shynra practice ? exam 2 Flashcards

Question

Fragments of a cytoplasmic pathogen are presented to T cells by A. direct engagement of cell surface pattern recognition receptors. B. macropinocytosis into γ/δ T cells. C. MHC class I molecules to CD8+ T cells. D. phagocytosis and presentation to CD4+ T cells. E. placement into endocytic vesicles or complexing with class II MHC

Answer 1

C. MHC class I molecules to CD8+ T cells ``` Peptides derived in cytoplasm are presented by class I MHC molecules. Pattern recognition receptors do not present peptides to T cells nor do γ/δ TT cells. CD8+ T cells recognize peptide fragments presented by class I MHC molecules. They are not processed in endocytic vesicles for presentation by class II MHC to CD4+ T cells. ```

Answer 2

E. the interface between antigen-presenting cells and T cells. The immunologic synapse is the interface between T cells and APCs. It does not refer to the recognition and binding by pattern recognition receptors. CD4+ T cells are restricted to the recognition of peptide presented by MHC II molecules. The selective unresponsiveness of T cells is called tolerance or anergy. T-cell receptors do not recognize soluble molecules.

Answer 3

D. Th1 cells CD4+ Th1 cells recruit and activate macrophages to destroy intracellular pathogens. Antigenpresenting cells are not T cells. Cytotoxic T lymphocytes are CD8+. Th0 and Th2 cells, although also being CD4+, do not engage in this activity.

Answer 4

C. CD8+ cytotoxic T cells destroy the infected cell. Once activated, cytotoxic T lymphocytes can bind and destroy infected cells expressing peptideMHC I complexes recognized by their T-cell receptors. Neither B cells nor CD4+ T cells recognize peptide-MHC I. T helper cells – whether Th0, Th1, or Th2 – are CD4+ and do not recognize peptide-MHC I.

Answer 5

C. signaling from the B-cell receptor. Activation of a naïve B calls requires the engagement of its BCR (immunoglobulin). The B cell does not require interaction with antigen-presenting cells such as dendritic cells. The IgD and lgM on its surface have the same epitope specificity. Turnover of cytoplasmic molecules by proteasomes is a normal ongoing activity, but is not involved in the naïve B cell's activation. The isotype switch occurs only after B cell interaction with TH cell.

Answer 6

C. anergy. Anergy is a state of nonreactivity that occurs when a lymphocyte receives a stimulus through its TCR or BCR in the absence of the additional appropriate signals provides by antigen-presenting cells or T cells. Allergy involves the degranulation of mast cells following binding of antigen to lgE molecules already affixed to the mast cell surfaces. Apoptosis is the programmed death of a cell through degradation of its nucleic acids. Autoimmunity is the active response of the immune system against self-epitopes. Hyper- sensitivity is a response mediated by activated lymphocytes or their products. Allergy is one form of hypersensitivity.

Answer 7

C. CD4+CD25+ Treg cells CD4+CD25+ Treg cells inhibit various responses against self-epitopes as well as some responses against epitopes associated with infectious agents and tumors. Antigen-presenting cells do not have this capacity. Anergized cells are inactive. Follicular dendritic cells are involved in the display of antigen to B cells in the LNs. Naïve T cells require activation before they can begin to carry out any of their effector functions.

Answer 8

D. Naïve T cells Dendritic cells are professional APCs which control the activation of naïve T cells cells. Anergized T cells remain refractory to subsequent engagement of peptide-MHC and remain quiescent. B cells do not require binding of peptide-MHC for activation. Mast cells become activated and degranulated via the binding of antigen to lgE molecules already affixed to the mast cell surfaces. Natural killer cells do not have receptors for binding peptide-MHC.

Answer 9

E. Th1 cells produce IFN-γ but not IL-4, and Th2 cells produce IL-4 but not IFN-γ The signature cytokines of Th1 and Th2 cells are IFN-γ and IL-4, respectively. IL-5 and IL-13 are also very specific for Th2 cells. IL-1 is not typically produced by helper T cells of either subset. IL- 2 is produced by Th1 cells. Both Th1 and Th2 cells are CD4+ helper T cells, and therefore are both restricted to recognizing peptide antigens bound to class II MHC molecules. The trafficking patterns of Th1 and Th2 cells differ, and this is related to differences in the expression of adhesion molecules and chemokine receptors. Th1 cells express abundant functional ligands for E-selectin and P-selectin and the chemokine receptors CXCR3 and CCR5, which bind to various chemokines found at sites of active innate immune responses. Th2 cells bind poorly to endothelial selectins and express less CXCR3 and CCR5.

Answer 10

A. B7-1 Although naive CD8+ T cells require second signals, such as B7 costimulation, in order to differentiate into effector cytolytic T lymphocyte (CTL), once differentiated, the CTL can kill a target cell that does not express costimulatory molecules. The CTL only requires one signal for killing of the target cell, which depends on the T cell receptor binding to a peptide-class I MHC complex on the surface of the target cell. Tight adhesion between the CTL and target cell is also required, and this is often mediated by T cell integrin LFA-1 binding to target cell ICAM-1.

Answer 11

C. CD40L If the patient’s sister is also affected with hyper-IgM syndrome, then the inheritance pattern is autosomal recessive. Both the AID and CD40 genes are located on autosomal chromosomes, and mutations in both have been identified as causes of hyper-IgM syndrome. However, only a mutation in CD40 will result in reduced macrophage function and susceptibility to Pneumocystis carinii pneumonia, as is observed in this patient.

Answer 12

C. Naive B cells recognize intact proteins, generate peptide fragments of these proteins, and present them in complexes with MHC molecules to differentiated helper T cells. T cells and B cells cannot recognize the same protein antigen molecule simultaneously because T cells only recognize peptide-MHC complexes. B cells bind intact proteins, internalize them via surface Ig, and then present peptide-MHC complexes to helper T cells, not to naive T cells. The helper T cells specific for the peptide-MHC complexes have been differentiated from naive T cells that recognized the same peptide-MHC complexes presented by dendritic cells. Follicular dendritic cells display intact protein antigens to previously activated (but not naive) B cells during the germinal center reaction. Collaboration of T cells and B cells requires direct contact of T cells and B cells specific for the same antigen, even though the antigen recognition events are not simultaneous, because the bidirectional activation requires membrane-bound molecules (i.e., CD40 ligand on the T cells and CD40 on the B cells).

Answer 13

B. Alternative processing of primary RNA transcripts to remove the transmembrane domain and include a secretory tail piece Primary transcripts of Ig genes include sequences encoding both transmembrane and secretory tail piece domains. Alternative splicing of these transcripts determines which form of Ig is ultimately made. V(D)J recombinases are not involved in modifications of Ig heavy chain expression, and switch recombinases are only involved in changes in DNA related to isotype switching. Membrane Ig is not cleaved to form secretory Ig.

Answer 14

B. CD40 Cytokines play essential roles in regulating the switch to particular heavy chain isotypes. IFN-γ is important in switching to the IgG isotype, whereas TGF-β is a stimulator of IgA production. The cytokine that promotes IgE production is IL-4, but this is not an answer choice. However, the process of isotype switching in general is known to depend on signaling through CD40L-CD40, and is also dependent on the activity of the enzyme activation-induced deaminase (AID). CD28 is a costimulatory molecule that is important for T cell activation and CD40L up-regulation. However, other costimulatory molecules are also present on T cells that can cause up-regulation of CD40L. IL-2 is a growth factor cytokine for T cells.

Answer 15

D. ABO blood group antigen T cell–independent antigens consist of polysaccharides, glycolipids, and nucleic acids with multiple repeated epitopes, so that maximal cross-linking of the B cell receptor is induced, thus bypassing the need for T cell help. Of the answer choices, the best choice is the ABO blood group antigen, because of its polyvalent glycolipid structure. Lysozyme and the Rh factor are protein antigens. Benzene and glucose-6-phosphate are not polyvalent

Answer 16

B. CD4+ T cells The superantigen exotoxins of Staphylococcus aureus and Streptococcus pyogenes are among the most potent T cell mitogens known. The superantigens able to bind MHC class II and the TCR simultaneously. Toxic shock syndrome is a complication of Staphylococcus aureus and Streptococcus pyogenes infections in which bacterial toxins act as superantigens, activating very large numbers of CD4+ T cells and generating an overwhelming immune-mediated cytokine avalanche that manifests clinically as fever, rash, shock, and rapidly progressive multiple organ failure, often in young, previously healthy patients

Answer 17

D. to present nonself-peptides associated with MHC class I molecules to CD4+ T cells ``` The APC presents peptide-MHC class I to CD8+ T cells and peptide-MHC class II to CD4+ T cells. The other statements are all features of an APC such as a dendritic cell. ```

Answer 18

C. 3 Three DNA rearrangements are required. First, D5J2 rearrangement occurs, followed by V17D5J2. This permits synthesis of IgM and IgD molecules using V17D5J2. The third rearrangement is the class switch of V17D5J2CµCδ to V17D5J2Cγ2, leading to the synthesis of IgG2 molecules.

Answer 19

E. more than 1,200,000 specificities While 1,200,000 would be the product of all possible combinations of genes, many more antibody specificities are likely to be generated as a result of junctional diversity at the sites of V, D, and J gene segment joining (caused by imprecise joining, deletions, and nucleotide insertions) and somatic hypermutation.

Answer 20

D. alternative RNA splicing The simultaneous synthesis of lgM and IgD is made possible by the alternative splicing of the primary RNA transcript 5’-VDJ-CµCδ-3’ to give either 5’-VDJ-Cµ-3’ or 5’-VDJ-Cδ-3’.

Answer 21

D. The VDJ segments coding for an Ig VH region may associate with different heavy-chain constant-region genes. ``` The association of VDJ segments coding for an Ig VH region with different heavy-chain constantregion genes is the basis of isotype or class switching. ```

Answer 22

D. inheritance of multiple C-region genes The presence of multiple CH region genes does provide the basis for functional diversity of lg molecules but does not contribute to the diversity of antigen-specific receptors.

Answer 23

D. somatic hypermutation Of the mechanisms described for generating diversity of Ig molecules, only somatic hypermutation affects the antigen binding site after antigen stimulation.

Answer 24

E. involve rearrangement of heavy-chain gene segments The earliest events in B-cell differentiation take place in fetal liver and bone marrow in the adult and involve rearrangement of heavy-chain V, D, and J gene segments.

Answer 25

E. all of the above All the molecules are expressed on the surface of the mature B cell.

Answer 26

E. Nothing happens Cytokines secreted by antigen-activated T cells only regulate the activities of other cells involved in that immune response by binding to cytokine receptors (e.g., high-affinity IL-2R ) expressed by these cells. Such cytokine receptors are upregulated only on anti gen-activated T cells that bear the appropriate TCR for that antigen; because they are not upregulated on antigennonspecific T cells in the vicinity, these cells will not be activated by IL-2.

Answer 27

A. It is produced primarily by activated macrophages IL-2 is produced almost exclusively by activated T cells.

Answer 28

C. The interaction between peptide-MHC class II on an APC and the TCR of an appropriate CD4+ T cell is necessary and sufficient for full T-cell activation. ``` Peptide-MHC class II interacting with the TCR is the crit-ical, antigen-specific first signal required for CD4+ T-cell activation, but costimulatory or second signals are required for full activation ```

Answer 29

C. They cannot kill CD4+ T cells. ``` A CD8+ CTL can kill any cell expressing an MHC class I molecule in association with a nonselfpeptide, including, for example, a CD4+ T cell infected with HIV. ```

Answer 30

C. IL-4 and IL-5 are required for the production of antibody during the response T cell-independent antigens, because they do not generate T-cell-derived cytokines, do not produce IL-4 or IL-5. Thus, no isotype switching or memory cell induction occurs in the response to T cell-independent anti gens.

Answer 31

D. mRNA specific for µ chains As a consequence of the rearrangement of the VDJ to Cα in the lgA-producing cell, the gene will have been deleted. The other DNA sequences and mRNA species will be found in the cell.

Answer 32

D. There is limited diversity in the repertoire of IgM antibodies produced. This is a common presentation of hyper-IgM syndrome. Patients with this disease have B cells that are unable to undergo isotype switching, and therefore contain only IgM in the serum but very low levels of IgG, IgA, and IgE. Clinically, these patients are susceptible to bacterial infections and often present with a history of recurrent pneumonia, otitis media, and gastrointestinal infections. Mutations in genes coding for CD40L, CD40, and activation-induced deaminase (AID) have been identified in these patients. During an immune response, T cell interactions with B cells via CD40L-CD40, as well as active AID, are both essential for numerous processes, including isotype switching, somatic mutation, and germinal center formation. Thus, patients with hyper-IgM syndrome produce antibodies that typically have a lower affinity for antigen (due to the lack of somatic mutation) and do not develop large follicles containing a light zone and dark zone (germinal center) within lymph nodes. Mechanisms of generation of diversity of the Ig repertoire should not be impaired in this patient. Although somatic mutation of variable regions will be impaired, this will not be manifest in IgM antibodies. In addition, patients with either CD40L or CD40 mutations, but not AID mutations, will have an increased susceptibility to certain intracellular infections (such as Pneumocystis carinii pneumonia), because the

Answer 33

D. IL-5 IL-5 is recognized as the major maturation and differentiation factor for eosinophils in mice and humans. Over-expression of IL-5 significantly increases eosinophil numbers in vivo. Conversely, mice lacking a functional gene for IL-5 or the IL-5 receptor alpha chain (IL-5Rα) display a number of developmental and functional impairments in eosinophil lineages. IL-5 critically regulates expression of genes involved in proliferation, cell survival and maturation and effector functions of eosinophils. Thus, IL-5 plays a pivotal role in innate immune responses and eosinophilia

Answer 34

C. Th1: IFN-γ, Th2: IL-4, Th17: IL-22 T helper cells can be subdivided into IL-2/IFN-γ-secreting Th1, IL-4/IL-5-secreting Th2, and IL- 17/IL-22-secreting Th17 cells.

Answer 35

D. Deletion in the thymus via induction of apoptosis Somatic recombination of TCR genes in immature thymocytes results in some cells with useful TCR specificities, but also many with useless or potentially self-reactive specificities. Thus thymic selection mechanisms operate to shape the T-cell repertoire. Thymocytes that have a TCR with low affinity for self-peptide–MHC complexes are positively selected to further differentiate and function in adaptive immunity. Clonal deletion by apoptosis is the major processes in the thymus that eliminate self-reactive T cells. Although these processes are thought to be efficient, they fail to control self-reactivity in all circumstances. Thus, peripheral tolerance processes exist wherein self-reactive T cells become functionally unresponsive due to the presents Treg cell clones specific to the same Ag.

Answer 36

C. CD4 CD4 is a critical component of the T cell receptor complex that recognizes peptides bound to MHC class II molecules. This can be observed at all stages of T cell development, activation, and function. CD4 has been termed a co-receptor to indicate that its most important activity is to bind class II MHC and to transduce positive activating signals in conjunction with the T cell recepto

Answer 37

E. IgM ``` IgM is the first immunoglobulin class to be expressed on the surface of the developing B-cells, shortly followed by IgD. Early mature B-cells co-express IgM and IgD antibodies of identical antigen specificity ```

Answer 38

B. Differential splicing. Differential (alternative) splicing of a primary RNA transcript can produce antibody either with or without exons encoding a hydrophobic transmembrane sequence which leads to retention of antibody in the cell surface membrane.

Answer 39

D. 3 amino acids ``` This is too short to directly transmit a signal into the cell following antigen binding, a function carried out by the Ig-alpha and Ig-beta accessory molecules. ```

Answer 40

B. 1-5%. Although they constitute a minority of the peripheral blood T-cells in man, gamma delta T-cells are more heavily represented in intestinal epithelium and in skin.

Answer 41

B. Diversity (D). The T-cell receptor alpha chain genes do not possess D gene segments, although the delta chain genes do. However, because the delta chain locus is found entirely within the alpha chain locus and is located between the V alpha and the J alpha gene segments, any alpha chain gene rearrangements lead to the loss of the delta chain gene segments, including all of the D delta segments.

Answer 42

A. Codominant The MHC molecules encoded by both parental genes are expressed. .

Answer 43

B. Ig-alpha and Ig-beta Ig-alpha and Ig-beta possess C-terminal cytoplasmic regions which become phosphorylated upon cross-linking of membrane immunoglobulin, leading to a rapid mobilization of intracellular calcium.

Answer 44

D. A heterodimer. There are two versions of the T-cell receptor, both of which are heterodimers consisting of an alpha chain and a beta chain, or a gamma chain and a delta chain

Answer 45

E. CD3 CD3 is a molecule composed of five polypeptide chains (CD3-gamma, -delta, and - epsilon plus zeta-zeta, eta-eta or zeta-eta), which transduces the antigen recognition signal received by the T-cell receptor heterodimer to the inside of the cell

Answer 46

B. B cells, dendritic cells and macrophages. These cells are able to present processed endogenous antigen to CD4+ T-cells

Answer 47

E. Surface immunoglobulin. B-cells express surface immunoglobulin of a specificity created by that cell's particular immunoglobulin gene recombination. A totally different gene set encodes the T-cell receptor for antigen.

Answer 48

D. Becomes anergic In the absence of costimulator, a cell becomes anergic and incapable of subsequent response to the specific antigen.

Answer 49

A. CD28 An alternative ligand for B7, present on activated T-cells, is CTLA-4.

Answer 50

A. Phosphorylates and thereby activates phospholipase C gamma 1 The tyrosine kinase activates the phospholipase, which accelerates the hydrolysis of phosphatidylinositol 4,5-diphosphate to diacylglycerol and inositol 1,4,5-triphosphate

Answer 51

D. Accelerates hydrolysis of phosphatidylinositol diphosphate The enzyme splits phosphatidylinositol diphosphate to diacylglycerol and inositol triphosphate

Answer 52

B. The Fos/Jun transcription factors The MAP kinase JNK phosphorylates Jun, which then binds as a binary complex with Fos to the AP-1 site.

Answer 53

C. The initial interaction between TCR and MHC is unstable. One of the main functions of the immunological synapse is thought to be to cement the initially unstable interactions between TCR and MHC in order that optimal activation of the T-cell can occur.

Answer 54

B. Depends on T-cell recognition of antigen processed by the B-cell. ``` The native antigen binds to B-cell surface Ig, is taken inside the cell, processed and the peptide placed as a complex with class II MHC on the cell surface where it is recognized by T-helper cells. ```

Answer 55

C. Rapidly phosphorylates the Ig-alpha and Ig-beta chains of the surface Ig receptor. Within one minute of surface Ig ligation there is rapid phosphorylation of the Ig-alpha and Ig-beta chains and a subsequent rise in intracellular calcium.

Answer 56

A. CD40 and CD40L. Costimulatory signals arising from the interaction of CD40 on the resting B-cell with CD40L (CD40 ligand, CD154) on the activated T-helper cell ensure effective B-cell activation.

Answer 57

C. CD4 CD4 on helper T-cells binds to the non-polymorphic part of the MHC class II molecule

Answer 58

A. CD28 B7 (CD80 and CD86) on the antigen-presenting cell ligating CD28 on the T-cell provides the main costimulatory signal for the activation of resting T-cells.

Answer 59

D. Activation of protein tyrosine kinase. Activation of protein tyrosine kinase activity is responsible for subsequent activation of membrane components by phosphorylation

Answer 60

E. CD40 The costimulatory signal provided by the CD40L/CD40 interaction is necessary for the activation of resting B-cells by helper T-cells. Note that CD40L is the abbreviation for CD40 ligand, which is also known as CD154.

Answer 61

A. By binding to specific receptors The cell-type specificity of cytokines is provided by the regulated expression of specific cytokine receptor genes. Many cytokine receptors consist of more than one polypeptide. For example, the IL-2 receptor is composed of an alpha chain (CD25) of low affinity and a beta chain of intermediate affinity; when both are expressed together they form the high affinity IL-2 receptor.

Answer 62

E. IL-2 receptor. The hematopoietin receptor family contains a large number of members each of which comprises one or two polypeptide chains responsible for cytokine binding and an additional shared (common) chain involved in signal transduction

Answer 63

B. Binds IL-2 with high affinity. The alpha beta heterodimeric form of the IL-2 receptor has an affinity (Kd) of 10-11 M (10 pm), whereas the alpha chain alone binds IL-2 with low affinity, and the beta chain alone with medium affinity.

Answer 64

C. To upregulate expression of MHC class II. There is synergism between IFN-gamma and TNF in the upregulation of surface MHC class II molecules on, for example, cultured pancreatic insulin-secreting beta cells.

Answer 65

D. IL-4 IL-4, together with IL-5, IL-6, IL-10 (mouse only) and IL-13 is characteristically produced by Th2 cells.

Answer 66

B. CD40L CD40 ligand (CD154) on the T-helper cell engages CD40 on the resting dendritic cell, resulting in upregulation of costimulatory molecules such as B7 on the now activated dendritic cell.