Immunology - Shnyra questions (3)
Which immune system cell is primarily responsible for the formation of granuloma in the lungs of TB patients? A. Cytotoxic T cells B. Dendritic cells C. Eosinophils D. Natural killer cells E. Th1 cells
Correct answer E Granulomas are the product of the immune system effort to control Mycobacterium replication. The two cells responsible for formation of the granuloma are macrophages and Th1 cells. There are relatively few cytotoxic T cells (choice A), dendritic cells (choice B), and natural killer cells (choice D) present in or near the granuloma. Eosinophils (choice C) do not appear to participate in the immune response against Mycobacterium.
Which of the following cytokines supports proliferation and differentiation of developing lymphocytes in the primary lymphoid tissue IL-1 IL-4 IL-7 IL-12 IL-18
Il-7 IL-1 is an inflammatory cytokine produced by phagocytes to promote inflammation Il-4 supports Th2 differentiation Il-12 and Il-18 operate to differentiate Th1 CD4 cells
IFN‐gamma and TNF (TNF alpha) can act synergistically: A. To downregulate expression of MHC classes I. B. Because IFN‐gamma downregulates expression of TNF receptors. C. To upregulate expression of MHC class II. D. Because they both bind to the same receptor. E. Because they cross‐link IFN‐gamma and TNF beta receptors
The correct answer is C MHC class II genes are expressed constitutively in only by professional APCs. IFN‐gamma induces the expression of class II MHC which can be enhanced by TNF.
Activation of the complement system, directly results in which one of the following outcomes? A. Enhanced phagocytosis B. Expression of Toll‐like receptors on phagocyte cell surface C. Enhancement of immune‐mediated neutralization D. Proliferation of T cells E. Interaction of Fc receptors with antibodies bound to antigens on the pathogen cell surface
A Activation of complement has three outcomes: promotion of inflammation through recruitment of phagocytes (C3a, C5a), opsonization to enhance phagocytosis by complement receptor expressing phagocytes (C3b, C4b), and target cell killing (C5b‐C9). Expression of Toll‐like receptors is constitutive on phagocytes although this expression can be increased (choice B). Neutralization (choice C) is the process of blocking pathogen binding to host receptors (usually accomplished by antibodies), and is not a function of complement activation. Complement activation does not directly result in T‐cell proliferation (choice D). Complement activation does not directly promote antibody binding to Fc receptors (choice E).
T cells stimulated by peptide MHC complexes, displayed APC in the absence of costimulation undergo which one of the following processes activation anergy apoptosis differentiation proliferation
Anergy activation differentiation and proliferation are T cell outcomes following TCR interaction with peptide MHC complexes in the presence of costimulatory signals CD28-CD80/86 Apoptosis is a signal generated in T cells through FAS-FASL interaction (CD95, CD95L) & TNF-TNFR interactions. Anergy is a state of unresponsiveness that is upon preexposure to the same Ag even in the presence of appropriate costiumation, the T cells remain unable to proliferate although they do see to produce cytokines
Which one of the following leukocytes is considered a "granulocyte"? A. Macrophage B. Neutrophil C. Dendritic cell D. Natural killer cell E. Natural killer T cell
B Granulocytes are immune cells that contain granules in their cytoplasm. These granules are filled with enzymes and other inflammatory mediators which are released upon activation of the granulocytes. Neutrophils, eosinophils and basophils are considered granulocytes. Although both NK cells and NKT cells have granules, they are referred to as large, granular lymphocytes, not granulocytes. Monocytic cells such as dendritic cells and macrophages (choices A and C) lack distinct cytoplasmic granules.
Dendritic cells, Mø, and what other cell types are considered professional APC capable of presenting an Ag to a Th cell B cells Basophils eosinophils mast cells Neutrophils
B cells Professional APCs are those that express both MHC I and II molecules. Basophils, eos, mast, np all do not express MHC II and thus cannot present Ag to CD4 T cells. MHC I expressed on all NUCLEATED cells (sans RBCs) In addition the cells above do not express the machinery for processing exogenous antigens
Antigen presenting cells (APCs) are required for T‐cell recognition of specific antigen and activation. APCs accomplish this task by presenting antigen in the context of which of the following molecules? A. T‐cell receptor (TCR) B. Toll‐like receptor (TLR) C. Major histocompatibility complex (MHC) D. Killer inhibitory receptor (KIR) E. Fc receptor (FcR)
C APCs express TLR, FcR, and MHC. TLR (choice B) are innate pattern recognition receptors (PRR) which detect microbial antigens and initiate proinflammatory cytokine production by phagocytes (APCs as well). FcR (choice E) are important in the process of opsonization (FcR binding to antibody bound to the antigen on the pathogen surface and subsequent phagocytosis via this interaction). All nucleated somatic cells express MHC class I while only the professional APCs (B cells, macrophages, and dendritic cells) also express MHC class II. MHC displays antigens for recognition by T cell receptors (TCRs) (choice A).
Downregulation of T cell activation is achieved by the binding of which molecule on the T cell with CD80/86 on the DC CD4 CD8 CD45 CD28 CD152
CD152/CTLA-4 CD4 and CD8 are involved in binding MHC during MHC:TCR interaction. CD4 binds with B2 on MHC II and CD8 binds with A3 on MHC I. CD45 is a cell surface marker for hematopoietic cells CD28 indeed binds CD80.86 but the signal conveyed is stimulatory rather than inhibitory as for CD152/CTLA-4 CTLA-4 constitutively expressed on Tregs
The intracellular signal initiated by antigen binding to the T cell receptor is generated by which set of molecules expressed on the T cell membrane CD3 CD4 CD28 CD45 CD152
CD4 function is to stabilize the interaction of TCR and MHC during T cell activation CD28 is the costimulatory receptor for B7 molecules which promotes activation of T cell response CD45 is a cell surface marker of activation status but it does not function in TCR signaling CD152 or CTLA-4 is an inhibitor
T helper cells interacting with the Ag presenting DC signals generated by the molecular interactions of the TCR with the MHC peptide complex. Additionally, costimulation is required to amplify the initial TCR signals provided through the T cells CD28, which one of the following DC molecules does CD28 interact with CD4 CD8 CD45 CD80/86 CD152
CD80/86 CD4/CD8 are T cell markers that interact with MHC I and II CD45 is a cell surface protein found on hematopoietic cells. CD45R(O) found on memory cells CD152 is CTLA-4 - binds B7 or CD80/86 and stops stimulation of T cell B7 is expressed on APC and is used to engage CD28 thus promoting T cell activation. CTLA-4 CD152 has a higher affinity for B7 than does CD28...thus providing a means of inhibiting T cell activation status.
Which one of the following cytokines plays the most important role in protection against intracellular growth (reactivation) of Mycobacteria tuberculosis? A. Interferon‐gamma B. lnterleukin‐2 C. lnterleukin‐5 D. lmerleukin‐10 E. Tumor necrosis factor
Correct answer A In the formation of granulomas, two cell types predominate, Th1 cells and macrophages. Activated macrophages produce IL‐12 which promotes Th1 differentiation. In turn, Th1 cells produce IFN‐gamma to further activate macrophages. IL‐2 (choice B) is important in promoting early proliferation of Th1 cells but chronic infection (granuloma) with Mycobacterium would result in activation‐induced cell cytotoxicity (AICC) driven by IL‐2. IL‐5 (choice C) and IL‐10 (choice D) is produced by Th2 cells which do not play a role in Mycobacterium immunity. TNF (choice E) is produced by Th1 cells but in vivo studies suggest it only synergizes with IFN‐gamma in the containment of the bacterium.
If a person had a genetic defect affecting perforin production, which cells and immune function would be affected? A. Cytotoxic T cells and natural killer cells/cell killing B. Dendritic cells/antigen presentation C. Eosinophils and basophils/granule production D. Macrophages and neutrophils/phagocytosis E. Mast cells/fusion of granules to cell membrane
Correct answer A Perforin forms pores in the target cells and allows the passage of granzymes into the cytoplasm of the cells. Granzyme then initiates the process of apoptosis. Only cytotoxic T cells and N K cells produce perforin/granzyme while dendritic cells (choice B), eosinophils/basophils (choice C), macrophages/neutrophils (choice D) , and mast cells (choice E) do not produce these molecules.
Neutrophils are attracted to the sites of extracellular bacterial infections by which two important chemotactic substances? A. Bacterial mannose and lipopolysaccharide B. Complement C5a and IL‐8 (CXCL‐8) C. Histamine and complement C3b D. Interleukin‐7 and interleukin‐16 E. Leukotriene B4 and granulocyte colony‐stimulating factor (G‐CSF)
Correct answer B Bacterial mannose and lipopolysaccharide (LPS) (choice A) serve as ligands for pattern recognition receptors found on phagocytes. Histamine is a vasoactive amine released upon degranulation of mast cells, while C3b is an opsonin (choice C). IL‐7 and IL‐16 function in cell activation and survival but do not operate in chemotaxis (choice D). While leukotriene B4 is a pro‐inflammatory product of mast cell activation, G‐CSF is a growth stimulating factor for cells (choice E). Only the cleavage product C5a and IL‐8 are both recruiting factors for neutrophils.
A 1‐year‐old female presented with symptoms of systemic autoimmunity (lupus, diabetes, and arthritis), and upon genetic analysis it was found that the patient had a mutation in the Foxp3 gene locus. Which one of the following is an explanation for the clinical symptoms observed? A. Patient cannot produce antigen presenting cells B. Patient cannot generate regulatory CD4CD25 T cells C. Patient is unable to produce antibodies D. Patient cannot produce anti‐inflammatory cytokines E. Patient NK cells have no inhibitory signal
Correct answer B CD4+CD25+ T regulatory (Treg) cells or natural Treg cells function in peripheral tolerance to prevent self‐antigen‐specific T‐cell activation. This is accomplished by still undefined cell‐contact inhibitory mechanisms. What has been determined is that those inhibitory mechanisms are a product of the Foxp3 gene; thus, cells with active gene expression of Foxp3 (as determined by quantitative PCR) are regulatory T cells. Foxp3 is a unique gene to Treg cells and not expressed in other cell types.
A 36‐year‐old woman with severe allergy to yellow jackets was stung multiple times at a soccer game. Within minutes she developed respiratory distress and became unconscious. Which mediator is primarily responsible for this reaction? A. Complement B. IgG C. Histamine D. TNF E. Norepinephrine
Correct answer C This is an allergic response to the yellow jacket venom involving mast cell degranulation. As a consequence of degranulation, histamine is released. Complement proteins (choice A) are a set of serum proteins which bind to microbial surfaces in order to promote opsonization and cell killing through formation of the membrane attack complex. IgG is an antibody isotype which can initiate complement activation and serve to promote opsonization of pathogens. TNF or tumor necrosis factor is a proinflammatory cytokine released by phagocytes and activated T cells, which elicits inflammatory activity. Norepinephrine is a hormone a hormone and neurotransmitter that plays a role during stress responses but is not responsible for allergic reaction.
Following an initial expansion of B cells in response to microbial peptides, a memory pool of B cells is generated and maintained in the individual in many cases throughout life. Recently, it was discovered that two memory cell types were generated in response to microbial challenge. Upon re‐challenge with the microbe, the patient is protected from infection. Which one of the following explanations accounts for this observation? A. Circulating memory B cells are actively producing antibodies in the absence of antigen B. Circulating memory B cells will produce antibodies, however, only upon encounter with the microbial antigen C. Long‐lived plasma cells are actively producing antibodies in the absence of antigen D. Long‐lived plasma cells will produce antibodies, however, only upon encounter with the microbial antigen E. TLR signaling to the circulating memory B cells will induce rapid production of antibodies in response to antigen encounter
Correct answer C Following an initial B‐cell proliferative event, cells termed plasmablasts differentiate into longlived plasma cells which traffic to the bone marrow and reside there actively producing antibodies to the specific antigen against which they were originally expanded (choice D). Circulatory memory B cells (choice A) also exist but do not actively secrete antibody and appear to serve as replacements for the long‐lived plasma cells in the bone marrow over time (choice B). TLR signaling in memory B cells has not been described to impact antibody production as these circulating cells appear not to synthesize the antibodies (choice E).
Plasma cells secreting lgA are especially abundant in which body site? A. Bone marrow B. Germinal centers of cervical lymph nodes C. Lamina propria of mucosa D. Thoracic duct E. White pulp of the spleen
Correct answer C IgA is the isotype associated with mucosal immunity. While it can be produced in other anatomical regions, it is abundant in the mucosa. The bone marrow (choice A) contains long‐lived plasma cells producing antibodies. Germinal centers (choice B) within the cervical nodes could also produce lgA, but B cells in the lamina propria produce significantly more IgA. The thoracic duct (choice D) is the lymph vessel responsible for returning cells and fluid from the lymph back into circulation. The white pulp of the spleen (choice E) contains areas of B cell differentiation into plasma cells and can produce IgA, but as IgA is an important neutralizing agent in the mucosa, it is localized in high levels within the mucosa.
A 4‐year‐old child has atopic dermatitis due to severe allergies to dust animal dander, and many kinds of pollens. Mediators released from which cell type are responsible for the clinical manifestations immediately following exposure to these substances? A. B cells B. Macrophages C. Mast cells D. Th1 cells E. Th2 cells
Correct answer C Allergens such as dust, animal dander, and pollen bind to IgE expressed on the surface of mast cells. Such IgE is produced during the first exposure to the allergen and this IgE binds to high affinity Fc receptors on mast cells. This is known as sensitization. Secondary encounter with the allergen results in binding of the antigen to the IgE and activation of the mast cells (degranulation). Macrophages (choice B) play a role in type IV delayed‐type hypersensitivity. B cells (choice A) produce the initial antibodies (lgE) to the allergen but do not release vasoactive amines as does mast cells. Th1 cells (choice D) are the mediators of type IV hypersensitivity and Th2 cells (choice E) do promote the IgE production but again are not responsible for the mediators.
Which cells utilize reactive oxygen and nitrogen species and lysosomal enzymes to kill pathogens? A. Cytotoxic T cells B. Natural killer T (NKT) cells C. Macrophages D. Natural killer (NK) cells E. Th1 cells
Correct answer C All of the cells listed have the capacity to kill target cells. Cytotoxic T cells (choice A) or activated CD8+ T cells kill primarily through Fas‐FasL interactions and/or production of granzyme/perforin. NK (choice D) and NKT (choice B) cells use killer activating receptor (recognize MHC class I negative cells) signaling and produce granzyme/ perforin. Th1 (choice E) cells can produce TNFbeta and IFN‐gamma which has been shown to cause cell death. Only macrophages (choice C) express inducible NADH‐oxidase and NO‐synthase.
Which cytokine is essential for T cell proliferation and is also necessary for the production of CD25 positive T reg cells IL-2 IL-3 IL-4 IL-5 IL-6
IL-2 Il-3 is a differentiating factor for plasmacytoid DC Il-4 and Il-5 are involved in differentiation and growth of Th2 Il-6 is proinflammatory cytokine & surpasses Treg IL-6 & TGF-b --> Th17 cells
The difference between tolerance and immunity depends upon the maturation status of the antigen presenting dendritic cells. What is the T‐cell outcome of an antigen presentation event by a mature dendritic cell? A. Anergy B. Apoptosis C. Activation D. Ignorance E. Suppression
Correct answer C Maturation indicates that the dendritic cell (DC) has been stimulated by Toll‐like receptor binding to pathogen components. It, in turn, upregulates the expression of B7 (costimulatory molecules) on the surface of the DC. Together with the MHC‐peptide complex, the DC can now provide sufficient signaling to promote T cell activation. Such interactions deficient in B7 result in anergy (choice A). Apoptosis (choice B) signals are the result of ligand‐receptor interactions involving Fas‐Fas ligand or TNF‐related interactions. Ignorance (choice D) is the result of antigens being sequestered from access to T cells; thus, the T cells remain ignorant of the antigen presence (iminunoprivileged sites such as the sex organs utilize this mechanism). Suppression (choice E) is an active process mediated by cytokines or regulatory cells such as regulatory T cells.
A person develops a viral infection and both T and B cells become activated to fight the infection. In which way is antigen recognition by B cells different from antigen recognition by T cells? A. B cells home to the paracortex of lymph nodes where they recognize the antigens trapped by helper T cells B. B cells recognize the antigens that have been processed and presented by follicular dendritic cells C. B cells undergo receptor editing to change receptors that fail to bind to an antigen D. B cells utilize membrane immunoglobulin molecules to bind to antigen in its natural state E. The antigen receptors on a single B cell have a broad specificity, and are able to recognize several chemically unrelated antigens
Correct answer D CD4+ and CD8+ T cells can only respond to antigens once they have been processed and loaded onto major histocompatibility complexes (MHC) and displayed by antigen presenting cells. B cells recognize antigens directly. Upon initial B‐cell encounter with antigen, B cells traffic to the paracortex of the lymph nodes to interact with helper T cells. This interaction involves CD40 ligand‐CD40 which promote B‐cell expansion as plasma cells (choice A). Once receiving the CD40 signal, the B cells traffic back into the lymphoid follicle and form a germinal center. Antigen is presented to the developing B cells by follicular dendritic cells, FDC (choice B). Only B cells expressing the highest affinity immunoglobulin receptors will remain bound to the FDC. All otherB cells will undergo apoptosis. Helper T cells then produce the appropriate cytokines for isotype switching and cell survival signals are provided through CD40 ligand‐CD40 interactions. Some of the B cells differentiate into antibody‐producing plasma cells while others become memory B cells which leave the lymph node and traffic to the bone marrow where they remain as long‐lived plasma cells. Receptor editing occurs in the bone marrow when B cells are undergoing central tolerance and involves rearrangement of lg genes (choice C). Like all adaptive receptors each one is specific for only one antigen unlike innate receptors which recognize the conserved sequence on pathogens.
The interaction of which molecule on the membrane of cells with its ligand induces apoptosis? A. B7 (CDS0/86) B. CD40 C. CTLA‐4 (CD152) D. Fas (CD95) E. Fe receptor (CD16)
Correct answer D B7 (choice A), expressed on antigen‐presenting cells, provides costimulatory signals for T‐cell activation/suppression depending upon the interacting receptor. CD40 (choice B) is the receptor for CD40L. Signals generated by CD40L‐CD40 interactions result in activation as in the case for B cells or maturation when occurring in dendritic cells. CTLA‐4 (choice C) signaling mediated by binding with B7 from antigen presenting cells, suppresses T cell activation. FcR (choice E) are surface receptors that bind to Fc regions of antibodies and result in antibody‐dependent cell cytotoxicity (ADCC) or opsonization. Only Fas‐FasL interactions result in apoptosis caspase activation.
A 14‐year‐old girl presented with an itchy, erythematous rash following exposure to poison ivy. Which term describes the role of poison ivy oils in this response? A. Allergen B. Carrier C. Cytokine D. Hapten E. Immunogen
Correct answer D Haptens are small molecules which do induce an immune response only in the presence of a carrier. Carriers (choice B) are usually protein in nature and associate with haptens. Allergens (choice A) are agents which stimulate an IgE response and subsequent re‐exposure activates mast cells to degranulate and cause type I hypersensitivity reactions. Cytokine (choice C) production is a result of hapten binding but does not define the role of urushiol (poison ivy oil). Immunogens (choice E) are chemicals which elicit an immune response. This response is correct but is a broad answer to the question posed.
Which type of hypersensitivity is associated with reactions to poison ivy oil? A. Type I B. Type II C. Type III D. Type IV
Correct answer D Type I (immediate hypersensitivity) (choice A) is an immune response mediated by IgE triggering of mast cell and basophil degranulation. Type II (choice B) are antibody‐mediated responses in which antibodies against cellular or extracellular matrix antigens may deposit in any tissue expressing the target antigen. Thus, the disease is normally tissue‐specific. An example of type II hypersensitivity is Goodpasture syndrome and myasthenia gravis. Type III (choice C) are immunecomplex mediated events where antibodies to soluble antigens bind and form complexes which deposit in areas of high pressure such as blood vessel branches and the kidney glomeruli. An example of type III hypersensitivity is systemic lupus erythematosus. Poison ivy induces delayedtype hypersensitivity.
Which cell type is primarily responsible for the inflammation seen in poison ivy rash? A. B cells B. Cytotoxic T cells C. Eosinophils D. Natural killer cells E. Th1 cells
Correct answer E B cells (choice A) are associated with responses of type I, II, and III hypersensitivity. Cytotoxic T cells (choice B) can produce a type IV hypersensitive (cell‐media ted) response by killing target cells expressing the antigen such as in rheumatoid arthritis. Eosinophils (choice C) can] participate in type I as they express Fe receptors for IgE. Natural killer cells (choice D) are recruited participants in inflammatory responses but are not primarily responsible for hypersensitivity reactions. Delayed‐type hypersensitivity reactions are primarily driven by Th1 cells producing IFN‐gamma although Th17 cells and macrophages are also activated.
Which cells are the source of IL‐4, IL‐5, IL‐10, and IL‐13? A. B cells B. Macrophages C. Mast cells D. Th1 cells E. Th2 cells
Correct answer E B cells (choice A) can produce IL‐4 and IL‐10. Macrophages (choice B) can produce IL‐10. Mast cells (choice C) can produce IL‐4. Th1 (choice D) cells do not produce any of these cytokines as these factors tend to suppress Th1 activation and differentiation.
Which one of the following represents the mechanism by which immune complexes (ICs) are normally cleared from the circulation? A. lCs are solubilized by C3a B. ICs are solubilized by C5a C. Factor1 releases complement‐bound ICs to bind with complement receptors found on splenic/hepatic neutrophils D. Red blood cells capture lCs from blood via Fc receptors E. C3b solubilizes ICs and attaches to red blood cells via complement receptors
Correct answer E Defects in the complement pathway are associated with IC diseases due to the fact that complement is important for the removal of ICs that occur during normal B‐cell immune responses to pathogens. ICs are created by soluble (or cell surface) antigen interaction with secreted antibodies. This normally results in opsonization and phagocytosis; however, another mechanism of clearance is mediated in the spleen and liver by macrophages. C3 cleavage product, C3b, binds to the ICs and is attached to complement receptors on red blood cells. These cells then pass through the spleen and liver, and a tissue factor removes the ICs from the red blood cells and resident macrophages take up the ICs for degradation (choices A‐D).
Which of the following is the site at which lymphocytes can leave the blood and gain entry into the lymph nodes and what lymphocyte cell surface protein mediates such access? A. Lymphoid follicle: CD4 B. Germinal center: CD62L (L‐selectin) C. Lymphoid follicle: CD62L (L‐selectin) D. Periarterial lymphatic sheath (PALS): CCR7 E. High endothelial venules (HEV): CD62L (L‐selectin)
Correct answer E Lymphocytes traffic between the blood and lymph circulation in order to maintain surveillance of the body for foreign invaders. In order for T cells to gain access to the lymph nodes from the circulation, specialized zones called high endothelial venules provide connections from the blood to the lymph node. The cells must arrest at the HEV via integrin binding, through CD62L found on naive T cells, and then those arrested cells follow a chemokine (chemotactic) gradient extravasating through the endothelial cells of the HEV into the cortex of the lymph node. Lymphoid and germinal center follicles (choices A‐C) are areas in the lymph node where B cells and plasma cells, respectively, are found in high concentration. Periarterial lymphatic sheath (choice D) is the site in the spleen white pulp where T cells are heavily concentrated.
Which immune system cells recognize body cells with reduced expression of MHC class I molecules? A. Cytotoxic T cells B. Dendritic cells C. Macrophages D. Natural killer cells E. Neutrophils
D Cytotoxic T cells (choice A) are CD8+ T cells which recognize antigens presented on MHC class I act to kill targets expressing those antigens. Dendritic cells (choice B) are specialized antigen presenting cells. Macrophages (choice C) and neutrophils (choice E) are phagocytes. Only natural killer cells recognize MHC class I expression on the surface of cells and kill those cells that have lost expression.
A 45‐year‐old female presents with anorexia and some abdominal pain. Fecal smears reveal the presence of Taenia eggs, products of a parasitic tapeworm infection. Which one of the following cells would be most effective in defense against this parasite? A. Platelets B. Erythrocytes C. Neutrophils D. Eosinophils E. Monocytes
D Platelets and erythrocytes serve as blood components and do not generate immune responses against parasites (choices A and B). Neutrophils (choice C) are cells which may engage the parasite but the most effective response is generated by eosinophils which express Fc epsilon receptors. These receptors allow the eosinophils to bind to IgE directed against parasitic microbes. Such binding will result in antibody‐dependent cell cytotoxicity or ADCC. Monocytes (choice E) are generated in the bone marrow and circulating blood cells which can differentiate into macrophages and dendritic cells. However, these cells would not be as effective as the eosinophils in killing the parasite.
Which one of the following represents the major role of negative selection in the thymus Elimination of self reactive T cells Expansion of non self reactive T cells Maturation of professional APC such as DC expression of TCR on mature T cells Differentiation of TH1/Th2 CD4 T cells
Elimination of Self reactive T cells 90% of all T cells that are produced are eliminated during negative selection. Thymic medullary epithelial cells express the AIRE gene (autoimmune regulator gene) and synthesize all self antigens for presentation on MHC molecules to maturing Thymocytes Those T cells that respond too strongly or weakly undergo apoptosis Those responding intermediately are provided survival factors and complete maturation, and they migrate out of thymus to seed the lymphoid organs in the body. While there may be some expansion of nonself-reactive T cells due to provided survival/growth factors, this is not the major role of negative selection. DC do mature but only serve to present self antigens. TCR expression is completed following positive selection Differentiation of CD4 T cells occurs after Ag exposure in the periphery (tissue, spleen, LN)
Antigens from which one of the following microbes would be presented on MHC Class I molecules by macrophages Ascaris lumbricoides Candida Albicans Hemophilus influenzae Influenza virus Streptococcus pneumoniae
Influenza virus MHC Class I molecules express endogenous antigens, that were derived from the presenting cell interior. A. Lumbricoides is a parasitic worms C. Albicans a fungus H. Influenzae & S. Pneumoniae are extracellular bacteria, all will generally only produce exogenous Ag due to their inability to invade cells. Influenza virus by nature is an intracellular parasite and thus endogenous antigens would be loaded onto MHC Class I and presented to T cells
A blood sample from an individual with Systemic lupus erythematous was studied in a research project mapping TCR specificities. Many T cells were discovered to express receptors specific for autologous antigens. Failure of which process in the thymus leads to large number of auto reactive T cells in the patients blood affinity maturation antigen processing hematopoiesis negative selection Receptor edition
Negative selection Affinity maturation refers to the process whereby immune receptors for specific Ag during a response are mutated to generate high affinity Ab, thereby allowing formation of memory cells with the most reactive receptors to sense antigens upon reencounter. Ag processing is the process of breaking down and loading antigen onto MHC molecules for surface recognition by responding T cells. Hematopoiesis is the production of blood cellular components such as many types of immune cells and occurs in the bone marrow. Receptor editing is a B cell process occurring in the Bone marrow during development and serves a s mode to reconfigure BCR light chain that recognizes self antigen
Positive selection in the thymus occurs when thymocytes express functional versions of which of the following critical molecules: CD28 Fc receptor MHC I MHC II TCR
TCR immature T cells (+/+) interact with MHC I and II thymic epithelial cells and following this interaction, the T cell assumes a single positive status either CD4 or CD8 and express a functional TCR. CD28 is a T cell surface molecules involved in costimulation signals, however it is not relevant for positive selection. While Fc receptors and MHC I molecules are expressed by T cells, Fc receptors serve as a means to interact with Ab and MHC to present Antigens to T cells. T cells do not express MHC II molecules
Expression of MHC genes is: A. Codominant. B. Dominant for maternal genes. C. Dominant for paternal genes. D. Dependent on thymic selection. E. Totally dependent on the antigenic exposure of the individual.
The correct answer is A Because of the polygeny of the MHC, every person will express at least three different Ag presenting MHC class I molecules and three MHC class II molecules on his or her cells. In fact, the number of different MHC molecules expressed on the cells of most people is greater because of the extreme polymorphism of the MHC. There are more than 200 alleles of some human MHC class I and class II genes. The particular combination of MHC alleles found on a single chromosome is known as an MHC haplotype. Expression of MHC alleles is codominant, with the protein products of both the alleles at a locus being expressed in the cell, and both gene products being able to present antigens to T cells.
Activation of resting B‐cells by T‐helpers depends directly upon costimulatory interaction between: A. CD40 and CD40L. B. B7 and CD28. C. B7 and CTLA‐4. D. CD4 and MHC class II. E. ICAM‐1 and LFA‐1
The correct answer is A CD40L/CD40 interactions exert profound effects on B cells. CD40 signaling in B cells promotes germinal center (GC) formation, immunoglobulin (Ig) isotype switching, somatic hypermutation of the Ig to enhance affinity for Ag, and finally the formation of long‐lived plasma cells and memory B cells.
Cytokines always act: A. By binding to specific receptors. B. In an autocrine fashion. C. At long range. D. Antagonistically with other cytokines. E. Synergistically with other cytokines.
The correct answer is A Cytokines act on their target cells by binding specific membrane receptors. Many cell functions are regulated by members of the cytokine receptor superfamily. Signaling by cytokine receptors depends upon their association with the Janus kinases (JAKs), which couple ligand binding to tyrosine phosphorylation of signaling proteins recruited to cytokine receptor complex. Among these signaling proteins are unique family of transcription factors named the signal transducers and activators of transcription (STATs). The receptors and their corresponding cytokines have been divided into several families based on their structure and activities.
The main costimulatory signal for activation of resting T‐cells is provided by ligation of: A. CD28 B. Surface Ig C. LFA‐1 D. VLA‐4 E. IL‐2
The correct answer is A The ability of naive (resting) T cells to clonally expand and acquire effector functions depends on the strength of signals received by the TCR and by an array of co‐stimulatory receptors — the most prominent of which is CD28.
The T‐cell ligand binding B7 on a professional antigen‐presenting cell is: A. CD28 B. CD2 C. LFA‐1 D. ICAM‐1 E. VCAM‐1
The correct answer is A The current model of T cell activation requires two signals. The first signal is Ag specific, requiring T cell receptor recognition and binding to MHC/Antigen presented by an antigen presenting cell. The second signal is nonspecific, resulting from the binding of B7 ligand on the APC with its receptor, CD28, on the T cell. If both signals are provided, the T cell will proliferate and secrete cytokines.
Which of the following is C3 convertase of the classical pathway is whereas C3 convertase of the alternative pathway? A. C1a; C3bBb B. C4bC2a; C3bBb C. C3bCR1; C3bBb D. C4bC2a; C3bCR1 E. C1a; C3bCR1
The correct answer is B Complement can be activated through three pathways: classical, lectin, and alternative. The *classical pathway* is activated when C1q binds to antibody attached to antigen, activating C1r and C1s, which cleave C4 and C2. C4 and C2 cleavage products form the classical and lectin pathway C3 convertase, C4bC2a, which cleaves C3 into C3b and C3a. The *alternative pathway* (AP) is activated when C3 undergoes spontaneous hydrolysis and forms the initial AP C3 convertase, C3(H2O)Bb, in the presence of Factors B and D, leading to additional C3 cleavage and eventual formation of the AP C3 convertase (C3bBb). *Properdin* facilitates AP activation by *stabilizing AP converses.*
Dendritic cells can be driven from a resting state to an activated state by the T‐cell surface molecule: A. TCR B. CD40L C. CD28 D. B7 E. CD40
The correct answer is B Interaction of T‐helper cells expressing CD40 ligand (CD40L) with its cognate CD40 receptor on DCs leads to a mature DC phenotype, characterized by increased capacity of antigen presentation to cytotoxic T cells.
T‐cell help for antibody production: A. Depends on T‐cell recognition of native antigen bound to B‐cell surface Ig. B. Depends on T‐cell recognition of antigen processed by the B‐cell. C. Involves class I MHC on the B‐cell. D. Can occur in X‐irradiated mice. E. Is a feature of the antibody response to pneumococcal polysaccharide.
The correct answer is B T cells recognize only processed Ags. CD4+ T helper cells recognizing peptide Ag within MHC class II (not class I MHC) is required for differentiation of plasma and memory cells form Ag activated B cells. Proliferation (activation) of T and B cells will not occur in X‐irradiated mice. Pneumococcal polysaccharides are TI antigens for there is no activation of T cells.
The molecules mediating signal transduction following antigen binding to cell surface immunoglobulin on a B‐cell are called: A. Ig Fc B. Ig‐alpha and Ig‐beta C. MHC D. CD4 E. CD8
The correct answer is B B‐cell receptor complex usually consist of an Ag‐binding subunit (BCR) and a signaling subunit, which is a disulfide‐linked heterodimer of Ig‐Alpha (CD79A) and Ig‐Beta (CD79B) proteins.
The following is characteristic of B‐ but not T‐cells: A. Class I MHC. B. CD3. C. Measles virus receptor. D. Polyclonal activation by concanavalin A. E. Surface immunoglobulin.
The correct answer is B Cluster of differentiation 3 (CD3) is a multimeric protein complex and is composed of four distinct polypeptide chains; epsilon (ε), gamma (y), delta (δ) and zeta (ζ), that assemble and function as three pairs of dimers (εy, εδ, ζζ). The CD3 complex serves as a T cell co‐receptor that associates noncovalently with TCR. The CD3 protein complex is a defining feature of the T cell lineage, therefore anti‐CD3 antibodies can be used effectively as T cell markers.
The percentage of human peripheral blood T‐cells bearing a gamma delta T‐cell receptor is: A. 30-80%. B. 1‐5%. C. 100%. D. 0%. E. Only present during mycobacterial infections.
The correct answer is B Gamma delta (yd) T cells are the prototype of "unconventional" T cells and represent a relatively small subset of T cells in the body, about 5%. This sets them apart from the classical and much better known CD4+ helper T cells and CD8+ cytotoxic T cells that are defined by ab TCRs. The majority of *yd T cells* are *activated* in an *MHC‐independent manner*, in striking contrast to MHC restricted ab T cells. *ab T cells show TCR‐dependent activation* by certain low molecular weight phosphorylated molecules of microbial origin. Most *yd T cells* also *recognize stress‐induced surface markers* on infected cells and tumors. Some reports suggest recognition of virus proteins by certain yd T cells.
The alpha/beta heterodimeric form of the IL‐2 receptor: A. Is downregulated on activated cells. B. Binds IL‐2 with high affinity. C. Is found only on T‐cells. D. Uses CD45 as an alpha chain. E. Allows rapid dissociation of bound IL‐2.
The correct answer is B IL‐2 is a 15 kDa cytokine secreted as a soluble molecule by activated T cells IL‐2 can bind to the IL‐2 receptor (IL‐2R) subunit CD25 (also known as IL‐2Rα) with a dissociation constant (K d) of ~10−8 M. This interaction induces a distinct conformational change in IL‐2 that increases its affinity for the IL‐2R subunit CD122 (also known as IL‐2Rβ). Subsequently, the IL‐2-CD25 dimer recruits CD122 followed by the common cytokine receptor y‐chain, another subunit of the IL‐2R. This quaternary IL‐2-IL‐2R complex has a K d of ~10−11 M.
A chromosome on which T‐cell receptor alpha chain gene rearrangement has occurred lacks which of the following gene segments: A. Joining (J). B. Diversity (D). C. Variable (V). D. Constant (C). E. TCR beta chain.
The correct answer is B T cell receptors recognize foreign Ags which have been processed as small peptides and bound to MHC molecules at the surface of APC. Each T cell receptor is a dimer consisting of one alpha and one beta chain or one delta and one gamma chain. Both the alpha and beta loci include V (variable), J (joining), and C (constant) segments. The beta locus also includes diversity (D) segments whereas the alpha does not.
The nuclear AP‐1 site responsible for 90% of IL‐2 enhancer activity binds: A. The Oct - 1 transcriptional factor. B. The Fos/Jun transcription factors. C. The nuclear factor of activated T‐cells (NFAT). D. The NF‐kappa B transcriptional factor. E. Polyclonal mitogenic agents such as concanavalin A.
The correct answer is B The activity of the IL‐2 promoter is regulated by a number of transcription factors. Among these, the activity of NFkB, nuclear factor of activated T cells (NF‐AT) and activator protein 1 (AP‐1) is rapidly induced during activation and is critically involved in the expression of IL‐2 during T cell stimulation. A plethora of physiological and pathological stimuli induce and activate a group of DNA binding proteins that form AP‐1 dimers. These proteins include the *Jun and Fos transcription factors*
MHC class II molecules are found on: A. Virtually all cells in the body. B. B cells, dendritic cells and macrophages. C. Only gamma‐interferon activated cells. D. Virtually all nucleated cells in the body. E. Only on virally‐infected cells.
The correct answer is B The main function of MHC class II molecules is to present processed Ags, which are derived primarily from exogenous sources, to CD4+ T‐lymphocytes. MHC class II molecules thereby are critical for the initiation of the Ag‐specific immune response. Constitutive expression of MHC class II molecules is confined to professional antigen‐presenting cells (APC) of the immune system such as DCs, Mø, and B cells.
The T‐cell receptor link to MHC/peptide is enhanced by interaction between MHC class II on the antigen‐presenting cells with the following molecule on the T‐cell: A. LFA‐1 B. CD2 C. CD4 D. CD8 E. CD28
The correct answer is C CD4 and CD8 are members of the immunoglobulin supergene family of proteins, and function as co‐receptors with the TCR in binding MHC class II or class I molecules, respectively.
In the immunological synapse: A. The acetylcholine receptor in expressed on the T‐cell. B. Production of substance P by the antigen‐presenting cell is a key event. C. The initial interaction between TCR and MHC is unstable. D. Adhesion molecule pairs eventually move to the center of the synapse. E. The B7-CD28 interaction is redundant.
The correct answer is C The immunological synapse between T cells and APCs is a specialized structure formed at the Tcell : APC interface, consisting of two concentric rings of molecules. The immunological synapse forms because the initial interaction between the cells is not very tight.
Cross‐linking of B‐cell surface receptors: A. Is a characteristic feature of thymus‐dependent antigens. B. Lowers the intracellular Ca++ concentration. C. Rapidly phosphorylates the Ig‐alpha and Ig‐beta chains of the surface Ig receptor. D. Requires contiguity of 2 B‐cell epitopes of different specificity on the same antigen molecule. E. Cannot be achieved by anti‐idiotypic antibodies.
The correct answer is C BCR cross‐linking induces rapid and robust phosphorylation of Igα and Igβ. It is common feature for activation by TD and TI antigens.
Antibody‐dependent cell‐mediated cytotoxicity (ADCC) is carried out by which of the following? A. NK cells and FcyRI B. neutrophils and FcyRI C. NK cells and FcyRIII D. macrophages and FcyRIIB2 E. mast cells and FcεRI
The correct answer is C NK cells play a major role in cancer immunotherapies that involve tumor‐antigen targeting by monoclonal antibodies (mAbs). NK cells express a variety of activating and inhibitory receptors that serve to regulate the function and activity of the cells. In the context of targeting cells, NK cells can be "specifically activated" through FcγRIIIA which mediates Antibody‐dependent cell mediated cytotoxicity (ADCC).
Protein tyrosine kinase activity following T‐cell stimulation: A. Phosphorylates and thereby activates phospholipase C gamma 1. B. Is an inherent property of the T‐cell receptor alpha and beta chains. C. Is an inherent property of CD3. D. Is unaffected by herbimycin A. E. Is unrelated to phosphorylation of the CD3‐associated zeta chains.
The correct answer is C Stimulation of the T‐cell antigen receptor (TCR) leads to the activation of signaling pathways that are essential for T‐cell development and the response of mature T cells to antigens. The TCR has no intrinsic catalytic activity, but TCR engagement results in tyrosine phosphorylation of downstream targets by nonreceptor tyrosine kinases. Three families of tyrosine kinases have long been recognized to play critical roles in TCR‐dependent signaling. They are the Src (LCK and Fyn), (Syk) ζ‐ associated protein of 70 kDa (ZAP‐70), and Tec families of kinases. The trigger for *TCR dependent signaling cascades* is the recruitment and activation of the *Src* family kinases *Lck and Fyn*, leading to the *phosphorylation of tyrosine* residues within the immunoreceptor tyrosine based activation motifs *(ITAMs) of the CD3* subunits of the TCR.
Which of the following is characteristically produced by the Th2 CD4 cells which provide help for antibody production, but not by Th1 cells? A. IFN‐gamma B. Lymphotoxin (TNF‐beta) C. GM‐CSF D. IL‐4 E. IL‐1
The correct answer is D Mossman and Coffman published their seminal paper in 1986 showing dichotomy in CD4+ Th cell subsets based on cytokine‐producing potential and showed that there is a reciprocal expression pattern of IL‐4 and IFN‐y in Th2 and Th1 cells, respectively.
Which one of the following events occurs earliest in T‐cell signaling: A. Activation of phospholipase C. B. Activation of protein kinase C. C. Production of inositol triphosphate. D. Activation of protein tyrosine kinase. E. Mobilization of intracellular calcium.
The correct answer is D TCR signal transduction is initiated by the recognition of cognate peptide-MHC molecules. The first molecule to be recruited to the TCR-CD3 complex is the *SRC* family kinase member *LCK*, which *phosphorylates ITAMs* of the *CD3 chain*, CD3δ chain, CD3ε chains and the ζ‐chains. *Phosphorylation of the ITAMs* enables the *recruitment of ZAP70 (Syk)* (ζ‐chain associated protein kinase of 70 kDa), its phosphorylation by LCK and its activation. *Activated ZAP70* phosphorylates *four key tyrosine* residues on linker for activation of T cells *(LAT)*.
The early increase in phospholipase C gamma 1 activity following T‐cell stimulation: A. Represents a sensitive regulatory negative feedback control mechanism. B. Dephosphorylates protein tyrosine kinase inhibitors. C. Accelerates hydrolysis of diacylglycerol. D. Accelerates hydrolysis of phosphatidylinositol diphosphate. E. Accelerates hydrolysis of inositol triphosphate.
The correct answer is D Phospholipase Cγ1 (PLCγ1) is an important signaling effector of T cell receptor (TCR) which, after activation, hydrolyzes the membrane lipid phosphatidylinositol 4,5‐bisphosphate (PIP2) to generate diacylglycerol (DAG) and inositol 1,4,5‐trisphosphate PIP3.
The T‐cell receptor for antigen is: A. Derived from the immunoglobulin gene pool by alternative splicing. B. A tetramer. C. A homodimer. D. A heterodimer. E. A single chain molecule.
The correct answer is D T cell receptors recognize foreign Ag which have been processed as small peptides and bound to MHC molecules at the surface of APC. Each T cell receptor is a heterodimer consisting of one alpha and one beta chain or one delta and one gamma chain.
When a resting naive T‐cell engages only its specific MHC/peptide complex displayed on the surface of a fibroblast it: A. Undergoes blast cell formation. B. Produces IL‐2. C. Moves from Go to G1 of the cell cycle. D. Becomes anergic. E. Secretes IL‐1.
The correct answer is D T lymphocytes play a key role in immunity by distinguishing self from nonself peptide antigens and regulating both the cellular and humoral arms of the immune system. Acquired, antigen specific unresponsiveness is an important mechanism by which T cell responses to antigen are regulated in vivo. Clonal anergy is the term that describes T cell unresponsiveness at the cellular level. Anergic T cells do not proliferate or secrete interleukin (IL)‐2 in response to appear private antigenic stimulation. Anergy can be induced by submitogenic exposure to peptide antigen in the absence of a costimulatory signal provided by soluble cytokines or by interactions between costimulatory receptors CD28 on T cells and counter‐receptors on antigen‐presenting cells (CD80/CD86).
Which Igα‐associated tyrosine kinase phosphorylates the cytoplasmic tail of CD19 involved in signal transduction in activated B cells? A. CD81 B. Blk C. Fyn D. Lyn E. Syk
The correct answer is D The cell surface glycoprotein *CD19* and the *Src*‐related protein tyrosine kinase *Lyn* are key mediators of positive and negative signaling in B cells, respectively. Protein tyrosine kinase Lyn, which is activated by the antigen receptor, can be readily co‐immunoprecipitated with CD19 suggesting this is the enzyme responsible for the antigen receptor mediated tyrosine phosphorylation of CD19.
The T‐cell receptor antigen recognition signal is transduced by: A. The TCR alpha chain. B. The TCR beta chain. C. CD1. D. CD2. E. CD3.
The correct answer is E CD3 molecules are assembled together with the TCR heterodimer. CD3 possess a characteristic sequence motif for tyrosine phosphorylation, known as ITAMs (immunoreceptor tyrosine‐based activation motifs). The TCR polypeptides themselves have very short cytoplasmic tails, and all proximal signaling events are mediated through the CD3 molecules. TCR‐CD3 complex interaction plays an important role in mediating cell recognition events.
T‐cell CD40L provides a costimulatory signal to B‐cells by ligating: A. Surface Ig B. MHC class II C. CD28 D. CD19 E. CD40
The correct answer is E CD40/CD40L is a pair of complementary transmembrane glycoproteins expressed on immune cells. CD40L ligates CD40 expressed on B cells and thus stimulates downstream signaling pathways in B cell activation.
A Cytokine receptor which is a member of the hematopoietin receptor family is: A. IL‐8 receptor. B. IFN gamma receptor. C. TNF (TNF‐alpha) receptor. D. IL‐1 receptor. E. IL‐2 receptor.
The correct answer is E The hematopoietins constitute a family of structurally related proteins that includes many cytokines, growth factors and hormones. Cytokines of the hematopoietic system include interleukins (ILs), colony‐stimulating factors (CSFs), interferons, erythropoietin (EPO) and thrombopoietin (TPO). IL‐2 and IL‐2 receptor are required for generation of T cells
Vaccination operates to generate a humoral immune response to the immunogenicity. Which one of the following represents the critical function of the resultant humoral response in protecting vaccinated patients from future infections by targeted pathogenic agents Opsonization extravasation neutralization Complement activation ADCC
neutralization antibodies generated by the vaccination are produced by antigen specific memory B cells which reside in the bone marrow. These Ab (most likely IgG) can promote opsonization, Fe receptor mediated phagocytosis, and complement activation as well as ADCC. However the infectious agent in most cases will have colonized tissues by the time these mechanisms act to limit growth. The most critical function of a vaccine mediated humoral response is to generate Ab which block attachments of infectious agents to host cell surfaces or neutralization. This blockade completely inhibits microbial colonization and ensures protection from the pathogen. Extravasation refers to the process whereby immune cells can leave the circulation and enter tissues generally to migrate into areas of inflammation IOT destroy pathogens`
