Abbas Assessments

Which of the following statements correctly describes the migratory behavior of naïve T lymphocytes? A. They recirculate from blood into lymph nodes via high endothelial venules, and back into blood via lymphatics B. They recirculate from blood into inflamed tissues via activated post capillary venules, and back into blood via lymphatics C. They migrate into the thymus via high endothelial venules, where they mature into effector T cells, which then enter the blood via lymphatics D. They are stationary within lymph nodes and do not migrate E. After maturation in the thymus, they migrate into the blood via draining lymphatics and enter the spleen via high endothelial venules

A. They recirculate from blood into lymph nodes via high endothelial venules, and back into blood via lymphatics Naïve T cells enter lymph nodes via high endothelial venules, a process dependent on the chemokine receptor CCR7 and L-selectin on the naïve T cells. If after several hours the naive T cell is not activated by antigen, it will exit the lymph node via efferent lymphatics, and flow via lymph channels back into the blood. Naïve T cells do not migrate into peripheral sites of inflammation, and although they are formed in the thymus, they do not exit via lymphatics but rather via blood vessels. Migration of naïve T cells into spleen is not via high endothelial venules (which are not present in the spleen).

A child born with homozygous mutations in a gene required for T follicular helper cell differentiation will be able to make antibodies against which of the following antigens? Tetanus toxoid Influenza hemagglutinin Bee venom proteins ABO blood group antigens Rh factor antigen

ABO blood group antigens T cell-independent antigens include polysaccharides, glycolipids and nucleic acids with multiple repeated epitopes, which may cross-link the B cell receptor maximally and thus bypass the need for T cell help. Of the choices given, the best choice is the ABO blood group antigen, because of its polyvalent glycolipid structure. The other antigens are all proteins, antibody responses to which require T cell help, including help from T follicular helper cells.

The immune system associated with mucosal tissues includes organized lymphoid structures where specialized adaptive immune responses are initiated. Which of the following is not included in mucosal associated lymphoid tissues? Tonsils Peyer's patches Axillary lymph nodes Mesenteric lymph nodes Adenoids

Axillary lymph nodes Axillary lymph nodes drain the skin and soft tissues of the upper extremities, and not mucosal tissues. Tonsils and adenoids are sites of adaptive immune responses to microbes in the oral cavity and pharynx. Peyer's patches and mesenteric nodes are sites of initiation of adaptive immune responses to microbes in the gut.

All of the following molecules are opsonins that facilitate efficient phagocytosis of microbes by neutrophils and macrophages EXCEPT: A. C3b B. C5a C. C-reactive protein D. IgG E. Mannose-binding lectin

B. C5a C5a is a peptide released after cleavage of C5 protein upon activation of the complement cascade. It stimulates the influx of neutrophils to the site of infection, thus acting as a chemoattractant, not as an opsonin. C3b (covalently bound to microbes on which complement activation has taken place) and IgG bound to antigen, are potent opsonins, because phagocytes have receptors for both C3b and the Fc region of IgG. C-reactive protein and mannose-binding lectin also can coat microbes and be recognized by phagocyte receptors; thus they serve as opsonins.

Detection of antibodies specific for a particular microbe is commonly used as evidence of prior infection by that microbe. To obtain these antibodies, blood is collected into tubes and allowed to clot. Antibodies are found in the fraction of the blood that remains fluid after clotting. What is this fluid fraction called? A. Plasma B. Serum C. Lymph D. Water E. Urine

B. Serum Clots form from the cellular elements of blood, including platelets, and a meshwork of cross-linked coagulation proteins. The acellular fluid phase that is left after clotting is called serum, which contains most of the soluble protein elements of whole blood, except clotting factors. Plasma is the acellular fluid fraction of unclotted blood, and apart from coagulation proteins that form the clot, it contains all of the soluble protein components of whole blood, including antibodies. Lymph is extracellular fluid derived from blood; it may contain antibodies. Urine is the fluid filtrate of blood exclusively produced and excreted by the kidneys. It normally does not contain antibodies.

The most important costimulators for naïve T cell activation are which of the following? ICOS Ligand B7-1 and B7-2 PD-L1 and PD-L2 OX40 -Ligand FAS Ligand

B7-1 and B7-2 B7-1 (CD80) and B7-2 (CD86) are the major costimulators required for naïve T cell activation. They are expressed on mature myeloid DCs, and bind to CD28 on the T cells. ICOS-Ligand and OX40 ligand are costimulators for previously activated T cells; their receptors are not expressed on naïve T cells. PD-L1 and PD-L2 bind to PD-1 on T cells, which inhibits T cell activation. FAS Ligand binds to FAS on T cells, and induces apoptotic cell death.

Which of the following is NOT part of the innate immune response to extracellular bacteria? Complement activation by peptidoglycan Complement activation by mannose Activation of phagocytes by Toll-like receptors Bacterial killing by natural killer (NK) cells Acute inflammation

Bacterial killing by natural killer (NK) cells Although natural killer cells are part of the innate immune system, they kill infected cells, not extracellular organisms. Innate immune responses to extracellular bacteria include both the alternative complement pathway (activated by peptidoglycan and lipopolysaccharide) and the lectin pathway (activated by mannose-binding lectin). Activation of phagocytes by Toll-like receptors and acute inflammation are key components of the innate immune response to extracellular bacteria.

Which is the most reliable indicator for increasing risk of opportunistic infections and other AIDS related disorders in HIV infected individuals? Anti-HIV p24 titers Blood viral load Body weight Blood CD4+ T cell count Blood CD8+ T cell count

Blood CD4+ T cell count The progression to AIDS in patients with HIV infection is best followed by the CD4+ T cell count, and counts less than 200 indicate great risk for opportunistic infections, Kapsosi sarcoma, and lymphomas. Viral load may be high early after infection, and than stay low for many years, becoming high again at the time CD4+ counts drop below 200. CD8+ T cell counts may become low late in disease. Anti-HIV antibodies are detected early and stay high.

The germinal center reaction generates long lived plasma cells which secrete protective high affinity B cells for many years. Where do these cells reside? Bone marrow Thymus Parathyroid Skin Splenic red pulp

Bone marrow Plasmablasts generated in the germinal center migrate to the bone marrow, and differentiate into long-lived plasma cells, which remain active antibody secreting cells for months to years.

Which of the following is a feature of Natural Killer (NK) cells? A. They express antigen receptors that directly bind antigens on the surface of microbes B. They are activated by recognizing microbial peptides bound to host class I MHC molecules C. They kill virally infected cells by a perforin/granzyme dependent mechanism D. Upon activation, they secrete abundant interleukin-4 E. They secrete natural IgM antibodies

C. They kill virally infected cells by a perforin/granzyme dependent mechanism NK cells are activated by binding various ligands expressed on infected or stressed target cells. NK cells are inhibited by binding self class I MHC, a feature of healthy cells, but often not of virally infected or otherwise unhealthy cells. Upon activation, NK cells release perforin and granzymes from cytoplasmic granules, and these proteins work together to induce apoptosis of the target cell.

How does the complement system enhance B lymphocyte activation? -Generation of the membrane attack complex on B cell membrane allows calcium ions (Ca++) to enter the B cell and stimulate calcium-dependent enzymes -Opsonization of protein antigens with C3b promotes B cell phagocytosis of protein antigens, enhancing B cell-T cell collaboration -C1q binding to membrane IgM will activate BCR signaling -C3d bound to a microbial surface will bind to complement receptor 2 (CR2) on B cells, generating kinase activity by the CR2-CD19-CD81 complex -C5a binding to its receptor on B cells stimulates Ig heavy chain gene expression

C3d bound to a microbial surface will bind to complement receptor 2 (CR2) on B cells, generating kinase activity by the CR2-CD19-CD81 complex CR2 is expressed on B cell membranes in a complex with CD19 and CD81. CR2 binds to C3d, a proteolytic product of C3b that remains covalently bound to microbial surfaces after complement activation. If CR2 binds C3d on a microbe at the same time that microbial surface antigens bind to membrane Ig, signaling through the CR2-CD19-CD81 complex enhances BCR signaling resulting in enhanced B cell activation.

Which of the following is an example of G protein-coupled receptor (GPCR)? T cell antigen receptor (TCR) The B cell antigen receptor (BCR) CD4 Interlukin-2 (IL-2)receptor Chemokine receptor CCR7

Chemokine receptor CCR7 All chemokine receptors, including CCR7, are GPCRs. The lymphocyte antigen receptors (TCR, BCR), CD4, and IL-2 receptor signal via associated proteins or non-receptor tyrosine kinases.

Which of the following is one of the major functions of chemokines in the immune system? A. Increase affinity of leukocyte selectins for their ligands on endothelial cells. B. Stimulate proliferation of B cells in response to antigen C. Increase vascular permeability during the innate immune response to microbes D. Maintain the spatial separation of B and T lymphocytes within lymphoid tissues E. Form pores in bacterial membranes

D. Maintain the spatial separation of B and T lymphocytes within lymphoid tissues Chemokines have three major functions in the immune system. 1. Chemokines activate leukocytes to increase integrin affinity, which is needed for stable arrest of leukocytes on endothelial cells before they can migrate into tissues 2. Chemokines promote movement of leukocytes towards the source of the chemokines such as an infected phagocyte. 3. Distinct chemokines that are continually produced in follicles or interfollicular regions of lymphoid tissues maintain the location of B cells in the follicles and T cells outside the follicles.

Monoclonal antibodies used as drugs or diagnostic reagents are characterized by all of the following EXCEPT: A. Single antigen specificity B. Production by a B cell hybridoma C. Single isotype D. Monovalent, with one antigen-binding site E. Known antigen specificity

D. Monovalent, with one antigen-binding site Monoclonal antibodies are, by definition, identical antibodies of a single isotype and antigen specificity, produced by a single clone of cells. They are usually produced in vitro by clonal B cell hybridomas and are structurally normal, with at least two antigen-binding sites and a known specificity. Tumors of B lymphocytes (e.g., myelomas) may produce monoclonal antibodies, usually of unknown specificity, or often single chains of antibody molecules.

All of the following are known mechanisms by which extracellular bacteria evade the immune system EXCEPT: Capsules that prevent phagocytosis Inhibition of class I MHC expression Genetic variation of surface antigens Inhibition of complement activation Scavenging of reactive oxygen intermediates

Inhibition of class I MHC expression Class I MHC restricted T cells generally are not involved in immune responses to extracellular bacteria, because these microbes rarely survive within phagocytes and do not provide antigens to the class I MHC pathway of antigen presentation. Therefore, inhibition of class I MHC expression would not be an effective evasion mechanism, although it is effective for viruses. Encapsulated bacteria, such as pneumococci, cannot be readily phagocytosed without opsonization. Antigenic variation is used by Neisseria species, Escherichia coli, and Salmonella typhimurium to avoid recognition by antibodies. Many bacteria produce inhibitors of complement activation. Catalase-producing staphylococci scavenge reactive oxygen species produced by activated phagocytes.

A major function of TH1 cells is to activate macrophages. Which molecules expressed by TH1 cells are essential for this function? IL-1 and TNF CD8 and Fas ligand IL-17 and NO Interferon γ and CD40 ligand IL-4 and ICOS

Interferon γ and CD40 ligand TH1 cells activate macrophages via secreted interferon γ and membrane CD40 ligand, which bind respectively to interferon γ receptors and CD40 on the macrophages. TH1 cells express CD4 and not CD8. Although TH1 cells express Fas ligand, this molecule does not activate macrophages, but rather binds to Fas on various cell types and induces apoptotic cell death. IL-17 and NO are not made by TH1 cells. IL-4 is not made by TH1 cells, and ICOS does not activate macrophages.

Which of the following functions of antibodies does NOT require Fc receptors specific for IgG? Phagocytosis of antibody opsonized antigens by neutrophils Antibody mediated cellular cytotoxicity by NK cells Antibody mediated feedback inhibition of B cells Neonatal immunity mediated by maternal antibodies transported through the placenta Neutralization of tetanus toxin by anti-tetanus antibodies

Neutralization of tetanus toxin by anti-tetanus antibodies Neutralization of microbes and toxins requires binding of antibody and no other effector functions. Neutrophils and macrophages utilize IgG Fc receptors (FcγR1 and FcγRII) to phagocytose IgG-opsonized antigens. Antibody feedback inhibition of B cells is mediated by FcγRIIB on the B cell. Neonatal immunity depends on transplacental transport of IgG via the neonatal Fc receptor (FcRn)

Which of the following is NOT a property of regulatory T cells (Treg)? Interleukin-2 receptor (CD25) expression Secretion of interferon-γ FoxP3 expression Secretion of transforming growth factor-β Inhibition of activation of effector T cells

Secretion of interferon-γ Most Teg are CD4+CD25+ T cells that express the FoxP3 transcription factor, and secrete TFGβ. Interferon γ is an inflammatory cytokine secreted by effector T cells, including TH1 cells and cytotoxic T lymphocytes.

In the class I MHC pathway of antigen presentation, cytoplasmic proteins are tagged for proteolytic processing by covalent linkage with which of the following molecules? Calreticulin Nuclear factor (NF)-κB Tapasin Ubiquitin Calnexin

Ubiquitin In the class I pathway, proteins are tagged for proteasomal processing by covalent addition of several copies of the polypeptide ubiquitin. Ubiquitin-dependent proteasomal proteolysis is also important in many other cellular processes besides antigen presentation. For example, NF-κB is a transcription factor whose activation is dependent on ubiquitination and proteasomal degradation of an inhibitor (called IκB). Calreticulin, tapasin, and calnexin regulate the assembly of class I MHC proteins within the endoplasmic reticulum.

At the peak of a CD8+ T cell response to a new microbe, what is the fold increase in the number of microbe-specific T cells in an individual compared to the number of naïve CD8+ T cells specific for the microbe before infection? ~100 ~1000 ~10000 ~100,000

~100,000 CD8+ T cells undergo tremendous clonal expansion in response to antigen stimulation. CD4+ clonal expansion is less, on the order of 1000 to 10,000 fold.

A patient presents to an emergency room complaining of chronic cough, night sweats and fevers. A chest X-ray shows multiple nodules in the hilar regions of both lungs. A sputum sample stains positive for mycobacteria, and a rapid molecular test for Mycobacterium tuberculosis is positive. What type of immune response is taking place in the lung nodules? An antibody mediated autoimmune response An innate immune response with abscess formation An immune complex vasculitis A superantigen induced polyclonal T cell response A chronic delayed type hypersensitivity reaction with granuloma formation

A chronic delayed type hypersensitivity reaction with granuloma formation Mycobacterium tuberculosis infection often results in a chronic TH1 response and formation of granulomas due to persistence of bacterial antigen in macrophages.

Experiments with inbred strains of mice have provided much of our knowledge of transplantation immunology. All mice of one inbred strain are genetically identical to one another and homozygous for all genes. Assume that strains A and B are inbred strains that differ from each other at all MHC gene loci but at no other loci. A mating of a strain A mouse with a strain B mouse (AxB) yields AxB F1 progeny. Which of the following skin grafts would NOT be rejected? AxB F1 donor to A recipient AxB F1 donor to B recipient A donor to AxB F1 recipient B donor to A recipient A donor to B recipient

A donor to AxB F1 recipient MHC molecules are responsible for almost all strong rejection reactions. The offspring of a mating between two different inbred strains will typically not reject grafts from either parent because all the MHC alleles of both parents are inherited by the offspring, and therefore their products are seen as self. Thus, an AxB recipient will not reject grafts from an A or B donor. However, a graft derived from an AxB F1 animal will be rejected by either an A or a B parent, because half the MHC gene products in the graft are foreign to either A or B strains. A or B recipients will reject grafts from B or A donors, respectively, because of MCH disparities.

One of the unique challenges facing the immune system is presence of many commensal non-pathogenic organisms on all the major barrier interfaces, including intestinal mucosa and skin. Our immune systems must be able to tolerate these commensals, while maintaining the ability to respond to invasion by these organisms and to respond to luminal pathogens. Which of the following statement about the relationship between the human microbiome and host is accurate? Commensal organisms on the skin or in the gut do not evoke strong immune responses if they invade through the a damaged epithelial barrier During pathogenic bacterial infections in the gut, the pathogen usually outnumbers nonpathogenic commensals The microbiome on the skin or in the gut lumen has little influence internal immune responses to antigens at other sites Although there are normally millions of bacterial organisms in the gut, most of these belong to only two major genera, Escherichia and Lactobacillus A human normally harbors about 10 times more microbial cells as human cells

A human normally harbors about 10 times more microbial cells as human cells A healthy human carries about 10^14 microorganisms, which is about 10 times the number of human cells. Although the vast a majority of these organisms are commensals and do not normally cause disease, if they breach the epithelial barrier, most are capable of inciting strong innate responses that can clear the infection and/or may contribute to significant disease, such as sepsis. Intestinal pathogens remain a tiny minority of the total number of bacteria, even during active disease caused by the pathogen. Gut flora comprise many hundreds of species in over 10 genera. Escherichia and Lactobacillus together comprise a minority of the gut flora.

Which of the following is a proinflammatory cytokine of major importance in innate immunity that has been successfully targeted by drugs to treat rheumatoid arthritis (RA)? A. Tumor necrosis factor (TNF) B. Transforming growth factor-β (TGF-β) C. Interleukin 10 D. Interleukin 2 E. Interferon γ

A. Tumor necrosis factor (TNF) TNF is secreted by macrophages in response to PAMPs and DAMPs and mediates acute inflammatory responses by activating endothelial cells and leukocytes. Anti-TNF antibodies and recombinant soluble TNF receptor-IgG fusion proteins have been highly successful in treating RA.

The required number of complexes of a microbial peptide and a particular class II MHC allele on the surface of an antigen-presenting cell to initiate a T cell response specific for the viral peptide is: One All the MHC molecules on the cell must be complexed with the peptide About 0.1% of the total number of class II MHC molecules on the cell surface Greater than 106 Zero

About 0.1% of the total number of class II MHC molecules on the cell surface As few as 100 complexes of a particular peptide and a particular class II MHC molecule are needed to activate naive T cells specific for that complex and thereby initiate a detectable T cell response. This represents less than 0.1% of the total class II MHC molecules on a typical antigen-presenting cell surface.

In the cannonical NF-κB signaling pathway downstream of the TNF receptor, TLRs, and antigen receptors, what role does IκB kinase (IKK) complex play? -IKK enters the nucleus and phosphorylates NF-κB that has bound to the promoters of proinflammatory genes -IKK binds to NF-κB, preventing it from entering the nucleus -Activated IKK phosphorylates IκBα, which leads to IκBα degradation, allowing NF-κB to enter the nucleus -IKK enters the nucleus and binds to the promoters of pro inflammatory genes IKK phosphorylates NFκB, allowing NF-κB to enter the nucleus

Activated IKK phosphorylates IκBα, which leads to IκBα degradation, allowing NF-κB to enter the nucleus NF-κB is kept in the cytoplasm by bound IκBα. The function of the IKK complex is to remove IκBα, allowing NF-κB to enter the nucleus and promote the transcription of proinflammatory genes. IKK must be activated by TRAF signals originating from cell surface receptors. This leads to activation of the IKKβ subunit of IKK which phosphoryaltes IκBα. Phosphorylated IκBα is then ubiquitinated and degraded by the proteasome.

Which of the following mechanisms accounts for the fact that all of the TCRs produced by a single T cell have identical β chains? X inactivation Light chain isotype exclusion Antigen receptor gene homozygosity Linkage disequilibrium Allelic exclusion

Allelic exclusion In TCR allelic exclusion, expression of the β chain gene encoded by a successfully recombined gene on one chromosome inhibits recombination of the β chain gene on the other chromosome. The inhibitory signals are generated by the pre-TCR. This ensures that the T cell will not produce receptors with two different β chains. However, allelic exclusion does not occur for TCR α chain genes, and many T cells may express TCRs with two different α chains. Heavy chain allelic exclusion occurs by a similar mechanism in B cell development.

An antigen-binding site of an IgG antibody molecule is composed of which of the following? Twelve hypervariable loops, three each on two heavy chains and two light chains Three hypervariable loops on a light chain Three hypervariable loops on a heavy chain Six hypervariable loops, three each on one heavy chain and one light chain Six hypervariable loops, three each on two heavy chains

An IgG molecule has two antigen binding sites. Each one is composed of six hypervariable loops, three that extend from the variable domains of a heavy chain and three that extend from the variable domains of the covalently linked light chain.

Which one of the following statements about peptide binding to MHC molecules is true? - MHC molecules preferentially bind peptides derived from foreign (e.g., microbial) proteins and not peptides derived from self proteins. - Each type of MHC molecule and each allelic variant of each type have a narrow specificity for a single peptide with a particular amino acid sequence. - The affinity of peptide binding to MHC molecules is higher, on average, after chemokine stimulation of a cell. - An MHC molecule has only one peptide-binding site, which accommodates only a single peptide at a time. - Peptide binding to class I MHC molecules involves noncovalent interactions, whereas peptide binding to class II MHC molecules is covalent.

An MHC molecule has only one peptide-binding site, which accommodates only a single peptide at a time. There is only one peptide-binding site in both class I and class II MHC molecules that can fit only a single peptide at one time. MHC molecules do not distinguish foreign from self proteins; self-nonself discrimination is achieved by T cells. Each MHC molecule has a broad specificity for large numbers of peptides with varying sequences, although there are some structural constraints that result in each type of MHC molecule binding a different subset of peptides. The affinity of peptide-MHC interactions is not altered by chemokines. Peptide binding to both class I and class II MHC molecules involves only noncovalent interactions.

Which of the following is an approved monoclonal antibody cancer therapy directed against a cell surface oncogene product? Anti-TNF for rheumatoid arthritis Anti-CD20 for B cell lymphomas Anti-IL-2R for T cell lymphomas Anti-CTLA-4 for melanoma Anti-Her2/neu for breast cancer

Anti-Her2/neu for breast cancer Her2/neu (Human epidermal growth factor receptor 2) is a signaling protein that is not mutated but markedly overexpressed in many breast cancers because of gene amplification. Overexpressed Her2/neu provides constitutive growth signals to the tumor cells, and therefore the Her2/neu gene is an oncogene. Anti-Her2/neu antibody is a widely used therapy for breast cancers that overexpress this protein. The antibody probably works by NK cell-mediated cytotoxicity targeting the tumor cells. TNF is not an oncogene product and rheumatoid arthritis is not a cancer. CD20 and IL-2R are also not oncogene products, although they are expressed on B cell and T cell malignancies, and have been targeted by therapeutic antibodies. CTLA-4 is not an oncogene product, but rather a T cell protein that inhibits T cell responses. Anti-CTLA4 therapy is used to enhance anti-tumor T cell responses.

IgG has a longer half life in the blood than most other plasma proteins. This property is important for maintaining protection against pathogens, and has lead to the design of drugs with long half lives because they contain the part of IgG responsible for the long half life. Which of the following is the basis for prolonged IgG half life? Binding of C1q to the IgG Fc region Binding of the IgG Fc region the poly Ig receptor on gut epithelial cells Binding of the IgG variable regions to ubiquitous blood antigens Binding of the J chain to the IgG joining region Binding of the IgG Fc region to the neonatal Fc receptor (FcRn)

Binding of the IgG Fc region to the neonatal Fc receptor (FcRn) IgG molecules are internalized by endothelial cells and macrophages, and bind the FcRn in the membrane of endosomes. FcRn sequesters the IgG molecules, shunting them away from lysosomal degradation, and releases them back into the circulation.

CTLA-4-Ig is a soluble recombinant protein containing the ligand binding portion of CTLA-4 fused to the Fc portion of IgG. It is an approved drug used to treat autoimmune diseases. How does it work? Binds to CTLA-4 on T cells and induces inhibitory signals Binds to CTLA-4 and blocks its ability to bind to B7-1 and B7-2 Binds to B7-1 and B7-2 on antigen presenting cells, and blocks their ability to bind to CD28 on T cells Binds to inhibitory Fc receptors on B cells and inhibits the production of autoantibodies Binds to cytotoxic T lymphocytes and blocks their ability to kill other cells

Binds to B7-1 and B7-2 on antigen presenting cells, and blocks their ability to bind to CD28 on T cells CTLA-4-Ig is a costimulatory blocker. It has high affinity for B7-1 and B7-2, and therefore blocks costimulation by these molecules, which is required for naïve T cell activation. CTLA-4-Ig is not anti-CTLA-4 and does not bind to CTLA-4. The Ig Fc portion of the drug prolongs half-life, but is not involved in the immune inhibitory function of the drug.

Although differences in MHC proteins between graft donors and recipients is the underlying cause of immunological graft rejection, matching MHC alleles between donor and recipient is not of critical importance for success of transplantation of most organs and tissues, because of the efficacy of immunosuppressive drugs. Which of the following is the exception, where MHC matching is necessary for successful transplantation? Liver Kidney Lung Heart Bone marrow

Bone marrow Perhaps because of the high expression of MHC molecules, including class II MHC, on hematopoietic cells, bone marrow donors and recipient must be carefully matched to permit successful engraftment and reduce risk of graft vs. host disease. Usually donors are chosen who are completely matched with the recipient at the HLA-A, -B and -DR loci

In the class I MHC pathway of antigen presentation, peptides generated in the cytosol are translocated into the endoplasmic reticulum in which of the following ways? By ATP-dependent transport via TAP By passive diffusion By receptor-mediated endocytosis Through membrane pores Via the proteasome

By ATP-dependent transport via TAP The TAP1/TAP2 heterodimer is an ATP-dependent pump that delivers peptides generated by the proteasome into the endoplasmic reticulum.

A previously healthy young European woman who had not been immunized against measles virus became infected with the virus while traveling in Africa. She developed a rash, high fever, cough, and runny nose, and then fully recovered after 4 days. A blood test performed 2 months later, after her return to Europe, showed the presence of high affinity IgG antibodies specific for measles virus antigens. Which of the following proteins was NOT necessary for the production of these high affinity IgG antibodies? CD40 Ligand Activation induced deaminase (AID) Class II MHC CXCR5 C reactive protein (CRP)

C reactive protein (CRP) CRP, an acute phase reactant induced by the liver in response to innate inflammatory cytokines, has little influence on B cell activation. All the other proteins listed are essential for the germinal center reaction that generates B cells producing high affinity IgG antibodies. CD40 ligand expressed on helper T cells binds to CD40 on B cells in the germinal center, providing signals that induce expression of AID, which is required for both class switching from IgM to IgG (and other isotypes). AID is also required for increased affinity of the antibodies produced in response to an infection. Class II MHC is essential for a B cell to present protein antigens to and receive helper signals from CD4+ T cells, which are required for isotype switching and affinity maturation. CXCR5 is a chemokine required for attracting B cells and T follicular helper cells into the germinal center in response to the chemokine CXCL13.

Which of the following is the nonpolymorphic molecule that is structurally homologous to the class I MHC α chain, associates with β2-microglobulin, and displays lipid antigens for recognition by NKT cells? CD1 CD2 CD3 CD4 CD8

CD1 CD1 is encoded outside the MHC, but is structurally homologous to class I MHC molecules. Some subsets of T cells, all with relatively invariant T cell receptors, recognize lipid or glycolipid antigens bound to CD1 on antigen-presenting cells. CD2, CD3, CD4, and CD8 are all present on T cells. Although they are members of the Ig superfamily, like class I MHC, they are not otherwise homologous to class I MHC and do not bind and display antigens for T cell recognition.

What role does CD4 and CD8 on T cells play in the early signaling events during T cell activation? -Like CD3 and ζ proteins, CD4 and CD8 contain ITAMs in their cytoplasmic tails that serve as docking sites for protein tyrosine kinases (PTKs) -CD4 and CD8 have intrinsic phosphatase activity in their cytoplasmic tails that remove phosphates from ITAMs on CD3 and ζ proteins -When CD4 and CD8 bind to MHC molecules on antigen presenting cells, the MHC molecules become active kinases that activate the APCs -CD4 and CD8 have Src family PTKs associated with their cytoplasm tails, which are brought into proximity of and phosphorylate the CD3 and ζ ITAMs upon antigen recognition. -Upon antigen recognition, the cytoplasmic tails of CD4 and CD8 became phosphorylated and bind JAK family kinases, which then phosphorylate STAT family proteins.

CD4 and CD8 have Src family PTKs associated with their cytoplasm tails, which are brought into proximity of and phosphorylate the CD3 and ζ ITAMs upon antigen recognition. Lck, a Src family PTK, is noncovalently associated with the cytoplasmic tails of both CD4 and CD8, and Lck phosphorylates CD3 and ζ chain ITAMs when CD4 and CD8 bind to MHC molecules during antigen recognition. CD4 and CD8 do not have ITAMs, intrinsic kinases, phosphatases or JAK kinase binding sites in their cytoplasmic tails. MHC molecules also do not have intrinsic kinase activities.

It has been postulated that regulatory T cells reduce available B7 costimulators on APCs, and this is one possible mechanism by which the Tregs inhibit immune responses. Which of the following molecules is expressed on regulatory T cells (Treg) and functions to block B7-mediated costimulation PD-1 CTLA-4 CD28 CC127 (IL-7 receptor) Fas ligand

CTLA-4 Treg express CTLA-4, and CTLA-4 is a high affinity receptor for B7-1 and B7-2. Treg function depends on CTLA-4, and it is likely that one mechanism of Trge suppression of effector T cell responses is to competitively bind B7-1 and B7-2 on dendritic cells presenting self antigens to naïve T cells, or remove B7 molecules from these APCs. This results in reduced costimulation, which would prevent the induction of effective immune responses.

In the T cell calcium signaling pathway induced by antigen recognition, which enzyme and transcription factor are activated? IκB kinase, NFκB Jun kiniase (JNK), AP-1 Erk kinase, Fos JAK3, STAT4 Calcineurin, NFAT

Calcineurin, NFAT In the calcium pathway, TCR signaling leads to an increase in cytosolic calcium ion (Ca++) concentration, which activates the phosphatase calcineurin, leading to dephosphorylation of the transcription factor NFAT. Dephosphorylated NFAT enters the nucleus and stimulates transcription of various genes that promote T cell proliferation and differentiation. Calcineurin inhibitors, such as cyclosporin and tacrolimus, are widely used as immunosuppressant drugs for transplant recipients

Which of the following mechanisms contributes most to both Ig and TCR diversity? Multiple possible combinations of the different V, D, and J segments Changes in the nucleotide sequences at the junctions between recombined V, D, and J segments Somatic mutation of variable genes Isotype switching Polymorphism

Changes in the nucleotide sequences at the junctions between recombined V, D, and J segments Junctional diversity is caused by deletions and additions of base pairs between V, D, and J segments during somatic recombination, resulting in new junctional sequences not present in the germline. This accounts for the majority of Ig and TCR diversity. Combinatorial diversity is the second major mechanism for diversity, based on the large number of different V, D, and J segments inserted in the germline that can be used during somatic recombination, but it contributes much less to diversity than does junctional variability. Somatic mutation of variable genes occurs during the germinal center reaction in B cells only, and its impact on diversity is far less than the mechanism of junctional diversity. Isotype switching (of Ig molecules only) changes the non-antigen-binding region and does not contribute to diversity of antigen receptor specificity. Polymorphism refers to the presence of different alleles of a gene in the population, not in an individual, and is not a mechanism of diversity of the antigen receptor repertoires.

Which of the following statements about microbial antigen presentation is correct? -Class I MHC molecules display peptides derived mainly from cytosolic microbial proteins for recognition by CD8+ T cells -Class I MHC molecules display peptides derived mainly from cytosolic microbial proteins for recognition by CD4+ T cells -Class II MHC molecules display peptides derived mainly from cytosolic microbial proteins for recognition by CD4+ T cells -Class II MHC molecules display peptides derived mainly from extracellular microbial proteins for recognition by CD8+ T cells -Class II MHC molecules display peptides derived mainly from extracellular microbial proteins for recognition by B cells

Class I MHC molecules display peptides derived mainly from cytosolic microbial proteins for recognition by CD8+ T cells CD8+ T cells are class I MHC restricted, and most peptides that are displayed by class I MHC are derived from proteasomal processing of cytosolic proteins.

The combination of TCR and costimulatory signals induces naïve T cells to express IL-2 and high affinity IL-2 receptors. This results in which of the following functional responses by the T cell? Clonal expansion Interferon γ expression CD40 ligand expression Granule exocytosis Migration out of a lymph node

Clonal expansion IL-2 is the major autocrine growth factor for T cells. Naïve T cells express two chains of the IL-2 receptor which bind IL-2 with low affinity. Antigen and costimulatory signals induce IL-2 production and expression of a third chain (CD25) of the receptor, which increases the affinity for IL-2. The T cell thus enters the cell cycle in response to IL-2 signals, and undergoes several rounds of proliferation, thereby expanding the clone of T cells specific for the inciting antigen.

Which of the following best describes indirect presentation of allogeneic MHC molecules? Donor allogeneic MHC molecules are shed from graft cells, inserted into recipient antigen presenting cells, loaded with recipient peptides, and presented to recipient T cells Donor allogeneic MHC molecules are taken up by recipient antigen presenting cells, processed into peptides, and the peptides are presented on recipient MHC molecules to recipient T cells, similar to processing and presentation of microbial proteins Donor allogeneic MHC molecules are taken up by recipient antigen presenting cells, processed into peptides, and the peptides are presented on recipient MHC molecules to donor T cells Donor allogeneic MHC molecules are taken up by donor antigen presenting cells, processed into peptides, and the peptides are presented on unprocessed donor allogeneic MHC molecules to recipient T cells Recipient MHC molecules are taken up by donor antigen presenting cells, processed into peptides, and the peptides are presented on donor allogeneic MHC molecules to recipient T cells

Donor allogeneic MHC molecules are taken up by recipient antigen presenting cells, processed into peptides, and the peptides are presented on recipient MHC molecules to recipient T cells, similar to processing and presentation of microbial proteins In the indirect pathway, donor MHC molecules are processed and presented by recipient antigen-presenting cells (APCs) in the same manner that foreign protein antigens are presented in conventional immune responses to foreign antigens. Recipient T ells that recognize the peptides derived from the allogeneic MHC molecules in complex with self MHC proteins respond and mediate graft rejection. There is no mechanism by which intact allogeneic MHC molecules from donor cells can be inserted into host antigen presenting cells. Although it is possible that peptides derived from either donor or recipient MHC molecules may be loaded onto donor MHC molecules in donor antigen presenting cells, recognition of these complexes would be a form of direct recognition of allogeneic MHC, since intact donor MHC is being presented along with the peptide.

Fingolimod is a drug used to treat autoimmune disease, which blocks the function of sphingosine-1 phosphate (S1P) by binding to its receptor S1PR1. Patients treated with fingolimod become lymphopenic, i.e. they have low numbers of lymphocytes in the blood. Why? A. S1P binding to S1PR1 is required for T cell maturation in the thymus B. S1P binding to S1PR1 stimulates lymphocyte clonal expansion C. S1P binding to S1PR1 blocks lymphocyte migration out of the blood into lymph nodes D. S1P binding to S1PR1 inhibits lymphocyte apoptosis E. S1P binding to S1PR1 on lymphocytes is required for exit of lymphocytes from lymphoid tissues

E. S1P binding to S1PR1 on lymphocytes is required for exit of lymphocytes from lymphoid tissues The exit of naive T cells from lymph nodes and thymus requires the lipid chemoattractant S1P, which binds to S1PR1 on T cells. S1P is present at high concentrations in the blood and lymph compared with lymphoid tissues. Naive T cells in the blood have little surface S1PR1 because the high blood concentration of S1P causes receptor down regulation. When a naive T cell enters a lymph node, it takes several hours for the surface S1P1R to be re-expressed. This allows time for a naive T cell to interact with antigen-presenting cells and be activated. Activated T cells also transiently express the protein CD69, which binds to and down regulates S1PR1, thus enabling the T cell to remain in the lymph node long enough to complete the initial activation program. Following activation, the T cell loses CD69 and, since it is not exposed to S1P. it re-expresses S1PR1 and is thus directed down the S1P concentration gradient out of the lymph node and into the efferent lymphatics. Fingolimod interferes with this process, so that T cells remain trapped within lymph node and thymus.

Which one of the following statements concerning autoimmune disease is true? Autoimmunity manifests as organ-specific, not systemic, disease Infectious microorganisms are frequently present in autoimmune lesions Effector mechanisms in autoimmunity include circulating autoantibodies, immune complexes, and autoreactive T lymphocytes Among the genes associated with autoimmunity, associations are particularly prevalent with class I MHC genes Many autoimmune diseases show higher incidence in males than in females

Effector mechanisms in autoimmunity include circulating autoantibodies, immune complexes, and autoreactive T lymphocytes Various effector mechanisms are responsible for tissue injury in different autoimmune diseases. These include circulating autoantibodies, immune complexes, and autoreactive T lymphocytes. Autoimmune diseases may be either systemic (e.g., systemic lupus erythematosus) or organ specific (e.g., type 1 diabetes mellitus, multiple sclerosis). Among the genes associated with autoimmunity, the strongest associations are with MHC genes and usually with class II MHC genes (ankylosing spondylitis is an exception). In most cases of autoimmunity, infectious microorganisms are neither present in lesions nor detectable in patients when autoimmunity develops; this suggests that lesions in autoimmunity result not from the infectious agent directly but from host immune responses that may be triggered by microbes. Finally, many autoimmune diseases show higher incidence in females than in males, although the reasons for this are not well understood.

Children with C3 deficiency are at high risk for serious bacterial and fungal infections. Which of the following explains the importance of C3 in defense against these microbes? - Fragments of C3 generated by both classical and alternative pathway C3 convertases serve as important opsonins for phagocytosis of the microbes - Fragments of C3 generated only by the classical pathway C3 convertase serve as important opsonins for phagocytosis of the microbes - Fragments of C3 generated only by the alternative pathway C3 convertase serve as important opsonins for phagocytosis of the microbes - Fragments of C3 generated by both classical and alternative pathway C3 convertases bind to microbes and serve as ligands recognized by activating receptors on NK cells - Fragments of C3 generated by both classical and alternative pathway C3 convertases serve as important stimulants of helper T cell cytokine secretion

Fragments of C3 generated by both classical and alternative pathway C3 convertases serve as important opsonins for phagocytosis of the microbes All three complement activation pathways (classical, alternative, and lectin) generate C3 convertases, which are multi-protein enzyme complexes that cleave C3 into C3a and C3b. C3b binds covalently to microbial surfaces, and acts as an opsonin that binds to complement receptor 1 (CR1) on phagocytes. This opsonization role of C3b is essential for clearance of many pathogens. C3a has proinflammatory properties, including chemoattraction of leukocytes and endothelial activation. C3 fragments do not play a role in NK cell recognition of microbes, nor do they stimulate T cell cytokine production.

Which of the following is a human class I MHC molecule? HLA-DR HLA-DP HLA-B I-A CD8

HLA-B The human class I MHC molecules are HLA-A, HLA-B, and HLA-C. The human class II MHC molecules are HLA-DP, HLA-DQ, and HLA-DR. I-A is a mouse class II MHC molecule. CD8 is not an MHC molecule, but it binds to class I MHC molecules.

Receptor editing is a mechanism to achieve self tolerance if a self reactive lymphocyte develops. How, where, and when does self editing work? - High avidity self antigen recognition by an immature B cell in the bone marrow leads to reactivation of RAG genes, production of a new Ig light chain, and a change in the B cell specificity. - High avidity self antigen recognition by an immature T cell in the thymus leads to production of a new TCR and a change in the T cell specificity. - High avidity self antigen recognition by an immature B cell in the bone marrow leads to enzymatic alteration of Ig light chain proteins, and a change in the B cell specificity. - High avidity self antigen recognition by an immature T cell in the thymus leads to enzymatic alteration of the TCR α chain, and a change in the T cell specificity. - High avidity self antigen recognition by an immature B cell in the bone marrow leads to reactivation of RAG genes, additional heavy chain V-D-J recombination events, production of a new Ig heavy chain, and a change in the B cell specificity.

High avidity self antigen recognition by an immature B cell in the bone marrow leads to reactivation of RAG genes, production of a new Ig light chain, and a change in the B cell specificity. Receptor editing occurs only in immature B cells in the marrow after high avidity recognition of self antigens, is due to re-expression of the RAG-1 and -2 genes and rearrangement of a previously rearranged Ig light chain gene locus.

Which one of the following factors generally favors tolerance to an antigen and not stimulation of an immune response? High doses of antigen Short-lived persistence of antigen Cutaneous portal of entry Presence of adjuvant Costimulator expression on antigen-presenting cells

High doses of antigen High doses of antigens, especially administered without adjuvants, favor peripheral tolerance, often by the induction of anergy or apoptosis. Antigens that induce immune responses are typically present for short durations, and are associated with adjuvants that enhance antigen presentation and costimulatory molecule expression.

A college student develops a blistering rash on his legs a day after returning from a camping trip. He visits the student health clinic and a nurse makes the diagnosis of a poison ivy reaction, a form of contact hypersensitivity to organic chemicals called urushiols produced by the poison ivy plant. Which of the following statements about this student is correct? His rash is caused by mediators released by mast cells after the crosslinking of anti-urushiol antibodies bound to mast cell IgE Fc receptors His rash is caused by activation of memory CD4+ and CD8+ T cells specific for peptides of urushiol-modified self proteins, and secretion of inflammatory cytokines by the T cells Because the rash took more than 24 hours to develop since exposure to the poison ivy, the student most likely had never been exposed to poison ivy before His rash is caused by anti-urushiol antibodies that bind to the urushiols in the skin and activate complement The best treatment for this students condition is epinephrine

His rash is caused by activation of memory CD4+ and CD8+ T cells specific for peptides of urushiol-modified self proteins, and secretion of inflammatory cytokines by the T cells Contact hypersensitivity to urushiols is mediated by memory T cells that emerge after at least one previous encounter with these compounds. The urushiols covalently modify self proteins in the skin, including MHC molecules, which are processed and presented to and activate CD4+ and CD8+ T cells. The rash will usually take at least 24 hours to fully develop because it requires the recruitment of the T cells to the skin, local activation of these cells by antigen, and secondary recruitment of inflammatory cells. Epinephrine is not used to treat contact hypersensitivity, but rather to treat severe immediate hypersensitivity reactions with life threatening cardiovascular and respiratory complications.

Which of the following proinflammatory mediators are preformed and stored in mast cell granules? Prostaglandin D2 Leukotriene D4 Histamine IL-4 Chemokines

Histamine Mast cell granules contain various enzymes and vasoactive amines, including histamine. Prostaglandins and leukotrienes are short lived lipid mediators rapidly formed by arachidonic acid metabolism and releases upon mast cell activation. Cytokines, such as IL-4 and chemokines, are newly expressed by gene transcription upon mast cell activation and secreted.

Alternative macrophage activation is characterized by which one of the following? Reactive oxygen species (ROS) generation IL-1 production Microbial killing IL-10 and TGFβ secretion IL-4 and IL-13 secretion

IL-10 and TGFβ secretion Alternatively activated macrophages secrete the anti-inflammatory cytokines IL-10 and TGFβ. They also enhance angiogenesis and fibrosis. ROS generation, IL-1, and microbial killing are characteristic of classically activated macrophages. IL-4 and IL-13 are cytokines made by TH2 cells, which induce alternative macrophage activation.

TH2 cells are defined in part by production of which of the following cytokines? TNF IL-1 IL-2 IL-4 IFNγ

IL-4 TH1 cells are defined by production of IFNγ. TH2 cells are defined by production of IL-4, IL-5, and IL-13. TH17 cells are defined by production of IL-17A, IL-17F, and IL-22. Many T cells produce combinations of various cytokines, and polarized cells expressing restricted cytokine profiles tend to develop upon chronic or repeated stimulation.

Which of the following is one way a cytokine made by TH2 cells contributes to atopic disease (allergy)? IL-17 stimulates TNF production by macrophages IL-5 activates eosinophils IL-13 activates macrophages to produce nitric oxide IL-4 induces B cell class switching to IgA IL-22 causes mast cell degranulation

IL-5 activates eosinophils Atopic diseases often involve eosinophil activation and the release of pro-inflammatory and tissue damaging granule contents, such as major basic protein. TH2 cells underlie these events because they produce IL-5. IL-17and IL-22 are not made by TH2 cells. IL-13 does not activate macrophages to produce nitric oxide. IL-4 does induces B cell class switching to IgE not IgA

A one year old boy with a history of severe infections is found to have very few circulating mature T cells or NK cells, but normal numbers of B cells. Genetic studies reveal he has X-linked severe combined immunodeficiency syndrome. Defective signaling by the receptor for which cytokine is the underlying cause of this disease? IL-1 IL-2 IL-4 IL-7 GM-CSF

IL-7 X-linked severe combined immunodeficiency syndrome (X-linked SCID) caused by mutations in the common γ chain which is a signaling polypeptide in the multimeric cytokine receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Although signaling from all of these receptors would be defective in X-linked SCID, only IL-7 is required for early development of T cells and NK cells in the thymus of humans

All of the following are accurate statements about neonatal immunity EXCEPT: -Transfer of maternal IgG across the placenta is mediated by an Fc receptor structurally similar to class I MHC. -IgA is absorbed in the gut from breast milk and re-secreted by the infant into the bronchial mucosa. -IgA secretion into breast milk involves transport through breast epithelial cells, and is dependent on the poly-Ig receptor. -Transport of IgG across the neonatal intestinal epithelium is mediated by an Fc receptor structurally similar to class I MHC. -Loss of maternal antibodies is partly responsible for increased frequency of infections in infants at about 6 months of age.

IgA is absorbed in the gut from breast milk and re-secreted by the infant into the bronchial mucosa. IgA is secreted into breast milk via poly-Ig receptor-mediated transcellular transport, but it is not reabsorbed in the infant's gut. Rather, IgA remains in the lumen of the alimentary canal as a defense against intestinal microbes. IgG from breast milk is reabsorbed into the circulation from the gut lumen by the class I MHC-like neonatal Fc receptor (FcRN). This same receptor also mediates transplacental transport of IgG. Passive immunity mediated by maternal antibodies wanes with time; at about 6 months, infants have a nadir of circulating antibodies because maternal antibodies are depleted and antibodies produced by the infant have not reached maximal levels. This nadir corresponds to a period of increased susceptibility to infections, which is even more exaggerated in children with immunodeficiency diseases.

A 48 year old mother of two children with a history of post-streptococcal glomerulonephritis and chronic renal failure has been undergoing various tests in preparation for a possible kidney transplant. Among the first tests done was ABO blood typing. It was determined she was Type A. Which antibodies does she have circulating in her blood? IgM specific for Group A antigen IgG specific for Group B antigens IgM specific for Group B antigen IgG specific for Group A antigen IgB specific for Group B antigen

IgM specific for Group B antigen Blood group antigens are multimeric glycolipid antigens, not proteins, and therefore the antibodies against these antigens are largely IgMs. Type A individuals will only make anti-B antibodies and will be tolerant to Group A antigen, since the blood group antigens are ubiquitously expressed on many cell types and developing B cells will see group A antigens and be tolerized. Similarly, type B individuals will only make anti-A antibodies, type AB individuals will not make anti-A or anti-B, and type O individuals will make both anti-A and anti-B antibodies. The reason individuals make antibodies against the blood groups antigens that they do not produce is because gut flora produce the same or similar molecules, and early during life. Mature B1 cells are exposed to these antigens and are activated and differentiate into antibody secreting cells that produce the anti-blood group IgM antibodies.

Which of the following statements about immune responses to tumors is true? T cells specific for tumor antigens cannot be found in most human tumor patients Antibodies specific for tumor antigens cannot be found in many human tumor patients The presence of lymphocytic infiltrates in certain tumors is associated with a worse prognosis than lymphocyte-poor tumors of the same histologic type Immunodeficient individuals are more likely to develop certain forms of cancer than are immunocompetent individuals The host immune response is usually capable of eradicating common tumors once they are established

Immunodeficient individuals are more likely to develop certain forms of cancer than are immunocompetent individuals The types of tumors occur more frequently in immunocompromised hosts, such as AIDS patients or allograft recipients receiving chronic immunosuppressive therapy, are those with a viral etiology. Examples include Epstein-Barr virus-associated lymphomas and human papillomavirus-associated cervical and skin carcinomas. The most common types of cancers are carcinomas, originating from epithelial cells of organs such as the lung, colon, breast, and prostate. The question of whether or not these tumors occur more frequently in immunocompromised hosts than in the general population is unresolved, but if there is an increased frequency, it is not a major increase. Nonetheless, T cells and antibodies specific for molecules expressed exclusively or abundantly on tumor cells can be found in most tumor patients and lymphocytic infiltrates are a histologic indication of better prognosis for some tumors. However, the naturally occurring immune responses that occur against tumor antigens are usually not capable of eliminating tumors, at least without help of therapeutics.

The cytoplasmic tails of the signaling polypeptides found in lymphocyte antigen receptor complexes (BCR and TCR) contain regions that become phosphorylated upon antigen recognition and then bind ZAP family kinases. These regions are called: Immunoreceptor tyrosine-based activating motifs (ITAMs) Fc regions Toll-like IL-1R (TIR) domains Complementarity determining regions Nod like receptor ( NLR) domains

Immunoreceptor tyrosine-based activating motifs (ITAMs) ITAMs are found in the cytoplasmic tails of CD3 and ζ proteins of the TCR complex and Igα and Igβ proteins of the BCR complex. ITAMs contain pairs of tyrosine residues that become phosphorylated by Src family kinases after antigen recognition, and then serve as docking sites for ZAP70 in T cells or Syk in B cells. ZAP70 and Syk are tyrosine kinases that become active after binding to ITAMs and then phosphorylate adaptor proteins and other kinases.

All of the following statements regarding the direct presentation of alloantigens during transplant rejection are true EXCEPT: -Processing of allogeneic MHC molecules is not required for T cell recognition -A high percentage (~2%) of a graft recipient's T cells are capable of directly recognizing the MHC molecules encoded by a single non-self MHC allele -All the different MHC molecules expressed on a graft cell can potentially be directly recognized by recipient T cells, even if they carry different peptides in the peptide binding clefts -In direct presentation, peptide bound to the foreign MHC molecule is not involved in TCR recognition -Memory T cells can be involved in direct recognition of allogeneic MHC molecules, even if the recipient has never been exposed to the donor MHC molecules before

In direct presentation, peptide bound to the foreign MHC molecule is not involved in TCR recognition The direct presentation of allogeneic MHC molecules involves a cross-reaction of a T cell receptor selected to recognize self-MHC with a bound nonself peptide. This can occur because an allogeneic MHC molecule with a bound peptide can mimic the structures formed by self-MHC with bound foreign peptides. Peptides bound to allo-MHC contribute to the direct pathway of presentation in two ways. First, peptides are required for assembly and surface expression of MHC molecules. Second, peptides from graft cells may contribute to the structure seen by the recipient's alloreactive T cells, even if they are from nonpolymorphic proteins found in the recipient. In such cases, it is the combination of the peptide and polymorphic residues of the MHC molecule that is recognized. As many as 2% of an individual's T cells are capable of directly recognizing a single foreign MHC molecule, and such a high frequency of reactive T cells helps to engender a strong immune response. In addition, all of the MHC molecules on an allogeneic antigen-presenting cell are foreign to a recipient and therefore can be recognized by T cells, contributing to a strong rejection response. Many of these alloreactive T cells are memory T cells that were generated during previous exposure to other foreign antigens, hence making the initial response to alloantigens stronger and faster than primary immune responses to foreign microbes.

Most naïve T cell activation occurs where and in response to what? In the skin in response to cytokines In the infected tissues in response to antigen presentation by macrophages In the blood in response to antigen presentation by monocytes In the thymus in response to antigen presentation by thymic medullary epithelial cells In secondary lymphoid organs in response to antigen presentation by dendritic cells

In secondary lymphoid organs in response to antigen presentation by dendritic cells Naive T cells home to lymph nodes, and dendritic cells (DCs) carrying antigens from sites of infection drain into lymph nodes. The chemokine CCR7 directs the co-localization of both cell types. Other types of antigen presenting cell do not activate naive T cells efficiently because they do not migrate to where naïve T cells are, and/or they do not express the costimulatory molecules required for naïve T cell activation.

Defensins are an important part of the innate defense against bacterial invasion in the gut, and abnormalities in defensin production have been associated with various diseases. Which of the following statement about defensins is true? Defensins are peptides that exert lethal toxic effects on bacteria by blocking protein synthesis In the small bowel, the α-defensins are produced by Paneth cells located at the base of crypts Human defensins are secreted in a fully active form by cells in the gut after IL-1 stimulation Mast cell granules are rich in α-defensins Defensins are not produced in the colon

In the small bowel, the α-defensins are produced by Paneth cells located at the base of crypts Paneth cells located at the base of crypts of the small bowel are a major source of defensins. Defensins are peptides that exert lethal toxic effects on microbes by inserting into and causing loss of integrity of their outer phospholipid membranes. They are not inhibitors of protein synthesis. In addition, neutrophil granules, but not mast cell granules, are rich in α-defensins. Human defensins are produced constitutively by Paneth cells as inactive precursor proteins and active defensin peptides are generated by trypsin mediated cleavage. In the colon, β-defensins are produced by absorptive epithelial cells in the intestinal crypt.

Activated macrophages perform all of the following functions EXCEPT: Inhibition of fibroblast proliferation and angiogenesis within damaged tissues Production of lysosomal enzymes and reactive oxygen species that kill phagocytosed microbes Presentation of antigen to helper T cells Secretion of inflammatory cytokines such as tumor necrosis factor and interleukin-1 Production of nitric oxide, which helps kill microorganisms

Inhibition of fibroblast proliferation and angiogenesis within damaged tissues Activated macrophages, through the secretion of growth factors, promote fibroblast proliferation and angiogenesis which help repair damaged tissues.

Which of the following is NOT true about heavy chain isotype switching? It is induced by recombination of Ig constant region DNA segments It is defective in individuals lacking functional CD40 or CD40-ligand It is prominent in antibody responses to polysaccharides It generates antibodies with diverse effector functions Is induced by the AID, the enzyme that is also involved in somatic mutation of Ig V genes

It is prominent in antibody responses to polysaccharides Isotype switching requires signals from helper T cells, so it is most prominent in antibody responses to protein antigens and not T-independent polysaccharides. The molecular mechanism does involve "switch recombination" of Ig gene segments, which is stimulated by CD40L-CD40 interactions and AID. Antibodies of different ispotypes serve distinct functions.

Different types of immune responses may be required to protect against different types of pathogenic microbes. For example, antibody responses and complement activation are effective in combatting extracellular bacterial infections but not intracellular bacterial infections. Which of the following species is an intracellular bacterium and is therefore not susceptible to antibody-mediated immune mechanisms? Staphylococcus aureus Streptococcus pneumoniae Escherichia coli Clostridium tetani Legionella pneumophila

Legionella pneumophila Legionella pneumophila, the causative agent of legionnaire's disease, is a gram-negative intracellular bacterium. This bacterium produces a cytotoxin that causes cell lysis and acute lung injury and inflammation. Cell-mediated immunity is required for eradication of infection by this organism. The other bacteria listed are extracellular organisms.

All of the following have a direct role in mediating human immunodeficiency virus (HIV) entry into susceptible cells EXCEPT: CD4 MHC class I CCR5 CXCR4 Env

MHC class I Human immunodeficiency virus (HIV) entry into host cells occurs when gp120, a glycoprotein expressed on the HIV envelope, binds to CD4 expressed on host T cells. This induces a conformational change in gp120, promoting its binding to a chemokine coreceptor, such as CCR5 or CXCR4, on host cells. A conformational change in gp41, another glycoprotein expressed on the HIV envelope, exposes a fusion peptide, which inserts into the T cell membrane, allowing fusion of viral and cell membranes and subsequent infection of the host cell. Thus, CD4, CCR5, and CXCR4 are host proteins that are directly involved in mediating HIV entry into susceptible T cells, macrophages, and dendritic cells. Env, the HIV envelope glycoprotein that includes gp120 and gp41, is also directly involved in mediating HIV entry into host cells. In contrast, MHC class I molecules do not have a direct role in this process.

Among the genes that are associated with common autoimmune diseases, the strongest associations are with which of the following? Cytokine genes Autophagy genes Apoptosis genes MHC genes Antigen receptor signaling genes

MHC genes MHC genes, mainly class II MHC genes, are the most strongly associated with autoimmune diseases.

The human skin contains about 10 billion T cells. Most of these T cells have which of the following phenotypes? Memory T cells Naïve T cells Th17 cell Regulatory T cells CD8+ T cells

Memory T cells Most of the skin T cells are in the dermis, and have an effector memory phenotype. They are a mixture of CD4+ and CD8+ T cells.

MHC genes are the most polymorphic of any in the human genome. Which of the following statements about MHC polymorphism is true? HLA-A, HLA-B, and HLA-C represent three different alleles of the same gene. Many unrelated people have identical MHC alleles Only class I MHC genes are polymorphic; class II MHC genes are not. Most of the polymorphic residues in any MHC protein are located in the peptide binding groove. MHC polymorphism is a result of somatic recombination of inherited nonpolymorphic MHC gene segments.

Most of the polymorphic residues in any MHC protein are located in the peptide binding groove. MHC polymorphism are concentrated in the peptide binding groove, resulting in differences in the range of peptides that can bind to each allelic form on each type of class I or class II MHC molecules. HLA-A,-B, and -C are different types of class I MHC molecules, encoded by three different genes, each one of which has many different alleles in the population. It is very rare for two individuals to have identical HLA alleles, unless they are identical twins. Both class I and class II MHC genes are polymorphic, although class I MHC genes are more polymorphic. MHC genes are not somatically rearranged, but rather the allelic variations are encoded in the germline and are inherited.

Experimental autoimmune encephalomyelitis (EAE) is a mouse model of a human organ-specific autoimmune disease mediated by T lymphocytes. In EAE, rodents are immunized with proteins found in the myelin sheath of central nervous system neurons. EAE is a model for which of the following human diseases? Rheumatoid arthritis Autoimmune myocarditis Systemic lupus erythematosus Diabetes mellitus type 1 (insulin-dependent) Multiple sclerosis

Multiple sclerosis Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis, a central nervous system (CNS) demyelinating disease with an autoimmune etiology. EAE is induced by immunizing mice with antigens normally present in CNS myelin, in conjunction with adjuvant, which is necessary to stimulate the innate immune system. One to 2 weeks after immunization, animals develop an encephalomyelitis, characterized by perivascular infiltrates composed of lymphocytes and macrophages in the CNS white matter, followed by demyelination. Both TH1 and TH17 cells contribute to the disease. Neurologic lesions can be mild and self-limited or chronic and relapsing, depending on the animal species and strain and antigen-adjuvant preparation used.

Which of the following microbes induces two forms of disease, depending on the genetics of the host, one form characterized by weak cell mediated immunity and widespread proliferation of the microbe in macrophages, and the second form characterized by strong cell mediated immunity and destructive granulomatous inflammation? Candida albicans Vibrio cholerae Corynebacterium diphtheriae Epstein Barr virus Mycobacterium leprae

Mycobacterium leprae Mycobacterium leprae cause leprosy. In lepromatous leprosy, patients mount weak cell-mediated responses to M. leprae antigens, and the bacteria proliferate within macrophages and cause destructive lesions in the skin and underlying tissue. In tuberculoid leprosy there is strong T cell-mediated immunity with granulomas that damage sensory nerves. Patients with the tuberculoid form of leprosy produce IFN-γ and IL-2 in lesions (indicative of TH1 cell activation), while patients with lepromatous leprosy produce less IFN-γ and sometimes more IL-4 and IL-10 (suggestive of TH2 cells).

A particular species of microbe evades the immune system by several mechanisms, including inhibiting phagosome fusion with lysosomes, degrading reactive nitrogen intermediates generated by nitric oxide synthetase, and inhibition of class II MHC expression. Which of the following is most likely to be this species of microorganism? Streptococcus pyogenes Candida albicans Clostridium tetani Poliovirus Mycobacterium tuberculosis

Mycobacterium tuberculosis The mechanisms listed in the question would provide protection for an intracellular organism that lives within phagosomes of macrophages, such as Mycobacterium tuberculosis. Mycobacterium tuberculosis and legionella pneumophilia inhibit formation of phagolysosome formation. Fusion of phagosomes with lysosomes exposes internalized microbes to a toxic environment of low pH, proteolytic enzymes, and reactive oxygen intermediates. Streptococcus pyogenes and Clostridium tetani are extracellular bacteria that do not survive inside phagocytes. Candida albicans is a fungus that also lives and grows outside of cells. Poliovirus replicates in the nucleus and cytoplasm of cells but does not reside within phagosomes.

Augmenting patients' own immune responses to products of oncogenes or tumor suppressor genes is a theoretically good strategy for tumor immunotherapy. Which of the following is one reason why this is true? Oncogene and tumor suppressor gene products are usually cell surface proteins easily accessible to anti-tumor antibodies Oncogene and tumor suppressor gene products are often mutant forms of normal proteins, and therefore responses against them will not cross react with normal cells and cause autoimmunity Oncogene and tumor suppressor gene products are often mutant forms of normal proteins, and therefore cancer patients will mount immune response targeted to these proteins, and these responses can be augmented by various means Oncogene and tumor suppressor gene products are usually secreted proteins that will be readily presented by the class II MHC pathway to helper T cells The oncogene or tumor suppressor gene product is likely important for the malignant phenotype, making it unlikely that mutant tumor cells not expressing the oncogene or tumor suppressor gene will evade this approach

Oncogene and tumor suppressor gene products are often mutant forms of normal proteins, and therefore cancer patients will mount immune response targeted to these proteins, and these responses can be augmented by various means Many tumor bearing patients naturally develop T cell and antibody responses to oncogene and mutated tumor supressor gene products, which although not effective, can be augmented by immunizations, cytokines, and other methods. Oncogene products may be cell surface, cytosolic or nuclear proteins, but they are typically not secreted and they tend to activate CD8+ CTLs. The similarity of oncogene and tumor suppressor gene products to normal proteins may actually increase the likelihood that immune responses to these proteins will cross react with normal cells and cause autoimmunity. Most tumors have multiple oncogene and tumor suppressor gene mutations, and do not depend on just one to maintain the malignant phenotype. The dependence of tumors on these mutated genes limits the ability of the tumors to generate loss variants but does not promote anti-tumor immunity by itself.

All of the following are associated with immune responses to intracellular bacteria EXCEPT: Interferon-γ production by bacterial-antigen-specific CD4+ T cells Opsonization of infected cells by complement Interleukin-12 production by macrophages Granuloma formation Cytotoxic T lymphocyte killing of infected macrophages

Opsonization of infected cells by complement Complement opsonizes extracellular microbes, not infected cells. Fragments of the complement C3 protein that remain covalently attached to microbial surfaces, including C3b and iC3b, mediate phagocytosis of the microbes by complement receptor expressing phagocytes. Intracellular bacteria often stimulate a TH1 response in which CD4+ T cells secrete interferon (IFN)-γ. Interleukin-12 secretion by dendritic cells and infected macrophages promotes TH1 differentiation and IFN-γ production. If the microbes successfully resist killing within phagosomes, chronic antigen stimulation leads to granuloma formation. Often, intracellular bacterial antigens will leave the phagosome and enter the cytoplasm, where they will enter the class I MHC antigen presentation pathway and stimulate a CD8+ cytotoxic T lymphocyte response.

Which of the following molecules is involved in the principal mechanism by which the adaptive immune system fights cancer? Perforin Complement C3 IgG TGF-β Interleukin-2

Perforin Cytotoxic T lymphocyte (CTL) killing of tumor cells is the principal known mechanism for tumor immunity in vivo. This requires class I MHC expression by the tumor cells. In addition, natural killer cells (NK cells) can kill tumor cells that lack class I MHC. CTLs and NK cells employ the same mechanism to kill tumor cells, which depends on perforin and granzyme B release from cytoplasmic granules. Although antibodies (e.g., IgG) and complement can kill tumor cells in vitro and tumor-specific antibodies can be detected in patients, it is not known if antibody or complement plays a significant role in tumor immunity in vivo. TGF-β (transforming growth factor-β) is an immunoregulatory cytokine produced by T cells and other cell types. TGF-β does not kill tumor cells. Interleukin-2 has been used in protocols to treat certain tumors, but its effect is indirect and it does not directly kill tumor cells.

Which of the following events initiates activation of the alternative complement pathway? C1q binding to a microbial surface Spontaneous cleavage of C3 to C3b Complement receptor 1 (CR1) binding of C3b Factor I cleavage of C3 Mannose-binding lectin (MBL) binding to a microbial surface

Spontaneous cleavage of C3 to C3b The alternative pathway is initiated when C3b, generated by spontaneous cleavage of C3 in the fluid phase, covalently binds to a cell surface. C1q is required for initiation of the classical pathway. It does not bind directly to cell surfaces but rather to the constant regions of two Ig molecules, which may be bound to cell surface antigens. Factor I is a protease that cleaves C3b and C4b and regulates both alternative and classical pathways. CR1 on phagocytes binds C3b-opsonized microbes. Mannose-binding lectin (MBL) binds to mannose on microbial surfaces to initiate the lectin pathway.

In both B and T cell development, there is stage when a pre-antigen receptor (pre B cell receptor or pre T cell receptor) is expressed. Which of the following accurately describes an important function of these pre-antigen receptors? -Positively select for lymphocytes that have successfully undergone a first round of V-D-J recombination required to express functional antigen receptors -Negatively select for self-reactive lymphocytes -Instruct the differentiation of the lymphocytes into different subsets of effector cells -Positively select lymphocytes that recognize microbial antigens -Bind to chemokines that keep the lymphocytes from migrating out of the generative lymphoid organs

Positively select for lymphocytes that have successfully undergone a first round of V-D-J recombination required to express functional antigen receptors Signals generated by the pre-antigen receptors are required for survival of developing lymphocytes. Since the pre B cell receptor contains an Ig μ heavy chain, and the pre T cell receptor contains a TCR β chain, only developing lymphocytes that have successfully rearranged Ig μ or TCR β genes will survive, and have a chance of rearranging and expressing Ig light chain or TCR α chain genes. Therefore, the pre-antigen receptors provide a checkpoint mechanism by which useless cells that will never be able to express an antigen receptor are purged. The pre-antigen receptors do not stimulate lymphocyte differentiation into effector cells, but they do stimulate proliferation and further molecular events in development of mature naïve lymphocytes. Since pre-antigen receptors are not fully formed antigen receptors, they cannot mediate selection for or against self or foreign antigens, and they have no chemokine binding capacity.

Which one of the following is a property of mast cells but not of basophils? Present next to small blood vessels in normal tissues Express high levels of surface FcɛRI receptors Have cytoplasmic granules containing histamine Cannot proliferate as mature cells Are recruited into tissues from the circulation

Present next to small blood vessels in normal tissues Mast cells differ from basophils in that they are constitutively present in skin, mucosal tissues and other sites and do not circulate in blood. Mast cell progenitors in the bone marrow migrate to peripheral tissues as immature cells and undergo differentiation in situ. Mature mast cells are found throughout the body, predominantly near blood vessels and nerves and beneath epithelia; they are also present in lymphoid organs. Basophils can be thought of as the circulating counterpart of mast cells. Both mast cells and basophils express high surface levels of FcɛRI, bind IgE, and can be triggered by antigen binding to the IgE. They both contain granules with histamine and protease mediators. In contrast to mature basophils, mature mast cells retain the ability to proliferate. Only basophils are recruited into tissues from blood circulation.

A 15 year old boy with a history of multiple episodes of severe abdominal pain is found to have evidence of intravascular hemolysis, including hemoglobinuria and an elevated reticulocyte count. Further workup included flow cytometry of his red blood cells, and showed a lack of cell surface GPI (glycosyl-phosphatidyl-inosityl)-linked proteins. A diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) was made. What is the basis of the loss of red blood cells (RBCs) in this patient? -Phagocytosis of RBCs by splenic macrophages is increased because normally GPI linked proteins inhibit phagocytes -RBCs are unusually sensitive to complement-mediated lysis because of the lack of C1 inhibitor (C1 INH), which normally regulates C1r and C1s activity in the classical pathway of complement -RBCs are unusually sensitive to complement lysis because of the lack of CD59, which normally inhibits membrane attack complex formation on host cells, and CD55 (decay accelerating factor), which normally inhibits the formation of C3 convertases on host cells -RBCs are unusually sensitive to complement lysis because of the lack of complement receptor 1 (CR1), which normally promotes Factor I mediated cleavage of C3b and C4b on host cells -RBCs are unusually susceptible to osmotic lysis because GPI linked proteins normally serve as ion transport channels in the RBC membrane

RBCs are unusually sensitive to complement lysis because of the lack of CD59, which normally inhibits membrane attack complex formation on host cells, and CD55 (decay accelerating factor), which normally inhibits the formation of C3 convertases on host cells CD59 (and CD55) are GPI-linked complement regulatory proteins that are normally present in RBC membranes, and are missing in PNH, leaving patients at risk for episodic bouts of compliant mediated hemolysis. GPI linked proteins on RBCs are not known to influence phagocytosis, nor are they components of ion transport channels. Although CR1 does regulate complement activation on host cells, it is not a GPI linked protein and would not be missing in this patient. C1 INH is not a GPI linked protein, and CI INH deficiency causes another disease, called hereditary angioneurotic edema.

Why do Ig and TCR genes only undergo rearrangements in B and T cells and not other cell types? The hepatmer/nonamer recombination signal sequences (RSSs) adjacent to V, D, and J gene segment are present only in B and T cells The Ig and TCR α genes are deleted in other cell types Recombinase activating genes (RAG-1 and RAG 2) are expressed only in developing lymphocytes Activation induced deaminase (AID) is expressed only in developing lymphocytes DNA-dependent protein kinase is only expressed in developing lymphocytes

Recombinase activating genes (RAG-1 and RAG 2) are expressed only in developing lymphocytes A complex of RAG-1 and RAG-2 is the V-(D)-J recombinase that recognizes RSSs adjacent to V, D, and J gene segment, and cuts the DNA at these locations. This is an essential step for V-(D)-J rearrangements. The RAG proteins are only expressed in developing B and T cells, and only at certain times during development. The actual inherited Ig and TCR gene sequences in developing lymphocytes before recombination occurs, including coding gene segments and RSSs, are identical to the sequences in all other cells. AID is required for Ig gene switch recombination and somatic mutation of Ig V genes, but does not play a role in antigen receptor V-(D)-J rearrangements. DNA-dependent protein kinase is a DNA repair enzyme necessary but not sufficient for the antigen receptor rearrangements, and it is not unique to B and T cells.

Which of the following proteins involved in attenuation of immune signaling become associated with immunoreceptor tyrosine inhibitory motifs (ITIMs)? E3 ubiquitin ligases SH2 domain-containing tytrosine phosphatases (SHP-1, SHP-2) Suppressors of cytokine signaling (SOCS) CTLA-4 PD-1

SH2 domain-containing tytrosine phosphatases (SHP-1, SHP-2) ITIMs are found in the cytoplasmic tails of inhibitory receptors on NK cells, T cells, and B cells. ITIMs bind SHP-1, SHP-2, and SH2 domain-containing inositol phosphatase (SHIP). These phosphatases remove phosphates from tyrosines in signaling intermediates downstream of activating receptors. The other choices are not associated with ITIMs. E3 ubiquitin ligases are intracellular enzymes that tag proteins for lysosomal and proteosomal degradation, and some E3 ubiquitin ligases, such as Cbl-b, are involved in endocytosis and degradation of the TCR. Suppressors of cytokine signaling (SOCS) inhibit JAK-STAT and TLR signaling. CTLA-4 and PD-1 are membrane proteins that inhibit T cell activation when they bind ligands on other cells.

Which of the following is the most common known primary immunodeficiency, with a prevalence of 1 in 700 white individuals? X-linked agammaglobulinemia Selective IgA deficiency Common variable immunodeficiency Chronic granulomatous disease Chédiak-Higashi syndrome

Selective IgA deficiency Selective IgA deficiency is the most common (known) primary immunodeficiency and is believed to affect approximately 1 in 700 white individuals. Most cases occur sporadically. Whereas many patients show no clinical symptoms, others experience occasional respiratory infections and diarrhea. In rare cases, patients present with severe, recurrent infections that lead to permanent intestinal and airway damage, with other associated autoimmune disorders.

Which of the following statements about B cell tolerance is NOT true? Somatic mutation of Ig genes is a mechanism of central B cell tolerance. Exclusion of B cells from follicles is a mechanism of peripheral B cell tolerance. Functional anergy is a mechanism of peripheral B cell tolerance. Receptor editing is a mechanism of central B cell tolerance. Down-regulation of antigen receptor expression is a mechanism of central B cell tolerance.

Somatic mutation of Ig genes is a mechanism of central B cell tolerance. Somatic mutation of Ig genes occurs during B cell responses to antigens, e.g. in germinal centers, and is not a mechanism of central tolerance. Strong recognition of self antigen in the bone marrow may result in B cell apoptosis, antigen receptor down-regulation, or receptor editing, whereby V(D)J recombination is reinitiated and light chain gene usage is altered; all these are mechanisms of central B cell tolerance. In peripheral B cell tolerance, B cells may become anergic or they may be excluded from entry into follicles, owing in part to failure of expression of CCR5 chemokine receptors.

What are M cells? A type of mucosal B cell that secretes IgM Lamina propria macrophages that ingest bacteria that have invaded through the intestinal epithelium Alveolar macrophage that secrete surfactant Specialized intestinal epithelial cells that transport antigens or microbes into Peyer's patches A type of intestinal dendritic cell that tolerizes T cells to food antigens.

Specialized intestinal epithelial cells that transport antigens or microbes into Peyer's patches M cells are intestinal epithelial cells with short villi, and engage in transport of intact microbes or molecules across the mucosal barrier into gut-associated lymphoid tissues, such as Peyer's patches, where they are handed off to DCs.

A renal allograft recipient was given immunosuppressive drugs to prevent rejection. One of these drugs was a calcineurin inhibitor, called cyclosporin. Which of the following sequences best describes the signaling pathway that cyclosporine blocks? IL2 Receptor ...JAK1 ...Ca++... Calcineurin...STAT5 TLR ...MYD88... Calcineurin...IκB Kinase ...NFκB TCR... PLCγ1 ...IP3... Ca++ ...Calcineurin... NFAT TLR... K+ ... Calcineurin...TRIF...IRF3 TGFβ... Calcineurin... SMAD 3 ...SMAD4

TCR... PLCγ1 ...IP3... Ca++ ...Calcineurin... NFAT Calcineurin is a serine/theronine phosphatase that removes a phosphate residue on cytosolic NFAT, allowing translocation to the nucleus and induction of transcription of genes required for T cell proliferation, including genes encoding IL-2 and the high affinity IL-2 receptor chain CD25. Calcineruin inhibitors, such as cyclosporine or tacrolimus, will therefore inhibit T cell responses against alloantigens, and prevent graft rejection. The increased Ca++ that leads to calcinuerin activation is induced by TCR signaling which leads to activation of phsopholipase Cγ 1 (PLCγ1), which generates inositol trisphosphate (IP3) , which stimulates the release of Ca++stores from the endoplasmic reticulum. The placement of calcineurin in the other signaling pathways listed is incorrect.

Which type of T cell is most important for defense against extracellular bacteria and fungi? TH1 TH2 TH17 Cytotoxic T lymphocyte NKT cell

TH17 Activated TH17 cells simulate acute inflammatory responses with neutrophil rich infiltrates. These responses protect against extracellular microbes. Patients with defects in TH17 differentiation suffer from mucocutaneous candidiasis and recurrent Staphylococcus aureus infections.

Which type of T cell is most likely to promote acute neutrophillic inflammatory responses that defend against extracellular bacteria and fungi? TH1 TH2 TH17 CTL T follicular helper

TH17 IL-17 produced by TH17 cells induces many cell types to make chemokines such as IL-8, and cytokines such as IL-1 and TNF, all of which enhance neutrophil recruitment into tissues. TH1 cells and CTLs, which secrete IFNγ, are more typically associated with chronic inflammatory infiltrates rich in activated macrophages, and TH2 cells are associated with eosinophil-rich inflammation. T follicular helper cells do not promote inflammatory responses, but rather help B cells in germinal center reactions.

The differentiation of each major CD4+ T cell subset is controlled by a subset defining transcription factor. Which of the following correctly pairs each subset with its transcription factor? TH1:T-bet; TH2:GATA3; TH17:RORγT TH1:GATA3; TH2:T-bet; TH17:RORγT TH1:T-bet; TH2: RORγT; TH17: GATA3 TH1: RORγT; TH2:GATA3; TH17: T-bet TH1: GATA3; TH2:RORγT; TH17: T-bet

TH1:T-bet; TH2:GATA3; TH17:RORγT T-bet, GATA3, and RORγT are sometimes called "master regulators", and they are required for differentiation and function of the differentiated T cells. In each case the transcription of the subset defining cytokine genes is regulated by the subset defining transcription factors. Other transcription factors are also required for the differentiation of each subset.

Which enzyme contributes to antigen receptor junctional diversity by adding random nucleotides at the junctions between V, D, and J segments and is also useful as a marker of neoplasia of pro-B and pro-T cells? Terminal deoxyribonucleotidyl transferase (TdT) Activation-induced deaminase (AID) Recombinase activating gene-1 (RAG-1) DNA-dependent protein kinase DNA polymerase

Terminal deoxyribonucleotidyl transferase (TdT) Terminal deoxyribonucleotidyl transferase (TdT) is the enzyme that adds random nontemplate nucleotides (called N nucleotides) at the junctions between V, D and J segments, mainly in the recombined Ig heavy chain and TCRβ chain genes. The enzyme is expressed mainly during the time in B cell and T cell development when the IgH and TCRβ chain genes are undergoing recombination. Activation-induced deaminase is an enzyme involved in somatic mutation and isotype switching of Ig genes. Recombinase activating gene-1 (RAG-1) is a component of the V(D)J recombinase that mediates the joining of the discrete gene segments, and DNA-dependent protein kinase participates in the recombination and joining process, but these enzymes do not contribute on their own to junctional diversity.

Adaptive immunity to pathogens in the intestinal lumen is mediated in part by antibodies. Which of the following statements about these antibodies is true? They are mainly IgM antibodies They are secreted by B cells located in the gut lumen The B cells that secrete the antibodies are first activated and differentiate in gut associated lymphoid tissues IL-12 is required for B cells to class switch to the isotype of these antibodies The homing of B cells that produce these antibodies to the gut depends on the expression of VLA-4 (α4β7) integrin.

The B cells that secrete the antibodies are first activated and differentiate in gut associated lymphoid tissues Most of the antibodies in the gut lumen are IgA antibodies, secreted by lamina propria B cells that were primed and differentiated in mucosal associated lymphoid tissues (e.g Peyer's patches). TGFβ, and not IL-12, is the main cytokine driving isotype switching to IgA, but other non cytokine factors are also involved. The IgA producing B cells then enter the blood and home back to the lamina propria. B cell migration out of lamina propria venules depends on expression of the α4β7 integrin and CCR9 on the B cells. The IgA that is secreted in the lamina propria is transported across the gut epithelium into the lumen by the poly-Ig receptor.

One of the major ways innate immunity protects against viral infections is by the production of type I interferons (interferons α and β). Which of the following statements about type I interferons is NOT correct? Type 1 interferons are induced by viral RNA binding to endosomal Toll like receptors Type 1 interferons are induced by viral RNA binding in the cytosol binding to RIG like receptors Type 1 interferon gene expression is induced by interferon response factors (IRFs) The major source of type I interferons during viral infections are infected epithelial cells Type I interferons act on cells to resist inhibit viral replication and to induce class I MHC

The major source of type I interferons during viral infections are infected epithelial cells The major source of type I interferons during viral infections are plasmacytoid dendritic cells

Clinical trials have shown that blocking anti PD-1 antibodies enhances anti-tumor immune responses in cancer patients. Why do you think this therapy is effective? Tumors may evade T cell mediated killing by expressing PD-L1 Tumors may evade T cell mediated killing by expressing B7-1 and B7-2 Anti PD-1 treatment of cancer patients will decrease the numbers of T cells The cancer patients that show benefit from anti-PD-1 treatment are mainly T cell lymphomas The tumor cells in the treated patients express PD-1

Tumors may evade T cell mediated killing by expressing PD-L1 PD-1 is an inhibitory signaling molecule expressed on T cells which binds PD-L1 and PD-L2 on other cells. PD-L1 has been detected on many tumors including carcinomas and melanomas, and therefore it is possible that these tumors inhibit the activation of tumor specific T cells by engaging PD-1 on the T cells. It is also possible that the efficacy of anti-PD-L1 antibody may be related to enhanced activation of naive T cells by dendritic cells, which may also express PD-L1 and PD-L2. Most tumors do not express B7-1 or B7-2, but if they did this would likely enhance anti-tumor responses by costimulation of anti-tumor T cells. There is no reason to conclude that anti-PD-1 treatment would particularly be useful in enhancing immune responses against T cell lymphomas. The blocking anti-PD-1 antibody would not be expected to decrease numbers of T cells in the patients, but rather to increase numbers because it would enhance T cell activation.

Which one of the following is a correct description of the basic symmetric core structure of an IgG antibody? One heavy chain and two light chains One constant domain and one variable domain. Two heavy chains and one light chain Two heavy chains and two light chains One heavy chain and one light chain

Two heavy chains and two light chains Two γ heavy chains are covalently linked to each other, and each heavy chain is covalently linked to one light chain (κ or λ). IgM molecules contain 5 covalently linked copies of the basic IgM core structure, and IgA contain two copies. Each IgG heavy chain has one variable domain and three constant domains, and each light chain has one variable domain and one constant domain.

A child with a mutation in the gene encoding one of the polypeptide chains of the integrin LFA-1 (CD11aCD18) suffers from recurrent serious bacterial and fungal infections, and the sites of infection contain few inflammatory leukocytes. Which of the following accurately describes a required function of the LFA-1 integrin that is missing in this child? a. LFA-1 on endothelial cells binds to carbohydrate ligands on neutrophils and monocytes, causing these leukocytes to stably arrest on the endothelial surface. b. LFA-1 on neutrophils and monocytes binds to ICAM-1 on endothelial cells causing the leukocytes to stably arrest on the endothelial surface. c. LFA-1 on leukocytes binds to chemokines in tissues, which direct leukocytes to migrate into sites of infection d. LFA-1 on endothelial cells binds to VCAM-1 on T cells, which supports migration of activated T cells into tissues e. LFA-1 on neutrophils binds to ICAM-1 on bacterial cell walls, which supports phagocytosis of the bacteria.

b. LFA-1 on neutrophils and monocytes binds to ICAM-1 on endothelial cells causing the leukocytes to stably arrest on the endothelial surface. LFA-1 is a leukocyte integrin that binds to the Ig superfamily adhesion molecule ICAM-1 on endothelial cells. LFA-1:ICAM-1 interactions allow rolling leukocytes to come to a full stop and stably adhere to the endothelium, a necessary step before the leukocytes can migrate between endothelial cells and out into tissue sites of infection. Genetic deficiencies in LFA-1 (called leukocyte adhesion deficiency-1) result in a failure of neutrophils and leukocytes to migrate to sites of bacterial and fungal infections, as well as defects in migration and activation of lymphocytes.