice: Given the enormous heterogeneity of antigen receptors expressed on the populations of naive B and T lymphocytes, the adaptive immune response relies on a process whereby the rare lymphocyte that binds to the antigen is first induced to proliferate, before it can perform its effector function. For B cells, there is a clever mechanism that ensures that the specificity of the antibody secreted by the plasma cell will recognize the same pathogen that initially stimulated the B cell antigen receptor and induced B cell proliferation. This mechanism is: A. The naive B cell expresses an array of different B cell antigen receptors, and randomly chooses which specificity of antibody to secrete as a plasma cell. B. The naive B cell expresses a single specificity of B cell antigen receptor, and then up-regulates the expression of this receptor so it can bind tightly to the pathogen. C. The plasma cell proliferates after it has finished secreting antibody to generate more plasma cells with specificity for the pathogen. D. The plasma cell traps secreted antibody molecules in its extracellular matrix and uses these antibodies to bind to the pathogen. E. The naive B cell expresses a membrane-bound form of the antibody as a receptor, and secretes that same antibody when it differentiates into a plasma cell.
E. The naive B cells expresses a membrane-bound form of the antibody as a receptor, and secretes that same antibody when it differentiates into a plasma cell.
9.12 Multiple choice: When macrophages in the lung are infected with an intracellular bacterium, such as Mycobacterium tuberculosis, they are activated by the interactions of their pattern recognition receptors with the microbe. These activated macrophages will then: A. Migrate to the marginal sinus of the draining lymph node to activate naive CD4 T cells B. Increase their phagocytic properties to scavenge dead and dying neighboring cells C. Migrate to the liver where they will remove dying cells from the blood D. Migrate to the red pulp of the spleen where they will remove immune complexes from the circulation E. Up-regulate MHC class II and B7 molecules to amplify CD4 T cell responses in the lung
E. Up-regulate MHC class II and B7 molecules to amplify CD4 T cell responses in the lung
When macrophages in the lung are infected with an intracellular bacterium, such as Mycobacterium tuberculosis, they are activated by the interactions oftheir pattern recognition receptors with the microbe. These activated macrophages will then: A. Migrate to the marginal sinus of the draining lymph node to activate naive CD4 T cells B. Increase their phagocytic properties to scavenge dead and dying neighboring cells C. Migrate to the liver where they will remove dying cells from the blood D. Migrate to the red pulp of the spleen where they will remove immune complexes from the circulation E. Up-regulate MHC class II and B7 molecules to amplify CD4 T cell responses in the lung
E. Up-regulate MHC class II and B7 molecules to amplify CD4 T cell responses in the lung
There are two types of dendritic cells: conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs). Among the following description, match the each description to the feature of cDCs or pDCs (in the order of i to vi). (i: ) act in early defense (innate immune response) against viral infection. (ii: ) are abundant at barrier tissue sites, such as the intestines, lung, and skin. (iii: ) are very active in phagocytosis using complement receptors and Fc receptors, and carbohydrate recognizing C-type lectins. (iv: ) perform macropinocytosis to engulf large volumes of surrounding fluid (or bacteria, viruses). (vi: ) express TLRs and RIG-I-like receptors and produce abundant antiviral type I interferons (IFN / ). A. (i, cDCs) (ii, cDCs) (iii, cDCs) (iv, cDCs) (vi, pDCs) B.(i, cDCs)(ii, cDCs)(iii, cDCs)(iv, pDCs)(vi, pDCs) C.(i, pDCs)(ii, pDCs)(iii, cDCs)(iv, cDCs)(vi, pDCs) D.(i, pDCs)(ii, cDCs)(iii, pDCs)(iv, cDCs)(vi, pDCs) E.(i, pDCs)(ii, cDCs)(iii, cDCs)(iv, cDCs)(vi, pDCs)
E.(i, pDCs)(ii, cDCs)(iii, cDCs)(iv, cDCs)(vi, pDCs) (i: pDCs) act in early defense (innate immune response) against viral infection. (ii: cDCs) are abundant at barrier tissue sites, such as the intestines, lung, and skin. (iii: cDCs) are very active in phagocytosis using complement receptors and Fc receptors, and carbohydrate recognizing C-type lectins. (iv: cDCs) perform macropinocytosis to engulf large volumes of surrounding fluid (or bacteria, viruses). (vi: pDCs) express TLRs and RIG-I-like receptors and produce abundant antiviral type I interferons (IFN / ).
In cell culture experiments, purified B cells expressing IgM can be induced to switch to producing IgE by stimulating them with an antibody to CD40 (a stimulatory antibody) plus the cytokine IL-4. In an individual undergoing an immune response, these signals would normally be provided by: A.Germinal center stromal cells B.Other B cells in the germinal center C.Follicular dendritic cells in the germinal center D.Any CD4 T cell in the same lymph node E.TFH cells in the germinal center
E.TFH cells in the germinal center
IgM antibodies are much more efficient than IgG at activating the complement cascade. However, under certain circumstances, IgG antibodies will activate the complement pathway. One example of a situation in which IgG binding to its antigen will not trigger the complement cascade is when: A.The IgG antibodies bind to a multivalent soluble antigen in solution, such as a polysaccharide structure shed from a bacterial pathogen. B.The IgG antibodies bind to a viral capsid protein that is present in more than 100 copies on the viral particle surface. C.The IgG antibodies bind to a bacterial surface by recognizing a repetitive polysaccharide component of the bacterial capsule D.The IgG antibodies are binding self-antigens such as chromatin released from dead cells. E.The IgG antibodies are neutralizing a bacterial toxin protein by blocking the receptor-attachment site on the toxin.
E.The IgG antibodies are neutralizing a bacterial toxin protein by blocking the receptor-attachment site on the toxin.
what is responsible for anergy?
E3 ligase GRAIL
Enzyme-Linked Immunosorbent Assay (ELISA)
ELISA uses an enzyme conjugated to antibody and the color generating substrate of the enzyme
Following their activation, naive CD4 T cells differentiate into one of several subsets of effector T cells. This developmental choice is determined by which specific cytokines the T cells are exposed to during their activation; in turn, the cytokines that are produced will reflect the nature of the infecting pathogen. In order for this system to be flexible enough to produce all five effector CD4 subsets (TH1, TH2, TH17, TFH, and iTreg):
Each naive CD4 T cell must express all of the STAT proteins.
double negative cells
Early T cells that display surface markers c-kit, CD44, CD25 but lack both CD4 and CD8 surface markers are known as:
Each subset of effector T cells produces a distinct array of secreted factors known as cytokines. One common feature of nearly all effector T cell responses is the rapid production of increased numbers of macrophages, granulocytes, and dendritic cells from the bone marrow. This response occurs due to:
Effector T cell production of GM-CSF that traffics to the bone marrow
When T cells are activated by recognizing peptide:MHC complexes on dendritic cells in the lymph node, they up-regulate the receptor CD69. For T cells expressing a given T-cell receptor, the initial strength of the T-cell receptor signal can be modulated by varying the number of peptide:MHC complexes on the dendritic cells, or by varying the affinity with which the T cell-receptor binds to the peptide:MHC complexes. As a result, T cells stimulated with stronger T-cell receptor signals will maintain high expression of CD69 for one or two days longer that if those same T cells were stimulated with weaker T-cell receptor signals. Therefore, T cells stimulated with weaker T-cell receptor signals are likely to:
Egress from the lymph node 1-2 days earlier than T cells stimulated with stronger T-cell receptor signals
Which of the following is MOST likely to simulate/activate a memory T cell?
Either a B cell, dendritic cell, or a macrophage
Diapedesis
Endothelial and neutrophil CD31 (PECAM)
Even when the complement cascade fails to proceed beyond generating the C3 convertase, complement activation is effective at inducing pathogen uptake and destruction. This process of immune protection is mediated by:
Engagement of complement receptors on phagocytes by C3b and its cleavage products which promotes phagocytosis
The thymic cortex has a substantial population of macrophages in addition to the developing T cells (i.e., thymocytes). These macrophages are extremely useful because they:
Engulf apoptotic thymocytes
While CD28 co-stimulation is important for the initial activation of naive T cells, other co-stimulatory molecules function at later stages of the T cell response. Several of these other co-stimulatory molecules are members of the TNF-receptor family, and function by activating the transcription factor, NFB. Therefore, stimulation of these co-stimulatory TNF-receptors on activated T cells is likely to:
Enhance T cell survival
While CD28 co-stimulation is important for the initial activation of naive T cells, other co-stimulatory molecules function at later stages of the T cell response. Several of these other co-stimulatory molecules are members of the TNF-receptor family, and function by activating the transcription factor, NFkB. Therefore, stimulation of these co-stimulatory TNF-receptors on activated T cells is likely to:
Enhance T cell survival
At early timepoints following an infection, examination of lymph node CD4 T cells responding to the pathogen would show a heterogeneous population of cells representing several different effector lineages. Likewise, the cytokines produced by these cells would include IFN, IL-4, and possibly others. However, approximately one week later at the peak of the T cell response, the pathogen-specific CD4 T cell population would be largely homogeneous in their production of a single effector subset cytokine profile. This change comes about due to:
Enhanced differentiation of newly activated CD4 T cells into one effector subset
At early timepoints following an infection, examination of lymph node CD4 T cells responding to the pathogen would show a heterogeneous population of cells representing several different effector lineages. Likewise, the cytokines produced by these cells would include IFN-gamma, IL-4, and possibly others. However, approximately one week later at the peak of the T cell response, the pathogen-specific CD4 T cell population would be largely homogeneous in their production of a single effector subset cytokine profile. This change comes about due to:
Enhanced differentiation of newly activated CD4 T cells into one effector subset
One striking feature of TCR interactions with peptide:MHC complexes is that amino acid residues in the MHC protein are as important to the TCR binding strength as are amino acid residues in the pathogen-derived peptide. This feature is in contrast to antigen recognition by antibodies, which is a direct interaction that is independent of other host proteins. Based on the different functions of T cells versus antibodies in the adaptive immune response, the fact that TCRs recognize components of both the MHC and the bound peptide exists to:
Ensure that TCRs are focused on recognizing antigens associated with host cells, and not those that are free in solution
One striking feature of TCR interactions with peptide:MHC complexes is that amino acid residues in the MHC protein are as important to the TCR binding strength as are amino acid residues in the pathogen-derived peptide. This feature is in contrast to antigen recognition by antibodies, which is a direct interaction that is independent of other host proteins. Based on the different functions of T cells versus antibodies in the adaptive immune response, the fact that TCRs recognize components of both the MHC and the bound peptide exists to:
Ensure that TCRs are focused on recognizing antigens associated with host cells, and not those that are free in solution NOTE: Correct. The functions of the T cells include killing host cells (in the case of virus infections) as well as activating macrophages (in the case of intracellular bacteria and protozoan infections). For these functions, it is essential that the T cell is not distracted by the presence of free pathogens in its environment, but instead, focuses on the host cell that requires assistance in eliminating the pathogen. The fact that TCRs only recognize pathogen-derived peptides when they are bound to surface MHC molecules ensures this single-minded focus of the T cell.
___________ is the part of the antigen to which an antibody _________.
Epitope; binds
MHC class I alpha chains to calnexin. When B2-microglobulin binds to and cytosolic proteins are broken down by proteasome. TAP takes these alpha chains calnexin is released and the complex binds to TAP. DRiPs broken down peptides to the endoplasmic reticulum. Then a peptide binds with the MHC class I molecule and finishes folding. Then the MHC class I molecule is released from the TAP complex exported to the cell membrane for presentation.
Explain how MHC class I presentation occurs
What is the Danger Hypothesis
Exposure to foreign antigen induces tissue damage that sends danger signals to generate activated T cells These danger signals are in the form of cytokines
MHC Class I Molecules
Expressed on the surface of cells as a 3 α globulin chain in a non-covalent association with β2- microglobulin
Empty MHC class I and MHC class II molecules are rapidly removed from the cell surface. This process prevents:
Extracellular peptides from binding these MHC molecules, as these peptides could be recognized by T cells leading to inappropriate T cell activation
Empty MHC class I and MHC class II molecules are rapidly removed from the cell surface. This process prevents:
Extracellular peptides from binding these MHC molecules, as these peptides could be recognized by T cells leading to inappropriate T cell activation NOTE: Correct. MHC class I molecules display peptides derived largely from cytosolic proteins, so it is important that these MHC molecules do not bind to extracellular peptides. MHC class II molecules present peptides derived from pathogens living in the vesicles, or from pathogens or antigens they have ingested. Again, it is important that these MHC molecules do not bind to extracellular peptides. In either case, surface MHC molecules binding to extracellular peptides could lead to healthy cells mistakenly being targeted for destruction or activation. Fortunately, when an MHC class I molecule at the surface of a living cell loses its peptide, its conformation changes, the b2-microglobulin dissociates, and the a chain is internalized and rapidly degraded. Thus, most empty MHC peptide class I molecules are quickly lost from the cell surface, largely preventing them from acquiring peptides directly from the surrounding extracellular fluid. This helps ensure that primed T cells target infected cells while sparing surrounding healthy cells. Empty MHC class II molecules are also removed from the cell surface. Although at neutral pH, empty MHC class II molecules are more stable than empty MHC class I molecules, they aggregate readily, and internalization of such aggregates is thought to account for their removal.
Initially after an infection, the majority of the T cells present in the tissue at a site of infection are not specific for the infecting pathogen, but over the course of several days, this changes and antigen-specific T cells become enriched at this site. This is because:
Extravasation from blood into tissues is determined by homing molecules, not antigen specificity. NOTE: Yes. In the early stage of the adaptive immune response, only a minority of the effector T cells that enter infected tissues will be specific for pathogen. This is because activation of the endothelium of local blood vessels by inflammatory cytokines induces expression of selectins, integrin ligands, and chemokines that can recruit any circulating effector or memory T cell that expresses the appropriate trafficking receptors, irrespective of its antigenic specificity. However, specificity of the reaction is rapidly increased as the number of pathogen- specific T cells increases and recognition of antigen within the inflamed tissue retains them there.
Initially after an infection, the majority of the T cells present in the tissue at a site of infection are not specific for the infecting pathogen, but over the course of several days, this changes and antigen-specific T cells become enriched at this site. This is because:
Extravasation from blood into tissues is determined by homing molecules, not antigen specificity..
Initially after an infection, the majority of the T cells present in the tissue at a site of infection are not specific for the infecting pathogen, but over the course of several days, this changes and antigen-specific T cells become enriched at this site. This is because:
Extravasation from blood into tissues is determined by homing molecules, not antigen specificity.. NOTE: Yes. In the early stage of the adaptive immune response, only a minority of the effector T cells that enter infected tissues will be specific for pathogen. This is because activation of the endothelium of local blood vessels by inflammatory cytokines induces expression of selectins, integrin ligands, and chemokines that can recruit any circulating effector or memory T cell that expresses the appropriate trafficking receptors, irrespective of its antigenic specificity. However, specificity of the reaction is rapidly increased as the number of pathogen- specific T cells increases and recognition of antigen within the inflamed tissue retains them there.
C3a and C3b are fragments of C3 that are generated by two different enzymes.
FALSE
In generating a B cell receptor gene, Vkappa segments sometimes join to Clambda segments
FALSE
The enzymes that cleave C3 and C4 are referred to as convertases
FALSE
The switch in constant region use from IgM to IgD is mediated by DNA rearrangements
FALSE
B cell epitopes can be deduced with great accuracy from the primary structure of a protein
FALSE NOTE: As discussed in the previous question, B cells recognize protein antigens in their fully folded form. Unfortunately, it is extremely difficult to predict how a protein will fold, even if you have it's primary sequence. So it is virtually impossible to deduce the 3-dimensional epitope a B cell would recognize just based on primary amino acid sequence.
Expression of the beta-subunit of the IL-2 receptor indicates T cell activation.
FALSE NOTE: Expression of the high-affinity alpha chain of the IL-2 receptor (CD25) indicates T cell activation.
Most eukaryotic genes are encoded in a set of exons that are brought together to form a contiguous protein coding sequence by the process of mRNA splicing. In contrast, immunoglobulin genes use somatic recombination of gene segments and not mRNA splicing to generate the final mRNA that is translated into protein.
FALSE NOTE: For the light chain, the joining of a V gene segment to a J gene segment creates an exon that encodes the whole light chain V region. This joining also brings the light chain V region sequences close to a constant region sequence so that the two DNA regions are separated by only a short intron. To make a complete immunoglobulin light-chain messenger RNA, the V-region exon is joined to the C-region sequence by RNA splicing after transcription. This process is similar for heavy chains, although there is a third gene segment (the D region) that also undergoes recombination to form the final V-region exon. Again, recombination is followed by transcription and then splicing to generate the final mRNA.
Following TCR or BCR signaling, the most important events downstream of kinase activation are the activation of transcription factors leading to new gene expression.
FALSE NOTE: Four important signaling modules are activated downstream of the TCR or BCR. In addition to transcription factor activation, the three additional modules lead to increased cellular metabolic activity, actin polymerization and cytoskeletal reorganization, and increased integrin adhesiveness and clustering.
All immunoglobulin molecules on the surface of a given B cell have the same isotype.
FALSE NOTE: Multiple isotypes can appear on the surface of a single B cell. For instance, mature naïve B cells express both IgD and IgM.
Our immune system efficiently kills all categories of microbes that attempt to colonize our bodies.
FALSE NOTE: Not all microbes are pathogens, and our immune system does not attempt to eliminate all non-pathogenic microbes. Consequently, many body surfaces are colonized by large numbers of non-pathogenic microbes. These are called commensal micro-organisms, and they are found in places like the gastrointestinal (GI) tract, skin, and oral mucosa.
The C3 convertase amplifies the process of complement activation by generating large amounts of C3b and cleaving large numbers of C5 molecules.
FALSE NOTE: The C3 convertase does generate large numbers of C3b molecules which become attached to the pathogen surface in the vicinity of the convertase. BUT this enzyme can only cleave C5 when bound to a molecule of C3b, generating the C5 convertase. The generation of the C5 convertase occurs at a much lower level than the C3 convertase, and many fewer molecules of C5 than C3 are cleaved.
The acute phase response contributes to infection control by producing molecules that promote pathogen opsonization and complement activation. This response is only induced by direct action of microbial components on hepatocytes in the liver.
FALSE NOTE: The acute phase is induced by inflammatory cytokines (TNF-a, IL-1b, IL-6) produced by the host in response to infection. These cytokines act on hepatocytes to produce a variety of proteins, including C-reactive protein, MBL, surfactant proteins, and fibrinogen. Many of these proteins bind pathogens, but not host cells, and contribute to pathogen clearance by promoting phagocytosis and complement activation.
In a lymph node, nTreg cells are able to inhibit the responses of other T cells in their vicinity. This inhibition is specific, as the nTreg cell and the naive T cell must share the same antigen specificity.
FALSE NOTE: nTreg cells in a lymph node function primarily by acting on antigen-presenting cells to down-regulate their co-stimulatory activity and their inflammatory cytokine production. Based on this mechanism, it is not necessary that the nTreg cell and the naive T cell whose response is inhibited share the same antigen specificity.
Mucosal surfaces and external epithelia are major routes of pathogenic infection. Mucosal surfaces are found in tissues such as the gastrointestinal tract, the reproductive tract and the mouth and respiratory tract. While the mouth and respiratory tract are routes of virus but not bacterial infections, the gastrointestinal tract is the route for bacterial but not virus infections.
FALSE NOTE: Both bacterial and virus infections can use both the mouth and respiratory tract and the gastrointestinal tract. There is no route of infection that is specific for a single category of pathogen.
In a lymph node, nTreg cells are able to inhibit the responses of other T cells in their vicinity. This inhibition is specific, as the nTreg cell and the naive T cell must share the same antigen specificity.
FALSE NOTE: nTreg cells in a lymph node function primarily by acting on antigen-presenting cells to down-regulate their co-stimulatory activity and their inflammatory cytokine production. Based on this mechanism, it is not necessary that the nTreg cell and the naive T cell whose response is inhibited share the same antigen specificity.
(t/f) secreted antibodies have a higher level of specificity as membrane-bound immunoglobulin
FALSE. they have the SAME specificity as membrane bound immunoglobulin.
MHC class I surface expression is dependent on an abundant source of pathogen-derived peptides. Thus, in uninfected cells, nearly all of the MHC class I proteins are degraded and never reach the cell surface.
FASLE NOTE: In uninfected cells, peptides derived from self proteins fill the peptide-binding groove of the mature MHC class I molecules and are carried to the cell surface. Some of the newly synthesized MHC proteins fail to find a peptide cargo, and do undergo degradation, but this is not the majority of MHC class I molecules synthesized.
Secretory IgA produced in the epithelium of mucosal surfaces has several functions in protective immunity. Among these are neutralization of pathogens or toxins in the gastrointestinal tract lumen or in epithelial cell endosomes, neutralization of pathogens or toxins that cross the epithelial barrier, and transport of pathogens or toxins across M cells for delivery to lamina propria dendritic cells. All of these functions share the common feature that they:
Fail to induce local inflammation in the gastrointestinal epithelium
12.5 True/False: Oral inoculation with rotavirus, an intestinal pathogen, induces adaptive immune responses that are initiated in gut-associated lymphoid tissue, such as mesenteric lymph nodes and Peyer's patches. The rotavirus-specific effector T cells that are generated in this response are never found in the circulation, but home directly from the lymphoid tissue to the epithelium without ever leaving the intestinal environment.
False
4.1 True/False: The antibody protein has two functional domains, one for antigen binding and a second to confer specific effector functions. These two functional domains are encoded by the antibody light chain and antibody heavy chain polypeptides, respectively.
False
9.14 True/False: Naive T cells scan the dendritic cells in the cortical region of the lymph node as they migrate. The initial encounter of T cells with dendritic cells is mediated by interactions between the T-cell receptor and the peptide:MHC complexes on the dendritic cell.
False
9.24 True/False: In a lymph node, nTreg cells are able to inhibit the responses of other T cells in their vicinity. This inhibition is specific, as the nTreg cell and the naive T cell must share the same antigen specificity.
False
In a lymph node, nTreg cells are able to inhibit the responses of other T cells in their vicinity. This inhibition is specific, as the nTreg cell and the naive T cell must share the same antigen specificity.
False
Most eukaryotic genes are encoded in a set of exons that are brought together to form a contiguous protein coding sequence by the process of mRNA splicing. In contrast, immunoglobulin genes use somatic recombination of gene segments and not mRNA splicing to generate the final mRNA that is translated into protein.
False
Naive T cells scan the dendritic cells in the cortical region of the lymph node as they migrate. The initial encounter of T cells with dendritic cells is mediated by interactions between the T-cell receptor and the peptide:MHC complexes on the dendritic cell.
False
T or F: The immune response is a dynamic process that initiates with an antigen-independent response, which becomes more focused and powerful as it develops antigen specificity. Once the adaptive immune system develops, a single type of response is capable of eliminating any type of pathogen.
False
The antibody protein has two functional domains, one for antigen binding and a second to confer specific effector functions. These two functional domains are encoded by the antibody light chain and antibody heavy chain polypeptides, respectively.
False
True or False: Diacylglycerol (DAG) is one of the two products generated when PLC- cleaves the membrane phospholipid, PIP2. This small lipid mediator remains associated with the plasma membrane and induce calcium entry into the cell.
False
True or False: If the donor HLA haplotype matches that of the recipient's, there will be no rejection to the transplanted organ, even without immunosuppression treatment.
False
True or False: Like other antibodies, IgE is mainly found in body fluids.
False
True or False: One form of SCID is DiGeorge syndrome (DGS), in which the thymic epithelium fails to develop normally. Without the proper inducive thymic environment, T cells cannot mature, and both cell-mediated immunity and T-cell-dependent antibody production are impaired. However, if infants diagnosed with DGS receive bone marrow transplants (hematopoietic stem cells) from healthy donors, their T-cell-dependent immunity will be restored.
False
True or False: The acute phase response contributes to infection control by producing molecules that promote pathogen opsonization and complement activation. This response is only induced by direct action of microbial components on hepatocytes in the live.
False
True or False: The antibody protein has two functional domains, one for antigen binding and a second to confer specific effector functions. These two functional domains are encoded by the antibody light chain and antibody heavy chain polypeptides, respectively.
False
True or False: The generation of a complete coding sequence for an antibody heavy chain involves a process of DNA rearrangement that links V, D, and J gene segments together to form the exon that encodes the heavy chain V region. A similar type of DNA rearrangement is also utilized for the simultaneous expression of IgM and IgD antibodies by the same B cell.
False
True/False: All mammalian TLRs have been shown to directly bind to microbial products, leading to TLR signaling.
False
True/False: Alloreactivity refers to the ability of T cells to respond to allelic polymorphisms in MHC molecules when mixed with antigen-presenting cells from a genetically different individual. The T-cell receptors involved in alloreactive responses are recognizing amino acid sequences on foreign MHC molecules and do not interact at all with the peptides bound to these MHC molecules.
False
True/False: B-cell receptors and T-cell receptors share a mechanism for generating diversity, and also share overall structural homology both in their V domains and their C domains. This is because the two proteins have nearly identical functions in the immune responses mediated by their respective cell types.
False
True/False: Chemokines are small chemoattractant molecules made by epithelial cells, tissue macrophages, and endothelial cells in response to infection or injury. They differ slightly in sequence and structure based on the cells that secrete them, but all of them act to recruit both monocytes and neutrophils from the blood.
False
True/False: In a lymph node, nTreg cells are able to inhibit the responses of other T cells in their vicinity. This inhibition is specific, as the nTreg cell and the naive T cell must sharethe same antigen specificity.
False
True/False: In some infectious diseases, antibodies specific for the pathogen are not essential for clearing a primary infection with that pathogen, but are essential in preventing re-infection by the same pathogen. This protective role of pathogen-specific antibodies is not useful for any clinical applications
False
True/False: In the sea urchin, a massive diversification of innate recognition receptors has occurred, resulting in the presence of over 200 TLR genes, over 200 NOD-like receptor genes, and over 200 scavenger receptor genes in the genome of these organisms. These receptors are unlikely to contribute to an enhanced innate immune response in sea urchins, because nearly all of these genes are pseuodgenes.
False
True/False: Like innate sensors of infections (TLRs, NLRs, RLRs), antibodies frequently recognize nucleic acids of pathogenic organisms.
False
True/False: MHC class I surface expression is dependent on an abundant source of pathogen-derived peptides. Thus, in uninfected cells, nearly all of the MHC class I proteins are degraded and never reach the cell surface.
False
True/False: Most eukaryotic genes are encoded in a set of exons that are brought together to form a contiguous protein coding sequence by the process of mRNA splicing. In contrast, immunoglobulin genes use somatic recombination of gene segments and not mRNA splicing to generate the final mRNA that is translated into protein.
False
True/False: Mucosal surfaces and external epithelia are major routes of pathogenic infection. Mucosal surfaces are found in tissues such as the gastrointestinal tract, the reproductive tract and the mouth and respiratory tract. While the mouth and respiratory tract are routes of virus but not bacterial infections, the gastrointestinal tract is the route for bacterial but not virus infections.
False
True/False: Naive T cells scan the dendritic cells in the cortical region of the lymph nodeas they migrate. The initial encounter of T cells with dendritic cells is mediated by interactions between the T-cell receptor and the peptide:MHC complexes on the dendritic cell
False
True/False: Once B cells begin secreting antibodies, they cease dividing and have a life-span of only a few days
False
True/False: Oral inoculation with rotavirus, an intestinal pathogen, induces adaptive immune responses that are initiated in gut-associated lymphoid tissue, such as mesenteric lymph nodes and Peyer's patches. The rotavirus-specific effector T cells that are generated in this response are never found in the circulation, but home directly from the lymphoid tissue to the epithelium without ever leaving the intestinal environment.
False
True/False: Our immune system efficiently kills all categories of microbes that attempt to colonize our bodies.
False
True/False: The C3 convertase amplifies the process of complement activation by generating large amounts of C3b and cleaving large numbers of C5 molecules.
False
True/False: The acute phase response contributes to infection control by producing molecules that promote pathogen opsonization and complement activation. This response is only induced by direct action of microbial components on hepatocytes in the liver.
False
True/False: The antibody protein has two functional domains, one for antigen binding and a second to confer specific effector functions. These two functional domains are encoded by the antibody light chain and antibody heavy chain polypeptides, respectively.
False
True/False: The classical and lectin pathways of complement activation converge at the step of C3 activation. However, the initiating steps of each pathway use protein components and enzymatic mechanisms that share no similarity with each other.
False
True/False: The different classes of immunoglobulins differ in the sequences of their heavy chain constant regions. As a result, each class of antibody has distinct effector functions. Nonetheless, they are all found at about equal concentrations in the serum of healthy individuals.
False
True/False: The generation of a complete coding sequence for an antibody heavy chain involves a lymphocyte-restricted process of DNA rearrangement that links V, D, and J gene segments together to form the exon that encodes the heavy chain V region. A similar type of DNA rearrangement is also utilized for the simultaneous expression of IgM and IgD antibodies by the same B cell.
False
True/False: The invariant chain protein, Ii, has only one function in MHC class II antigen presentation. This function entails Ii protein occupying the peptide-binding site of each newly synthesized class II protein, thereby preventing nascent MHC class II proteins from binding peptides or misfolded proteins in the endoplasmic reticulum.
False
Once B cells begin secreting antibodies, they cease dividing and have a life-span of only a few days.
False NOTE: B cells proliferate in the primary focus for several days, and this constitutes the first phase of the primary humoral immune response. Some of these proliferating B cells differentiate into antibody-synthesizing plasmablasts in the primary focus. Plasmablasts are cells that have begun to secrete antibody, yet are still dividing and express many of the characteristics of activated B cells that allow their interaction with T cells.
In generating a B cell receptor gene, Vkappa segments sometimes join to Clambda segments (True or False)
False, V(kappa) gene segments and C(lambda) are located on separate chromosomes and cannot be brought together during gene rearrangment.
Like variable regions of the heavy chain of the B cell receptor, TCR variable genes are all encoded in three segments.
False, the variable regions of the beta and delta TCR genes are encoded in three segments, analogous to the V, D, and J segments of the Ig heavy-chain variable region. The V(alpha) and V(gamma) regions are encoded in two segments.
The generation of a complete coding sequence for an antibody heavy chain involves a lymphocyte-restricted process of DNA rearrangement that links V, D, and J gene segments together to form the exon that encodes the heavy chain V region. A similar type of DNA rearrangement is also utilized for the simultaneous expression of IgM and IgD antibodies by the same B cell.
False-B cells expressing IgM and IgD have not undergone class switching, which requires irreversible changes to the DNA. Instead, the two antibody types are simultaneously expressed by differential splicing of the same primary mRNA transcript.
The different classes of immunoglobulins differ in the sequences of their heavy chain constant regions. As a result, each class of antibody has distinct effector functions. Nonetheless, they are all found at about equal concentrations in the serum of healthy individuals.
False-The major classes of immunoglobulins do differ in the sequences and structures of their heavy chain constant regions. These differences do determine the effector functions mediated by each class of antibody. In the serum of healthy individuals, different antibody classes are found at vastly different concentrations, from the most abundant (IgG1 at 9 mg/ml) to the least abundant
3.24 True/False: Chemokines are small chemoattractant molecules made by epithelial cells, tissue macrophages, and endothelial cells in response to infection or injury. They differ slightly in sequence and structure based on the cells that secrete them, but all of them act to recruit both monocytes and neutrophils from the blood.
False.
6.11 True/False: The invariant chain protein, Ii, has only one function in MHC class II antigen presentation. This function entails Ii protein occupying the peptide-binding site of each newly synthesized class II protein, thereby preventing nascent MHC class II proteins from binding peptides or misfolded proteins in the endoplasmic reticulum.
False.
6.21 True/False: Alloreactivity refers to the ability of T cells to respond to allelic polymorphisms in MHC molecules when mixed with antigen-presenting cells from a genetically different individual. The T-cell receptors involved in alloreactive responses are recognizing amino acid sequences on foreign MHC molecules and do not interact at all with the peptides bound to these MHC molecules.
False.
True or False: Cytotoxic T-cells that lack expression of perforin are more defective in killing target cells than those that lack granzymes.
False.
2.22 True/False: The C3 convertase amplifies the process of complement activation by generating large amounts of C3b and cleaving large numbers of C5 molecules.
False. C5 convertase = C3 convertase (C4b2a) + C3b
The switch in constant region use from IgM to IgD is mediated by DNA rearrangements
False.The switch in expression from the mu to the delta heavy chain occurs by mRNA splicing, not by DNA rearrangement. Switching to all other heavy-chain classes is mediated by DNA rearrangements.
FasDD
Fas death domain
A few days after virus infection is cleared, the majority of virus-specific CD8 T cells start to die. Death of these T-cells is caused by:
Fas-induced Apoptosis
The kinetics of a typical CD8 T cell response to an acute virus infection in mice is shown in Figure Q11.18. In this example, the virus is cleared by ~day 7 post-infection, and starting at ~day 10 post-infection, the majority of the virus-specific CD8 T cells die. The death of these virus-specific CD8 T cells is caused by:
Fas-induced death or cytokine withdrawal
The kinetics of a typical CD8 T cell response to an acute virus infection in mice is shown in the figure below. In this example, the virus is cleared by ~day 7 post-infection, and starting at ~day 10 post-infection, the majority of the virus-specific CD8 T cells die. The death of these virus-specific CD8 T cells is caused by:
Fas-induced death or cytokine withdrawal
The kinetics of a typical CD8 T cell response to an acute virus infection in mice is shown in the figure below. In this example, the virus is cleared by ~day 7 post-infection, and starting at ~day 10 post-infection, the majority of the virus-specific CD8 T cells die. The death of these virus-specific CD8 T cells is caused by: IMAGE ON PHONE
Fas-induced death or cytokine withdrawal NOTE: Yes. When an infection is effectively repelled by the adaptive immune system, most effector T cells undergo 'death by neglect,' removing themselves by apoptosis. The resulting 'clonal contraction' of effector T cells appears to be due both to the loss of pro-survival cytokines that are produced by antigenic stimulation, such as IL-2, and to the loss of expression of receptors for these cytokines. While many effector T cells die from the loss of survival signals and the activation of the Bim-mediated intrinsic pathway of apoptosis, effector T cell death can also occur via the extrinsic pathway of apoptosis that is activated by signaling via members of the TNF receptor superfamily, particularly Fas (CD95).
The kinetics of a typical CD8 T cell response to an acute virus infection in mice is shown in the figure below. In this example, the virus is cleared by ~day 7 post-infection, and starting at ~day 10 post-infection, the majority of the virus-specific CD8 T cells die. The death of these virus-specific CD8 T cells is caused by:
Fas-induced death or cytokine withdrawal NOTE: Yes. When an infection is effectively repelled by the adaptive immune system, most effector T cells undergo 'death by neglect,' removing themselves by apoptosis. The resulting 'clonal contraction' of effector T cells appears to be due both to the loss of pro-survival cytokines that are produced by antigenic stimulation, such as IL-2, and to the loss of expression of receptors for these cytokines. While many effector T cells die from the loss of survival signals and the activation of the Bim-mediated intrinsic pathway of apoptosis, effector T cell death can also occur via the extrinsic pathway of apoptosis that is activated by signaling via members of the TNF receptor superfamily, particularly Fas (CD95).
IgG4
Fc region does not activate complement -uniquely can exchange one H+L chain with other IgG4 -Most IgG4 molecules in circulation have two different antigen-binding sites- functionally monovalent -anti-inflammatory- only effector function is neutralization -increase level in allergic individuals- reduce severity of rxn
Some individuals with repetitive exposure to high doses of Schistosoma mansoni develop resistance to re-infection by this helminthic parasite. In contrast, other individuals remain highly susceptible. Population studies showed that resistant individuals had increased numbers of circulating eosinophils in their blood compared to susceptible individuals, and further, that these eosinophils had increased levels of:
FcRII, the low affinity IgE receptor
Peptide/MHC and TCR binding
First signal for T cell activation Interaction between peptide/MHC class II complex and Vα + Vβ of the TCR
How many peptides can MHC class 1 groove bind?
Fit 8-11 amino acids in length Can bind to and present a large number of different peptides
Binding of conformation epitopes of ___________________ takes place over an ____________________________.
Folded proteins; extended surface areas
False
Following TCR or BCR signaling, the most important events downstream of the activation of ZAP-70 or SYK, respectively, are the activation of transcription factors leading to new gene expression.
True
Following TCR or BCR signaling, the most important events downstream of the activation of ZAP-70 or SYK, respectively, are the activation of transcription factors leading to new gene expression.
IPEX syndrome is a genetic disease due to mutations that disrupt the function of an important transcription factor expressed in subset of CD4 T cells. Individuals with this disease generally begin showing symptoms shortly after birth. This disease is often fatal. One of the most prominent symptoms of IPEX is severe gastrointestinal inflammation accompanied by severe diarrhea. This transcription factor is most likely:
FoxP3
In all cells (except B cells) Ig genes are in a _______________ form that ____________ be expressed
Fragmented; CANNOT
Macrophages were isolated from the spleen or the intestinal lamina propria, and stimulated in vitro with the indicated TLR ligands. Twenty-four hours later, the culture supernatants were tested for the amounts of IL-10, the IL-12p40 subunit (shared between IL-12 and IL-23), and for IL-12, and the results are shown in Figure Q12.9.
Function as anti-inflammatory cells
Gut-associated lymphoid tissue
GALT; those lymphoid tissues associated with the gut
Effector caspases are activated downstream of both extrinsic and intrinsic pathways of apoptosis. Consequently, cells lacking one or more of these enzymes show defects in apoptosis. An alternative means of eliminating the activity of an effector caspase would be to:
Generate a form of the pro-caspase with a mutation in the initiator caspase cleavage site
Effector caspases are activated downstream of both extrinsic and intrinsic pathways of apoptosis. Consequently, cells lacking one or more of these enzymes show defects in apoptosis. An alternative means of eliminating the activity of an effector caspase would be to:
Generate a form of the pro-caspase with a mutation in the initiator caspase cleavage site. NOTE: Yes. If this cleavage site is mutated, the caspase could not be activated. Like many other proteases, caspases are synthesized as inactive pro-enzymes. Inactive caspases are called pro-caspases. In pro-caspases. the catalytic domain is inhibited by an extra domain of the protein called the pro-domain. Pro-caspases are activated by other caspases that cleave the protein to release the inhibitory pro-domain. There are two classes of caspases involved in the apoptotic pathway: initiator caspases and effector caspases. Initiator caspases promote apoptosis by cleaving the pro-domain of inactive caspases to activate them. Effector caspases, once activated, then initiate the cellular changes associated with apoptosis. The extrinsic pathway uses two related initiator caspases, caspase 8 and caspase 10, whereas the intrinsic pathway uses caspase 9 as its iniator. Both pathways then merge and use caspases 3, 6, and 7 as effector caspases. To induce apoptosis, effector caspases cleave a variety of proteins that are critical for cellular integrity and also activate enzymes that promote DNA fragmentation and death of the cell.
Effector caspases are activated downstream of both extrinsic and intrinsic pathways of apoptosis. Consequently, cells lacking one or more of these enzymes show defects in apoptosis. An alternative means of eliminating the activity of an effector caspase would be to:
Generate a form of the pro-caspase with a mutation in the initiator caspase cleavage site. NOTE: Yes. If this cleavage site is mutated, the caspase could not be activated.
Following a primary HIV infection, our immune system:
Generates a response that efficiently controls viral replication.
In B cells _________________ gene segments are rearranged into ________________ genes.
Germ-line DNA; functional
Antibodies are
Glycoproteins
The antibody binds to an antigenic determinant or epitope, commonly:
Glycoproteins, polysaccharides, glycolipids, and proteoglycans
Short answer: Cytotoxic granules released from cytotoxic T cells contain proteins that enter target cells and induce apoptosis. Do any of the mechanisms of apoptosis induction by cytotoxic effector T cells rely on the protein APAF-1? If so, which pathway?
Granzymes made by cytotoxic effector T cells cleave bid, which releases cytochrome c, and activates APAF-1, which activates caspases.
what gene segments encode the V region of an antibody?
H chain (c14) kL chain(c2), IL chain(c22) gene loci
The first drug treatment for HIV licensed in the US was zidovudine (AZT), a reverse transcriptase inhibitor. However, AZT has now been completely replaced by HAART as the recommended treatment for HIV-infected individuals. The use of HAART, rather than AZT, is preferred because:
HAART is a combination therapy that reduces the possibility of viral escape mutants
Specialize cell type involved in the entry of lymphocytes into lymph nodes
HEVs (High endothelial venules)
Cells within one person expresses up to how many HLA class II molecules
HLA DP, DQ, and DR molecules are co-dominantly expressed in cells expressing HLA class II molecules
What are the three independent genes encode for MHC class I
HLA-A HLA-B HLA-C
MHC Class II region is made up of what 3 gene sets
HLA-DP HLA-DQ HLA-DR Each has an α chain and a β chain (eg. HLA-DPA encodes its α chain and HLA-DPB gene encodes β chain)
"MHC ______" refers to the complete set of HLA alleles that a person possesses on chromosome 6
Haplotype
Mature T lymphocyte homing
Have a down-regulation of CD62L, but have an upregulation of CD44 and CD49d/CD29 Lymphocytes leave lymph nodes and move into tissues and skin
Neutralizing antibodies are effective at preventing infection or toxicity mediated by pathogens or their toxic products. In fact, nearly all vaccines currently in use function by eliciting neutralizing antibodies. One example is the tetanus vaccine, in which neutralizing antibodies are generated against an inactivated form of the tetanus toxin (i.e., the tetanus toxoid). The most important feature of a neutralizing antibody is:
Having high affinity for the antigen
Somatic hypermutation of V gene segments involves ______ chain immunoglobulin V genes
Heavy
________________ constant regions define five main isotypes of antibodies: Ig___, Ig___, Ig___, Ig___, and Ig____.
Heavy- chain; A;D;E;G;M
The T-cell receptor is a:
Heterodimer
CTLs mediate a powerful and lethal immune response to infected host cells. Which of the following steps is NOT involved with CTL activation and function?
Histamine is released from cytoplasmic granules recruiting macrophages to the site of infection
CTLs mediate a powerful and lethal immune response to infected host cells. Which of the following steps is NOT involved with CTL activation and function?
Histamine is released from cytoplasmic granules recruiting macrophages to the site of infection.
Which human chromosome contains MHC
Human chromosome 6
HLA is
Human leukocyte antigen
Salmonella typhimurium is a Gram-negative bacterial pathogen that infects its host via the gastrointestinal (GI) tract. Early in infection, the bacteria enter and replicate in gut epithelial cells, where the infection provokes a type 3 response, including the development of TH17 cells, in the GI tract. However, this type 3 response in the GI tract does not eradicate the pathogen, as S. typhimurium has evolved strategies to evade the TH17 response and to spread systemically by infecting and replicating in macrophages. Therefore, a second phase of the immune response is required to completely eliminate the pathogen from the body, as has been demonstrated in mouse models of S. typhimurium infection. These experiments in mouse models likely showed that:
IFN- is required to clear S. typhimurium from the body.
Toxoplasma gondii is a single-celled parasitic protozoan that infects and replicates in macrophages. It is common in the environment, and is transmitted to humans by the ingestion of undercooked meat or by accidental ingestion of the parasite's oocytes from contaminated water or cat litter. Infected individuals with healthy immune systems are generally asymptomatic, and rapidly clear the infection. However, in AIDS patients, infections of Toxoplasma gondii can lead to severe disease and even death. To investigate the immune mechanisms important in controlling Toxoplasma gondii, a mouse model of the infection was developed. Mice were infected with the protozoa at a dose where the majority of the mice survive the infection, and at the same time, were injected with a neutralizing antibody to a cytokine made by T cells (anti-'X' IgG). A second group of mice received the protozoa plus a control IgG antibody, as shown in the figure. Based on this information, the most likely candidate for cytokine 'X' is:
IFN-gamma
Toxoplasma gondii is a single-celled parasitic protozoan that infects and replicates in macrophages. It is common in the environment, and is transmitted to humans by the ingestion of undercooked meat or by accidental ingestion of the parasite's oocytes from contaminated water or cat litter. Infected individuals with healthy immune systems are generally asymptomatic, and rapidly clear the infection. However, in AIDS patients, infections of Toxoplasma gondii can lead to severe disease and even death. To investigate the immune mechanisms important in controlling Toxoplasma gondii, a mouse model of the infection was developed. Mice were infected with the protozoa at a dose where the majority of the mice survive the infection, and at the same time, were injected with a neutralizing antibody to a cytokine made by T cells (anti-'X' IgG). A second group of mice received the protozoa plus a control IgG antibody, as shown in the figure. Based on this information, the most likely candidate for cytokine 'X' is: PICTURE ON PHONE
IFN-gamma
Salmonella typhimurium is a Gram-negative bacterial pathogen that infects its host via the gastrointestinal (GI) tract. Early in infection, the bacteria enter and replicate in gut epithelial cells, where the infection induces the development of TH17 cells in the GI tract. However, this response does not eradicate the pathogen, as S. typhimurium has evolved strategies to evade the TH17 response and to spread systemically by infecting and replicating in macrophages. Therefore, a second phase of the immune response is required to completely eliminate the pathogen from the body, as has been demonstrated in mouse models of S. typhimurium infection. These experiments in mouse models likely showed that
IFN-gamma is required to clear S. typhimurium from the body
Salmonella typhimurium is a Gram-negative bacterial pathogen that infects its host via the gastrointestinal (GI) tract. Early in infection, the bacteria enter and replicate in gut epithelial cells, where the infection induces the development of TH17 cells in the GI tract. However, this response does not eradicate the pathogen, as S. typhimurium has evolved strategies to evade the TH17 response and to spread systemically by infecting and replicating in macrophages. Therefore, a second phase of the immune response is required to completely eliminate the pathogen from the body, as has been demonstrated in mouse models of S. typhimurium infection. These experiments in mouse models likely showed that:
IFN-gamma is required to clear S. typhimurium from the body.
TH1 - macrophage-activating effector molecules
IFN-gamma, GM-CSF, TNF-alpha, CD40 ligand, Fas ligand
In the case of intracellular bacteria or protozoan infections, tissue-resident dendritic cells and macrophages stimulate ILC cells to produce a cytokine:
IFN-y
Toxoplasma gondii is a single-celled parasitic protozoan that infects and replicates in macrophages. It is common in the environment, and is transmitted to humans by the ingestion of undercooked meat or by accidental ingestion of the parasite's oocytes from contaminated water or cat litter. Infected individuals with healthy immune systems are generally asymptomatic, and rapidly clear the infection. However, in AIDS patients, infections of Toxoplasma gondii can lead to severe disease and even death. To investigate the immune mechanisms important in controlling Toxoplasma gondii, a mouse model of the infection was developed. Mice were infected with the protozoa at a dose where the majority of the mice survive the infection, and at the same time, were injected with a neutralizing antibody to a cytokine made by T cells (anti-'X' IgG). A second group of mice received the protozoa plus a control IgG antibody, as shown in Figure Q11.10.
IFN-y
While innate immune responses to all types of infections induce local inflammatory responses due to activation of blood vessel endothelial cells, some components of the innate response differ depending on the nature of the pathogen. In the case of intracellular bacterial or protozoan infections, tissue-resident dendritic cells and macrophages produce a cytokine that stimulates ILC cells to produce:
IFN-y
While inducing apoptosis in target cells is the main way in which CD8 cytotoxic T cells eliminate infection, they also release the cytokines ____________, which contribute to host defense in several ways
IFN-γ, TNF-α, and LT-α
When DC signals TGF-Beta and IL-6 what signals can not be produced
IL-12 IFN-gamma and IL-4
Following an acute virus infection in which the host clears the virus by approximately one week post-infection, a population of virus-specific memory CD8 T cells is maintained and can be detected for months to years post-infection. In mice with a knockout of a single cytokine, however, virus-specific memory CD8 T cells cannot be maintained and disappear over time as shown in the figure below. Base on this information, the most likely identity of the cytokine that is missing in these knockout mice is _____________.
IL-15
Following an acute virus infection in which the host clears the virus by approximately one week post-infection, a population of virus-specific memory CD8 T cells is maintained and can be detected for months to years post-infection. In mice with a knockout of a single cytokine, virus-specific memory CD8 T cells cannot be maintained, and disappear over time as shown in Figure Q11.23. The most likely identity of the cytokine that is missing in these knockout mice is:
IL-15
Following an acute virus infection in which the host clears the virus by approximately one week post-infection, a population of virus-specific memory CD8 T cells is maintained and can be detected for months to years post-infection. In mice with a knockout of a single cytokine, however, virus-specific memory CD8 T cells cannot be maintained and disappear over time as shown in the figure below. Base on this information, the most likely identity of the cytokine that is missing in these knockout mice is _____________.
IL-15 NOTE: Yes. The homeostatic mechanisms governing the survival of memory T cells differ from those for naive T cells. Memory T cells divide more frequently than naive T cells, and their expansion is controlled by a shift in the balance between proliferation and cell death. The survival of memory T cells requires signaling by the receptors for the cytokines IL-7 and IL-15. IL-7 is required for the survival of both CD4 and CD8 memory T cells. In addition, IL-15 is critical for the long-term survival and proliferation of CD8 memory T cells under normal conditions. In the absence of IL-15 (or the IL-15R), memory CD8 T cells slowly disappear from the population.
Following an acute virus infection in which the host clears the virus by approximately one week post-infection, a population of virus-specific memory CD8 T cells is maintained and can be detected for months to years post-infection. In mice with a knockout of a single cytokine, however, virus-specific memory CD8 T cells cannot be maintained and disappear over time as shown in the figure below. Base on this information, the most likely identity of the cytokine that is missing in these knockout mice is _____________. IMAGE ON PHONE
IL-15 NOTE: Yes. The homeostatic mechanisms governing the survival of memory T cells differ from those for naive T cells. Memory T cells divide more frequently than naive T cells, and their expansion is controlled by a shift in the balance between proliferation and cell death. The survival of memory T cells requires signaling by the receptors for the cytokines IL-7 and IL-15. IL-7 is required for the survival of both CD4 and CD8 memory T cells. In addition, IL-15 is critical for the long-term survival and proliferation of CD8 memory T cells under normal conditions. In the absence of IL-15 (or the IL-15R), memory CD8 T cells slowly disappear from the population.
IL-2 receptor has a much higher affinity for
IL-2
the initial encounter of a niave T cells with specific antigen in the presence of co-stimulatory signal induced synthesis of
IL-2 along with the IL-2 receptor
T-cell activation requires antigen being displayed in the context of an APC and interaction between co-stimulatory molecules on the APC and the T cell. In addition to these two signals, T-cell activity is often influenced by cytokines. Which of the following is an example of how cytokines can influence T-cell activity in the presence of MHC presentation and co-stimulatory ligand interaction?
IL-2 triggers T-cell proliferation.
Which cytokine is produce by TH2 CD4 T-cells, but not TH1 CD4 T-cells?
IL-4
if DC produced IL-12 and IFN gamma and IL-4 which signal can it not produced
IL-6 and TGF-beta
Which cytokine is important for maintaining T-cell memory?
IL-7
Which autoimmune disease is cause by mutations in a single gene?
IPEX syndrome Single Gene: Missense mutation in FoxP3 ------- Also caused by defects in Treg cells and defects in CD25
BTK
ITK
MHCg
If a bone marrw transplant from a MHCFxG mouse was given cell repsonse induced by which of the following APC types? to an MHCG recipient; there would be a large secondary T
True
If an antigen (cooties A) is injected into the thymus of fetal mice, this will induce a large increase in peripheral T cells able to response to APC's presenting MHC: Cooties A peptides
You wish to determine the frequency of class-I restricted T cells in an HIV-infected individual that are specific for a peptide generated from gp120 (a component of the virus). Assume that you know the HLA type of the patient. What method would you use and how would perform the analysis? Be as specific as you can.
If the HLA (human MHC) type is known, MHC tetramers bound to the peptide generated from gp120 and labeled with a fl uorescent tag can be used to specifically label all of the CD8 T cells in a sample that has T-cell receptors capable of recognizing this complex of HLA and peptide.
5 immunoglobulin classes
IgA, IgD, IgE, IgG, IgM -Different C regions have different effector function
Reovirus is an enteric virus that infects mice by adhering to intestinal M cells and then using M cell transport to enter Peyer's patches. Mice that were orally inoculated with reovirus cleared the primary infection, and upon secondary challenge 21 days later, had no detectable virus in their Peyer's patches. In contrast, naive controls that did not receive the primary inoculation had >103 PFU of virus/mg of tissue following oral challenge with virus. The protective response induced by the primary oral inoculation would also be eliminated in:
IgA-deficient mice
Allergic reactions are predominantly associated with ______.
IgE
IL-4 and 5
IgE production
Most abundant antibody in the internal fluids
IgG
The most abundant antibody in blood is:
IgG
Different classes (isoptypes) of antibodies
IgG (y), IgM(u), IgD(d), IgA(a), IgE(e) - all have significant functional differences (H chain and C region)
Individuals with a genetic polymorphism in the Fc receptor, FcRIIa (CD32), have an increased susceptibility to bacterial meningitis (inflammation of the membranes (meninges) surrounding the brain and spinal cord) caused by the encapsulated bacterium, Neisseria meningitidis. This polymorphism reduces the efficiency with which the phagocytes expressing FcRIIa bind to the constant region of this receptor's target antibody. The reason this FcRIIa-dependent response it the major form of protection against Neisseria meningitidis is because:
IgG antibodies are the major isotype able to diffuse into tissues.
The hinge region present in _____, ______, _____ but NOT in _____, ______.
IgG, IgA, IgD; IgE, IgM
_______ is the first antibody produced by B cells
IgM
Mature B cells express
Igs (B cell receptor or BCR)
A robust response by the child's T cells.
In a mixed lymphocyte reaction, T cells from individual A make a robust response to antigen-presenting-cells from individual B, as long as the two individuals express different alleles of molecules. Up to 10% of the T cells from individual A may contribute to this response. If one performed this test using responder T cells from a child and antigen-presenting cells from one parent, the result would be
Do CD4 and CD8 form multimers?
In contrast to CD8, CD4 is not thought to dimerize.
What is the difference between the epitopes recognized by BCRs vs TCRs?
In contrast, the epitopes recognized by T-cell receptors need not lie on the surface of the molecule, because the T-cell receptor recognizes not the antigenic protein itself but a peptide fragment of the protein.
True
In signal transduction, binding of antigens phosphorylate the tyrosine residues (ITAMS)
Where would you MOST likely find a TLR that recognizes RNA?
In the endosome/lysosome
The Bcl-2 protein was first identified based on its overexpression in a subset of B cell lymphomas, where it was shown to promote the resistance of the tumor cells to apoptosis. Subcellular localization experiments would show that Bcl-2 is present:
In the mitochondria where it blocks cytochrome c release
The Bcl-2 protein was first identified based on its overexpression in a subset of B cell lymphomas, where it was shown to promote the resistance of the tumor cells to apoptosis. Subcellular localization experiments would show that Bcl-2 is present:
In the mitochondria where it blocks cytochrome c release. NOTE: Yes. Anti-apoptotic Bcl-2 family proteins function by binding to the mitochondrial membrane to block the release of cytochrome c. The anti-apoptotic Bcl-2 family members are induced by stimuli that promote cell survival. The best known of the anti-apoptotic proteins is Bcl-2 itself. The Bcl2 gene was first identified as an oncogene in a B-cell lymphoma, and its overexpression in tumors makes the cells more resistant to apoptotic stimuli and thus more likely to progress to an invasive cancer. Other members of the inhibitory family include Bcl-XL and Bcl-W.
The Bcl-2 protein was first identified based on its over-expression in a subset of B cell lymphomas, where it was shown to promote the resistance of the tumor cells to apoptosis. Sub-cellular localization experiments would show that Bcl-2 is present:
In the mitochondria where it blocks cytochrome c release. NOTE: Yes. Anti-apoptotic Bcl-2 family proteins function by binding to the mitochondrial membrane to block the release of cytochrome c.
Bone marrow
In which compartment does central tolerance occur in developing B cells?
Which is an example of an immune escape mechanism used by some tumor cells?
Increased expression of PD-L1
Infections of intracellular pathogens (e.g., mycobacteria, listeria, toxoplasma, viruses, etc.) cause a rise in the numbers of monocytes in the blood, a symptom known as monocytosis. In the cases of these infections, monocytosis is likely caused by:
Increased production of monocytes in the bone marrow induced by TH1 cytokines
During inflammatory response vascular permeability:
Increases
The 'hygiene hypothesis' has been proposed as an explanation for the rapid increase in allergies and asthma incidence in Western countries over the last half century. One line of evidence supporting this hypothesis is:
Individuals of African descent have higher incidence of atopic disease when living in Western countries
Allergic responses to inhaled antigens occur when an individual is first sensitized to the antigen (i.e., the allergen), inducing an immune response, and then has a subsequent exposure to the same antigen. The sensitization phase is characterized by:
Induction of a CD4 T-cell type II immune response
IL-4 TGF-B = A and b
Inhibition of a TH1 response occurs via which cytokines
The co-stimulatory signaling step does what?
Initiates a cascade of INTRAcellular and nuclear events that measurable change the behavior of responding T cells
Strong adhesion/arrest
Integrins on leukocytes bind endothelial ICAMs
MHC Class II and CD4 binding
Interaction between invariable region of MHC class II and CD4 enhances ability of T cell to respond to antigen -Clusters CD4 with TCR to form signaling complex
Rolling
Interaction of endothelial selectins with ligands on leukocytes
Double positive T-cell
Interaction with Thymic Epithelial cells and medullary dendritic cells. Both negative and positive selection occurs in this stage. Double positive T-cell receptor includes Pre T-cell receptor- α & βchain, CD3, Zeta, CD4+ and CD8+
Unlike B lymphocytes, T lymphocytes do not generate a secreted form of their antigen receptor after they are activated and proliferate. This is because the effector functions of T cells are restricted to:
Interactions with other cells, such as virus-infected cells or other immune cells
Unlike B lymphocytes, T lymphocytes do not generate a secreted form of their antigen receptor after they are activated and proliferate. This is because the effector functions of T cells are restricted to:
Interactions with other cells, such as virus-infected cells or other immune cells NOTE: The effector functions of T cells are all restricted to interactions with other host cells, and not with the pathogen directly. These effector functions include killing of cells infected with intracellular pathogens (cytotoxic T cells), activation of B cells and macrophages (helper T cells), and suppressing the activity of other lymphocytes (regulatory T cells).
CD28
Interacts with B7 molecules on B cell and APCs Acts as co-stimulatory signal for T cell activation Required in addition to MHC interaction to activate T cell
CD152
Interacts with B7 molecules to provide a negative signal to activated T cell
CD2
Interacts with CD58 on many different cells
Controls development and differentiation of T cells
Interleukin 2(IL2) is a cytokine that
Mice lacking IL-15 or the IL-15R chain have substantially reduced numbers of type b IELs, including both : and : T-cell receptor-positive subsets. Normal numbers of type b IELs can be restored in il15-/- mice by cell-type specific expression of IL-15 in:
Intestinal epithelial cells
The mechanism of cross-presentation by dendritic cells is an essential pathway for generating CD8 T cell responses to some intracellular pathogens. If this pathway did not exist, we would be highly susceptible to:
Intracellular pathogens that do not infect and replicate in dendritic cells
The mechanism of cross-presentation by dendritic cells is an essential pathway for generating CD8 T cell responses to some intracellular pathogens. If this pathway did not exist, we would be highly susceptible to:
Intracellular pathogens that do not infect and replicate in dendritic cells
The mechanism of cross-presentation by dendritic cells is an essential pathway for generating CD8 T cell responses to some intracellular pathogens. If this pathway did not exist, we would be highly susceptible to:
Intracellular pathogens that do not infect and replicate in dendritic cells NOTE: Correct. Some pathogens may infect somatic cells but not directly infect phagocytes such as dendritic cells. In this case, dendritic cells must acquire antigens from exogenous sources in order to process and present antigens to T cells. For example, to eliminate a virus that infects only epithelial cells, activation of CD8 T cells will require that dendritic cells load MHC class I molecules with peptides derived from viral proteins taken up from virally infected cells. This exogenous pathway of loading MHC class I molecules is called cross-presentation, and is carried out very efficiently by some specialized types of dendritic cells.
The antigen receptor on a T cell recognizes a degraded fragment of a protein (i.e., a peptide) bound to a specialized cell surface peptide-binding receptor called an MHC molecule. One key aspect of this system is that the peptides displayed on MHC molecules can be derived from intracellular proteins. This mode of antigen recognition is particularly important in allowing the adaptive immune response to detect infections by:
Intracellular pathogens, such as viruses and some protozoa
The antigen receptor on a T cell recognizes a degraded fragment of a protein (i.e., a peptide) bound to a specialized cell surface peptide-binding receptor called an MHC molecule. One key aspect of this system is that the peptides displayed on MHC molecules can be derived from intracellular proteins. This mode of antigen recognition is particularly important in allowing the adaptive immune response to detect infections by:
Intracellular pathogens, such as viruses and some protozoa NOTE: Intracellular pathogens, such as viruses and some protozoa, cannot be eliminated by antibody-based mechanisms once they have begun replicating in host cells. In order to detect these intracellular pathogens, a system that surveils the intracellular status of host cells is needed. T cells fulfill this function by recognizing peptides on cell surface MHC receptors. The MHC receptors can pick up pathogen-derived peptides from within the infected cell and display them on the cell surface for T cells to 'see.'
Antibodies with other effector mechanisms are produced by
Isotype switching or class switching
Secondary (or peripheral) lymphoid organs are sites for initiation of adaptive immune responses. Given the rarity of lymphocytes specific for any given antigen and the vast amount of body tissue that must be protected, the system of secondary lymphoid tissues is efficient because:
It concentrates antigens in centralized locations for rare lymphocytes to encounter
Secondary (or peripheral) lymphoid organs are sites for initiation of adaptive immune responses. Given the rarity of lymphocytes specific for any given antigen and the vast amount of body tissue that must be protected, the system of secondary lymphoid tissues is efficient because:
It concentrates antigens in centralized locations for rare lymphocytes to encounter NOTE: Yes. This allows the naive T and B lymphocytes to spend their time traveling from lymph node to lymph node looking for their antigen, making the encounters between lymphocytes and antigens much more efficient. The system of secondary lymphoid organs is important in promoting interactions between rare antigen-specific lymphocytes and their antigens. Instead of requiring each naive lymphocyte to traffic into every nook and cranny of the body, the pathogens and their products are brought to centralized locations and concentrated there.
The adaptive immune system uses multiple strategies to generate diversity in our ability to mount responses to a wide array of infectious microorganisms. These strategies include the generation of diverse repertoires of B-cell and T-cell antigen receptors, as well as polymorphism of MHC genes. The polymorphism of MHC genes differs from the diversity of lymphocyte antigen receptors in that:
It creates diversity between individuals in the population rather than within a single individual
The adaptive immune system uses multiple strategies to generate diversity in our ability to mount responses to a wide array of infectious microorganisms. These strategies include the generation of diverse repertoires of B-cell and T-cell antigen receptors, as well as polymorphism of MHC genes. The polymorphism of MHC genes differs from the diversity of lymphocyte antigen receptors in that:
It creates diversity between individuals in the population rather than within a single individual.
The adaptive immune system uses multiple strategies to generate diversity in our ability to mount responses to a wide array of infectious microorganisms. These strategies include the generation of diverse repertoires of B-cell and T-cell antigen receptors, as well as polymorphism of MHC genes. The polymorphism of MHC genes differs from the diversity of lymphocyte antigen receptors in that:
It creates diversity between individuals in the population rather than within a single individual. NOTE: Correct. For several MHC class I and class II genes, there are more than 1000 alleles in the human population, far more than the number of alleles for other genes found within the MHC region. This polymorphism results in broad diversity of MHC protein expression between individuals in the population. In contrast, a single individual may express a dozen or so different MHC proteins (MHC class I and MHC class II), but all of the cells within the individual will express the same set of these MHC proteins.
Describe a multivalent antigen with a repeated epitope.
It is a multilobed pathogen that has a repeated epitope. So an antibody can bind the same pathogen multiple times.
Explain the route when antigens enter the gastrointestinal or respiratory tract
It lodges in the MALT and BALT where is will interact with macrophages and lymphocytes. Antibodies synthesized in these organs are deposited in the local tissue Lymphocytes entering the efferent lymphatics are carried through the thoracic duct to the circulation and are thereby redistributed to various tissue
Once expressed on the surface of host cells, an MHC protein remains stably associated with its bound peptide for several days. This highly stable peptide binding behavior is important because:
It prevents peptide exchanges on the cell surface, ensuring that peptide:MHC complexes are reliable indicators of the proteins present inside that host cell.
Once expressed on the surface of host cells, an MHC protein remains stably associated with its bound peptide for several days. This highly stable peptide binding behavior is important because:
It prevents peptide exchanges on the cell surface, ensuring that peptide:MHC complexes are reliable indicators of the proteins present inside that host cell. NOTE: Correct. If MHC molecules did not bind peptides stably, peptide exchange could occur on molecules present at the cell surface. Should this happen, the surface MHC molecules would no longer be providing the T cells with an indicator of the internal proteins present in the host cell, but instead, would be displaying peptides from extracellular proteins in the environment.
What are an alternative type of T cell receptor?
It was soon discovered that a minority population of T cells bore a distinct type of T-cell receptor made up of γ:δ heterodimers rather than α:β heterodimers. Unlike α:β T cells, γ:δ T cells do not generally recognize antigen as peptides presented by MHC molecules. γ:δ T-cell receptors seem to recognize their target antigens directly and thus probably are able to recognize and respond rapidly to molecules expressed by many different cell types. γ:δ T cells play an intermediate, or transitional, role between wholly innate and fully adaptive immune responses. many of the ligands seen by γ:δ T cells are induced by cellular stress or damage
J Segmenet
Juncture
Phosphorylate proteins
Kinases function in which of the following manners
Arms of Y
L chains paired with N-terminal pair of H chain - covalently linked by a disulfide bond
effector T cells express higher levels of LFA-1 and CD2 than do naive T cells but lose cell-surface ______ and does what
L-selectin and stops to recirculate through lymph node
Integrin dependent T-cell adhesion to antigen-presenting cells increases substantially following TCR stimulation. This increased integrin-dependent adhesion is mediated in part by:
LFA-1 conversion to a high affinity binding state
Infection of mice with the bacterial pathogen, Citrobacter rodentium, elicits a protective immune response in the gastrointestinal tract. This protective response is characterized by two sequential waves of IL-22 production, both induced by IL-23. The early wave of IL-22 production (<day 8 post-infection) is likely produced by:
Lamina propria ILC3 cells stimulated by dendritic cell-produced IL-23
IgG appears ______ in the primary immune response
Late
Lyn , Blk or Fyn
Lck
Mycobacterium leprae, the causative agent of leprosy in humans, is an intracellular pathogen that resides in the phagosome of macrophages. Leprosy presents in two main clinical manifestations. Tuberculoid leprosy results in the formation of granulomas and a cell-mediated immune response while lepromatous leprosy results in the production of high levels of IgG (hypergammaglobulinemia). If TH2 is produced in high levels during an leprae infection, which type of leprosy would result?
Lepromatous leprosy
Defects in LFA-1 gene lead to:
Leukocyte adhesion deficiency (LAD)
T cells are frequently at fault for causing damage in autoimmune disorders and in transplant rejection. As an immunologist, your dream is to discover a method for decreasing T-cell response to self-antigens. Which of the following would be the BEST target for your research?
Ligands that block the binding of one co-stimulatory molecule
_________ epitopes from proteins or carbohydrates can be bound within ________ or ____________.
Linear; clefts or grooves
Endothelial cell activation
Local secretion of pro-inflammatory cytokines
Match the step in neutrophil recruitment into inflamed tissues with the key effectors involved: endothelial cell activation rolling neutrophil activation strong adhesion/arrest diapedesis
Local secretion of pro-inflammatory cytokines Interaction of endothelial selectins with ligands on leukocytes Chemokine signaling Integrins on leukocytes bind endothelial ICAMs Endothelial and neutrophil CD31 (PECAM)
order of antibodies
M (D) G E A
Mucosa-associated lymphoid tissue
MALT; mucosal secondary lymphoid organs
Short answer: Chimeric mice are generated where approximately 50% of the cells in the animal are genetically MHC class I-deficient. The other 50% are deficient for the herpes virus receptor, HVEM, but do express MHC class I molecules. When these mice are infected with herpesvirus by intraperitoneal injection, a robust virus-specific CD8 T cell response is detected at day 7 post-infection in the spleens of the infected mice. Which cells are presenting herpesvirus antigens to prime the CD8 T cell response, and how did they acquire the viral antigens?
MHC class 1 positive dendritic cells prime the CD8 T cell response. They acquired the viral antigens by taking up virus particles by phagocytosis or by transfer from other dendritic cells.
CD8 positive cells recognize their antigen presented by which molecule?
MHC class I
____________ molecules present peptides from pathogens, commonly viruses, to CD8 T cells, which are specialized to kill any cell that they specifically recognize.
MHC class I
Co-dominant Expression
MHC class I and class II molecules are co-dominantly expressed Proteins transcribed from both maternal and paternal chromosomes A single individual expresses the same MHC class I molecule on all cells Differs from B and T cell receptors
Naive CD 8 T cells recognize ______ and differentiate into _____ and do what
MHC class I molecules cytotoxic effector T cells recognize and kill infected cells
Which cells express MHC class I?
MHC class I molecules present peptides from pathogens, commonly viruses, to CD8 cytotoxic T cells, which are specialized to kill any cell that they specifically recognize. Because viruses can infect any nucleated cell, almost all such cells express MHC class I molecules, although the level of constitutive expression varies from one cell type to the next Nonnucleated cells, such as mammalian red blood cells, express little or no MHC class I, and thus the interior of red blood cells is a site in which an infection can go undetected by cytotoxic T cells. Because red blood cells cannot support viral replication, this is of no great consequence for viral infection, but it might be the absence of MHC class I that allows the Plasmodium parasites that cause malaria to live in this privileged site.
naive CD 4 T cells recognize and differentiate into what
MHC class II molecules helper T cells and regulatory T cells
Which cells express MHC class II?
MHC class II molecules are normally found on dendritic cells, B lymphocytes, and macrophages—antigen-presenting cells that participate in immune responses—but not on other tissue cells
Region between MHC class I and class II contains genes that:
MHC class III genes that encode serum complement components (C2, C4 and factor B). 2 cytokines (tumor necrosis factor-α and -β. 2 heat shock proteins (hsp 70-1 and 70-2) 21-hydroxylase (enzyme used in steroid metabolism) Additional MHC class I genes (HLA-E, F & G), that are much less polymorphic than those discussed above and of mostly unknown function.
Ligands of NKG2d
MHC class Ib genes (MIC-1/B, RAET1)
True
MHC complexes must be able to persist on the cell surfaces
True
MHC genotype restricts antigen specificity of T cells
True
MHC molecules expressed on the cell are expressed in an autosomal codominant manner
In MHC class II, what are the conserved residues?
MHCII: Note that all of the peptides share a hydrophobic residue in position 1, a negatively charged residue [aspartic acid (D) or glutamic acid (E)] in position 4, and a tendency to have a basic residue [lysine (K), arginine (R), histidine (H), glutamine (Q), or asparagine (N)] in position 6 and a hydrophobic residue [for example, tyrosine (Y), leucine (L), phenylalanine (F)] in position 9.
MHCa mice that are irradiated and reconstituted with MHCa x b bone marrow would accept grafts from which of the following donors?
MHCa, MHCb, and MHCa x b
Most important APCs
Macrophages Dendritic cells B cells
The injection of tuberculin into the skin of a sensitized individual elicits:
Mantoux reaction
Anaphylaxis can be triggered by cross-linking of IgE receptors on:
Mast Cells
IgE binds strongly to:
Mast Cells
Negative Selection
Medullary Dendritic cells To strong of binding to MHC cells expressing self antigen are sent to apoptosis Results in down regulation of RAG1 and RAG2
It is well documented that antibody affinities for an immunizing antigen continue to increase upon successive rounds of immunization (i.e., secondary, tertiary, etc.). This is due to the fact that:
Memory B cells can re-enter germinal centers and undergo additional somatic hypermutation.
Memory T cells, effector T cells, and naïve T cells share several characteristics. Which of the following descriptions could only be said of memory T cells?
Memory T cells are activated by any APC
What cell type is MOST commonly associated with gut-associated lymphoid tissues (GALTs)?
Microfold (M) Cells
__________________ IgA found in the circulation
Monomeric
IgA forms ________________ and ____________.
Monomers; dimers
Individuals that lack all T cells have the most severe form of immunodeficiency (SCID) and will not survive past their first birthday without a bone marrow transplant from a healthy donor. These individuals fail to make antibody responses to the normal childhood vaccines because:
Most antibody responses require T cell help for the B cells
Large Pro-B cell
Mu chain is expressed at which stage of B cell development?
A mouse is infected with staphylococcal bacteria through a laceration in the skin of its paw. Dendritic cells are isolated from the tissue at the site of infection, and are incubated together with naïve staphylococcal-specific CD4 T cells. Seventy-two hours later, the proliferation of the CD4 T cells is measured as a readout for T cell activation. Surprisingly, the T cell response is quite poor compared to the response observed when the same T cells are mixed with a comparable number of dendritic cells isolated from the draining lymph node of the infected mouse. A comparison of the dendritic cells isolated from the two different sites would reveal:
Much higher levels of MHC and B7 molecules on the lymph node dendritic cells than those from the infected tissue
The skin and bodily secretions provide the first line of defense against infection. One response in this category that is common during upper respiratory virus infections is:
Mucus production NOTE: mucus production is a common response to upper respiratory virus infection. Other responses may also occur, such as fever, production of antibodies, or infiltration of white blood cells, but these are not 'bodily secretions.' Increased saliva is not a symptom common to upper respiratory infections.
In spite of their low affinity for binding to their antigen, IgM antibodies can be quite effective at promoting the elimination of extracellular bacterial infections. This is due to:
Multivalent binding of IgM pentamers to repetitive epitopes on bacterial surfaces
Isotypes differ in the distribution of ___________________________.
N-linked carbohydrate groups
When T-cells express defective ER calcium sensor protein, they secrete very little IL-2 because activation of transcription factor ______ is compromised.
NFAT
IkB
NFKB becomes activated by the degredation of which component?
Activation of which PRR does not lead to activation of transcription factors?
NLRP3
Alum is an FDA-Approved adjuvant used in human vaccines. It stimulates immunity by activating the pattern recognition receptor:
NLRP3
Which T cells express which CD8 subunits?
Naive T cells express CD8αβ, but the CD8αα homodimer can be expressed by highly activated effector and memory T cells
True
Naive T cells scan the dendritic cells in the cortical region of the lymph node as they migrate. The encounter of T cells with dendritic cells is mediated by interactions between the T-cell receptor and the peptide:MHC complexes on the dendritic cells
outline lymphocyte movement
Naive T lymphocytes leave the bloodstream across the specialized endothelial walls of blood vessels, called high endothelial venules or HEV, in the T cell areas of lymphoid organs. This specialized endothelium expresses a number of molecules involved in lymphocyte homing to the lymph node, in particular the homing receptor, GlyCAM-1, the adhesion molecule ICAM-1, and chemokines, such as MIP3β. The initial binding of the naïve T cell to the vascular endothelium is mediated by L-selectin binding to GlyCAM-1. Subsequently, binding of chemokines displayed on the extracellular matrix triggers tight adhesion of the integrin LFA-1 to its ligand, ICAM-1. The lymphocyte then is able to migrate across the endothelium and into the T cell area of the lymph node. The naïve T cell can now inspect dendritic cells in the lymph node for the presence of its specific antigen. If it does not recognize antigen, the T cell is not activated and passes out of the lymph node to return to the circulation. T cells that do meet their specific antigen in the lymph node are activated, and begin to proliferate and to mature into effector cells. Eventually, after a few days, these cells leave the lymph node and return to the circulation.
Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important effector mechanism in immunity to virus infections. This immune pathway has also been exploited for clinical applications. For instance, patients with various disorders, including rheumatoid arthritis and some B cell lymphomas, are treated with an antibody directed at CD20, a surface receptor expressed on all B cells. This antibody leads to the depletion of B cells from the patients by the actions of:
Natural killer (NK) cells
Which of the following is not a mechanism of peripheral tolerance? A. Anergy B. Clonal Contraction C. Induction of Tregs D. Supression by Tregs E. Negative selection
Negative selection
Which process would be increased in a double transgenic mouse that expresses both a transgenic TCR transgenic as well as the protein that the TCR recognizes?
Negative selection
True
Negative selection is predominantly by APC of bone marrow origin
Proteins found in the circulation travel throughout the body, including the thymus. One example is serum albumin. Developing T cells with T-cell receptors specific for peptides of human serum albumin bound to MHC class II molecules would likely be:
Negatively selected in the thymus and deleted from the mature repertoire
Inflammatory bowel disease (colitis) is a CD4 T-cell mediated disease that can be transferred to naive mice by administration of effector CD4 T cells that home to the gastrointestinal tract and induce inflammation. Simultaneous administration of neutralizing antibodies to IL-12p40 (a subunit of IL-23) can prevent the disease, as well as neutralizing antibodies to IL-23p19 (another subunit of IL-23). Disease symptoms can be exacerbated by administration of IL-23, but not of IL-12. These data strongly suggest that:
Neutralizing antibodies to IL-17 would prevent disease.
Inflammatory bowel disease (colitis) is a CD4 T-cell mediated disease that can be transferred to naive mice by administration of effector CD4 T cells that home to the gastrointestinal tract and induce inflammation. Simultaneous administration of neutralizing antibodies to IL-12p40 can prevent the disease, as can neutralizing antibodies to IL-23p19. Disease symptoms can be exacerbated by administration of IL-23, but not of IL-12. These data strongly suggest that
Neutralizing antibodies to IL-17 would prevent disease.
Inflammatory bowel disease (colitis) is a CD4 T-cell mediated disease that can be transferred to naive mice by administration of effector CD4 T cells that home to the gastrointestinal tract and induce inflammation. Simultaneous administration of neutralizing antibodies to IL-12p40 (a subunit of IL-23) can prevent the disease, as well as neutralizing antibodies to IL-23p19 (another subunit of IL-23). Disease symptoms can be exacerbated by administration of IL-23, but not of IL-12. These data strongly suggest that:
Neutralizing antibodies to IL-17 would prevent disease. NOTE: Yes. The data indicate a key role for TH17 cells and for their dependence on IL-23 to induce disease as the antibody neutralization data shows that both subunits of IL-23 are essential (IL-12p40 and IL-23p19) and that IL-23, but not IL-12, will exacerbate disease.
Inflammatory bowel disease (colitis) is a CD4 T-cell mediated disease that can be transferred to naive mice by administration of effector CD4 T cells that home to the gastrointestinal tract and induce inflammation. Simultaneous administration of neutralizing antibodies to IL-12p40 (a subunit of IL-23) can prevent the disease, as well as neutralizing antibodies to IL-23p19 (another subunit of IL-23). Disease symptoms can be exacerbated by administration of IL-23, but not of IL-12. These data strongly suggest that:
Neutralizing antibodies to IL-17 would prevent disease. NOTE: Yes. The data indicate a key role for TH17 cells and for their dependence on IL-23 to induce disease as the antibody neutralization data shows that both subunits of IL-23 are essential (IL-12p40 and IL-23p19) and that IL-23, but not IL-12, will exacerbate disease.
Infants born with the immunodeficiency disease X-linked agammaglobulinemia (XLA) have a block in B cell development, and fail to produce mature B cells. As a result, these infants lack the ability to produce antibodies. After birth, babies with XLA first begin to show symptoms of recurrent and persistent extracellular bacterial infections due to common environmental pathogens when they are 4-6 months of age. The reason these infants are healthy for the first 4-6 months after birth is because:
Newborn infants have high circulating levels of maternal IgG at birth.
Some viruses have mechanisms to down-regulate MHC class I protein expression on the surface of cells in which the virus is replicating. This immune evasion strategy might prevent effector CD8 cytotoxic T cells from recognizing and killing the virus-infected cells. Would this immune evasion strategy also prevent the initial activation of virus-specific CD8 T cells?
No, because dendritic cells would take up infected cells and cross-present viral peptides to activate CD8 T cells.
Some viruses have mechanisms to down-regulate MHC class I protein expression on the surface of cells in which the virus is replicating. This immune evasion strategy might prevent effector CD8 cytotoxic T cells from recognizing and killing the virus-infected cells. Would this immune evasion strategy also prevent the initial activation of virus-specific CD8 T cells?
No, because dendritic cells would take up infected cells and cross-present viral peptides to activate CD8 T cells. NOTE: Correct. The initial activation of CD8 T cells requires that the T cell recognizes viral peptide MHC class I complexes on dendritic cells, not on the infected cell itself. The mechanism that the dendritic cell uses to present viral peptides on its MHC class I proteins does not require that the virus replicate in the dendritic cell. Instead, the virus particles can be taken up from the extracellular milieu, or the dendritic cell can phagocytose dying infected cells. In either case, the viral proteins will be degraded into peptides and cross-presented on MHC class I molecules. In these scenarios, the virus is not replicating in the dendritic cell, and therefore cannot synthesize the proteins it might use to down-regulate MHC class I in the dendritic cell.
Self-reactive B cells can be eliminated from the repertoire at several stages of B cell maturation, including immature B cells that have already emigrated from the bone marrow into the circulation. This latter stage of tolerance induction is critical because
Not all self antigens are expressed or present in the bone marrow during B-cell development
Self-reactive B cells can be eliminated from the repertoire at several stages of B cell maturation, including immature B cells that have already emigrated from the bone marrow into the circulation. This latter stage of tolerance induction is critical because:
Not all self-antigens are expressed or present in the bone marrow during B cell development.
What are the features of an activated conventional dendritic cell when it arrives at the nearby lymph node?
Not phagocytic, High surface expression of MHC and B7 molecules
SLE Autoantigens
Nucleosome subunits of chromatin The spliceosome A ribonucleoprotein complex containing Ro and La ----- Gluten is NOT an SLE antigen
MHC class I molecules are expressed?
On almost every nucleated cell in the body Expressed coordinately-All molecules are expressed on the surface at the same time Expression can occur in the absence of MHC class II molecules
DNA encoding Igs is found in three unlinked gene groups.
One group encodes kappa () L-chains One lambda () L-chains One H-chains
One individual can have up to how many different MHC class I molecules and MHC class II molecules on a given cell.
One individual can have up to 6 different MHC class I molecules and 10-20 MHC class II molecules on a given cell.
In rare instances, B cells can be found that have two immunoglobulin light chain alleles, both of which are rearranged in frame, and can encode functional light chain proteins. Yet, on the surface of the B cell, only one of the two light chain proteins is detected in the membrane-bound immunoglobulin receptor. The reason these rare cells have two functional light chain rearrangements but only express one of the two light chains as part of the B-cell receptor is:
One of the two light chain proteins doesn't form a stable complex with the heavy chain expressed in this cell.
Approximately one in every three alpha:beta T cells expresses two different rearranged TCR-alpha chain proteins. Yet T cells are still considered to have 'clonal specificity' for recognizing antigen. The reason for asserting that each T cell has a single functional specificity for recognizing antigen is that:
Only one T-cell receptor expressed by each T cell will recognize peptide presented by self-MHC molecules.
Both MHC class I and MHC class II molecules are highly polymorphic genes in the human population, with tens to hundreds of different alleles co-existing in the population. This means that a comparison of the MHC protein sequences between two individuals would reveal amino acid differences between one individual and the next. However, these amino acid differences are not randomly distributed along the entire protein, but are clustered in certain locations. The panel in the diagram below that most correctly indicates the regions of greatest variability between different MHC proteins (shown by the red highlights) is: IMAGE ON PHONE
PICTURE C
Both MHC class I and MHC class II molecules are highly polymorphic genes in the human population, with tens to hundreds of different alleles co-existing in the population. This means that a comparison of the MHC protein sequences between two individuals would reveal amino acid differences between one individual and the next. However, these amino acid differences are not randomly distributed along the entire protein, but are clustered in certain locations. The panel in the diagram below that most correctly indicates the regions of greatest variability between different MHC proteins (shown by the red highlights) is: PICTURE
PICTURE C
The image below shows an MHC molecule (in blue) presenting a peptide (in turquoise). Which picture highlights the region of the peptide:MHC that interacts with T cell receptors (as indicated by the black outline)? IMAGE ON PHONE
PICTURE C
The image below shows an MHC molecule (in blue) presenting a peptide (in turquoise). Which picture highlights the region of the peptide:MHC that interacts with T cell receptors (as indicated by the black outline)? PICTURE
PICTURE C
Lymphocyte activation leads to robust proliferation and effector cell differentiation. The metabolic demands of these processes are met, in part, by up-regulation of glycolytic enzymes and nutrient transporters on the activated cell membrane. A key intermediate in the signaling pathway leading to enhanced glucose metabolism following antigen receptor stimulation is:
PIP3
Each RSS contains conserved _____________________________ and a conserved ______________________ sequence, separated by an intervening sequence of ___ or ___ base pairs. The intervening base pairs correspond to one or two turns of the DNA helix
Palindromic heptamer; AT-rich nonamer; 12 or 23
Type I Diabetes
Pancreatic B-islet cells are destroyed by *CD8+ T-cells*
___________ cleaves the _______ molecule into _______ pieces
Papain; IgG; three
IgM forms _______________.
Pentamers
MHC class II molecules traffic to the cell surface with CLIP in their binding sites
Peptide editing is an important component of antigen presentation for both MHC class I and MHC class II pathways, as it drives the preferential presentation of high- affinity binding peptides. For MHC class Il peptide editing, HLA-DM plays a key role. In the absence of HLA-DM:
MHC class II molecules traffic to the cell surface with CLIP in their binding sites
Peptide editing is an important component of antigen presentation for both MHC class I and MHC class ll pathways, as it drives the preferential presentation of high- affinity binding peptides. For MHC class Il peptide editing, HLA-DM plays a key role. In the absence of HLA-DM:
What are the Paired Interactions at the Surface of the APC and the CD4+ T Cell
Peptide/MHC and TCR • MHC Class II and CD4+ (adhesion and activation) • Co-‐stimulator Pairs: B7 with CD28 and CD152, CD40 with CD40L • Adhesion Molecules: CD54 (ICAM1) with LFA-‐1, CD58 with CD2
Which peptides bind to MHC class I? Where does MHC class I bind peptides?
Peptides that bind to MHC class I molecules are usually 8-10 amino acids long. Longer peptides are thought to bind, however, particularly if they can bind at their carboxy terminus, but they are subsequently shortened to 8-10 amino acids through cleavage by exopeptidases present in the endoplasmic reticulum, which is where MHC class I molecules bind peptides.
True
Phospholipase-Ý initiates three important signaling pathways
Most effector T cells migrate out of secondary lymphoid organs and into tissues to exert their function. In which of the cases shown in the figure below will the TH1 effector cell undergo long-lived interactions with its target cell, an infected macrophage? Assume all of the target cells shown below are infected with the pathogen recognized by the specific TH1 cells.
Picture A
Most effector T cells migrate out of secondary lymphoid organs and into tissues to exert their function. In which of the cases shown in the figure below will the TH1 effector cell undergo long-lived interactions with its target cell, an infected macrophage? Assume all of the target cells shown below are infected with the pathogen recognized by the specific TH1 cells. PICTURE ON PHONE
Picture A
CD3 in the T- cell complex
Plays a chaperone for transporting new TCR to cell surface Is identical on the surface of all T cells
Wild-type mice infected with one strain of Influenza A virus (PR8) by intranasal inoculation are protected from intranasal infection by a related Influenza A virus (Beijing), a phenomenon known as cross-protection. These infections are generally localized to the upper respiratory tract. Mice with a homozygous single gene defect in 'gene X' have greatly impaired cross-protection to Influenza A-Beijing following immunization with Influenza A-PR8 by the intranasal route. Gene X likely encodes:
Poly Ig receptor
6.17 Short answer: Multiple mechanisms contribute to create a wide diversity in MHC protein expression between different individuals in the population. In addition to the genetic polymorphism of MHC genes, what additional mechanism(s) contribute to this diversity? LOOK AT PIC
Polygeny and co-dominant expression of MHC proteins.
Which of the following does NOT occur shortly following oligomerization of the BCR upon antigen binding?
Positioning of CD3 to allow for phosphorylation if its ITAM motifs
Cortex
Positive selection in T cell development occurs in the
______ is a common consequence of TCR and CCR7 signaling.
Positive selection.
975 Kohler and Milstein developed a procedure to create cell lines producing __________________, ___________________ and ___________________ antibodies (mAb).
Predetermined; monospecific; monoclonal
Hyperacute graft rejection is caused by:
Preformed antibodies
What determines if a particular cell will respond to a particular cytokine?
Presence or absence of the receptor for that cytokine
Some pathogenic microorganisms encode proteins, such as the Staphylococcus Protein A, that bind to immunoglobulin constant region domains with high affinity. These microbial proteins provide a benefit to the microorganism by:
Preventing antibodies bound to the microbe from binding to Fc receptors on phagocytes
VDJ recombination occurs during which phase of B-cell development?
Pro-B cell
Receptor editing
Process by which t autoreactive recept
On the cell surface of an antigen-presenting cell, what is the structure recognized by the a:B T-cell receptor?
Processed peptide antigen plus MHC
True
Progenitor cells that migrate from the bone marrow to the thymus are not yet committed to the T cell lineage. T cel lineage commitment occurs as a result of signals received by the progenitor cell from thymic epithelial cells.
True
Progenitor cells that migrate from the bone marrow to the thymus are not yet committed to the T cell lineage. T cell lineage commitment occurs as a result of signals received by the progenitor cell from thymic epithelial cells.
When Ag binds Igs, the B cells
Proliferates and then differentiates into a plasma cell
MHC class I associated peptides are generated by _____ in the _____
Proteasomes Cytosol
Antibodies are the secreted form of
Proteins known more generally as immunoglobulins (Igs)
When complement proteins are covalently deposited onto the surface of a bacterium, this can sometimes lead to direct lysis of the bacterium. However, more commonly, the deposition of complement proteins onto the bacterial surface does not directly harm the bacterium. Instead, these complement proteins aid in bacterial elimination by:
Providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacterium.
When complement proteins are covalently deposited onto the surface of a bacterium, this can sometimes lead to direct lysis of the bacterium. However, more commonly, the deposition of complement proteins onto the bacterial surface does not directly harm the bacterium. Instead, these complement proteins aid in bacterial elimination by:
Providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacterium. NOTE: The protective immune response elicited by a complement-tagged bacterium is the uptake and degradation of the bacterium by phagocytes, which is triggered by activation of complement receptors (not Fc receptors). Macrophages and neutrophils both express complement receptors. In addition to aiding in bacterial engulfment, binding of the complement proteins on the bacterium to the complement receptors on the phagocyte can also enhance the production of microbicidal effector functions in the phagocyte. During complement activation, products of the complement cascade get deposited on pathogens that can bind to complement-specific receptors on phagocytic immune cells.
The ______ shepherds the splicing of the immunoglobulin gene segments
RAG complex
Large Pre-B
RAG-1 and RAG-2 briefly turned off during which satge of B cell development?
Large Pre-B
RAG-1 and RAG-2 briefly turned off during which satge of I cell development?
RAG complex
RAG1 RAG2 and high mobility group of proteins
The β and δ chains are constructed from
Rearrangement of V, D, and J gene segments
Genomic ________________________ is an essential feature of lymphocyte ____________________.
Rearrangement; differentiation
The innate immune response together with antibodies are generally not effective at clearing infections established by pathogens that replicate inside host cells. The evolution of T cells has provided a means for the immune response to 'see' intracellular infections based on the ability of T cells to:
Recognize pathogen-derived peptides on host MHC surface molecules
The formation of a DNA coding sequence for the variable region of Ig involves ___________ (SELECT ALL THAT APPLY)
Recombination of signal sequences DNA rearrangements the 12/23 rule
The formation of a DNA coding sequence for the variable region of Ig involves ___________ (SELECT ALL THAT APPLY)
Recombination of signal sequences DNA rearrangements the 12/23 rule
There are unique ___________________________________________ (RSSs) flanking each germ-line V, D, and J gene segment
Recombination signal sequences
Helicobacter pylori is a human gastrointestinal (GI) pathogen that can lead to a state of chronic GI inflammation in some individuals, and has been linked to gastric ulcers and other diseases. Studies have shown that human mucosal gastric biopsies of infected individuals have dendritic cells producing IL-23, and that human monocytes isolated and cultured from healthy individuals produce IL-23, but not IL-12, in response to stimulation with live H. pylori. Given these findings, which of the following responses would be enhanced in the GI tract of H. pylori-infected individuals compared to uninfected individuals?
Recruitment of neutrophils
Cells arising from Hematopoietic cell lineages:
Red blood cells Lymphocytes Dendritic Cells Granulocytes NOT ENDOTHELIAL CELLS
Several effector T cell functions are mediated by cell surface molecules on the effector cell interacting with binding partners on the target cells. In the case of the CD40-CD40 ligand interaction, effector CD4 T cells express CD40 ligand, which binds to CD40 target cells. Individuals with a genetic deficiency in CD40 ligand expression show greatly reduced antibody responses, particularly to protein antigens which require CD4 TFH cell interactions with B cells. Another expected defect in these individuals would be:
Reduced activation of macrophages by TH1 cells
In the late 1990s, compounds that functioned as leukotriene receptor antagonists were approved for the treatment of asthma. The first such drug, zafirlukast, inhibits the actions of a major receptor for leukotrienes, known as CYSLTR1 (cysteinyl leukotriene receptor 1). One would predict that patients on this drug would show: (Hint: Leukotrienes are small proinflammatory lipid mediators produced and released by activated mast cells)
Reduced bronchoconstriction
The compound LE135 is an inhibitor of the retinoic acid receptor, and blocks signaling through this receptor. In a mouse model of inflammatory bowel disease (IBD), inflammation in the gastrointestinal (GI) epithelium is significantly exacerbated if animals are treated with LE135. Analysis of the CD4 T cell subsets found in the GI epithelium of LE135-treated mice compared to controls with IBD would likely show:
Reduced numbers of iTregs in the LE135-treated mice
IL-10-deficient mice develop spontaneous colitis, a disease due to chronic inflammation in the gastrointestinal (GI) tract. However, when these mice are housed in germ-free conditions, in which they lack all commensal microbes in their GI tract, no colitis was observed. In addition, one would expect germ-free IL-10-deficient mice to also show:
Reduced production of IgG antibodies compared to conventionally housed il10-/- mice
The TNF family of cytokines and their receptors are critical for the development of secondary lymphoid organs, such as the lymph nodes and Peyer's patches. As a consequence, knockout mice lacking expression of LT- fail to develop most of these structures. Reconstitution of irradiated LT--deficient mice with bone marrow stem cells from wild-type mice (e.g., LT--sufficient) would:
Restore the missing follicular dendritic cells but not the missing lymphoid structures in the recipient mice
3Immunological Ignorance
Result of a periphe antigern
Clonal deletion
Result of persistent
Integrins
Role in T cell adhesion to APCs and endothelial cells- LFA-1, VLA-4
Salmonella typhimurium is the causative agent of typhoid fever, and infects the host by translocating across the intestinal epithelium. Recent studies have shown that S. typhimurium produces an effector protein called SopB that induces intestinal enterocytes to differentiate into M cells. This is beneficial to the bacteria because:
S. typhimurium gains access to the host by crossing the intestinal epithelium inside M cells.
SLP-65
SLP-76
True
Scaffold proteins are often phosphorylated at multiple sites, allowing the recruitment of several different signaling proteins.
True
Second messengers, such as calcium ions (ca+), are chemical mediators commonly used in intracellular signaling pathways
Co-‐stimulator Pairs: B7 with CD28 and CD152, CD40 with CD40L
Second signal is provided by co-‐stimulators, which enhance signals delivered by MHC‐peptide‐TCR interaction ¤B7 family binds CD28 & CD152 on T cell (induced by T cell activation) ¤CD40 (Constitutive on dendritic cells, macrophages and B cells) binds CD40L on T cell (upregulated by peptide-‐MHC binding TCR) ¤CD40-‐interaction increases amount of B7 on APC ¤Enhances the B7-‐CD28 interaction. ¤CD40-CD40L interaction is also important in T cell-‐B cell interactions
What else is necessary to activate naïve T cells?
Second signal is required Possibly generated by tissue damage Explanation proposed by the Danger Hypothesis
Where does the antigen-driven activation (proliferation and differentiation) of B and T cells take place?
Secondary lymphoid organs
9.5
Selectins
Short answer: The entry of naive T cells from the blood into lymph nodes and mucosal lymphoid tissues occurs by a process that involves similar steps and similar adhesion molecules to the process by which leukocytes are recruited into sites of inflammation. Yet naive T cells do not enter tissues at sites of inflammation, but rather, home to lymphoid tissues. Which class of adhesion molecules direct the specific homing of naive T cells to lymphoid tissues?
Selectins
2Isotypic exclusion
Selection of either 1
Not all self-antigens are expressed or present in the bone marrow during B cell development
Self-reactive B cells can be eliminated from the repertoire at several stages of B cell maturation, including immature B the circulation. This latter stage of tolerance induction is cells that have already emigrated from the bone marrow into critical because:
Not all selfantigens are expressed or present in the bone marrow during B cell development
Self-reactive B cells can be eliminated from the repertoire at the circulation. This latter stage of tolerance induction is cells that have already emigrated from the bone marrow into several stages of B cell maturation, including immature B critical because:
V(D)J Recombinase
Set of enzymes needed to recombine V, D, and J gene segments
False
Several small GTPases play critical roles in antigen receptor signaling pathways. When activated by binding to GTP, these mediators induce changes in cytoskeletal organization, adhesion, and metabolism, but have no role in transcription factor activation
True
Several types of pathogens encode proteins that function as superantigens, which activate massive numbers of T cells in an individual, which are of no value.
Induce activation of any t cell whose t cell receptor uses a particular vb region bound by that superantigen.
Several types of pathogens encode proteins that function as superantigens, which activate massive numbers of T cells in an individual. One example is the staphylococcal enterotoxins that cause food poisoninf. These superantigens are the exception to the general rule that T cells only recognize specific peptide: MHC complexes, because they:
The type of antigen bound by an antibody depends on the ________ of the ____________________________.
Shape; antigen-binding site
Neutrophil defensins are:
Short peptides
A) Lipid rafts
Signaling molecules are found in specialized regions called?
True
Signaling receptors may be part of a complex or they may be transmembrane
What effect can mutations in a peptide or MHC molecule have on a T cell's response?
Simply changing a leucine to isoleucine in the peptide, for example, is sufficient to alter a T-cell response from strong killing to no response at all. Mutations of single residues in the presenting MHC molecules can have the same effect.
Antigens that are _________ molecules can be bound within ________________________.
Small; deep pockets
__________, _____________ form of IgD, IgE and IgG are always _________________.
Soluble, secreted; monomers
The γζ T Cells
Some T cells have γ and δ chains in association with CD3 and ζ for T cell receptor - Differ from αβ TCR in many ways: - They can bind directly to protein - Do not require APC presentation on MHC molecules - Most do not have CD4 or CD8 on surface
The addition and subtraction of nucleotides at the junctions between V, D, and J gene segments creates antibody proteins with wide variations in the numbers of amino acids in their CDR3 regions. This variability in CDR3 length is important as:
Some antibodies bind relatively flat surfaces and others bind deep clefts in the antigen.
Other Pathways of Antigen Processing and Presentation
Some antigens can interact with empty MHC molecules at the cell surface or displace loaded peptide with new higher affinity peptide APCs can also generate peptides for CD8+ presentation by process known as crosspriming- where exogenous enzymes are presented via MHC class I
What is the major organ in the body in which antibodies are synthesized and from which they are released into the circulation?
Spleen
Where do immature B-cells finish their maturation?
Spleen
Which of the following is a location where naïve TCcells could be activated to become CTLs?
Spleen
IL-23 is a cytokine made by macrophages and dendritic cells in response to extracellular bacterial and fungal infections. Mice with a genetic defect in the production of IL-23 are highly susceptible to the gastrointestinal bacterial pathogen, Citrobacter rodentium. Thus, unlike wild-type mice which clear the infection, mice that fail to produce IL-23 succumb to the bacteria and die 1-2 weeks post-infection. Yet, this cytokine does not directly act on the bacteria nor does it function to recruit the granulocytes that are needed to eliminate the pathogen. Instead, IL-23:
Stimulates IL-17 and IL-22 production by ILC3 cells
When mice are born, their intestinal lamina propria lacks TH17 effector cells. These cells develop after birth due to:
Stimulation by antigens derived from commensal microbes that populate the gastrointestinal tract after birth
TCR-APC interaction
Stimulation of a T cell, in this case a CD4 T cell, by the antigen presenting cell involves the interaction of the T cell receptor and coreceptor molecules with the MHC:peptide complex, as well as the interaction between CD80 and CD28. The interaction of the antigen presenting cell with the T cell causes signals to pass in both directions, signaling the antigen presenting cell to express additional costimulatory molecules, such as CD40. At the same time, signals through the T cell receptor and CD28 induce the T cell to express CD40 ligand. The interaction between CD40L and CD40 results in full activation of the CD4 T cell. Activation of CD8 T cells also requires multiple receptor-ligand interactions. The same activation signals induce the antigen presenting cell to express other costimulatory molecules, such as 4-1BB ligand (4-1BBL), while the initial activation of CD8 T cells induces the expression of 4-1BB. Binding of 4-1BBL to 4-1BB is thought to be required for the full activation of CD8 T cells.
The final stages of T cell development occur in the thymic medulla, after the developing cells become CD4 or CD8 single-positive. One important change that occurs during this final maturation is:
Strong signaling through the TCR no longer induces cell death
Induce activation of any T cell whose T-cell receptor uses a particular Vß region bound by that superantigern
Superantigens are the exception to the general rule that T cells only recognize specific peptide: MHC complexes, because they:
Which method is most characteristically used by trypanosomes to escape the immune response?
Switching of VSGs (variable surface glycoproteins)
Which disease is NOT an organ-specific autoimmune disease?
Systemic Lupus erythematosus
What does the T-cell do in it cytoplasm in response to activation and binding to APC?
T cell appears to reorganize structure of its cytoskeleton and cell membrane. ¤Lipid rafts of cholesterol and glycosphingolipids normally form microdomains in the T cell membrane. ¤In an activated T cell, these lipid rafts move to the synapse, drawing with them intracellular signaling components ¤This also pushes molecules not involved in APC-‐T cell interactions away from the contact area.
They almost always consist of a linear sequence of amino acids.
T cell epitope
They are generally located in the interior of a protein antigen
T cell epitope
They generally arise from protein antigens
T cell epitope
For each of the following statements, indicate whether it is true only of B cell epitopes, only of T cell epitopes, or if it is true for both types of epitopes. Assume it is a large antigen. They almost always consist of a linear sequence of amino acids. They are generally located in the interior of a protein antigen They are generally located on the surface of a protein antigen The lose their immunogenecity when a protein antigen is denatured by heat Multiple different epitopes may occur in the same antigen They generally arise from protein antigens Their immunogenecity may depend on the three-dimensional structure of the antigen
T cell epitope T cell epitope B cell epitope B cell epitope BOTH T cell epitope B cell epitope
8 : γ chains
T cell receptors in the embryonic stage consist of:
T cell activation
T cell that becomes activated when it interacts with a dendritic cell. The T cell is labeled with a dye that fluoresces when it binds calcium ions. At the moment the T cell is not activated. Its intracellular calcium concentrations are low, and so little green fluorescence is visible. As the T cell contacts the surface of the dendritic cell, we can see it suddenly fluoresce bright green as it becomes activated. However, it still continues to move, crawling over the surface of the dendritic cell, perhaps to sample the cell's display of peptide:MHC complexes. Eventually the T cell loses interest. While it is still contacting the dendritic cell you can see the fluoresence start to fade. The T cell then migrates away from the dendritic cell.
thymona acute lymphoblastic leukemia Sezary syndrome Adult T cell leukemia All of the above
T cell tumors consist of:
What cells differentiate only partially within the bone marrow?
T cells
The deep cortical area or paracortical region contains
T cells and DC.
secrete immunoglobulins
T cells are capable of doing all the following expect:
why do T cell become in active or anergy?
T cells become anergic so that self-reactive T cells do not undergo clonal expansion and aquir effector function that could be directed against self tissue
Initially after an infection, the majority of the T cells present in the tissue at a site of infection are not specific for the infecting pathogen, but over the course of several days, this changes and antigen-specific T cells become enriched at this site. This is because:
T cells do not use their T-cell receptors during extravasation from blood into tissues.
True
T cells expressing y:d T-cell receptors have been found to recognize a diversity of ligands, including parhogen-derived proteins, self-peptides, and stress-induced molecules.6
What are the two types of T cells?
T cells fall into two major classes distinguished by the expression of the cell-surface proteins CD4 and CD8 CD8 is expressed by cytotoxic T cells, while CD4 is expressed by T cells whose function is to activate other cells. We now know that CD8 recognizes MHC class I molecules and CD4 recognizes MHC class II
The experiment shown in the figure below uses two strains of mice that differ in their MHC genes. Strain A is H-2a and Strain B is H-2b. Mice of each strain are infected with the virus LCMV, and T cells are isolated at day 8 post-infection. These T cells are mixed with target cells that express either H-2a or H-2b; in each case, the target cells are either uninfected or infected with LCMV. After a four-hour incubation of T cells with target cells, the percentage of target cells lysed by the T cells is shown in the graph. The explanation for the results of this experiment is: GRAPH
T cells from mice of strain A only recognize viral peptides on target cells expressing H-2a.
The experiment shown in the figure below uses two strains of mice that differ in their MHC genes. Strain A is H-2a and Strain B is H-2b. Mice of each strain are infected with the virus LCMV, and T cells are isolated at day 8 post-infection. These T cells are mixed with target cells that express either H-2a or H-2b; in each case, the target cells are either uninfected or infected with LCMV. After a four-hour incubation of T cells with target cells, the percentage of target cells lysed by the T cells is shown in the graph. The explanation for the results of this experiment is: IMAGE ON PHONE
T cells from mice of strain A only recognize viral peptides on target cells expressing H-2a. NOTE: Correct. This experiment illustrates the concept of MHC restriction. When T cells are primed in a mouse expressing H-2a, they will only recognize and kill target cells expressing H-2a MHC molecules, if those target cells are infected with the same virus used to prime the mice. The same holds true for mice of strain B. The fact that T cells from each mouse strain recognize their syngeneic MHC molecules on LCMV-infected target cells rules out any lack of response of one strain to the virus, and rules out any lack of infectivity of target cells by the virus.
efferent lymphatic circulation
T cells leaving lymph node after divided and differentiated and become vector cells
Selection, growth occur in the cortex; migration to the medulla; release of mature T cells to peripheral circulation
T cells migrate from the bone marrow to the thymus for migration. What is the corrext sequence for T cells in the thymus?
Phagocytic cells
T lymphpocytes are incapable of functioning as:
Which type of T helper cell inhibits inflammation?
T reg
Cell-mediated response or Cellular immunity is
T-cell mediated responses. Which their participation in adaptive immune responses is as varied as the T-cell subsets and cytokines they produce.
Which of the following lists the types of cells that act as cytotoxic effector cells?
TC cells, NK-T cells, and NK cells.
Foxp3
TF that induces production of TGF-beta and IL-10 - regulated upstream by TGF-beta - in microenvironment with lots of TGF-beta, will get a lot of Treg cells- also making more TGF-beta, which keeps loop going - MPs induce production of IL-6 when activated, which induces Bcl6 (TF) - same TGF-beta and IL-6 that activate those cells activate RORgammaT
T-bet
TF that turns on IFN-gamma and IL-23 receptor genes so T cells commit to becoming TH1 cells - induces IL-2, IFN-gamma and many other cytokines characteristic of TH1 cells
In cell culture experiments, purified B cells expressing IgM can be induced to switch to producing IgE by stimulating them with an antibody to CD40 (a stimulatory antibody) plus the cytokine IL-4. In an individual undergoing an immune response, these signals would normally be provided by:
TFH cells in the germinal center
when DCs produced IL-6 what effector cells is produced
TH 1
if DC produced IL-12 and IFN gamma what effector cell in produced
TH1 which is to kill macrophage infection
if a DC singal TGF-beta and IL-6 what effector cells is produced
TH17
Which type of T helper cell regulates allergic reactions and protects against extracellular pathogens?
TH2
if DC produced IL-4 what effector cells is produced
TH2 for parasit infection
what convert the immature tissues dendritic cells into a mature dendritic cells
TLR signaling signals received from chemokines
Which type of T helper cell inhibits inflammation?
TREG
A single molecule of IgM can activate the C1q component of the classical complement pathway
TRUE
Although each B cell carries two alleles encoding the immunoglobulin heavy and light chains, only one allele is expressed.
TRUE
Dendritic cells primarily encounter antigen in peripheral tissues, leading to activation and migration of these tissue dendritic cells to the closest lymph node to activate T cells.
TRUE
MBL has a function in the lectin pathway analagous to that of IgM in the classical pathway, and MASP-1 and MASP-2 are analogous to components in the C1 complex.
TRUE
Antigen-presenting cells express both class I and class II MHC molecules on their cell membranes
TRUE NOTE: ALL nucleated cells express MHC I, so APCs also express MHC I in addition to MHC II
A rabbit immunized with human IgG3 will produce antibody that reacts with all subclasses of IgG in humans
TRUE NOTE: All the subclasses are similar enough that anti-IgG isotype antibodies produced in the rabbit would be able to bind all human IgG subclasses, even though the rabbit was only injected with IgG3.
The extravasation of neutrophils into tissues at sites of infection or inflammation requires changes to both the endothelium and to the neutrophil that are induced by chemokines and cytokines produced in the infected tissue.
TRUE NOTE: Both the endothelium and the neutrophils respond to cytokines and chemokines made in the tissue in response to infection. For the endothelium, the changes include vascular dilation and up-regulation of P-selectin, E-selectin, and ICAM molecules. For the neutrophil, the chemokines bound to proteoglycans on the surface of the endothelial cells induce a conformational change in the integrins on the surface of the neutrophil, converting them into high affinity binding partners for the ICAMs on the activated endothelium.
For cells of the innate immune system, each individual cell has multiple pattern recognition receptors, allowing it to recognize many different pathogens. In contrast, cells of the adaptive immune system each express a unique antigen receptor that has a single specificity for pathogen recognition.
TRUE NOTE: Cells of the innate immune system generally express multiple pattern recognition receptors. Each of these receptors recognizes a conserved feature of a class of pathogens. Therefore, a single innate immune cell can respond to a multitude of different pathogens. In contrast, the antigen receptor on B and T lymphocytes is clonally distributed; each single cell expresses only one version of this receptor, and has a single binding specificity.
Unlike innate immune responses, adaptive immune responses are initiated in secondary lymphoid organs. However, the innate immune response to an infection in a tissue has a pivotal role in inducing T-cell responses in the nearest lymph node by activating tissue dendritic cells and inducing their migration to the lymph node.
TRUE NOTE: Dendritic cells can be activated via their TLRs and other pathogen-recognition receptors, by tissue damage, or by cytokines produced during the inflammatory response. Activated dendritic cells migrate to the lymph node and express the co-stimulatory molecules that are required, in addition to antigen, for the activation of naive T cells. In the lymphoid tissues, these dendritic cells present antigen to naive T lymphocytes and prime antigen-specific T cells to divide and mature into effector cells that reenter the circulation.
All immunoglobulin molecules on the surface of a given B cell have the same idiotype.
TRUE NOTE: Idiotype refers to the antigen-specificity of an antibody. Since all BCRs on a single B cell are identical, they all recognize the same antigen. That means they all have the same antigen-specificity and the same idiotype.
In the absence of an infection, most granulocytes (neutrophils, eosinophils, basophils) are found circulating in the blood, whereas other subsets of myeloid cells reside in tissues.
TRUE NOTE: Mast cells and macrophages are both cells of the myeloid lineage. These are tissue-resident cells that are poised to respond rapidly if an infectious microbe enters their tissue of residence. But granulocytes remain in circulation until they are recruited to sites of inflammation by activation of an inflammatory response.
Most antigens induce a response from more than one T cell or B cell (more than one clone, or version of a TCR or BCR).
TRUE NOTE: Most antigens have multiple different epitopes, each of which can bind to a different T cell and/or B cell. Each of these cells recognizing one of the epitopes will become activated and proliferate (aka expand). Because multiple cells (with distinct receptors) are activated, this is called a polyclonal response.
A large protein antigen can generally be bound by many different antibody molecules simultaneously
TRUE NOTE: Most proteins are large enough that multiple antibodies can bind them simultaneously.
Many B cell epitopes are non-sequential amino acids brought together by the tertiary conformation of a protein antigen.
TRUE NOTE: Since B cells recognize antigens in their native, folded, 3D conformation, most of the amino acids bound by the BCR are not near each other in the protein's primary sequence (the epitope is discontinuous).
The C3 convertase of the alternative complement pathway can be formed using C3b created by any pathway, amplifying the overall magnitude of complement activation regardless of which of the three pathways initiated the complement activation initially.
TRUE NOTE: The C3 convertase of the alternative pathway contains C3b, allowing it to generate more of itself and amplify the overall level of C3b formed. Since C3b is a common intermediate for all three pathways of complement activation, once the initial C3b is generated by any of the pathways, the recruitment of factor B, and cleavage by factor D can proceed. By this mechanism, the initial C3b generated forms an amplification loop leading to more C3b, regardless of how the initial C3b was made.
The hypervariable regions make significant contact with epitope
TRUE NOTE: The hypervariable regions of antibodies are the CDRs (complementarity determining regions) and the CDRs are what makes contacts with the epitope.
The generation of optimal CD8 T cell memory following a primary infection requires CD4 T cell help for the responding CD8 T cells. This requirement for CD4 T cell help would not be completely replaced by supplying high levels of the cytokine IL-2 during the primary CD8 T cell response.
TRUE NOTE: The mechanism underlying the requirement for CD4 T cells is not completely understood. It may involve two types of signals received by the CD8 T cell, those received through CD40 and those received through the IL-2 receptor. CD8 T cells that do not express CD40 are unable to generate memory T cells. Although many cells could potentially express the CD40 ligand needed to stimulate CD40, it is most likely that CD4 T cells are the source of this signal. Therefore, in addition to providing the cytokine IL-2, CD4 T cells must interact with the responding CD8 T cells to provide CD40 ligand stimulation of CD40 on the CD8 T cells.
The spleen is a secondary lymphoid organ that performs several functions. In addition to its role as a site for initiating adaptive immune responses, the spleen is important in removing dead or damaged red blood cells from the circulation. Its immune function is important because blood-borne pathogens will not be transported to draining lymph nodes via the lymph fluid.
TRUE NOTE: The spleen is important for trapping blood-borne pathogens so they can be taken up and degraded by dendritic cells for presentation to T lymphocytes to initiate adaptive immune responses. Since these pathogens will not drain into lymph nodes (since they are in the blood, not in tissues - which have fluids that drain into lymph), having a localized place where they can collect and be scanned by immune cells is critical for not leaving the body defenseless (or with vastly fewer defenses) for blood-borne pathogens.
Unlike innate immune responses, adaptive immune responses are initiated in secondary lymphoid organs. However, the innate immune response to an infection in a tissue has a pivotal role in inducing T-cell responses in the nearest lymph node by activating tissue dendritic cells and inducing their migration to the lymph node.
TRUE NOTE: Dendritic cells can be activated via their TLRs and other pathogen-recognition receptors, by tissue damage, or by cytokines produced during the inflammatory response. Activated dendritic cells migrate to the lymph node and express the co-stimulatory molecules that are required, in addition to antigen, for the activation of naive T cells. In the lymphoid tissues, these dendritic cells present antigen to naive T lymphocytes and prime antigen-specific T cells to divide and mature into effector cells that reenter the circulation.
The generation of optimal CD8 T cell memory following a primary infection requires CD4 T cell help for the responding CD8 T cells. This requirement for CD4 T cell help would not be completely replaced by supplying high levels of the cytokine IL-2 during the primary CD8 T cell response.
TRUE NOTE: The mechanism underlying the requirement for CD4 T cells is not completely understood. It may involve two types of signals received by the CD8 T cell, those received through CD40 and those received through the IL-2 receptor. CD8 T cells that do not express CD40 are unable to generate memory T cells. Although many cells could potentially express the CD40 ligand needed to stimulate CD40, it is most likely that CD4 T cells are the source of this signal. Therefore, in addition to providing the cytokine IL-2, CD4 T cells must interact with the responding CD8 T cells to provide CD40 ligand stimulation of CD40 on the CD8 T cells.
IgG is able to change its conformation/configuration based on antigen spacing
TRUE -unstructured region in middle of H chain forms a flexible hinge region
T cells require __ signals to be activated
TWO
Wiskott-Aldrich syndrome is an immunodeficiency disease that causes a defect in antibody responses. The most severe defects are in antibody responses to protein antigens, which are dependent on CD4 effector TFH cells providing cytokines to the B cell. The protein defective in individuals with the disease, known as WASp, functions in cytoskeletal reorganization and polarization through its role in promoting actin polymerization. This immune defect could be fixed by a gene therapy approach that restored WASp expression in:
Tcells
Antibodies that bind with high affinity to some viral surface proteins require heavy chain CDR3 loops of unusual length. Whereas the average human heavy chain CDR3 length is ~15 amino acids, antibodies with VH CDR3 loops of >30 amino acids are readily detected in the repertoire. Which enzyme is responsible for these unusually long CDR3 loops?
Tdt
Antibodies that bind with high affinity to some viral surface proteins require heavy chain CDR3 loops of unusual length. Whereas the average human heavy chain CDR3 length is ~15 amino acids, antibodies with VH CDR3 loops of >30 amino acids are readily detected in the repertoire. These antibody heavy chains with CDR3 lengths of >30 amino acids would likely be missing in individuals lacking:
Terminal deoxy nucleotidyl transferase (TdT)
B-cells that originally express IgM can be induced to produce IgA. In an individual, the signals to switch from IgM to IgA production is provided by:
Tfh cells in germinal center
Which type of T helper cell regulates allergic reactions and protects against extracellular pathogens?
Th 2
NK cells do not express TCR molecules, yet they bind to MHC class I molecules on potential target cells. Explain how NK cells lacking TCRs can specifically recognize infected cells.
The "missing self " model has been used to explain how NK cells detect infected or tumor cells. If a potential target cell expresses normal levels of class I MHC molecules, inhibitory receptors on the NK cell (KIR, CD94, NKG2) induce a signal transduction cascade that abrogates NK lytic activity. Th ese negative signals override pro-killing signals generated via ligands binding to activating receptors on the NK cell (NKR-P1 and others). Some tumor cells and virally infected cells, however, reduce their expression of class I MHC and no longer stimulate NK inhibitory receptors. In this case, the activating (pro-killing) receptor signal dominates.
CR2 (CD21), CD81 and CD19
The B cell co-receptor is made up of:
False
The B cells first produced in a fetus are called B-2 cells
The alternative pathway of complement activation has an important role in innate immunity, due to its ability to greatly amplify the amount of C3b deposited onto the pathogen surface. This amplification occurs because:
The C3 convertase of the alternative pathway contains C3b, and can generate more of itself.
Inbred strains of mice often generate highly polarized CD4 T cell responses to specific infections that are dominated by one subset of effector cells. In the case of Balb/c mice infected with the intracellular protozoan Leishmania major, a robust CD4 T cell response is elicited, generating large numbers of L. major-specific T cells; however, this response does not eliminate the pathogen, and instead the mice succumb to the infection. One likely explanation for this finding is:
The CD4 T cell response produces effector cytokines that do not activate macrophages
Inbred strains of mice often generate highly polarized CD4 T cell responses to specific infections that are dominated by one subset of effector cells. In the case of Balb/c mice infected with the intracellular protozoan Leishmania major, a robust CD4 T cell response is elicited, generating large numbers of L. major-specific T cells; however, this response does not eliminate the pathogen, and instead the mice succumb to the infection. One likely explanation for this finding is:
The CD4 T cell response produces effector cytokines that do not activate macrophages.
What part of the MHC class I molecule is responsible for binding to peptides?
The Groove of MHC class I molecule and is Comprised of the α1 & α2 domains
IgM antibodies are much more efficient than IgG at activating the complement cascade. However, under certain circumstances, IgG antibodies will activate the complement pathway. One example of a situation in which IgG binding to its antigen will not trigger the complement cascade is when:
The IgG antibodies are neutralizing a bacterial toxin protein by blocking the receptor-attachment site on the toxin.
True
The LAT:Gads:SLP-76 complex that assembles following TCR stimulation provides the scaffold for initiating multiple downstream signaling modules, leading to actin polymerization, integrin activation, and gene expression.
Which of the following is a location where naïve TC cells could be activated to become CTLs?
The Spleen
True
The TCR and BCR lack intrinsic signaling molecules. They must associate with signaling molecules having ITAMs before signaling can take place.
True
The TCR signaling module leading to transcription factor activation is dependent on phospholipase-C-y (PLC-y). This is a critical step.
Generating two small second messengers that act on multiple target proteins in the T cell
The TCR signaling module leading to transcription factor activation is dependent on the enzyme phospholipase-C-y (PLC-y). The mechanism by which PLC-y activates multiple transcription factors is by:
T Cell Differentiation occurs in
The Thymus
Mice lacking the poly Ig receptor (pIgR) have an immunodeficiency disease characterized by increased susceptibility to mucosal infections and an increase in the penetration of commensal microbes into the body's tissues. Yet, a genetic deficiency in the production of IgA antibodies is the most common form of human immunodeficiency, and is generally a mild disease and often even asymptomatic. This dichotomy can be explained by:
The ability of pIgR to transport IgM across the gut epithelium
Individuals with the HIV-induced immunodeficiency disease AIDS have a progressive loss in the number of CD4 T cells in their bodies. These patients have a greatly increased rate of life-threatening disease caused by the inability of their immune system to control infections of the intracellular bacterium, Mycobacterium tuberculosis (Mtb). Mtb infects macrophages and then replicates in the cell's phagosomes. The most important immune mechanism lacking in these patients that leads to their increased susceptibility to Mtb is a defect in:
The activation of macrophages by TH1 effector cells
Immunological Synapse
The area of contact between the MHC-‐peptide of the APC and the TCR of the T cell is the immunological synapse ¤Includes adhesion pairs and B7-‐CD28 interactions. ¤Includes signaling molecules recruited from inside the T cell and proteins of the cytoskeleton ¤Synapse functions to sustain intracellular signaling
α1, β1 make up what?
The binding groove of MHC class 2
Naive T cells are isolated and left untreated or treated with 'compound X' for 1 hour. Following this, the T cells are incubated with a range of concentrations of a soluble form of ICAM-1 that has been conjugated to a fluorescent dye (soluble-ICAM-1-FITC). Fifteen minutes later, the cells are washed, and the relative amount of fluorescence bound to the cells is measured. The results of this assay are shown in Figure Q9.6.
The chemokine ligand for CCR7
Naive T cells are isolated and left untreated or treated with 'compound X' for 1 hour. Following this, the T cells are incubated with a range of concentrations of a soluble form of ICAM-1 that has been conjugated to a fluorescent dye (soluble-ICAM-1-FITC). Fifteen minutes later, the cells are washed, and the relative amount of fluorescence bound to the cells is measured. The results of this assay are shown in the figure below. Based on this data, the most likely identity of Compound X is
The chemokine ligand for CCR7
Naive T cells are isolated and left untreated or treated with 'compound X' for 1 hour. Following this, the T cells are incubated with a range of concentrations of a soluble form of ICAM-1 that has been conjugated to a fluorescent dye (soluble-ICAM-1-FITC). Fifteen minutes later, the cells are washed, and the relative amount of fluorescence bound to the cells is measured. The results of this assay are shown in the figure below. Based on this data, the most likely identity of Compound X is _________________.
The chemokine ligand for CCR7 NOTE: Yes. Signaling through chemokine receptor CCR7 on naive T cells induces LFA-1 to change conformation to the high-affinity state. This greatly increases its affinity for integrin binding. Therefore, after treatment with the ligand for CCR7 (which is CCL21), naive T cells would show maximal binding to ICAM-1 at a lower concentration of soluble-ICAM-1 than the untreated cells.
Naive T cells are isolated and left untreated or treated with 'compound X' for 1 hour. Following this, the T cells are incubated with a range of concentrations of a soluble form of ICAM-1 that has been conjugated to a fluorescent dye (soluble-ICAM-1-FITC). Fifteen minutes later, the cells are washed, and the relative amount of fluorescence bound to the cells is measured. The results of this assay are shown in the figure below. Based on this data, the most likely identity of Compound X is _________________. IMAGE ON PHONE
The chemokine ligand for CCR7 NOTE: Yes. Signaling through chemokine receptor CCR7 on naive T cells induces LFA-1 to change conformation to the high-affinity state. This greatly increases its affinity for integrin binding. Therefore, after treatment with the ligand for CCR7 (which is CCL21), naive T cells would show maximal binding to ICAM-1 at a lower concentration of soluble-ICAM-1 than the untreated cells.
An immunodeficient mouse strain is identified, that has a single gene defect causing its disease. Mice with this defect have greatly impaired responses to protein antigens following subcutaneous immunization and also exhibit severely delays in the kinetics of their antibody responses. Analysis of their lymph nodes revealed profound alterations in the normal architecture, with a lack of organization of distinct T-cell and B-cell zones. A likely candidate for the defect in these mice is:
The chemokine receptor CCR7, which recruits B cells, T cells, and dendritic cells to lymph nodes.
CD 81, CR2, CD 19
The co-receptors on B cells include:
Classical MHC molecules function as peptide-binding receptors that present these peptides to alpha:beta T cells for recognition by alpha:beta T-cell receptors. MHC molecules can be detected in lineages as evolutionarily old as sharks, the same time at which T-cell receptors can be identified. Examination of shark MHC proteins indicates that these molecules likely function identically to human MHC molecules. This conclusion is based on:
The conservation of amino acid residues important in peptide binding in both shark and human MHC proteins
Antibody diversity is generated by multiple mechanisms, each of which contributes to the generation of antibodies with up to 1011 different amino acid sequences in their antigen-binding sites. Several of these mechanisms involve changes in the DNA sequences encoding the antibody heavy and light chain proteins. One mechanism that does not rely on changes to the DNA within the immunoglobulin heavy and light chain gene loci is, instead, dependent on:
The contributions of amino acids from both the heavy chain and the light chain to form the antigen-binding site
All of the following statements regarding Toll-like receptors are true except _____.
The cytoplasmic signaling domain contains regions specialized in detecting PAMPs.
All of the following statements regarding Toll-like receptors are true except _____. The cytoplasmic signaling domain contains regions specialized in detecting PAMPs. They sense molecules not found in or on human cells. They facilitate changes in gene expression. The extracellular domain detects the microbial component. They form either transmembrane homodimers or heterodimers
The cytoplasmic signaling domain contains regions specialized in detecting PAMPs.
An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure, the organisms have proliferated to dangerous levels. It is unlikely that this infant has a defect in B or T lymphocyte response because:
The defective immune response happens too quickly to be due to a B or T lymphocyte defect.
Phagolysosome
The enzyme Machinery in extracellular pathways of pathogen destruction is known as:
The importance of complement activation as an innate immune defense against infections is illustrated by:
The evolution of complement avoidance strategies by many pathogens
Cytotoxic T cells are rapid killers of infected target cells. Within minutes of the interaction of a cytotoxic T cell with a target cell, the program of apoptosis in the target cell is initiated. This rapid activity is a consequence of:
The expression and packaging of perforin and granzymes in cytotoxic granules prior to target cell encounter
Cytotoxic T cells are rapid killers of infected target cells. Within minutes of the interaction of a cytotoxic T cell with a target cell, the program of apoptosis in the target cell is initiated. This rapid activity is a consequence of:
The expression and packaging of perforin and granzymes in cytotoxic granules prior to target cell encounter NOTE: Yes. Cytotoxic T cells can kill their targets rapidly because they store preformed cytotoxic proteins in forms that are inactive in the environment of the cytotoxic granule. Cytotoxic proteins are synthesized and loaded into the granules soon after the first encounter of a naive cytotoxic precursor T cell with its specific antigen during T cell priming in the secondary lymphoid organ. Ligation of the T-cell receptor similarly induces de novo synthesis of perforin and granzymes in effector CD8 T cells, so that the supply of cytotoxic granules is replenished. This makes it possible for a single CD8 T cell to kill a series of targets in succession.
Cytotoxic T cells are rapid killers of infected target cells. Within minutes of the interaction of a cytotoxic T cell with a target cell, the program of apoptosis in the target cell is initiated. This rapid activity is a consequence of:
The expression and packaging of perforin and granzymes in cytotoxic granules prior to target cell encounter NOTE: Yes. Cytotoxic T cells can kill their targets rapidly because they store preformed cytotoxic proteins in forms that are inactive in the environment of the cytotoxic granule.
What influences expression of MHC molecules?
The expression of both MHC class I and MHC class II molecules is regulated by cytokines, in particular, interferons, released in the course of an immune response. Interferon-α (IFN-α) and IFN-β increase the expression of MHC class I molecules on all types of cells, whereas IFN-γ increases the expression of both MHC class I and MHC class II molecules, and can induce the expression of MHC class II molecules on certain cell types that do not normally express them.
A healthy intestinal mucosa is one in which induced adaptive immune responses to pathogenic infections are balanced by the lack of responses to innocuous food antigens and commensal microbes. This balance is maintained by an array of different subsets of effector T cells and regulatory T cells that reside in the intestinal epithelium and lamina propria. Although these different T cell subsets have diverse patterns of cytokine production and other effector functions, they share:
The expression of gut-homing chemokine receptor, CCR9
V Pre Delta 5 = A and B
The expression of rearranged heavy chain in B cells is "checked" for successful rearrangement by which of the following molecules?
Turning off activated proteins, activating proteins, amplifying intercellular signals, regulating transcription = all of the above
The function of receptors and signaling molecules are
Affinity Maturation
The increase in affinity of the antigen-binding sites of antibodies for the antigen that occurs during the course of an adaptive immune response.
Caspases 9 and 3
The initiator and an effector of intrinsic apoptosis include:
Vibrio cholerae causes an acute diarrheal illness that can be fatal if not treated. Several vaccines have been developed in an effort to prevent this disease. The oral cholera vaccine is a mixture of killed Vibrio cholerae bacteria plus additional inactivated cholera toxin protein. Efficacy studies of this vaccine indicate that it prevents 50-60% of the cases of cholera infection observed in non-vaccinated individuals. In contrast, injectable vaccines made from killed bacteria or purified bacterial subunits are substantially less effective at preventing infections. This is likely due to the fact that:
The injectable vaccine fails to elicit gut-homing immune responses.
What of the following can lead to initiation of an adaptive immune response?
The interaction of a naïve T cell with an antigen-presenting cell
In the cases of some infections, such as mice infected with adenovirus, the generation of effector cytotoxic CD8 T cell responses needed to clear the infection is dependent on the antigen-presenting dendritic cells receiving stimulation through the CD40 receptor on their surface, a process known as dendritic cell 'licensing'. In this infection system, the dendritic cell would likely receive CD40 receptor stimulation from:
The interaction with a CD4 effector cell expressing CD40 ligand
False
The invariant chain protein, li, has only one function in MHC class Il antigen presentation. This function entails li protein occupying the peptide-binding site of each newly synthesized class II protein , thereby preventing new MHC class II proteins from binding peptides or misfolded proteins in the endoplasmic reticulum.
What peptides bind to MHC class II?
The length of the peptides bound by MHC class II molecules is not constrained. Natural peptides that bind to MHC class II molecules are at least 13 amino acids long and can be much longer In most cases, long peptides bound to MHC class II molecules are trimmed by peptidases to a length of around 13-17 amino acids.
Immature B cell
The light chain is completely rearranged and lgM is expressed at which stage of B cell development?
What are the structural differences between MHC class I and MHC class II?
The major differences lie at the ends of the peptide-binding cleft, which are more open in MHC class II than in MHC class I molecules. Consequently, the ends of a peptide bound to an MHC class I molecule are substantially buried within the molecule, whereas the ends of peptides bound to MHC class II molecules are not.
False
The mechanism by which CTLA-4 inhibits T cell activation is by recruiting inhibitory phosphatases
False
The mechanism by which CTLA-4 inhibits T cell activation is by recruiting inhibitory phosphatases.
Secondary lymphoid organs, such as the lymph nodes, spleen, and mucosa-associated lymphoid tissues, each have distinct features that are important for their role in initiating immune responses focused on different anatomical compartments (i.e., the peripheral tissues, the blood, or the gastrointestinal tract, respectively). Yet these organs share some overall structural features, such as distinct T-cell and B-cell zones. One major difference between these organs is:
The mechanism by which antigens or pathogens enter the organ
The alternate and classical complement pathways differ in which of the following ways?
The mechanisms initiating activation.
You have a monoclonal antibody specific for LFA-1. You test the ability of a CTL clone to kill target cells for which the clone is specific, in the presence and absence of this antibody. Predict the relative amount of target cell killing you would expect in the presence, or absence, of the anti-LFA-1 antibodies. Explain your answer.
The monoclonal antibody to LFA-1 should block formation of the CTL-target-cell conjugate. Th is should inhibit killing of the target cell and, therefore, should result in diminished 51Cr release in the CML assay.
Given the enormous heterogeneity of antigen receptors expressed on the populations of naive B and T lymphocytes, the adaptive immune response relies on a process where a rare lymphocyte binds to antigen and is first induced to proliferate, before it can perform its effector function. For B cells, there is a mechanism that ensures that the specificity of the antibody secreted by the plasma cell will recognize the same pathogen that initially stimulated the B cell antigen receptor and induced B cell proliferation. Which of the following best describes that mechanism?
The naive B cell expresses a membrane-bound form of the antibody as a receptor, and secretes that same antibody when it differentiates into a plasma cell.
How are T cells receptors oriented to peptide:MHC when binding? In what way does binding occur?
The orientation revealed by these structures showed that the T-cell receptor is aligned diagonally over the peptide and the peptide-binding cleft Comparison of the three-dimensional structure of an unliganded T-cell receptor and the same T-cell receptor complexed to its peptide:MHC ligand shows that the binding results in some degree of conformational change, or 'induced fit,' particularly within the Vα CDR3 loop
Supra molecular adhesion complex
The point of contact between B cell and T cell is called?
membrane Mu heavy chain
The pre-B cell receptor consists of:
It aignals without binding to an extracellular ligand.
The pre-B-cell receptor provides an important signal that induces transition of pro-B cells to pre-B cells. An important characteristic of this receptor is that:
It signals without binding to an extracellular ligand.
The pre-B-cell receptor provides an important signal that induces transition of pro-B cells to pre-B cells. An important characteristic of this receptor is that:
Different individuals can have different numbers of functional V gene segments as well as different numbers of constant region genes. This type of genetic polymorphism between individuals indicates that:
The precise number of antibody gene segments in an individual is not important.
A mouse is immunized with a single 9 amino acid peptide derived from the influenza virus. This peptide binds to MHC class I and produces an epitope (peptide:MHC complex) recognized by a small number of naive CD8 T cells in the mouse. The peptide is mixed with CpG oligonucleotides that are ligands for TLR-9. Surprisingly, this immunization regimen generates a very poor cytotoxic CD8 effector response to targets coated with this peptide compared to immunization with a preparation of intact heat-killed influenza virus mixed with CpG oligonucleotides. The enhanced cytotoxic T cell response to the peptide observed following immunization with intact viral particles compared to the peptide alone is due to:
The presence of CD4 T cell epitopes in the intact virus
The upper respiratory tract of many individuals is colonized by Streptococcus pneumoniae bacteria. Infections caused by these bacteria, including pneumonia, meningitis, otitis media (ear infections), and sinusitis, are thought to occur in individuals lacking protective antibodies. For many years, IgG was thought to be the major antibody class responsible for protective immunity to S. pneumoniae, due to the ability of anti-bacterial capsule IgG antibodies to opsonize the bacteria and promote phagocytosis. However, in addition to IgG, pneumococcal polysaccharides elicit robust IgA antibody responses. It was traditionally thought that these IgA antibodies functioned in neutralization, by blocking bacterial attachment to mucosal epithelial cells. It is now known that IgA antibodies, like IgG, can function as opsonins, to induce phagocytosis and killing of IgA-coated pathogens. This function of IgA antibodies depends on:
The presence of IgA-specific Fc receptors on neutrophils and macrophages
Immunological memory in humans has been examined by assessing responses in individuals who were given the vaccinia virus to induce immunity against smallpox. Antiviral CD4 and CD8 T cell responses could be detected many years after the vaccinia immunization, but declined with an estimated half-time of about 10 years. In contrast, antiviral antibody responses were maintained at a relatively constant level, with a barely detectable decline over decades. The persistence of antiviral antibodies for years after immunization is likely due to:
The presence of long-lived antibody secreting plasma cells
Unlike somatic hypermutation, class switching occurs in discrete sequence regions upstream of the immunoglobulin heavy chain coding sequences (called switch regions). One key element in directing the enzyme AID to a specific switch region is the opening of the DNA duplex combined with polymerase stalling during active transcription in that region. A second key feature of directing AID to a specific switch region is:
The processed RNA from the switch region guides AID to this site in the DNA
True
The proteasome is a multicatalytic enzyme component involved in the breakdown of proteins in the cytosol
Where do the events of T-cell receptors that create a pool of memory cells occur?
The secondary lymphoid organs such as the lymph nodes and spleen
In response to an intracellular bacterial or viral infection, effector TH1 cells, macrophages, NK cells, and CD8 cytotoxic effector cells are all recruited to the site of infection. The coordinated recruitment of all of these cell types is orchestrated by:
The shared expression of chemokine receptors on these different cell types
What affects the strength of binding of CD8 to the MHC class I molecule?
The strength of binding of CD8 to the MHC class I molecule is influenced by the glycosylation state of the CD8 molecule; increasing the number of sialic acid residues on CD8 carbohydrate structures decreases the strength of the interaction. The pattern of sialylation of CD8 changes during the maturation of T cells and also on activation, and this likely has a role in modulating antigen recognition.
What is the difference between a B cell receptor and its corresponding antibody?
The structure of a B-cell receptor is identical to that of its corresponding antibody except for a small portion of the carboxy terminus of the heavy-chain C region. In the B-cell receptor, the carboxy terminus is a hydrophobic amino acid sequence that anchors the molecule in the membrane, and in the antibody it is a hydrophilic sequence that allows secretion.
Analysis of human milk from lactating mothers shows that it contains IgA antibodies against infections that were recent (<3 weeks earlier) and those from the distant past (>1 year). These antibodies are directed against a host of organisms, including viruses, such as enteroviruses, herpes simplex viruses, respiratory syncytial virus, rubella, reovirus, and rotavirus. In addition, IgA antibodies against many bacteria are found in human milk, including those reactive to E. coli, Shigella, Salmonella, Campylobacter, Vibrio cholerae, H. influenzae, S. pneumoniae, Clostridium difficile, C. botulinum, and Klebsiella pneumoniae. IgA antibodies to the parasite Giardia and the fungus, Candida albicans, are also seen in human milk. Since most of these infections were localized in the gastrointestinal tract of the mother, these IgA antibodies ended up in breast milk by:
The trafficking of gut-primed activated B cells from the mother's circulation into the lactating milk gland.
In a recent experiment, NK cells were collected from an MCMV infected mouse, 50 days after infection, and placed into a healthy mouse. Upon exposure to the MCMV virus, the healthy mouse quickly mounted an immune response. How could these results BEST be interpreted?
The transferred NK cells show memory and are quickly able to recognize MCMV infected cells in the healthy mouse.
Cytotoxic effector T cells also produce inflammatory cytokines such as IFN- and TNF- when their T-cell receptor recognizes peptide:MHC on a target cell. One effect of this cytokine secretion is to enhance the ability of CD8 effector T cells to recognize and kill other infected cells in the nearby vicinity. This enhanced activity is due to:
The up-regulation of MHC class I protein expression by IFN-
Cytotoxic effector T cells also produce inflammatory cytokines such as IFN-g and TNF-a when their T-cell receptor recognizes peptide:MHC on a target cell. One effect of this cytokine secretion is to enhance the ability of CD8 effector T cells to recognize and kill other infected cells in the nearby vicinity. This enhanced activity is due to:
The up-regulation of MHC class I protein expression by IFN-gamma
Cytotoxic effector T cells also produce inflammatory cytokines such as IFN-g and TNF-a when their T-cell receptor recognizes peptide:MHC on a target cell. One effect of this cytokine secretion is to enhance the ability of CD8 effector T cells to recognize and kill other infected cells in the nearby vicinity. This enhanced activity is due to:
The up-regulation of MHC class I protein expression by IFN-gamma.
Cytotoxic effector T cells also produce inflammatory cytokines such as IFN-g and TNF-a when their T-cell receptor recognizes peptide:MHC on a target cell. One effect of this cytokine secretion is to enhance the ability of CD8 effector T cells to recognize and kill other infected cells in the nearby vicinity. This enhanced activity is due to:
The up-regulation of MHC class I protein expression by IFN-gamma. NOTE: Inducing apoptosis in target cells is the main way in which CD8 cytotoxic T cells eliminate infection. However, most CD8 cytotoxic T cells also release the cytokines IFN-g, TNF-a , and LT-a , which contribute to host defense in other ways. IFN-g inhibits viral replication directly, and induces the increased expression of MHC class I molecules and of other proteins that are involved in peptide loading of these newly synthesized MHC class I molecules in infected cells. This increases the chance that infected cells will be recognized as target cells for cytotoxic attack.
The T Cell Receptor Complex has-
The α & βchains associate with CD3 and ζ(zeta) chains on surface of T cell
Effector memory T-cells (Tem) can be distinguished from central memory T-cells (Tcm) by:
Their lack of CCR7 expression
What are the classes of immunoglobulins?
There are five different classes of immunoglobulins, distinguished in their being constructed from C regions that have different structures and properties. These are known as immunoglobulin M (IgM), immunoglobulin D (IgD), immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin E (IgE).
The process of somatic hypermutation of antibody V regions sequences is initiated by the enzyme AID. This enzyme targets cytidine residues in the DNA sequence that are normally part of a G:C pair in the double-stranded DNA. Yet the hypermutation process generates mutations at both G:C and A:T base pairs of the original sequence because:
There are two different pathways of repair target, one targeting G:C and one targeting A:T base pairs.
The process of somatic hypermutation of antibody V regions sequences is initiated by the enzyme AID. This enzyme targets cytidine residues in the DNA sequence that are normally part of a G:C pair in the double-stranded DNA. Yet the hypermutation process generates mutations at both G:C and A:T base pairs of the original sequence because:
There are two different repair pathways that have different outcomes, one targeting G:C and one targeting A:T base pairs.
24) Consider the following mouse strains: 1. H-2d mice in which perforins have been knocked out 2. H-2d mice in which Fas ligand has been knocked out 3. H-2d mice in which both perforin and FasL have been knocked out Each strain is immunized with LCMV. One week after immunization, T cells from these mice are harvested and tested for cytotoxicity. Which of the following target cells would T cells from each strain be able to lyse? Explain your reasoning. A) Target cells from normal LCMV-infected H-2b mice B) Target cells from normal H-2d mice C) Target cells from H-2d mice in which both perforin and Fas have been knocked out
There are two pathways by which cytotoxic T cells kill target cells: one that is perforin dependent and one that uses FasL to induce death in Fas-expressing target cells. (And, as always, T cells will only lyse cells expressing the MHC-peptide combinations to which they are specific and restricted.) T cells from immunized perforin knockout H-2d mice will be able to lyse (d). (These T cells will depend on FasL-Fas interactions to kill. Target cells don't need to express perforin to be susceptible, but they do need to express Fas.) T cells from immunized Fas ligand knockout H-2d mice will be able to lyse (d), but they will also be able to lyse (e). These cells will depend on perforin-mediated pathways. Targets do not need to express perforin or Fas to be susceptible.) T cells from H-2d mice in which both perforin and Fas ligand have been knocked out will not be able to lyse any of the cell types
A mouse is immunized with the tetanus toxoid protein (inactivated toxin) in adjuvant. One week later, the entire population of splenic B cells are isolated from the mouse and mixed with tetanus toxoid-specific CD4 TFH cells plus the purified tetanus toxoid protein. Four days later, the total number of B cells in the culture and the number of tetanus toxoid-specific B cells are determined and compared to the starting population on the day of isolation. The results are shown in the figure below. The tetanus-specific B cells preferentially survive and proliferate because INSERT GRAPH PICTURE
They are the only B cells presenting the tetanus peptide to the TFH cells
A mouse is immunized with the tetanus toxoid protein (inactivated toxin) in adjuvant. One week later, the entire population of splenic B cells are isolated from the mouse and mixed with tetanus toxoid-specific CD4 TFH cells plus the purified tetanus toxoid protein. Four days later, the total number of B cells in the culture and the number of tetanus toxoid-specific B cells are determined and compared to the starting population on the day of isolation. The results are shown in Figure Q10.1.
They are the only B cells presenting the tetanus peptide to the TFH cells.
Studies in mice have shown that resident memory cells (TRM) most often take up permanent residence in the tissue where the initial infection that produced those memory cells occurred. In this location, they are poised to respond rapidly should that infection re-occur in that same location. In contrast, central memory cells (TCM) are primarily found in secondary lymphoid organs, where they can be activated to proliferate and differentiate into effector cells when stimulated by antigen-bearing dendritic cells following re-infection. The third subset of memory cells, effector memory cells (TEM), are recirculating cells that can readily enter tissues at sites of inflammation or infection and are poised to rapidly respond to re-infection. The subset of TEM cells provides an important component of protective immunity to re-infection by the same pathogen because:
They can protect against re-infection that occurs in a different site in the body than the primary infection.
Studies in mice have shown that resident memory cells (TRM) most often take up permanent residence in the tissue where the initial infection that produced those memory cells occurred. In this location, they are poised to respond rapidly should that infection re-occur in that same location. In contrast, central memory cells (TCM) are primarily found in secondary lymphoid organs, where they can be activated to proliferate and differentiate into effector cells when stimulated by antigen-bearing dendritic cells following re-infection. The third subset of memory cells, effector memory cells (TEM), are recirculating cells that can readily enter tissues at sites of inflammation or infection and are poised to rapidly respond to re-infection. The subset of TEM cells provides an important component of protective immunity to re-infection by the same pathogen because:
They can protect against re-infection that occurs in a different site in the body than the primary infection. NOTE: Yes. While re-infection with the same pathogen often occurs in the same location as the initial primary infection, this is not always the case. Therefore, the circulating effector memory T cells can patrol all tissues in the body, and are not restricted to a single tissue of residence.
Studies in mice have shown that resident memory cells (TRM) most often take up permanent residence in the tissue where the initial infection that produced those memory cells occurred. In this location, they are poised to respond rapidly should that infection re-occur in that same location. In contrast, central memory cells (TCM) are primarily found in secondary lymphoid organs, where they can be activated to proliferate and differentiate into effector cells when stimulated by antigen-bearing dendritic cells following re-infection. The third subset of memory cells, effector memory cells (TEM), are recirculating cells that can readily enter tissues at sites of inflammation or infection and are poised to rapidly respond to re-infection. The subset of TEM cells provides an important component of protective immunity to re-infection by the same pathogen because:
They can protect against re-infection that occurs in a different site in the body than the primary infection. NOTE: Yes. While re-infection with the same pathogen often occurs in the same location as the initial primary infection, this is not always the case. Therefore, the circulating effector memory T cells can patrol all tissues in the body, and are not restricted to a single tissue of residence.
Precursor CTLs are characterized by each of the following EXCEPT: they produce low amounts of IL-2 they lack cytotoxic activity they express CD4 they do not express CD25 they do not divide.
They express CD4
Precursor CTLs are characterized by each of the following EXCEPT: they produce low amounts of IL-2. they lack cytotoxic activity. they express CD4. they do not express CD25. they do not divide.
They express CD4
Studies in mice have shown that resident memory cells (TRM) most often take up permanent residence in the tissue where the initial infection that produced those memory cells occurred. In this location, they are poised to respond rapidly should that infection re-occur in that same location. In contrast, central memory cells (TCM) are primarily found in secondary lymphoid organs, where they can be activated to proliferate and differentiate into effector cells when stimulated by antigen-bearing dendritic cells following re-infection. The third subset of memory cells, effector memory cells (TEM), are recirculating cells that can readily enter tissues at sites of inflammation or infection and are poised to rapidly respond to re-infection. The subset of TEM cells provides an important component of protective immunity to re-infection by the same pathogen because:
They express the integrin E7 that binds to integrin ligands expressed on epithelial cells.
Experimental mouse models have been developed to study the mechanisms leading to the breakdown of self-tolerance and the onset of autoimmunity. One strategy is to express a foreign antigen, such as a viral protein, in a single defined cell type in a peripheral organ. For instance, the lymphocytic choriomeningitis virus (LCMV) glycoprotein has been expressed in β-islet cells of the pancreas by making a line of mice that is transgenic for a construct linking the LCMV-glycoprotein gene to the insulin promoter. In these transgenic mice, the LCMV protein is expressed only in pancreatic β-islet cells. Thymocytes with T-cell receptors specific for a peptide of LCMV-glycoprotein bound to MHC class I develop normally in the thymus, and do not undergo negative selection. The fate of these T cells once they emigrate from the thymus would likely be:
They would either be deleted in the periphery or would become unresponsive.
inhibits proliferation THI and TH2 cells
This cytokine-transforming growth factor(TGF)
False
Three major cell types, dendritic cells, macrophages, and B cells, present peptides bound to ONLY MHC class II molecules for recognition by CD4 cells
An individual with normal B cells but absence of T cells might have a defect in:
Thymic stromal cells
Naïve CD4+ and CD8+ T cells that have just finished developing leave the ______ and enter circulation.
Thymus
Primary lymphoid organs consist of
Thymus, bone marrow
Mechanical ways for fending off pathogens
Tight junctions. Mucus/tears/saliva. Ciliary escalator. Peristalsis in the gastrointestinal tract.
CD4 and CD8
Tighten adherence of T cells to Has adhesive and signal transduction properties
The ____________ the binding, the ________________ the antibody is to _________ from antigen
Tighter; less likely; dissociate
Affinity is the
Tightness of binding of an antibody binding site to an antigen
The W/Wv mouse strain is heterozygous for two different alleles of the gene encoding the growth factor receptor, c-kit, an important receptor expressed on hematopoietic progenitor cells in the bone marrow. The major defect in these mice is the absence of single lineage of hematopoietic cells. When these mice are challenged with larval Haemaphysalis longicornis ticks, they fail to become resistant to the ticks, in spite of generating high titers of anti-tick IgE antibodies. The cell type missing in the W/Wv mice is most likely:Natural Killer (NK) cells
Tissue-resident mast cells
Recombination signal sequences are conserved heptamer and nonamer sequences that flank the V, J, and D gene segments which undergo recombination to generate the final V region coding exon. Some of these have 12-nucleotide spacers between the heptamer and nonamer, and others have 23-nucleotide spacers. The reason recombination signal sequences come in these two forms is:
To ensure the correct assembly of gene segments so that a VH recombines to a DH and not to another VH, for instance
The exon encoding the V region of an immunoglobulin protein is generated by a process of somatic recombination. This recombination event brings V gene and J gene segments together:
To generate maximum diversity in the CDR3 sequence of the V region
Follicular helper T cells are a recent discovery in the Helper T-cell lineage. What is the primary role of TFH cells?
To help B cell development in germinal centers
Follicular helper T cells are a recent discovery in the Helper T-cell lineage. What is the primary role of TFHcells?
To help B cell development in germinal centers
The TCR and BCR are multi-subunit receptor complexes. Experiments examining the synthesis and transport of these receptors to the lymphocyte cell surface have shown that the signaling subunits of each receptor complex are required for transport of the ligand-binding receptor subunits to the cell surface. One possible reason for this stringent control on cell surface expression is:
To prevent surface expression of receptors that will bind ligand but fail to induce signals
What is the function of a memory T cell?
To provide an almost immediate response upon subsequent exposure to a specific pathogen
False
Toxins of CD8 T cells have no effect on healthy human tissues
The thoracic duct does what?
Transports lymph and lymphocytes to the vena cava
Strep throat is commonly caused by group A Streptococcus bacteria. A common symptom of strep throat is the presence of swollen lymph nodes in the neck. This symptom usually peaks about 2-4 days after the onset of the infection, and is due to:
Trapping and activation of antigen-specific lymphocytes in the lymph nodes of the neck
Which type of T helper cell inhibits inflammation?
Treg
(t/f) monoclonal antibodies are produced from a clone of antibody-producing cells
True
5.24 True/False: When a B cell differentiates into a plasma cell, it goes from expressing membrane-bound IgM to making mostly the secreted form of IgM. A deletion of the first polyadenylation site in the μ heavy chain gene would prevent activated B cells from making the secreted form of IgM. LOOK AT PIC
True
9.32 True/False: Cytotoxic T cells that lack expression of perforin are more defective in killing target cells than those that lack granzymes.
True
9.8 True/False: Unlike innate immune responses, adaptive immune responses are initiated in secondary lymphoid organs. However, the innate immune response to an infection in a tissue has a pivotal role in inducing T-cell responses in the nearest lymph node by activating tissue dendritic cells and inducing their migration to the lymph node.
True
Although each B cell carries two alleles encoding the immunoglobulin heavy and light chains, only one allele is expressed.
True
Antibody binding to a pathogen surface is greatly enhanced when both antigen-binding sites of the antibody are engaged at once, a feature known as bivalent binding. It is possible for antibodies to bind bivalently to a wide variety of components on many different pathogen surfaces due to the flexibility in the protein at the hinge region and at the V-C junction.
True
Cytotoxic T cells that lack expression of perforin are more defective in killing target cells than those that lack granzymes.
True
Linear, triangular, and square forms of antigen:antibody complexes exist.
True
T or F: Chimeric antigen receptor (CAR) T cells can recognize other target molecules besides peptide:MHC complexes
True
The TACI receptor on B cells, which binds to BAFF and APRIL, is important in IgA antibody secretion by B cells in the gastrointestinal lamina propria.
True
The generation of optimal CD8 T cell memory following a primary infection requires CD4 T cell help for the responding CD8 T cells. This requirement for CD4 T cell help would not be completely replaced by supplying high levels of the cytokine IL-2 during the primary CD8 T cell response.
True
True or False: All autoreactive CD4 T cells are not necessarily able to cause autoimmune diseases. Depending on the target tissue expressing the antigen recognized by the effector CD4 T cells, and the cytokines made by these effector T cells, autoimmune tissue damage may or may not occur.
True
True or False: B-cell receptors and T-cell receptors share a mechanism for generating diversity, and also share structural homology in their V domains.
True
True or False: During B-cell development, pre-B-cell receptors receive signals from self antigens for the lymphocytes to survive and proliferate?
True
True or False: Each family of NK cell receptors has members that promote NK cell activation, and members that send inhibitory signals when engaged. The difference between activating and inhibitory receptors lies in their association with accessory proteins that promote downstream signaling, or in their ability to recruit and activate inhibitory phosphatases, respectively.
True
True or False: In the majority of viral infections, CD8 T-cell activation requires CD4 T-cell help
True
True or False: Intestinal epithelium and lamina propria contain a large number of effector T cells, plasma cells, and cytokine-secreting leukocytes even in the absence of infection; however, such an inflammatory state does not cause tissue damage because their effects are balanced by the presence of Treg cells and production of anti-inflammatory cytokines such as IL-10.
True
True or False: Like TCR signaling, BCR signaling is initiated by a kinase phosphorylating tyrosine residues in ITAM motifs of BCR signaling subunits.
True
True or False: Naive T cells scan the dendritic cells in the cortical region of the lymph node as they migrate. The initial encounter of T cells with dendritic cells is mediated by interactions between the T-cell receptor and the peptide:MHC complexes on the dendritic cell
True
True or False: The classical and lectin pathways of complement activation converge at the step of C3 activation. Moreover, the initiating steps of each pathway use protein components and enzymatic mechanisms that share high similarity with each other.
True
True or False: Unlike innate immune responses, adaptive immune responses are initiated in secondary lymphoid organs. However, the innate immune response to an infection in a tissue has a pivotal role in inducing T-cell responses in the nearest lymph node by activating tissue dendritic cells and inducing their migration to the lymph node.
True
True/False: Antibody binding to a pathogen surface is greatly enhanced when both antigen-binding sites of the antibody are engaged at once, a feature known as bivalent binding. It is possible for antibodies to bind bivalently to a wide variety of components on many different pathogen surfaces due to the flexibility in the protein at the hinge region and at the V-C junction.
True
True/False: Cytotoxic T cells that lack expression of perforin are more defective in killing target cells than those that lack granzymes.
True
True/False: Dendritic cells are tissue resident myeloid cells that are highly phagocytic, like macrophages. However, dendritic cells do not play a major role in large-scale pathogen destruction; instead, they are important in initiating adaptive immune responses of T cells.
True
True/False: Each family of NK cell receptors has members that promote NK cell activation, and members that send inhibitory signals when engaged. The difference between activating and inhibitory receptors lies in their association with accessory proteins that promote downstream signaling, or in their ability to recruit and activate inhibitory phosphatases, respectively.
True
True/False: For cells of the innate immune system, each individual cell has multiple pattern recognition receptors, and can recognize many different pathogens. In contrast, cells of the adaptive immune system each express only a single antigen receptor, and have a single specificity for pathogen recognition.
True
True/False: In the absence of an infection, most granulocytes (neutrophils, eosinophils, basophils) are found circulating in the blood, whereas other subsets of myeloid cells reside in tissues.
True
True/False: Innate lymphoid cells and NK cells are effector cells that respond rapidly after encountering a pathogen. Several different subsets of innate lymphoid cells exist, and each is specialized to respond to a category of pathogen (e.g., viruses, extracellular bacteria, helminthic parasites, etc). Innate lymphoid cells reside primarily in tissues such as the lungs, the lining of the gastrointestinal tract, and the skin, because these sites represent the major routes of entry of pathogens into the body.
True
True/False: MHC class I molecules generally bind peptides that are 8-10 amino acids. Each allelic variant has preferences for the amino acid residues at key anchor positions, but will not bind every possible peptide containing the correct anchor residues.
True
True/False: Neutrophils regulate the production of active cathelicidins (a class of antimicrobial peptides) by segregating the inactive propeptide from the processing 4 enzyme that cleaves and activates it in two different types of cytoplasmic granules. These two types of granules are induced to fuse with phagosomes after ingestion of microbes, bringing the processing enzyme and the propeptide together.
True
True/False: Nitric oxide and superoxide radicals are toxic compounds that induce substantial DNA damage. When released by activated M1 macrophages, these compounds cause damage to microbial pathogens and may also cause damage to host cells in the vicinity
True
True/False: One factor that contributes to the enhanced secondary response to an antigen is the increased number of antigen-specific lymphocytes present after the primary response; these are known as memory cells.
True
True/False: Oral tolerance to food antigens and immune tolerance to gut microbiota share the property that foreign antigens encountered in the gastrointestinal (GI) tract—food and commensal microbes, respectively—do not elicit immune effector responses. Yet, these processes differ in that commensal microbes will still elicit protective adaptive immune responses if they cross the GI epithelium and enter the body.
True
True/False: Several pathogens produce proteins, either membrane-bound or secreted, that inactivate C3b that might be deposited on the pathogen surface. C3b is specifically targeted due to its central position in all three complement pathways.
True
True/False: T cells expressing : TCRs are distinct from those expressing : TCRs in that they do not generally recognize host cell responses to infections or tissue damage; rather they recognize components of the pathogen directly.
True
True/False: TH1, TH2, TH17, and T follicular helper (TFH) cells represent four different subsets of CD4 effector cells. Each of these subsets produces a distinct set of cytokines when stimulated, that in turn, act to mobilize distinct immune effector mechanisms. While TH1, TH2, and TH17 cells recruit and activate innate immune cells, TFH cells act to amplify the adaptive immune response.
True
True/False: The C3 convertase of the alternative complement pathway amplifies the overall magnitude of complement activation regardless of which of the three pathways initiated the complement activation initially.
True
True/False: The MHC locus encodes a large number of genes spanning over four million bp of DNA. These include many genes involved in antigen processing and presentation, as well as receptors recognized by non-conventional T cells and natural killer (NK) cells. In addition, the MHC locus encodes genes with no function in immunity at all.
True
True/False: The TACI receptor on B cells, which binds to BAFF and APRIL, is importantin IgA antibody secretion by B cells in the gastrointestinal lamina propria.
True
True/False: The extravasation of neutrophils into tissues at sites of infection or inflammation requires changes to both the endothelium and to the neutrophil that are induced by chemokines and cytokines produced in the infected tissue.
True
True/False: The generation of optimal CD8 T cell memory following a primary infection requires CD4 T cell help for the responding CD8 T cells. This requirement for CD4 T cell help would not be completely replaced by supplying high levels of the cytokine IL-2 during the primary CD8 T cell response.
True
True/False: The genes encoding MHC proteins are closely linked with genes encoding proteins involved in antigen processing and presentation. This genetic linkage facilitates the coordinate regulation of these genes by interferons.
True
True/False: The inflammatory response is characterized by four classic symptoms: heat, redness, pain, and swelling. In some instances, this response can be triggered by stimuli that are non-infectious such as asbestos, a process known as 'sterile inflammation.' When exposure to the stimulating trigger is persistent, a state of chronic inflammation can result. This process is likely to be detrimental to the health of the host.
True
True/False: The spleen is a secondary lymphoid organ that performs several functions. In addition to its role as a site for initiating adaptive immune responses, the spleen is important in removing dead or damaged red blood cells from the circulation. Its immune function is important because blood-borne pathogens will not be transported to draining lymph nodes via the lymph fluid.
True
True/False: Unlike innate immune responses, adaptive immune responses are initiated in secondary lymphoid organs. However, the innate immune response to an infection in a tissue has a pivotal role in inducing T-cell responses in the nearest lymph node by activating tissue dendritic cells and inducing their migration to the lymph node.
True
True/False: When a B cell differentiates into a plasma cell, it goes from expressing membrane-bound IgM to making mostly the secreted form of IgM. A deletion of the first polyadenylation site in the μ heavy chain gene would prevent activated B cells from making the secreted form of IgM.
True
True/False: When first discovered, investigators found it surprising that some single- gene defects causing immunodeficiency syndromes were associated with hypersensitivities to ionizing radiation, thereby leading to increased rates of cancer. The genes accounting for this dual impairment encode ubiquitously expressed DNA repair proteins.
True
Unlike innate immune responses, adaptive immune responses are initiated in secondary lymphoid organs. However, the innate immune response to an infection in a tissue has a pivotal role in inducing T-cell responses in the nearest lymph node by activating tissue dendritic cells and inducing their migration to the lymph node.
True
When a B cell differentiates into a plasma cell, it goes from expressing membrane-bound IgM to making mostly the secreted form of IgM. A deletion of the first polyadenylation site in the μ heavy chain gene would prevent activated B cells from making the secreted form of IgM.
True
False or True : Plasmacytoid dendritic cells (pDCs) are not thought to be involved in the antigen-specific activation of naïve T cells. If you think that the question of 9-49 is true, choose the correct reason from the following indications: pDCs express a protein to help the antigen-specific activation of naïve T cells. pDCs proves antigens efficiently to present peptide antigen on the surface of MHC class II molecule. pDCs express fewer MHC class II and co-stimulatory molecules on their surface. pDCs process antigens less efficiently than cDCs. pDCs do not cease the synthesis and recycling of MHC class II molecule after being activated. Thus, pDCs rapidly recycle their surface MHC class II molecules and so cannot present pathogen-derived peptide:MHC complexes to T cells for extended periods, as cDCs do. A. (i)+(ii), B. (i)+(ii)+(iii), C. (ii)+(iii)+(iv)+(v), D. (iii)+(iv)+(v), E. (ii)+(iv)+(v),
True D
PD-1 is a negative co-stimulatory signal expressed by tumor cells. What advantage would the expression of PD-1 have in a tumor cell avoiding the immune response?
Tumor cells can avoid being killed by activated TC cells.
Uncontrolled growth Prevention of apoptosis Disruption of gene expression All of the above
Tumors result from which important processes:
The basic immunoglobulin unit is composed of:
Two identical heavy chains and two identical light chains
Although the complement cascade can be initiated by antibodies bound to the surface of a pathogen, complement activation is generally considered to be an innate immune response. This is because:
Two of the three pathways for complement activation are initiated by constitutively produced recognition molecules that directly interact with microbial surfaces.
What are the types of light chains?
Two types of light chains, lambda (λ) and kappa (κ), are found in antibodies. A given immunoglobulin has either κ chains or λ chains, never one of each. The ratio of the two types of light chains varies from species to species. In mice, the average κ to λ ratio is 20:1, whereas in humans it is 2:1 and in cattle it is 1:20.
Expression of a CD8 alpha-alpha homodimer is characteristic of:
Type B intraepithelial lymphocytes (IELs)
False
Unlike TCR signaling, B cell receptor (BCR) signaling is not initiated by a Src-family kinase phosphorylating tyrosine resides in ITAM motifs of BCR signaling subunits.
The US Department of Health and Human Services has a stated goal for the seasonal influenza vaccine of vaccinating 80% of healthy (i.e., low-risk) individuals. This vaccine is formulated each year from the serotypes of influenza likely to be circulating in the population during the coming flu season. The reason this goal is not 100% of individuals is because:
Unvaccinated individuals are protected when 80% of people around them are vaccinated.
Many virus infections induce robust production of type I interferons, IFN- and IFN-. One example is the herpes simplex virus-1 (HSV-2), one of the most common sexually transmitted diseases in the US. Experiments that investigated the immune response to HSV-2 using a mouse model demonstrated essential roles for the DNA sensing Toll-like receptor, TLR9, and its downstream signaling adapter, MyD88, in the production of type I interferons following HSV-2 immunization. The type I interferon response to HSV-2 would be restored in Tlr9-/- mice by transferring into these mice wild-type:
Up-regulate MHC class II and B7 molecules to amplify CD4 T cell responses in the lung
The α and γ chains are constructed from
V and J gene segments and do not involve D gene segments
Immature B-cell
V-DJ rearrangement occurs at which stage of B cell development?
____ domains of light and heavy chains have ________________ regions (HV), flanked by __________________ (FR) regions.
V; hypervariable; framework
The ___ genes first undergo ________________.
V; rearrangement
Effector T cell epxress the integrin VLA-4, which allows them to bind to vascular endothelium bearing the adhesion molecules ________
VCAM-1
CDR3 is determined by what?
VDJ junction
Which is not a feature of germinal center B-cells?
VDJ recombination.
The variable lymphocyte receptors (VLRs) of lampreys represent a highly diverse set of proteins with structural similarity to the mammalian Toll-like receptors. Yet the VLRs and the lymphocytes that produce them are thought to be components of the lamprey's adaptive immune system. This is because:
VLRs are clonally distributed such that each lymphocyte expresses only one form of VLR.
______________ of an antibody is the ______________ number of antigenic ________________ with which an __________ can react
Valence; maximum; determinants; antibody
The V region of an antibody
Variability = great diversity Concentrated in the N-terminal region Paired V regions of a H and L chain - Form the antigen binding site - Two identical antigen binding sites
The V regions of light-chain comprised of two segments: __________________
Variable (V) and Joining (J)
Individuals with defects in the biochemical pathways needed for loading peptides onto MHC molecules show greatly increased susceptibility to virus infections. Experiments examining the MHC molecules present on the surface of host cells in these individuals would show:
Very low levels of total MHC proteins expressed on the cell surface.
Western Blotting
Very useful technique to identify a specific protein from a complex protein mixture
Flow Cytometry
Very useful technology to detect and isolate specific cells
Which domain corresponds to the antigen binding site of immunoglobulins?
Vh:Vl
V Segment
Viral
True
Virus infections induce production of interferons that act on infected cells to enhance their recognition by CD8 cytotoxic T cells
Nitric oxide
WHich of the following is NOT a component released from cytotoxic T cells?
In a recent experiment, NK cells were collected from an MCMV infected mouse, 50 days after infection, and placed into a healthy mouse. Upon exposure to the MCMV virus, the healthy mouse quickly mounted an immune response. How could these results BEST be interpreted?
What is measured by the cell-mediated lympholysis (CML) assay?
The germinal center is a region within the secondary B cell follicle where sustained B cell proliferation and differentiation take place. The processes of B cell proliferation and differentiation, including affinity maturation and class switching, require periodic interactions of the germinal center B cells with CD4 TFH cells. These periodic interactions between the B cells and TFH cells can occur:
When B cells cycle between the dark zone and the light zone of the germinal center
supramolecular activation complex (SMAC) / immunological synapse
When T cells are able to recognize their antigen on another cell, the zone of contact between the two cells forms the immunological synapse in which a cytotoxic T cell recognizing its target. the integrin α chain CD11a and a signaling molecule, lck. The cytotoxic granules in the CTL are labeled blue. The outer ring contains the adhesion molecule and the inner ring is divided into two parts: one containing the signaling molecules, and the other the secretory zone. Multiple synapses can be formed with the same antigen presenting cell, as we see here, where two CTLs are trying to kill the same target. Each has formed a synapse organized into discrete signaling and secretory zones
What happens when previously activated CD4 T cells recognize peptides bound to MHC class II molecules on B cells?
When previously activated CD4 T cells recognize peptides bound to MHC class II molecules on B cells, the T cells secrete cytokines that can influence the isotype of antibody that those B cells will choose to produce. Upon recognizing peptides bound to MHC class II molecules on macrophages, CD4 T cells activate these cells, again in part through cytokines, to destroy the pathogens in their vesicles
Pre B cell leukemia Mantle cell lymphoma Hodgkins lymphoma Multiple myleloma All of the above
Which of the following are B cell tumors?
T red cella express the transcription factoe FoxP3 and secretes THF which inhibits both Th1 and Th2 cells
Which of the following correctly describes T regulatory (T reg) cells?
Rolling in the HEV (high endothelial venule) exposes T cells to CCL21, which activates LFA-1 and promotes migration
Which of the following correctly describes events necessary for naive T cell entry in to the lymph node?
Dendritic cells
Which of the following does require activation by T cells?
Common granulocyte progenitor
Which of the following is NOT a cell that is produced from a common lymphoid progenitor?
HLA-DM
Which of the following molecules catalyzes the exchange of the CLIP (Class II associated invariant chain peptide) for an antigen peptide?
Double negative, CD44+, CD25-
Which of the following represent double negative 1 (DN1)
Double negative, CD44-, CD25-
Which of the following represents double negative 4 (DN4)
Cytotoxic granules released from cytotoxic T cells contain proteins that enter target cells and induce apoptosis. Do any of the mechanisms of apoptosis induction by cytotoxic effector T cells rely on the protein APAF-1? If so, which pathway?
Yes - Intrinsic pathway
Syk
ZAP-70
Most effector T cells migrate out of secondary lymphoid organs and into tissues to exert their function. In which of the cases shown in Figure Q9.25 will the TH1 effector cell undergo long-lived interactions with its target cell, an infected macrophage? Assume all of the target cells shown below are infected with the pathogen recognized by the specific TH1 cells.
a
A chronic infection inside the macrophage can be eliminated when the infected macrophage is recognized by
a TH1 cell
What is the thymus gland and where is it derived from?
a bilobed structure derived from the endoderm of the third and fourth pharyngeal pouches
Lymph nodes are composed of
a medulla with many sinuses and a cortex, which is surrounded by a capsule of connective tissue
antigen
a toxin or other foreign substance that induces an immune response in the body, especially the production of antibodies
Which of the following is the major antibody detected in human breast milk? a. Dimeric IgA b. IgD c. IgE d. IgG e. Pentameric IgM
a. Dimeric IgA
Which immunoglobulin is transported most efficiently across mucosal epithelium? a. Diveric IgA b. IgD c. IgE d. IgG e. Pentameric IgM
a. Diveric IgA
In secondary lymphoid tissues, which of the following routes do B cells take during their activation, proliferation and differentiation? a. HEV -> T cell zone -> medullary chords -> dark zone of germinal center -> light zone of germinal center b. HEV -> B cell zone -> T cell zone -> medullary chords -> light zone of germinal center c. HEV -> T cell zone -> dark zone of germinal center-> light zone of germinal center -> medullary chords d. HEV-> medullary chords -> T cell zone -> dark zone of germinal center -> light zone of germinal center e. HEV -> dark zone of germinal center -> light zone of germinal center -> T cell zone -> medullary chords
a. HEV -> T cell zone -> medullary chords -> dark zone of germinal center -> light zone of germinal center
A newborn derives passive immunity from its mother by transferring of ___ in a breast milk a. IgA b. IgD c. IgE d. IgG e. IgM
a. IgA
The five classes (isotypes) of immunoglobulins are ___ a. IgA, IgD, IgE, IgG, IgM b. IgA, IgC, IgD, IgE, IgG c. IgA, IgD, IgE, IgH, IgM d. IgA, IgD, IgD, IgE, IgG, IgK e. IgA, IgD, IgE, IgG, IgS
a. IgA, IgD, IgE, IgG, IgM
____ forms dimers, whereas ___ form pentamers: a. IgA; IgM b. IgG; IgD c. IgE; IgM d. IgD; IgM e. IgM; IgG
a. IgA; IgM
subsets of CD4 effector cells
a. TH1 cells produce cytokines that activate MPs, enabling them to destroy intracellular bacteria b. TH2 cells produce cytokines that recruit and activate eosinophils, mast cells, and basophils, and promote barrier immunity at mucosal surfaces c. TH17 cells secrete IL-17-family cytokines that induce local epithelial and stromal cells to produce chemokines that recruit neutrophils to sites of infection early in adaptive immune response d. TFH cells localize in B-cell follicles and produce cytokines of other subsets. -those producing IFN-gamma activate B cells to produce strongly opsonizing antibodies belonging to certain IgG subclasses (IgG1 and 3). -those producing IL-4 drive B cells to differentiate and produce immunoglobulins of other types, especially IgE e. TReg cells suppress T-cell activity and help prevent development of autoimmunity during immune responses
Which of the following is characteristic(s) of a large pre-B cell? a. VH, DH, and JH are successfully rearranged and u heavy chain is made b. V and J are rearranging at the light-chain locus c. u heavy chain and y or k light chain is made d. V is rearranging to DJ at the heavy-chain locus e. D and J is rearranging at the heavy-chain locus
a. VH, DH, and JH are successfully rearranged and u heavy chain is made
Membrane bound IgM and secretory IgM are produced by a process called: a. alternative RNA splicing b. isotype switching c. somatic recombination d. somatic hypermutation e. affinity maturation
a. alternative RNA splicing
Developing B cells that fail to make productive D to J heavy-chain rearrangements on both homologous chromosomes a. die by apoptosis in the bone marrow b. will rearrange heavy-chain loci multiple times unit la productive rearrangement is made c. undergo clonal proliferation d. upregulate expression of transcription factors E2A and EBF e. fail to rearrange V to DJ
a. die by apoptosis in the bone marrow
Heavy chain DH-JH rearrangement begins in the ___ cell stage a. early pro-B b. late pro-B c. large pre-B d. small pre-B e. immature B
a. early pro-B
The antigenic deterring region of an antigen is called ______ a. epitope b. isotype c. allotype d. idiotype e. hapten
a. epitope
The _____ contribute to antigen specificity of immunoglobulins and ____ make up the more conservative flanking regions: a. hypervariable regions (JV); framework regions b. constant domains; variable domains c. heavy chains; light chains d. variable gene segments; joining gene segments e. arrigenic determinatns complementarity determin regions
a. hypervariable regions (HV); framework regions
• Entry of lymphocytes into lymph nodes occurs in distinct stages that include
a. initial rolling of lymphocytes along the endothelial surface, b. activation of integrins c. firm adhesion d. diapedesis across the endothelial layer into the paracortical areas (t-zones)
______ involves successive rearrangement at the light-chain loci when reactivity to self antigen occurs during B-cell development in bone marrow a. receptor editing b. somatic hypermutation c. chromosomal translocation d. clonal deletion e. Energy
a. receptor editing
The enzyme responsible for initiating the recombination of V(D)J segments during somatic recombination is called: a. recombinase (RAG-1 and RAG-2) b. terminal deoxynucleotidyl transferase (TdT) c. activation induced deaminase (AID) d. DNA polymerase e. DNA ligase
a. recombinase (RAG-1 and RAG-2)
The enzymes responsible for initiating the recombination of V, D, and J segments during somatic recombination are ____ a. recombinase RAG-1 and RAG-2 b. terminal deoxynucleotidyl transferase c. exonuclease d. DNA polymerase e. DNA ligase
a. recominase RAG-1 and RAG-2
Lipopolysaccharide (LPS)'s binding to TLR-4 complex sends ____ for B cell activation a. signal #3 b. signal #2 c. signal #1 d. no signal e. all the signals
a. signal #3
The allelic exclusion of immunoglobulin gene expression by a B cell is make sure ____ a. that all the immunoglobulins produced by the B cell are homogenous b. that all the immunoglobulins produced by the B cell are heterogenous c. that the productivity of the B cell is increased d. that the two alleles are co-expressed e. that neither of two alleles are expressed
a. that all the immunoglobulins produced by the B cell are homogenous
An important advantage of having two gene loci (k and y) for the light chain is ____ a. that the likelihood of a successful rearrangement of light-chain genes increases b. that immunoglobulins are homogenous and not heterogenous in mature B cells c. that different effector functions are conferred by the two different light-chain loci d. that surrogate light-chain transcription cannot compete with k and y transcription and enables B-cell development e. all of the above
a. that the likelihood of a successful rearrangement of light-chain genes increases
immune reponse
ability to induce IgE Ab if exposed to some parasites - B cell committed to specific Ab clone - make rearranged genome, N nucs express Ab on cell surface - waiting for Ag to come in - Ag will crosslink Ag - will get signals from T cell teling to divide and differentiate from resting B cell to make Ab and secrete it - then may switch classes (from IgM to IgE, etc.)
Immunogenicity
ability to induce a humoral and/or cell-mediated immune response
Antigenicity
ability to specifically bind to an antibody or B cell and T cell receptors
what are the function of macrophages in the lymphoid tissues
act as scavengers of pathogens and apoptoic lymphocytes to prevent them from entering blood
TNF
activate MPs, induce production of N and O intermediates - source: TH1, some TH2, some CTL
What does TH 1 do?
activated B cells which does antibody producation
T-cell responses are initiated in peripheral lymphoid organs by
activated dendritic cells
which cells has CCR7?
activated dendritic cells
IFN-gamma
activates MP to get rid of mycobacterium inside, destroy it and cure infection
Interaction of B7 on APC with CD28 on T cell is required for
activating naïve CD4+ T cells to make IL-‐2. ¤ If this signal is lacking, the T cell may be inactivated (anergized)
licensing of DC=
activation of DC
Cytotoxic T cell granule release
adhesion molecule LFA-1 mediates initial contact with target cell, binding to ICAM-1. If the T cell receptor finds no specific antigen, the T cell is not stimulated and the two cells disengage. If the T cell receptor does find its specific antigen on the target cell and becomes activated, cytoplasmic organelles of the T cell move to face the target cell. This directs both granule release and new protein synthesis into the interface between the T cell and its target. Certain cytokines, such as IL-2 and IFN-γ, are released from the Golgi and directed to the target cell.
• Entry of lymphocytes into lymph nodes occurs in distinct stages that include a. initial rolling of lymphocytes along the endothelial surface, b. activation of integrins, c. firm adhesion, and d. diapedesis (transmigration) across the endothelial layer into the paracortical areas (T-cell zones). • These stages are regulated by coordinated interplay of
adhesion molecules and chemokines
Lymph nodes are highly efficient in trapping antigen that enters through the
afferent lymphatic vessels
In response to antigen stimulation, antigen-specific B cells proliferating within these germinal centers also undergo a process known as
affinity-maturation to generate clones of cells with higher affinity receptors (antibody) for the antigenic epitope that triggered the initial response
inability to make immunoglobulin
agammaglobulinemia
The delivery of antigen ( as intact antigens or antigen-MHC on DC) from infection to lymphoid tissue is actively
aided by the innate immune response
perforin
aids in delivering contents of granules into cytoplasm of target cell
because of T cell requirement to recognize peptide antigens presented by MHC molecules, what do effector T cells do
all effector T cells act on other host cells, and NOT on the pathogen itself
All immunogens are blank, but not all antigens are blank
all immunogens are antigens, but not all antigens are immunogens
A(n) ____ is a molecule that is used by immune cells for: communication. Interleukin chemoattractant chemokine cytokine all of the above
all of the above
Cross-regulation of various members of a subset of T cells is frequently observed with:
all tH cells
Recombination of Ig segments serves to __________________ (SELECT ALL THAT APPLY)
allow assembly of a complete BCR coding sequence promote BCR diversification
Recombination of Ig segments serves to __________________ (SELECT ALL THAT APPLY)
allow assembly of a complete BCR coding sequence promote BCR diversification
class I MHC
almost all body cells constitutively express class I (except erythrocytes and neurons)
The activation of T cells induced the synthesis of
alpha chain and the formation of the high-affinity heterotrimeric receptors
How do developing B cells make both IgM and IgD?
alternative mRNA splicing -same primary transcript, no rearrangement of DNA -each B cell produces immunoglobulin of a single antigen specificity
When lymph nodes interact with macrophages, T cells and B cells, it brings about
an immune response, manifested by the generation of antibodies and antigen-specific T cells
When neutrophils from a patient with defects in immune cell migration into infected tissues were isolated and tested using in vitro assays for extravasation and interactions between neutrophils and endothelial cells, it was found that the neutrophils could slowly roll along the endothelial vessel wall but were unable to arrest and migrate across the endothelium. The most likely protein deficient in these neutrophils is:
an integrin (e.g. LFA-1)
when a T cell recognizes antigen (signal 1) in the absence of co-stimulatory molecules , the T cell becomes
anergic deleted
When te cells are stimulated first with ANITGEN IN THE ABSENCE OF CO-STIMULATION, they become resistant to subsequwnt activation by specific antigen ene when they antigen was present by APCs expressing co-stimulatory molecules
anergy
You are a new member of a graduate research lab. Your research is to study the effects of a novel cytokine TNF-mu (TNF-μ). During the course of your research, you discover that TNF-μ induces monocyte maturation, inhibits eosinophil development, and begins a signaling cascade that promotes histamine release in mast cells. What term best describes the action of TNF-μ on eosinophils?
antagonistic
monoclonal antibodies induce......?
anti-immunoglobulins
M2 macrophage
anti-inflammatory macrophage
What is the effector molecule of humoral immunity?
antibodies
secreted ...............are produced by an alternative pattern of heavy chain RNA processing?
antibodies
opsonins
antibodies and complement proteins that coat pathogens, facilitating phagocytosis
where are antibodies found prior to encountering an antigen?
antibodies are membrane bound
catalytic antibodies
antibodies that can catalyze chemical reaction s
The medullary area of the lymph node contains
antibody-secreting plasma cells that have traveled from the cortex to the medulla via lymphatic vessels
Immunogen
antigen able to stimulate an immune response
Secondary Lymphoid organs are site of
antigen encounter, and activation to become effector and memory B or T cells.
B cells CONSTITUTIVELY EXPRESS HIGH LEVELS OF MHC CLASS II MOLECULES and high levels of specific peptide: MHC class II complexes which allows be cells to be targeted by
antigen specific CD 4 T cells that have been previously activated
Superantigens are:
antigens that can polyclonally activate T cells (see lecture on antigens) to produce large quantities of cytokines
TH1, TH2, TH17, and TFH T cells,
are helper T cells that activate their target cells
Areas of white pulp are located mainly
around small arterioles; the peripheral regions of which are rich in T cells
when macrophages process antigen how do they display them
as peptide: MHC calss II antigen
how are each of the five effector subtypes different from each other
associated with distinct signals, different transcription factors, and unique cytokines and surface markers
Receptors that are multivalent tend to bind to their ligands more strongly than receptors with a single binding site. What is the term used to describe this phenomenon?
avidity
The immunoglobulin heavy-chain gene consists of ____ segments, whereas the immunoglobulin light-chain consists of ____ segments a. k; lambda b. V, D, and J; V and J c. V and J; V, D and J d. P; N e. RAG-1; RAG-2
b. V, D, and J; V and J
The process that drives an increase in antibody affinity for antigen in germinal centers is known as ___ a. apoptosis b. affinity maturation c. antibody-dependent cell-mediated cytotoxicity d. opsoniation e. clonal expansion
b. affinity maturation
Which statement is correct? a. all antigens are immunogens b. all immunogens are antigens c. antigens are not immunogens d. immunogens are not antigens e. all antigens are immunogens and all immunogens are antigens
b. all immunogens are antigens
Which of the following is NOT a force involved in an antigen-antibody interaction? a. hydrogen bond b. covalent bond c. electrostatic bond. d. hydrophobic force e. van der Waals force
b. covalent bond
The forces used by the antibody/antigen interaction include all of these EXCEPT ____ a. electrostatic forces b. covalent bonds c. hydrogen bonds d. van der waals forces e. hydrophobic forces
b. covalent bonds
B cells are developed in the order of _____ a. early pro-B cell, large pre-B cell, late pro-Bcell, small pre-B cell b. early pro-B cell, late pro-B cell, large pre-B cell, small pre-B cell c. large pre-B cell, small pre-B cell, early pro-B cell, late pro-B cell d. large pre-B cell, early pro-B cell, small pre-B cell, late pro-B cell e. late pro-B cell, large pre-B cell, early pro-B cell, small pre-B cell
b. early pro-B cell, late pro-B cell, large pre-B cell, small pre-B cell
A B cell becomes an immature B cell ___ a. following productive rearrangement of variable region heavy chain gene segments in germ-line DNA b. following productive rearrangement of variable region light chain gene segments in germ-line DNA c. following class switching d. following affinity maturation e. following the formation of pre-B cell receptor
b. following productive rearrangement of variable region light chain gene segments in germ-line DNA
apoptosis is preferable to necrosis why
because apoptosis kills infected kill and pathogen but in necrosis intact pathogen is relased and can continue to infect healthy cells
cytotoxic T cells are selective why
because effector molecules are released from T-cell granules in a highly polar fashion
T cells are incapable of _________. Instead they ______
biding to antigens directly. ; recognize and bind to antigenic peptides when they come in contact with APCs (such as macrophages and DCs and MHC bound peptides.)
RAG complex containing RAG-1 and RAG-2 bind what?
bind RSSs, recruits other rSS, RAG cleaves DNA
Antibodies that are most effective are those that _______ the ____________________ of a pathogen.
bind; exposed surface
migration of naive T cell into peripheral lymphoid tissues depends on their
binding to high endothelial venules (HEVs)
L-selectin
binds to sugar decorating T cells - takes naive T cell out of circulation and into lymph node through HEV- recognize specific HEV lectins
Mature B cells differentiate to fully mature cells within the
bone marrow
dendritic cells arise within _____ and migrate via ______ to tissues throughout the body, and also directly to
bone marrow blod peripheral lumphoid organs
Cell mediated immunity includes ________________
both Th and Tc cells
Which of the following does NOT describe B-cell receptors? a. B-cell receptors are membrane bound b. B-cell receptors consist of a variable region and constant regions c. B-cell receptors lack specificity and can bind to a number of different antigens d. B-cell receptors possess specificity and can therefore bind only to unique epitopes e. B cell receptors undergo affinity maturation as a consequence of somatic hypermutation
c. B-cell receptors lack specificity and can bind to a number of different antigens
The B-cell co-receptor is composed of a. IgA; IgB; CD19 b. IgA; IgB; Lyn tyrosine kinase c. CR2 (CD21); CD19; CD81 d. CD14; CD19; CD81 e. CD40; MHC class II; CED19
c. CR2 (CD21); CD19; CD81
Which of the following describes two recombination signal sequences (RSS) required for a permuted somatic recombination event? a. VH 7-12-9:: 9-12-7 JH b. Vy 7-23-9:: 9-23-7 Jy c. DH 7-12-9:: 9-23-7 JH d. Vk 7-12-9:: 7-23-9 Jk e. VH 9-23-7:: 7-12-9 DH
c. DH 7-12-9:: 9-23-7 JH
Which of the following describes two recombination signal sequences (RSS) required for a permitted somatic recombination event? a. VH 7-12-9::9-12-7 JH b. Vlambda 7-23-9::9-23-7 Jlamda c. DH 7-12-9::9-23-7 JH d. VK 7-12-9::7-23-9 JK e. VH 9-23-7::7-12-9 DH
c. DH 7-12-9::9-23-7 JH
Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells is carried out by their ____ after cross-linking with the Fc regions of IgG1 or IgG3 a. FcyRI b. FcyRII c. FcyRIII d. FcaRI e. FceRI
c. FcyRIII
This antibody binds to FceRI receptor on mast cells a. IgA b. IgD c. IgE d. IgG e. IgM
c. IgE
Which immunoglobulin's main function is to mediate sensitization of mast cells? a. IgA b. IgD c. IgE d. IgG e. IgM
c. IgE
Which of the following is the least abundant isotope in the human serum a. IgA b. IgD c. IgE d. IgG e. IgM
c. IgE
FcyRIII receptor binds to ___ a. IgA b. IgD c. IgG d. IgE e. IgM
c. IgG
Which of the following is the most abundant isotope in the human serum? a. IgA b. IgD c. IgE d. IgG e. IgM
c. IgG
The surrogate light chain of a pre-B cell receptor is composed of a. E2A and EFB b. IgA and IgB c. VpreB and Y5 d. RAG-1 and RAG-2 e. Pax5 and CD19
c. VpreB and Y5 (lambda)
The mechanism that permits immunoglobulins to be synthesized in either a membrane-bound form or a secreted form is ___ a. allelic exclusion b. isotype switching c. alternative RNA splicing d. Ig gene recombination e. somatic mutation
c. alternative RNA splicing
The antigenic deterring region of an antigen is called ___ a. isotype b. allotype c. epitope d. idiotype e. hapten
c. epitope
The antigen-binding site of an immunoglobulin is formed from: a. the V regions of light chains only b. the C regions of heavy chains only c. paired V regions of a single heavy chain and a single light chain d. paired V regions of two light chains e. paired C regions of two heavy chains
c. paired V regions of a single heavy chain and a single light chain
Which of the following antibodies CANNOT be transported across endothelium or epithelium through transcytosis? a. IgG b. dimer IgA c. pentamer IgM d. IgE c. monmer IgA
c. pentamer IgM
The name given to a fully activated and differentiated B cell that secretes antibody is: a. T cell b. antigen-presenting cell c. plasma cell d. hematopoietic cell e. secretory cell
c. plasma cell
On the heavy-chain immunoglobulin gene locus, recombination signal sequences (RSS) flank ___ of the V segment, _____ of the D segment, and ______ of the J segment a. the 5' side; both sides; the 3' side b. the 5' side; the 5' side; the 5' side c. the 3' side; both sides ; the 5' side d. the 3' side; both sides; the 3' side e. both sides; both sides; both sides
c. the 3' side; both sides; the 5' side
The process involving receptor-mediated transport of antibodies from one side of a cell to the other is called a. phagocytosis b. exocytosis c. transcytosis d. signal transduction e. opsonization
c. transcytosis
CD8
can recognize MHC class I on surface of cells, and if cell is infected by virus or expressing a tumor transplantation antigen, CD8 cell can kill it - if cell is exposed to virus and IFN-gamma or is a professional APC, a TH1 cell can kill it via recognition of class II peptide
At the furthest branch of the trabecular artery
capillaries lead to lymphoid nodules; and ultimately the lymphocytes return to the venous circulation through the trabecular vein.
granzymes trigger apoptosis in the target cells by activating
caspases
addressins
cell adhesion molecules of vascular endothelial cells GlyCAM-1, CD34- expressed on HEVs in lymph nodes MAdCAM-1 - expressed on endothelium in mucosae,
Migration of naive T cells into peripheral lymphoid tissues depends on their binding to high endothelial venules (HEVs) through cell-cell interactions that are governed by
cell-adhesion molecules.
The migration of lymphocytes between various lymphoid and non-lymphoid tissue and their homing to a particular site is highly regulated by means of various
cell-surface adhesion molecules (CAMs) and receptors to these moleculces
Fc receptors
cell-surface receptor for for the Fc portion of immunoglobulin isotypes -there are different receptors for different isotypes and subtypes
Component complements their function: C3 C1 C4b, 2a, 3b MASP C6, C7, C8, C9
central component of all 3 begins classical pathway C5 convertase initiating protease of lectin pathway MAC complex
how does immunoglobulin function under diverse conditions? (hint: what do the chains do?)
chains are folded into compact and stable protein domains: Immunoglobulin domain (superfamily)
what is licensing of DC
changes in dendritics that allows them to activate T cells
activation of t cells does what in terms of cell surface molecules
changes the expression of several cell surface molecules
what binds to chemokine receptor CCR7
chemokine CCL21
lymphocytes entry into lymphoid tissues depends on
chemokines and adhesion molecules
CAD
chews up DNA between nucleosomes
types of anti-immunoglobulins
chimeric antibodies-foreign V region with human C region humanized antibodies- foreign CDR, human framework
Coding joint vs. signal joint
chromosome is a coding joint, signal joint is spliced DNA
once developed in the thymus, MATURE NAIVE T CELLS do what
circulate between blood and peripheral lymphoid tissues
T cells encounter their specific antigenon the surface of mature dendritic cells; they lose their ability to exit from the node and become activated to proliferate and to differentiate into effector T cells. After several days, these antigen-specific effector T cells regain the expression of receptors needed to exit from the node, leave via the efferent lymphatics, and enter the
circulation in greatly increased numbers.
Plasmacytoid dendritic cells are sentinels primarily for viral infections, and secrete _________.They are less efficient in priming naive T cells, but they express the intracellular receptors TLR-7 and TLR-9 for sensing viral infections.
class I interferons.
Which complement pathway would be most affected by an absence of RAG1 in developing B cells?
classical
Select the pathway that the following statements refer to (pathways can be used more than once) activated by recognition of antigen-antibody complexes uses the membrane attack complex active in C2 deficient mice activated by ficolins uses factor B involves protease activity C1r associated with this pathway
classical pathway all 3 pathways alternative pathway lectin pathway alternative pathway all 3 pathways classical pathway
antigen-presenting cells deliver three kinds of signals for what
clonal expansion differentiation of naive T cells
MHC class I groove is?
closed at both ends
Peyer's patches are
clusters of lymphocytes distributed in the lining of the small intestine
immature dendritic cells do not express
co stimulatory molecules
Alleles for MHC genes have ___________ expression, meaning that the product (polypeptide) of both parental genes are expressed on the cell surface.
co-dominant
proliferating T cells differentiate into effector T cells that do not require what
co-stimulation to act
- B cells do not constitutively express _______ but, as with dendritic cells and macrophages, they can be induced by microbial constituents to express _______
co-stimulatory activity CD40.
CD40 ligand is a
co-stimulatory signal
One way in which the immune system is able to generate antibodies of different specificities is by generating different combinations of heavy-chain and light-chain V regions. This is known as:
combinatorial diversity
CD45
comes in spliced variants RO- shorter one expressed on activated memory cells RA- expressed on naive cells and memory cells
Because of the central importance of IL-2 in initiating adaptive immune responses, what (e.g., FK506) inhibit this IL-2 dependent pathway.
common immunosuppressive drugs
B cell mechanism of antigen uptake is extremely efficient, ______ the specific antigen in the endocytic pathway.
concentrating
By circulating between the bloodstream and peripheral lymphoid tissues, naive T cells can make
contact with thousands of dendritic cells in the lymphoid tissues every day
what present antigens to and activate naive T cells in the adaptive immune response
conventional dendritic cells
what are the two classes of dendritic cells depending on the cell-surface markers
conventional dendritic cells plasmacytoid dendritic cells
Which of the following types of bonds would be LEAST likely in a receptor-ligand interaction?
covalent bond
lymphotoxin (LT-alpha, TNF-B)
critical in lymph node and spleen architecture, and important in MP organization - if abnormal, inducing immune responses is compromised
what is isotope switching regulated by
cytokines secreted by T cells
activated CD8+ T effector cells are also called
cytotoxic T cells
The principal mechansim of cytotoxic T cell action is the release of specialized _________ upon recognition of anitgen on the surface of a target cell.
cytotoxic granules
Each antigen binding site of an immunoglobin has ____ complemntarity deterring regions (CDRs) or hypervariable regions (HVs) a. 3 b. 4 c. 5 d. 6 e. 7
d. 6
Each binding site of an immunoglobulin has _ complementarity deterring regions (CDRs)/hypervariable regions (HVs). a. 3 b. 4 c. 5 d. 6 e. 7
d. 6
_____ forms dimers, whereas ______ forms pentamers a. IgG; IgD b. IgE; IgM c. IgD; IgM d. IgA; IgM e. IgM; IgG
d. IgA; IgM
A newborn derives passive immunity from its mother as a result of placental transfer of ___ during pregnancy a. IgA b. IgD c. IgE d. IgG e. IgM
d. IgG
A primary focus forms after a circulating mature (naive) B cell forms a conjugate pair with a ___ and migrate to the ___ of a lymph node a. TH cell; B-cell zone b. cytotoxic T cell; T cell zone c. follicular dendritic cell; germinal center d. TH cell; medullary cords e. CD40 ligand; T-cell zone
d. TH cell; medullary cords
The immunoglobulin heavy-chain gene consists of ____ segments, whereas the immunoglobulin light-chain gene consists of _____ segments a. K; lambda b. V and J; V, D, and J c. P; N d. V, D, and J; V and J e. RAG-1; RAG-2
d. V, D, and J; V and J
Antibody's biological functions include all of these EXCEPT ____ a. activation of the classical pathway of the complement system b. neutralization of pathogens c. activation of phagocytosis d. activation of T cells e. initiation of antibody-determined cell-mediated cytotoxicity (ADCC)
d. activation of T cells
Recombination of immunoglobulin gene segments serves to a. promote immunoglobulins diversification b. assemble a complete immunoglobulin coding sequence c. allow changes in coding information during a B-cell development d. all of the above e. none of the above
d. all of the above
IgM and IgD are co-expressed on mature (naive) B cells by a process called: a. isotype switching b. somatic recombination c. somatic hypermutation d. alternatives RNA splicing e. affinity maturation
d. alternative RNA splicing
Mature B cells are activated in ____ a. bone marrow b. thymus c. blood d. secondary lymphoid tissues e. none of the above
d. secondary lymphoid tissues
True
defective in killing target cells than those that lack Cytotoxic T cells that lack expression of perforin are more granzymes
Thymic involution
degeneration of thymic cells and replacement with adipose tissue
Hematopoietic stem cells cultured in the presence of which molecule differentiate into T cells rather than B cells?
delta ligands
Which type of professional antigen-presenting cells is most likely to activate a naïve T cell?
dendritic cell
Lymphocytes exit the blood and enter the lymph node by extravasating at the high-endothelial venules (HEVs) present in the lymph node cortex. Extravasation does NOT require which of the following?
dendritic cells
what are the different ways of activating T cells among dendritic cells, macrophages and B cells
dendritic cells take up, process and present all types of sources, drive initial clonal expansion and differentiation of naive T cells into effector T cells. Macrophage process and present intracellular pathogens and B cells process and present soluble antigen; both macrophages and B cell interact mainly with already primed effector CD 4 T cells
properties of APCs (dendritic cells, macrophages, and B cells)
dendritic cells: antigen uptake by phago- and macropinocytosis, co-stimulation delivery constitutive by mature, nonphagocytic lymphoid dendritic cells, effect results in activation of naive T cells - really effective at activating naive cells macrophages: phagocytosis, inducible by bacteria and cytokines, results in activation of macrophages. also co-stimulatory B cells: Ig specific to Ag, in lymphoid tissue and peripheral blood, results in delivery of help to B cell - all can take in, process, and present specif Ag with high efficiency of taking up cell - MHC expression low on immature dendritic cells, but once activate, go to LN, make high MHC - all can be induced by cytokines- B cells always exp. a lot of those - B7 - co-stimulatory molecule- constitutively expressed- can be induced again and again
types of immune responses
depend on what pathogen is, how it's coming it, what it's making - receptor-mediated endocytosis, opsonization by complement or antibody receptors (brought in and degraded) - exp class II - CD4 cells activated because want to make Ab against Ag
Primary Lymphoid organs are site of
development of immunocompetence as B or T cells
The mechanism that permits Ig to be synthesized in either membrane bound or secreted form is
differential RNA processing
The mechanism that permits Ig to be synthesized in either membrane bound or secreted form is ___________ (SELECT ALL THAT APPLY)
differential RNA processing
after 4-5 days of rapid proliferation induced by IL-2, activated cells do what
differentiate into effector T cells that synthesize all the molecules required for their specialized helper or cytotoxic function
B cells expressing BCRs bind
directly to antigens for which they are specific
The five effector subtypes are associated with
distinct singals
Priming antigen-presenting cells, principally dendritic cells, provide signal 3 in the form of various cytokines or express surface proteins that induce the development of CD4 T cells into
distinct types of effector cells
junctional diversity
diversity present in immunoglobulin and T cell receptor polypeptides that is created during the process of gene rearrangement by the addition or removal of nucleotides at the junctions between gene segments
CTLs
don't help with bacteria (doesn't express MHC, so won't be able to kill with CTL) - but can kill with Ab complement or by phagocytosis - if in gut, can coat with Ab - will leave as waste
Toll-like receptor 3 (TLR3) Pattern recognition receptor recognizes:
dsRNA
Stromal cells in bone marrow are critical for B cell development by providing with the following growth factors EXCEPT ______ a. stem cell factor (SCF) b. IL-7 c. stromal cell-derived factor 1 (SDF-1) d. pre-B cell growth-stimulating factor (PBSF) e. IL-4
e. IL-4
B cells at primary focus in a lymph node after activation with a T-dependent antigen differentiate into plasma cells that secrete predominantly _____ a. IgD b. IgE c. sIgA d. IgG e. IgM
e. IgM
The secreted form of this antibody is a pentamer of the basic H2L2 unit a. IgA b. IgD c. IgE d. IgG e. IgM
e. IgM
Which of the following is the first antibody produced in an immune response and can be detected in serum? a. IgA b. IgD c. IgE d. IgG e. IgM
e. IgM
which of the following corresponds to the antigen binding site of an immunoglobulin? a. VH: CH b. VL: CL c. CH: CL d. VH:CL e. VH:VL
e. VH:VL
Which of the following characterizes the B-1 cells that develop prenatally? a. They express CD5 b. They possess polyspecificity for bacterial polysaccharide antigens c. They arise early in embryonic development preceding the development of the majority subset of B-@ cells d. they have restricted V region repertoire e. All of the above
e. all of the above
Generation of combinatorial diversity of the antigen binding sites among immunoglobulins involves all of these EXCEPT___ a. RAG-1 and RAG-2 b. DNA rearrangment c. recombination signal sequence (RSS) d. one-turn/two-turn joining rules e. alternative RNA splicing
e. alternative RNA splicing
Mucosal epithelia of the gastrointestinal tract, eyes, nose, throat, the respiratory, urniary, and genital tracts, and the mammary glands are protect by a. IgG b. IgM c. IgE d. monomeric IgA e. dimeric IgA
e. dimeric IgA
Mucosal epithelia of the gastrointestinal tract, eyes, nose, throat, the respiratory, urniary, and genital tracts, and the mammary glands are protect by: a. IgG b. IgM c. IgE d. monomeric IgA e. dimeric IgA
e. dimeric IgA
The name given to a fully activated and differentiated B cell that secretes antibodies is: a. T cell b. antigen-presenting cell c. hematopoietic cell d. secretory cell e. plasma cell
e. plasma cell
gene regulation in B cell development
each B lymphocyte produces immunoglobulin of a single antigen specificity
most naive CD 8 t cells requires what to be activated
effector CD 4 t cells
Lymph, antibodies, and cells leave the lymph node through the
efferent lymphatic vessel which is just below medullary region
The spleen contains ___________ through which lymph empties into the _________ from which the cells continue their recirculation through the body and back to the afferent vessels
efferent lymphatic vessels; lymphatics
Which of the following is MOST likely to simulate/activate a memory T cell?
either b cell, dendritic, or macrophage
Fas and Fas ligand
enable T cell to kill target cell through same pathway as CTL but activated at different point
Blood lymphocytes must generally cross the
endothelial vascular lining of postcapillary vascular sites which are termed high endothelial venules (HEVs) to enter tissues
humanized antibodies
engineer CDR sequences onto human framework regions -heavy and light chain CDR loops of a human IgG are replaced by the corresponding CDR loops from the mouse monoclonal antibody -humanized antibody does not produce a strong anti-IgG response
CD4 TH17 cells
enhance neutrophil response, promote barrier integrity. pathogens: fungi - secrete IL-17 and recruit neutrophils to site of inflammation - fungal infections - also in autoimmune - LMS- in brain - also in scar tissue
Activation Induced cytidine deaminase (AID)
enzyme made only in proliferating B cells, causes cells to have mutant receptors which compete for antigen binding -converts C to U, then modified by normal DNA repair mechanisms
terminal deoxynucleotidyl transferase (TdT)
enzyme that inserts non-templates nucleotides (N nucleotides) into the junctions between gene segments during the rearrangement of the T cell receptor and immunoglobulin genes -increases immunoglobulin diversity by factor of 10
When a naive T cell recognizes its specific antigen it stops migration and profilerates (also known as clonal expansion) and differentiates into effector T cells and memory cells of identical antigen specificity. at the end of this period, what does the effector T cells do
exit into the efferent lymphatics and reenter the bloodstrea, through which they mighrate to the sites of infection
professional APCs
express MHC class II - MPs: CD4+ cells and are therefore susceptible to infection by HIV as well, since HIV invades immune cells through CD4+ receptor interactions. - lymphocytes: B cells: express (as B cell receptor) and secrete a specific antibody, can internalize the antigen, which bind to its BCR and present it incorporated to MHC II molecule, but are inefficient APC for most other antigens - dendritic cells: Activated DCs are especially potent TH cell activators because, as part of their composition, they express co-stimulatory molecules such as B7. This B7 co-stimulator of mature interdigitating dendritic cell (IDC) interacts with surface CD28 of naïve T-cell
The process by which Blood lymphocytes endothelial vascular lining of postcapillary vascular sites is called
extravastion
A hapten can stimulate antibody formation, but cannot bind antibody molecules true/false
false
All immunoglobulin molecules on the surface of a given B cell have the same isotype.
false
B cell epitopes can be deduced with great accuracy from the primary structure of a protein
false
C3a and C3b are fragments of C3 that are generated by two different enzymes.
false
Expression of the beta-subunit of the IL-2 receptor indicates T cell activation.
false
Following TCR or BCR signaling, the most important events downstream of kinase activation are the activation of transcription factors leading to new gene expression.
false
In a lymph node, nTreg cells are able to inhibit the responses of other T cells in their vicinity. This inhibition is specific, as the nTreg cell and the naive T cell must share the same antigen specificity.
false
In generating a B cell receptor gene, Vkappa segments sometimes join to Clambda segments
false
In some infectious diseases, antibodies specific for the pathogen are not essential for clearing a primary infection with that pathogen, but are essential in preventing re-infection by the same pathogen. This protective role of pathogen-specific antibodies is not useful for any clinical applications.
false
MHC class I surface expression is dependent on an abundant source of pathogen-derived peptides. Thus, in uninfected cells, nearly all of the MHC class I proteins are degraded and never reach the cell surface.
false
Most eukaryotic genes are encoded in a set of exons that are brought together to form a contiguous protein coding sequence by the process of mRNA splicing. In contrast, immunoglobulin genes use somatic recombination of gene segments and not mRNA splicing to generate the final mRNA that is translated into protein.
false
Mucosal surfaces and external epithelia are major routes of pathogenic infection. Mucosal surfaces are found in tissues such as the gastrointestinal tract, the reproductive tract and the mouth and respiratory tract. While the mouth and respiratory tract are routes of virus but not bacterial infections, the gastrointestinal tract is the route for bacterial but not virus infections.
false
Once B cells begin secreting antibodies, they cease dividing and have a life-span of only a few days.
false
Our immune system efficiently kills all categories of microbes that attempt to colonize our bodies.
false
The C3 convertase amplifies the process of complement activation by generating large amounts of C3b and cleaving large numbers of C5 molecules.
false
The acute phase response contributes to infection control by producing molecules that promote pathogen opsonization and complement activation. This response is only induced by direct action of microbial components on hepatocytes in the liver.
false
The enzymes that cleave C3 and C4 are referred to as convertases
false
The switch in constant region use from IgM to IgD is mediated by DNA rearrangements
false
(t/f) plasma cells have cell-surface antigen receptors
false.
complementarity-determining regions are flanked by what?
framework regions- correspond to b strands and remaining loops
what does GRAIL stand for
gene related anergy in lymphocytes
In order to respond effectively to a great diversity of parasite antigens, chordates have evolved several mechanisms of __________ to generate potentially infinite possible receptors.
genetic recombination
B cells are present mainly in
germinal centers
After antigenic stimulation, ________contain large numbers of B cells and plasma cell and they ....
germinal centers; synthesize and release antibodies
Innate immune cells use what to detect and respond to microbes and other foreign antigens?
germline-encoded receptors
GM-CSF
goes to bone marrow- induces production of more cells to fight infection
Which of the following is NOT an HIV-1 restriciton factor?
gp120 Those that are: TRIM5a SAMHD1 APOBEC3G Tetherin
has antimicrobial activity and at high concentrations is also able to induce apoptosis in target cells
granulysin
what trigger apoptosis
granzymes
what type of cytotoxic class is this...a family of serine proteases that TRIGGER APOPTOSIS
granzymes
Major cytotoxins of CD8+ cells are
granzymes preforin granulysin
MAdCAM-1
guides lymphocyte entry into mucosal lymphoid tissue such as Peyer's patches in gut. recognized by different selectins - velcro composed of intrgrins (bind different cell adhesion molecules) that helps cells interact - recognized by selectin through sugar side chain - can bind Ag and complement or MBL, etc.
T cells selected on a b haplotype thymus would be able to respond to antigen presented on which of the following haplotype antigen presenting cells?
haplotype b and haplotype a x b
granulysin
has antimicrobial actions and can induce apoptosis - activates cascade- results in apoptosis
APC
has both class I and II on surface
A naïve T cell refers to a T cell that:
has not yet encountered an antigen.
mature dendritic cells in the t cell zone increase their ability to active T cells in what 2 ways
have high levels of adhesion molecules, secrete chemokine CCL18 and attract naive T cells.
two types of RSS
heptameter and nonuser separated by 12 vs 23 amino acids
neutralizing antibodies
high affinity IgA and IgG antibodies that bind to pathogen and prevent their growth or entry into cells
mast cell
high-affinity receptor for IgE and induce production of specific classes of Ab
Arterial blood lymphocytes enter the spleen through the ________ and pass into the _______
hilus; trabecular artery (which becomes narrow and branched)
the effector T cells exit into the efferent lymphatics and reenter the bloodstream, through which they migrate to the sites of infection, the migration to the site of infection is also known as
homing
hybdiroma
hybrid cell lines that make monoclonal antibodies of defined specificity. they are formed by fusing a specific antibody producing B-LYMPHOCYTE WITH A MYELOMA CELL THAT GROWN IN TISSUE CULTURE AND DOES NOT MAKE ANY IMMUNOGLOBULIN CHAINS OF ITS OWN
is the C terminal associated with cell membranes hydrophobic or hydrophilic?
hydrophobic
AID deficiency
hyper- IgM syndrome -no somatic hypermutation or class switching, only produce low affinity IgM
An antigen binding site is formed from the .............. regions of a ...........V domain and a light chain ........ domain
hypervariable, heavy chain, V
APC will neither activate or inactive T cell if what is present
if only co-stimulatory molecule is present without specific antigen
Langerhans cells are a type of
immature conventional dendritic cells in the skin
induced maturation of tissue dendritic cells follow what steps
immature dendritic cells are activated via TLRs or PRRs, by damage tissues or by chemokines from the inflammatory response activated dendritic cells migrate to the lymph node and express co-stimulatory molecules that are needed for the activation of naive T cells. the mature dendritic cells present antigen to naive T cells and activate any antigen specific T ccells to divide and matuere into effector cells that reenter the circulation
one ability of a monoclonal antibody is to
immortalize B cells from immunized animals
monoclonal antibodies
immortalize B cells from immunized animals -antibody produces by a single clone of B lymphocytes so that all antibody molecules are identical in structure and antigen specificity -treat diseases by blocking signaling, target cells for NK - mediated clearance -can induce anti-immunoglobulins
T cells in circulation
immune surveillance - take temp of body, make sure all is ok. come into lymph node- if nothing there, return to circulation - if their specific Ag is in lymph node, all Ag-specific clones stay in lymph node temporarily to divide and differentiate - period where efferent doesn't have clones because all in lymph node
antisera
immunize animals, quality depends on purity of immunogen
CD2
immunoglobulin superfamily adhesion molecule in T cells that
ICAM-1
immunoglobulin superfamily adhesion molecule in activated vessels, lymphocytes, and dendritic cells that can see LFA-1 and Mac-1 ligand
LFA-3
immunoglobulin superfamily adhesion molecule in lymphocytes and APCs that binds CD2 ligand
ICAM-3
immunoglobulin superfamily adhesion molecule in naive T cells that binds to LFA-1 ligand
ICAM-2
immunoglobulin superfamily adhesion molecule in resting vessels that binds to LFA-1 ligand
TGF-B
important for Treg, TH17, and TFH - gives IgA and regulatory T cells - knockout = embryonic fatal
what would be the effect of nonfunctional gamma chain receptor?
in individuals without gamma chain, have null allele because cytokine chain is in 1/2 dozen immune receptors - one of forms of SCID because immune responses are dead without functional cytokine receptor for so many cytokines
HLA-G is expressed
in placental trophoblast cells, possibly preventing rejection of fetus by maternal immune system
Antigen recognition in the absence of co-stimulation leads to functional
inactivation or clonal deletion of peripheral T cells
inflammatory reaction at the site of infection does what
increase the number of blood plasma which increases drainage of extracellular fluid into the lymph taking with it free antigen
IFN-γ induces what and activates what
increased expression of MHC class I molecules actiavtes marcophages
CCR7 directs migration into lymphoid tissues and
increases expression of co-stimulatory molecules and MHC MOLECULES
VCAM-1
induced by all cytokines - immunoglobulin superfamily adhesion molecule in activated endothelium that binds VLA-4 ligand (located on an endothelial cell, binds to the integrin VLA-4 which are normally expressed on leukocyte plasma membranes, but they do not adhere to their appropriate ligands until the leukocytes are activated by chemotactic agents or other stimuli (often produced by the endothelium or other cells at the site of injury). Only then do the integrins undergo the conformational change necessary to confer high binding affinity for the endothelial adhesion molecules) In multiple sclerosis, the VLA-4 integrin is essential in the processes by which T-cells gain access to the brain by allowing the cells to penetrate the blood brain barrier that normally restricts immune cell access.)
what type of regulatory T cell is this, differentiate from naive CD 4 T cells in the periphery under the influence of particular environmental conditions
induced regulatory T cells or adaptive regulatory T cells
IL-4
induces exp. of GATA3 characteristic of TH2 cells - drives production of IL-4,5, and 10 by TH2 cells - microenvironment in which naive T cell is activated determines subset of T cells and effector function - important for killing - critical for certain Ab classes - class II molecules -> enhances ability to promote Ag - also a growth and survival signal for TH2 cells - but shuts dwon MP activation - good for mast cells - allergy - w/o, lack TH2 cells
RORgammaT
induces transcription and translation of IL-17. Also need IL-23 (1st cousin of IL-12- both made by APCs) - IL-12 and IFN-gamma -> T-bet -> in
Two different vaccines have been developed that protect vaccinated individuals against pneumococcal disease, a bacterial infection that causes pneumonia, meningitis and sepsis (blood stream infection). This disease is caused by the bacteria, Streptococcus pneumoniae. One vaccine, PPSV23, is a mixture of polysaccharides isolated from 23 different serotypes of S. pneumoniae. The second vaccine, PCV13, is a conjugate vaccine made from polysaccharides of 13 different serotypes of the bacteria conjugated to diphtheria toxoid (inactivated toxin protein). The PPSV23 vaccine is only given to adults, whereas infants and small children are given PCV13. This is because:
infant B cells are immature and don't respond to TI-2 antigens
The delivery of antigen from an infection to lymphoid tissues is actively aided by the innate immune response by what two ways
inflammatory reaction induced maturation of tissue dendritic cells
All of the following are functions of TH1 cells EXCEPT
inhibit anti-tumor responses
All of the following are functions of TH1 cells EXCEPT: can contribute to autoimmunity inhibit anti-tumor responses enhance APC activity. protects against intracellular pathogens. enhance TC activity.
inhibit anti-tumor responses
All of the following are functions of TH1 cells EXCEPT: can contribute to autoimmunity inhibit anti-tumor responses enhance APC activity. protects against intracellular pathogens. enhance TC activity.
inhibit anti-tumor responses
Immunofluorescence
instead of using enzyme, antibody can be conjugated with fluorochrome to detect antigen
In the GTP bound state, small GTPases contribute to signaling by:
interacting with target proteins and altering their activity.
During Ig VH recombination, the processes that contribute to additional diversity at the third complementarity-determining region include ____________. (SELECT ALL THAT APPLY)
introduction of the D gene segments into the heavy-chain V gene exonuclease cleavage of the ends of the gene segments P nucleotide addition N nucleotide addition
During Ig VH recombination, the processes that contribute to additional diversity at the third complementarity-determining region include ____________. (SELECT ALL THAT APPLY)
introduction of the D gene segments into the heavy-chain V gene exonuclease cleavage of the ends of the gene segments P nucleotide addition N nucleotide addition
isotope( class switching)
involves DNA recombination - dependent of AID (only in proliferating B cells) -new C segment brought into juxtaposition with rearranged V region- no change in antigen specificity -excises previously expressed C gene
TH17 does what
it activated naive CD 8 T cells for viral infections
what does it mean when a B cell is naive?
it has not encountered antigen (still mature B cell) -express IgM and IgD on cell surface
L chain isotypes
k and I isotypes, no functional differences -k more abundant in humans (2/3) of antibodies
as well as killing the host cells, the apoptotic mechansim may also directly do what
kill cytosolic pathogens
Which of the following is NOT a property of cytokines?
kinase activity
what is the germline configuration of the gene segments of an antibody?
l(leader peptide) ,v region,c region,
_______take up antigen in the skin, migrate to the peripheral lymphoid organs, and present antigens to T cel
langerhans cells
since langerhans cells do not have co stimulatory activity what must they do
langerhans leave the skin and center the lymphatic system, so the mature dendritic cells transfer antigen to resident dendritic cells.
when chemokine CCL21 binds to chemokine receptor CCR7 what happens this changes behavior in dendritic cells and this known as
licensing
LFA-1
ligand that can see ICAM-1, 2 and 3
The number of different antibodies that can produced by the human body seems
limitless
linear vs. conformational epitopes
linear is composed of successive amino acids of protein, conformational are brought together in 3D structure -only non-covalent forces -binding affinity depends on shape and composition of antigen binding site
T-‐B cooperation in response to TD Ag is called
linked recognition
IgG3
longer hinge region; most effective at complement activation, shorter half life -deficiency of IgG3- recurrent infection, chronic lung disease
initial phase of immune response(IgM)
low affinity of IgM. -cell surface monomer; secreted as pentamer with J chain pentamer form increases avidity -limited in effector functions: binding to antigen exposes complement binding site in C region
Secondary lymphoid organs are
lymph nodes and spleen, tonsils, Peyer's patch in small intestine, appendix
peripheral lymphoid organs are
lymph nodes, - spleen, - the mucosa-associated lymphoid tissues such as the Peyer's patches in the gut.
afferent lymphatic circulation
lymphatic circulation going into lymph node - draining tissue
Red bone marrow is site of
lymphocyte origin
Continual lymphocyte circulation is needed because:
lymphocytes have a small chance or recognizing a particular antigen.
The thymus is a
lymphoepithelial organ and consists of epithelial cells organized into cortical (outer) and medullary (central) areas that are infiltrated with lymphoid cells (thymocytes)
macrophages are found in most tissues including BC located primarily in
lymphoid tissues lymphoid tissues
chemokine CCL21 is produced by _____ and facilitate their migration through what and into what
lymphoid tissues and facilitates their migration through the lympahtics and into the local periphery lymphoid tissues
When vesicular stomatitis virus (VSV) is used to infect mice via footpad injection, viral particles are trapped in the draining lymph node (the popliteal lymph node) within 5 minutes of injection. These viral particles are then retained in the lymph node for many hours, where they can be visualized on cells that are interacting with B cells. The cells retaining the viral particles in the lymph node are not tissue-resident dendritic cells that have migrated to the lymph node with the virus, as this process takes much longer than 5 minutes. In which region of the lymph node would you expect to find the trapped viral particles and on which cells? The virus particles are trapped on___
macrophages in the subcapsular sinus
Within the lymph node, antigens interact with
macrophages, T cells, and B cells;
CD4 TH1 cells
main functions in adaptive immune response: activate infected MPs, provide help to B cells for Ab production. pathogens targeted: microbes in MP vesicles (mycobacteria, Leishmania), extracellular bacteria - help control bacteria that can set up intravesicular infections in MPs - kill target with virus expressing right MHC - enable B cells to make certain classes of Ab, secrete cytokines important for intracellular bacterial infections - secretes IFN-gamma - if B cell is in environment rich in CD4 TH1, will make IgA or IgG Ab, not IgM - if have IgG Ab to allergen, doesn't affect allergy symptoms - IgE is type I histocompatability mediated for allergies, IgG is type II/III for autoimmune - competition: IgG (10) prevents binding of IgE (5) to cell surface binding site, which prevents allergies
The primary or central lymphoid organs are those in which the
maturation of B and T lymphocytes into antigen-recognizing lymphocytes occurs. Where gene rearrangements occur to generate functional antigen-specific BCR and TCR expressed by B and T cells
where is immunoglobulin first made?
membrane bound- it is present on the b cell surface -hydrophobic sequence near C terminus of H chain- associates with cell membranes -initially synthesized into ER, must associate with invariant transmembrane proteins Iga and Igb in order to be transported to cell surface
At the same time as providing effector T cells, the primary T-cell response also generates_______, long-lived cells that give an enhanced response to antigen, which yields protection from subsequent challenge by the same pathogen
memory T cells
- CCL21 signaling through CCR7 not only induces the _____of dendritic cells into lymphoid tissue, but it also contributes to their ____
migration maturation
Naive T cells, the β and γ chains are expressed constitutively. They bind IL-2 with
moderate affinity
Cytotoxic granules are ______________ that contain distinct classes of cytotoxic effector proteins that are expressed specifically in cytotoxic T cells
modified lysosomes
Antigen
molecules that can be bound by antibodies or B feel and T cell receptors
chimeric antibodies
monoclonal antibody that combines mouse variable regions with human variable regions -(foreign V region with human C region)
Because the effector actions of cytotoxic T cells are so destructive, naive CD8 T cells require __________ than do naive CD4 T cells.
more co-stimulatory activity
IgG
most abundant in blood and lymph -hinge region= greatest conformational flexibility -increased simultaneous binding to two sites on pathogen and effector molecules (complement, Fc receptors -more functions: opsonization, placental transfer
IgG1
most abundant, intermediate in flexibility, susceptibility to proteolysis, complement activation
The skin and bodily secretions provide the first line of defense against infection. One response in this category that is common during upper respiratory virus infections is:
mucus production
on antigen recognition, naive T cells differentiate into effector T cells, what are those effector T cells
naive CD 8 T cells naive CD4 T cells
what type of regulatory T cell is this committed to a regulatory fate while still in the thymus
natural regulatory T cells
Apoptosis is therefore pregerable to
necrosis
In type III Immune response, both TH17 and ILC3 cells secrete IL-17 to activate:
neutrophils
langerhans cells are one type of immature dendritic cells that resides in the epidermis, they ingest antigens in various ways but have
no co-stimulatory activity
The _______ that are activated in apoptosis to destroy cellular DNA can also degrade viral DNA, preventing the assembly of virions and the release of infectious virus, which could otherwise infect nearby cells.
nucleases
HLA-DR
on Which of the following antigens is classified as an MHC class Il antigen?
Toll-like receptors are located _____.
on the plasma membrane and endosomal membranes
"arm" of antibody
one complete L chain covalently linked to N-terminal part of one H chain
The efficiency with which T cells screen each APC in lymph nodes is very high. Such efficiency is crucial for the initiation of an adaptive immune response, as only ________ is likely to be specific for a particular antigen
one naive T cell in 104-106
VLA-4
only on activated/effector cells
allelic exclusion:
only one H chain and one L chain are rearranged to produce functional genes
avidity
overall strength of binding
compostite hypervariable surface
pairing of L and H chains brings together HV loops from Vl and Vh
P nucleotides
palindromic nucleotides added to the junctions between immunoglobulin and T cell receptor gene segments during somatic recombinations that generate a rearranged variable region sequence. they are an inverse repeat (palindrome) of the nucleotide sequence at the end of the adjacent gene segments -opening of hairpin end can occur in several locations, introducing palindromic sequences
immature dendritic cells in the peripheral tissues encouter pathogens are activated by
pamps
Mice deficient in the enzyme MMP7, that cleaves prepro--defensin to the active -defensin, show an increased susceptibility to the enteric pathogen, Salmonella typhimurium. The cell type in the gastrointestinal (GI) epithelium most likely to express the highest levels of MMP7 is:
paneth cells
IgG is cleaved into Fab and Fc by what?
papain (protease)
antigenic determinant (epitope)
part of antigen to which antibody binds -wide range of chemical structures -can be multiple epitopes on complex macromolecules (multivalent) identical or different -antigen binding site of immunoglobulin varies according to epitope size and shape
TLR signaling incudes CCR7 and enhances processing of
pathogen-derived antigens
what induces migration to lymphoid organs and enhances antigen processing?
pathogen-induced TLR signaling in immature DCs
CD4+ T cells recognize:
peptides bound to MHC Class II
CD4+ T cells recognize:
peptides presented on MHC class II
Lysozyme splits:
peptidoglycan
what types of cytotoxic class is this....forms PORES in the target cell membrane for delivery of the contents of cytotoxic granules to target cell
perforin
cytotoxic effector proteins released by cytotoxic T cells
perforin, granzymes, and granulysin
Adaptive immune responses are initiated in the
peripheral lymphoid organs
what are the 4 different methods that immature dendritic cells in the peripheral lymphoid tissues and at the site of infections use to capture pathogens.
phagocytic receptors lectins different types of TLR's receptors for complements
immature conventional dendritic cells actively ingest antigens by many different mechansims that enable them to present antigens from virtually any type of pathogen, what are those mechanisms
phagocytosis macropinocytosis direct entry into the cytosol like viral infection cross presentation antigen transfer between dendritic cells
Most effector T cells migrate out of secondary lymphoid organs and into tissues to exert their function. In which of the cases shown in the figure below will the TH1 effector cell undergo long-lived interactions with its target cell, an infected macrophage? Assume all of the target cells shown below are infected with the pathogen recognized by the specific TH1 cells.
picture A
what produce interferon in the innate immune response
plasmacytoid dendritic cells
somatic hypermutation
point mutations at a high rate due to random process (1 substitution per V region sequence per cell division) -diversification of entire L and H chain V regions -immunoglobulin C regions and other genes not affected -dependent of AID
Specific recognition by the T-cell receptor identifies which target cell to kill, and the ___________ ensures that neighboring cells are spared
polarized release of the cytotoxic granules
Blood lymphocytes enter the lymph nodes through ________ and leave through the __________
post-capillary venules; efferent lymphatic vessels
IL-10
prevents APCs from presenting Ag - to shut down immune responses - shuts down Ag processing and presentation in MPs, cytokine release and TH1 cells - without anti-inflammatory cytokine, IBD and chron's disease result
The activation of naive T cells in response to antigen, their subsequent proliferation and differentiation into effector cells, and their acting on the target cells, constitute a
primary cell-mediated immune response.
The cortical region of lymph nodes contain
primary lymphoid follicles; after stimulation they enlarge to form secondary lymphoid follicles with germinal centers containing dense populations of lymphocytes (mostly B cells) that are undergoing mitosis.
Macrophages and B cells also present antigen to T cells, not to _____ it but to get specific help from effector T cells
prime
mature dendritic cells in the T-zones do what
primes naive T cells
The activation and clonal expansion of a naive T cell on its initial encounter with antigen is often called
priming
The activation and differentiation of naive T cells into effector T cells is called
priming
Mature conventional dendritic cells are primarily concerned with the activation of naive T cells. They express MHC proteins and costimulatory molecules for
priming naive T cells
what is the difference between professional APCs and non-professional APCs
pro=DC, macrophage, B cell MHC II and has co-stimulatory signals
finite maturation
progressively higher affinity antibodies as immune response proceeds
A naive T cell must meet its specific antigen ( as a peptide: MHC complex on APC) and be induced to
proliferate and differentiate into effector T cells
IL-2 receptor has a much higher affinity for IL-2, IL-2 then triggers what
proliferation survival and differenation of T cells into effector T cells.
TH17 cells are involved with all of the following EXCEPT:
protection from viral infections
TH17 cells are involved with all of the following EXCEPT: protection against bacterial infections. inflammatory response. protection against fungal infections. protection from viral infections autoimmunity.
protection from viral infections
TH17 cells are involved with all of the following EXCEPT: protection against bacterial infections. inflammatory response. protection against fungal infections. protection from viral infections. autoimmunity.
protection from viral infections
immunoglobulin domain
protein structure module consisting of about 100 amino acids that fold into a sandwich of 2 B sheets he'd together by a disulfide bonds. Immunoglobulin heavy and light chains are made up of a series of immunoglobulin domains.
CD4 TH2 cells
provide help to B cells for Ab production. pathogens targeted: helminth parasites - tell B cells to react with allergens, which program them to make IgE Ab - secretes lots of cytokines when activated by specific Ag - many different cell tty
Iga and Igb
provide signaling to intracellular proteins upon binding of antigen to cell-surface IgM
M1 macrophage
provides cytokine signal the naive T cell needs to be able to become TH1 cell
The reticuloendothelial system not only traps antigens, but also
provides loci (the secondary lymphoid organs) where antigen, macrophages, T cells, and B cells can interact within a very small area to initiate an immune response
Antigen NON-specific B cells are
pushed to the outside to form the mantle zone
Cytotoxic T cells can recycle to kill multiple targets. Each killing requires the same series of steps, including
receptor binding and the direct release of cytotoic protein that is stored int he granules
CTL
recognize specific class I - vecro holds those cells together - when binding, microtubule organizing center realigns with TCR and target cell interactions, which include perforin and other effector molecules - get realigned at tight junction between cells -releases contents in polarized fashion
S1P1 cell-surface molecule and damage prevention
recognizes phosphospingosine -lipid in blood and some tissues - receptor expressed on naive but not cells that have started to divide/differentiate! drop exp of receptor in those cells until leave LN - some drugs directed against it - block ability of activated T cells to leave LN and go into tissue - prevent further damage in MS - effector T cells leave LN/spleen and attack myelin - if have Ab that blocks interaction can also prevent activated T cells from leaving blood and going to tissues - hard to block specific immune responses with transplanted organs, only all or nothing
genes of VDJ recombinase
recombination activating genes: RAG-1 and RAG-2
IL-17
recruits neutrophils - important in autoimmune diseases
B cells develop immunocompetence in
red bone marrow
B-cell proliferation is triggered by IL-2, IL-4, and IL-5. Each of these cytokines is secreted by activated TH cells thus their action is:
redundant
Bcl6
regulates IL-2 and ICOS production by TFH cells
joining (j) segments
relatively short DNA sequence present in multiple different copies at all immunoglobulin and T cell receptor loci -at gene rearrangement, a J and V gene segment are joined directly in immunoglobulin light-chain genes and T cell receptor a and l chain genes, and via a D gene segment in the immunoglobulin heavy-chain gene and T cell receptors B and d chain-genes
Cytotoxic T cells attached to several different target cells _____________ (by reorient their Golgi apparatus and microtubuleorganizing center) toward each cell in turn and kill them one by one.
reorient their secretory apparatus
The activation of T-cells by denderitic cells in the mucosal immune system follows the same princile as the systemiic immune system but differs in the
route by which antigen is delivered and the subsequent circulation patterns of the effector cells.
By circulating between the bloodstream and peripheral lymphoid tissues, naive T cells can make contact with thousands of dendritic cells in the lymphoid tissues every day and do what
sample the peptide:MHC complexes on the dendritic cells
what cytotocix class acts as a SCAFFOLD in sorting and packing of perforin and the granzymes
serglycin
granzymes
serine protesases that activate apoptosis once in cytoplasm of target cell
the affinity of an antigen binding site is dependent on what?
shape and composition of antibody binding site
diversity segments
short DNA segment present in multiple versions in immunoglobulin heavy chain loci and in t cell receptor B and d loci. in the rearranged functional genes at these loci, a D gene segment connects the V and J gene segments. the D stands for diversity, because the D gene segments provide additional diversity in these receptor chains -h chain only
hypervariable regions/ complementarity determining regions (CDRs)
short regions of high diversity in amino acid sequence within the variable region of immunoglobulin and T cell receptor chains -3 HV regions in each V domain- correspond to 3 loops located at end of V domain farthest from C domain
variations in signal 3
signal 3 delivered by APC a. When pathogens are absent, TGF-Beta and lack of IL-6, IFN-gamma and IL-12 favor development of FoxP3-expressing- induced Treg cells TFG-B -> FoxP3 -> Treg b. Early in infection, IL-6 produced by dendritic cells acts with TGF-Beta to induce TH17 cells expressing TF RORgammaT, which are amplified by IL-23 IL-6, TGF-B-> RORgammaT, IL-23 -> TH17 c. TFH cells, which require IL-6 and Bcl-6 for function, provide help to B cells in the form of cytokines such as IL-21, and surface molecule ICOS. later, dendritic cells and other APCs produce cytokines such as IL-21, and surface molecule ICOS IL-6, Bcl-6 -> IL-21 -> TFH c. Later, dendritic cells and other APCs produce cytokines that promote either TH1 (IFN-gamma and IL-12) or TH2 (IL-4) and suppress TH17 development IFN-gamma, IL-12 -> TH1 IL-4 -> TH2 d. TH1 expresses T-bet, and TH2 cells express GATA3 T-bet -> TH1 GATA3 -> TH2
VCAM-1 is expressed where and what does it do
site of inflammation allows T cells to enter sites of infection
Lymph nodes are
small ovoid structures less than 1cm in diameter, found in various regions throughout the body
B and T cells express what kind of receptors?
somatically generated antigen-specific receptors that are NOT germline-encoded. They are translational products of multiple genes
Cytotoxic T cells kill only target cells bearing specific antigen while
sparing neighboring uninfected cells
IgE
specialized for recruiting effector functions of mast cells, eosinophils, basophils -receptor binds IgE in absence of antigen -antigen binding triggers anti-parasite response; major role in allergy
Immature dendritic cells resident in the _____ are ideally suited to sample antigens from ________, such as malaria parasites or bacteria during sepsis. • Dendritic cells also present _________ derived from transplanted organs, thus triggering graft rejection, • Dendritic cells present the environmental protein antigens that cause _______
spleen infectious agents present in the blood, alloantigens allergies
antigen binding
stimulates B cell proliferation and differentiation
signal signals for T-cell differentiation into the
subset of effector T cells
CD4 Treg cells
suppress T-cell and immune responses - in gut - mucosal immunity - *Expresses FoxP3 - shut off immune response at level of T cells and dendritic cells - IBD caused by response to all bacteria in gut, including normal gut flora - most ppl have lots of Treg cells in wall of intesting that tell gut bacteria is OK and don't need pro-inflammatory response - can get specific responses to other antigens/viral infections
what does t reg cells do
suppress T-cell response and prevent autoimmunity
B cells bind specific antigens through their cell-______, internalize, process, and then display peptide fragments as ______
surface Ig peptide:MHC class II complexes.
B cells are highly efficient at presenting antigens that bind to their
surface immunoglobulin
membranes of the immunoglobulin superfamily are found on the
surface of many different cells types
Co-stimulatory signal promotes
surivial and expansion of T cells
Despite the deletion of many self-reactive T cells in the thymus, some T cells specific for self antigens do
survive and entry the peripheral lymphoid tissues
T-cell activation by dendritic cells occurs in organ os
systemic immune system (lymph nodes and spleen)
if the DC produced TGF-beta signal what is effector cell is produced
t reg cells
induced maturation of tissues dendritic cells that do what
take up particulate and soluble antigens at the the site of infection
The host cells which effector T cells act are referred to as their
target cells
what does GRAIL do
target compenents of CD3 for degradation and this will lead to blocking T-cell receptor signaling
IL-5
target eosinophils on B cells makes Ab
Licensing on an NK cells refers to:
testing an NK cell to ensure that it will not target healthy host cells.
- Such efficiency is crucial for the initiation of an adaptive immune response, as only one naive T cell in 104-106 is likely to be specific for a particular antigen, and adaptive immunity depends on
the activation and expansion of these rare cells.
The subsets, particularly TH1, TH2, and TH17, are defined on
the basis of different combinations of cytokines they secrete
Mature B and T cells migrate through
the bloodstream and lymphatic system to the peripheral lymphoid tissues (such as lymph nodes and spleen)
clonal selection
the central principle of adaptive immunity -the mechanism by which adaptive immune responses derive only from individual antigen-specific lymphocytes, which are stimulated by the antigen to proliferate and differentiate into antigen specific effector cells
12/23 rule
the fact that V(D)J recombination can only occur between gene segments with particular lengths of spacer in the recombination signal sequences, which means that a Vh region cannot be joined directly to a Jh region without the involvement of Dh. -two types of spacer are 12 and 23 nucleotides in length
cytotoxic effector proteins that trigger apoptosis are contained in what
the granules of CD8 cytotoxic T cells
affinity maturation
the increase in affinity of the antigen binding sites of antibodies for antigen that occurs during the course of an adaptive immune response -the result of somatic hypermutation of the rearranged immunoglobulin V-gene region and the consequent selection of mutated B cells that make antigen receptors of higher affinity for their antigen
CD4 of Th cells interacts with
the invariable domain
coding joint
the joint between the ends of two rearranged immunoglobulin or T cell receptors (chromosome) -additional sequence diversity introduced by coding joint- junctional diversity
signal joint
the joint present in the circle of DNA that is formed as a byproduct of VDJ recombination and discarded (spliced DNA)
The spleen is
the largest of the secondary lymphoid organs and is highly efficient in trapping and concentrating foreign substances carried in the blood.
Where are RAG-1 and RAG- 2 made?
the lymphocytes only
V(D)J recombinase
the mechanism of gene rearrangement by which V,D, and J segments of immunoglobulin or T cell receptors are brought together, with elimination of intervening sequences of DNA to make functional variable region genes -somatic recombination -includes RAG-1 and RAG-2
signal 3 is dependent on
the nature of the third signal
S1P1 receptor is upregulated by naïve T cells and B cells after 12-18 hours if they fail to encounter antigen in the lymph node. This means all of the following EXCEPT:
the naïve cells will die by apoptosis.
C region
the part of an immunoglobulin or T cell receptor (or of its constituent polypeptide chains) that is of identical amino acid sequence in molecules of the same isotope but different antigen binding specificity -remaining parts of L and H chains, limited sequence variation
variable region
the part of an immunoglobulin or T cell receptor, or of its constituent polypeptide chains, that varies in amino acid sequence between isoforms with different antigen specificities -responsible for determining antigen specificity -concentrated in N-terminal L and H chains -v gene segments differ mostly in sequences of CDR1 and CDR2
recombination- activating genes
the recombination proteins that form the complex that carries out VDJ recombination -made only in lymphocytes
antigen binding site
the site on an immunoglobulin or T cell receptor molecule that binds a specific antigen (V region) -2 per molecule
Which of the following is a location where naïve TC cells could be activated to become CTLs?
the spleen
selections and integrins are found on
the surface of naive T cells
mucin like vacular addressins are found on
the surface of vascular endothelial cells
antibody repertoire
the total number of different specific antibodies that can be made by an individual, estimated at around 10^9
germline configurations
the unrearranged organization of the immunoglobulin and T cell receptor genes in the DNA of germ lines and in somatic cells other than T cells and B cells
The vena cava is
the vessel that carries blood to the right side of the heart, from where it is redistributed throughout the body
Precursor CTLs are characterized by each of the following EXCEPT
they express CD4
when T cells encounter their specific antigen on the surface of mature dendritic cells, what happens to them
they lose their ability to exit from the node and become activated to proliferate and to differentiate into effector cells.
what happens if the macrophage can not destroy the pathogen or apoptoic lympocytes it has ingested
they use antigen presentation to recruit the adaptive immune resonse ( help from T cells ) which will enchance their microbicidal activity
when chemokine CCL21 binds to chemokine receptor CCR7 what happens
this changes behavior in dendritic cells
Efferent lymphatic vessels eventually converge in the
thoracic duct
How many hyper variable regions are there per V domain?
three
The activation of naive T cells by APC involves what
three different types of singals
Naïve CD4+ and CD8+ T cells that have just finished developing leave the ______ and enter circulation.
thymus
Lymphocytes destined to become T cells migrate to the
thymus and develop immunocompetence there
Precursor cells destined to become mature T cells undergo final maturation within the ________
thymus gland (T for thymus)
Despite the deletion of many self-reactive T cells in the thymus, some T cells specific for self antigens do survive and enter peripheral tissues. This is evident from diseases in which such T cells become activated and cause
tissue-specific autoimmunity
The role of cell-mediated immunity is:
to find and eliminate cells infected with intracellular pathogens.
Although Macrophages and B cells also present antigen to T cells, they do not present antigen mainly to activate naive T cells, why do they present antigen to T cells then
to make use of effector function of T cells that have been previrously primed by conventional dendritic cells (effector T cells)
TCR
touches MHC of molecule, doesn't bind tightly. needs velcro of cells to come close enough for MHC to be inspected by TCR
The reticuloendothelial system is designed to
trap foreign antigens that have penetrated the body and to subject the, to ingestion and degradation by the phagocytic cells of the system
(t/f) sequential switching is regulated by cytokines secreted by T cells
true
A large protein antigen can generally be bound by many different antibody molecules simultaneously
true
A rabbit immunized with human IgG3 will produce antibody that reacts with all subclasses of IgG in humans
true
A single molecule of IgM can activate the C1q component of the classical complement pathway
true
All immunoglobulin molecules on the surface of a given B cell have the same idiotype.
true
Although each B cell carries two alleles encoding the immunoglobulin heavy and light chains, only one allele is expressed.
true
Antigen-presenting cells express both class I and class II MHC molecules on their cell membranes
true
Dendritic cells primarily encounter antigen in peripheral tissues, leading to activation and migration of these tissue dendritic cells to the closest lymph node to activate T cells.
true
For cells of the innate immune system, each individual cell has multiple pattern recognition receptors, allowing it to recognize many different pathogens. In contrast, cells of the adaptive immune system each express a unique antigen receptor that has a single specificity for pathogen recognition.
true
In the absence of an infection, most granulocytes (neutrophils, eosinophils, basophils) are found circulating in the blood, whereas other subsets of myeloid cells reside in tissues.
true
MBL has a function in the lectin pathway analogous to that of IgM in the classical pathway, and MASP-1 and MASP-2 are analogous to components in the C1 complex.
true
Many B cell epitopes are non-sequential amino acids brought together by the tertiary conformation of a protein antigen.
true
Most antigens induce a response from more than one T cell or B cell (more than one clone, or version of a TCR or BCR).
true
Nitric oxide and superoxide radicals are toxic compounds that induce substantial DNA damage. When released by activated M1 macrophages, these compounds cause damage to microbial pathogens and may also cause damage to host cells in the vicinity.
true
Oral tolerance to food antigens and immune tolerance to gut microbiota share the property that foreign antigens encountered in the gastrointestinal (GI) tract—food and commensal microbes, respectively—do not elicit immune effector responses. Yet, these processes differ in that commensal microbes will still elicit protective adaptive immune responses if they cross the GI epithelium and enter the body.
true
The C3 convertase of the alternative complement pathway can be formed using C3b created by any pathway, amplifying the overall magnitude of complement activation regardless of which of the three pathways initiated the complement activation initially.
true
The extravasation of neutrophils into tissues at sites of infection or inflammation requires changes to both the endothelium and to the neutrophil that are induced by chemokines and cytokines produced in the infected tissue.
true
The hypervariable regions make significant contact with epitope
true
The spleen is a secondary lymphoid organ that performs several functions. In addition to its role as a site for initiating adaptive immune responses, the spleen is important in removing dead or damaged red blood cells from the circulation. Its immune function is important because blood-borne pathogens will not be transported to draining lymph nodes via the lymph fluid.
true
Unlike innate immune responses, adaptive immune responses are initiated in secondary lymphoid organs. However, the innate immune response to an infection in a tissue has a pivotal role in inducing T-cell responses in the nearest lymph node by activating tissue dendritic cells and inducing their migration to the lymph node.
true
(t/f) isotope switching produces immunoglobulins with different c regions but identical antigen specificities
true -IgM is the first class of antibodies made
(T/f) the random recombination of gene segments produces diversity in the antigen-binding sites of immunoglobulins
true somatic recombinations are random
(t/f) antibodies are produced by effector B cells
true, (also known as plasma cells)
cytotox T cells can induced target cells to do what
undergo programmed cell death (apoptosis)
M and B cells most important function isn't to active T cells but to
use effector T cells
_________of signal 3 induce the differentiation of naive CD4 T cells down distinct effector pathways
various froms
The thoracic duct empties into the
vena cava which returns the blood to the heart, thus providing for the continual recirculation of lymphocytes.
Antibodies, complement proteins, and phagocytic cells provide effective protection against all of the following types of infections in the figure below, except ________ PICTURE ON PHONE
virus infected cell NOTE: Yes. Once a pathogen, such as a virus or intracellular protozoan, invades a cell and begins replicating in the cell, these mechanisms are no longer able to clear the infection. These intracellular stages of pathogenic infection require cellular responses, such as those mediated by T cells or NK cells. All extracellular forms of pathogens are targets for antibodies, complement, phagocytic cells and antibody-dependent immune clearance mechanisms.
Antibodies, complement proteins, and phagocytic cells provide effective protection against all of the following types of infections in the figure below, except ________ [PICTURE]
virus-infected cell
supramolecular activation complex (SMAC) or immunological synapse
when binding to their specific antigenic peptide:self-MHC complexes or to self-peptide:self-MHC complexes, the TCRs and their associated co-receptors cluster at the site of cell-cell contact
when do dendritic cells produced TGF-beta
when no pathogen is present
The environmental condition, such as exposure to various pathogens, determine what
which singal the priming antigen presenting cell will produce
The spleen is composed of
white pulp (rich in lymphoid cells) and red pulp (contains many sinuses as well as large quantities of erythrocytes and macrophages, some lymphocytes and a few other cell types)
dentritic cells process atnigens from a
wide array of pathogens
The domains MHC class II molecules are
α1, α2 β1 , & β2
Double Negative T-cell
βchains chain rearrangement a) D to J rearrangement b) V to DJ rearrangement
First T cells to appear are
γ:δ T cells Home to epidermis (dendritic epidermal T cells)
CD3 is made of
ε,γ, & δ chains
MHC class II region has genes for cell-surface markers including:
• HLA-DM (catalyze removal of CLIP and insertion of foreign peptide, see above) • HLA-DO (only expressed in B cells and thymic epithelial cells, is a negative regulator of HLA-DM-mediated peptide exchange) • Genes encoding TAP-1 and TAP-2 (peptide transporter) • LMP-2 and LMP-7, major subunits of the proteasome
