C. Incorrect! MHC class I molecules are not involved in the process of bridging in ADCC.

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1 Immunology - Problem Drill 13: T- Cell Mediated Immunity Question No. 1 of During Antibody-dependent cell mediated cytotoxicity (ADCC), the antibody acts like a bridge between the specific antigen bearing target cell and. Question #1 (A) Dendritic cells (B) Killer cells (C) MHC class I molecules (D) MHC class II molecules Neutrophils, Eosinophils, and Monocytes are the cells which participate in ADCC. B. Correct! The antibody acts like a bridge between the specific antigen bearing target cell and a killer cell. MHC class I molecules are not involved in the process of bridging in ADCC. MHC class II molecules are not involved in the process of bridging in ADCC. A number of different cell types including lymphocytes termed K cells can mediate Antibody-dependent cell mediated cytotoxicity (ADCC). The lineage of K cell is not known, but it seems similar to that of NK cells. The antibody, usually IgG, binds to an Fc receptor on the K cell & to an antibody combining site on the target cell as shown in the above figure. The antibody acts like a bridge between the specific antigen bearing target cell & a killer cell. Neutrophils, Eosinophils, & Monocytes can also participate in ADCC. Eosinophils, for example, are effective killers of antibody coated schistosomulae, the larval forms of schistosomes. The mechanism of killing involves binding of the eosinophil to the larva via an antibody molecule. The eosinophil releases basic proteins & other molecules from its granules, leading to the formation of pores in the target cell membrane. The organism dies because of the leaky membrane. Eosinophils can be activated by both monokines & certain lymphokines.

2 Question No. 2 of On contact with antigen, T cell develops into memory cells and effector cells providing what type of immune response? Question #2 (A) T Cell-Mediated Immune System (B) Humoral Immune response (C) Both A & B (D) None of the above A. Correct! On contact with antigen, T cell develops into memory cells and effector cells providing T Cell-Mediated Immune Response (CMI). Development of T cells into memory cells and effector cells is not the job of humoral immune response. T cell mediated immune response is solely involved in the development of T- cells into memory cells and effector cells. CMI is involved in the development of T- cells into memory cells & effector cells. The nature of antigenic stimulus is important in the induction of CMI. Each T cell bears a specific TCR for one epitope and combines with antigen carrying that epitope. On contact with antigen, T cell undergoes blast transformation, clonal proliferation and differentiation into memory cells and effector cells providing CMI. T cells recognize antigens only when presented with MHC molecules. Helper T cells recognize antigens only when presented on the surface of macrophages or other cells, complexed with MHC class-ii molecules. They then release lymphokines which activate macrophages, enabling them to kill intracellular pathogens. Cytotoxic T cells recognize antigen on the surface of infected cells, in association with MHC class-i molecules, secrete lymphokines and destroy the cells.

3 Question No. 3 of Cytotoxic granular proteins known as perforins are responsible for. Question #3 (A) Clonal anergy (B) Agglutination (C) Pore formation (D) Opsonization It s not correct. Clonal anergy refers to a physiological stage in which cells are unable to be activated by antigen. Antibodies combine with the surfaces of microorganisms or soluble antigens and cause them to agglutinate or precipitate. C. Correct! Cytotoxic granular proteins known as perforins are responsible for pore formation. Opsonization is the process by which macromolecules contained within the extracellular tissue fluid are internalized by cells. Cytotoxic T Lymphocytes store cytotoxic proteins in the form of granules in their cytoplasm & these proteins belong to two categories. One belongs to perforins involved in pore formation & the other belongs to granzymes or fragmentins responsible for hydrolysis or fragmentation of cellular products. Immediately following the CTL contact with target cell, Golgi stacks loaded with granzymes & granules loaded with perforins loaded with the perforins orient themselves and move towards the junction of cell contact. Perforin monomers are released from the granules by exocytosis into the junctional space between the two cells, make entry into the target cell & start breaking down target cell contents and hence destroy the target cell.

4 Question No. 4 of After establishing contact with target cell membrane perforin monomers undergo polymerization in the presence of. Question #4 (A) Calcium ions (B) Sodium ions (C) Magnesium ions (D) Potassium ions A. Correct! Perforin monomers undergo polymerization in the presence of calcium ions. Sodium ions are not required polymerization of perforins. Magnesium ions are not required polymerization of perforins. Potassium ions are not required polymerization of perforins. Perforin monomers are released from the granules by exocytosis into the junctional space between the two cells. As the perforin monomers establish contact with target cell membrane, they undergo polymerization in the presence of Ca2+ ions & forms cylinders with a pore size of 5-20nm on the target cell membrane. By this time perforins have established a multiple pipeline channel between the CTL & target cell, through this channel granzymes make entry into the target cell & start breaking down target cell contents. Granzymes are mostly proteases.

5 Question No. 5 of Macrophages, neutrophils, eosinophils and (NK) cells mediate what type of cytotoxic response? Question #5 (A) Specific (B) Non-specific (C) Antigen-specific (D) None of the above Specific response is mediated by cytotoxic T lymphocytes (CTLs). B. Correct! Macrophages, neutrophils, eosinophils & (NK) cells mediate non-specific type of immune response. Specific responses are also sometimes known as antigen specific immune response. That s not right answer, as the right answer is non-specific immune response. The principal role of CMI is to target and destroy the cell that harbors viruses, intracellular pathogens or are transformed cells. Both, antigen specific and antigen non-specific cells can contribute to the CMI. Accordingly, cell mediated cytotoxic response involves two major mechanisms: 1. Antigen-specific cytotoxic response mediated by cytotoxic T lymphocytes (CTLs). 2. Non-specific cytotoxic response mediated by macrophages and natural Killer (NK) cells. Both these responses lead to killing of target cells and lysis.

6 Question No. 6 of Cell mediated immunity involves two major defense strategies for killing the target cell that is. Question #6 (A) Secretion of cytokines & indirect cell-mediated killing (B) Non-secretion of cytokines & direct cell-mediated killing (C) Secretion of lymphokines & direct cell-mediated killing (D) Secretion of lymphokines & indirect cell-mediated killing The option reveals only one strategy of killing the target cell i.e. release of cytokines by the specific cell type, which can kill the target cell indirectly. The option reveals only one strategy of killing the target cell i.e. direct killing of the target cell. C. Correct! Cell mediated immunity involves two major defense strategies for killing the target cell that is: Secretion of lymphokines & direct cell-mediated killing The option reveals only one strategy of killing the target cell i.e. release of cytokines by the specific cell type, which can kill the target cell indirectly. Cell mediated immunity involves two major defense strategies: Secretion of lymphokines by T-helper cells. Direct cell mediated killing (lysis of the target cells) by Cytotoxic T-cells. The key cell types involved in cell mediated immunity are: For secretion of lymphokines: e.g. Helper T-cells. Killer cell activity: e.g. Cytotoxic T-cells.

7 Question No. 7 of Cell-mediated immunity (CMI) is not induced by. Question #7 (A) Killed vaccine (B) Live microbes (C) Intracellular pathogens (D) None of the above A. Correct! Cell-mediated immunity is not induced by killed vaccine. CMI is induced by live microbes. CMI is induced by intracellular pathogens. CMI is not induced by killed vaccine. Induction of Cell Mediated Immunity: The nature of antigenic stimulus is important in the induction of CMI. Each T cell bears a specific TCR for one epitope and combines with antigen carrying that epitope. On contact with antigen, T cell undergoes blast transformation, clonal proliferation and differentiation into memory cells and effector cells providing CMI. T cells recognize antigens only when presented with MHC molecules. Helper T cells recognize antigens only when presented on the surface of macrophages or other cells, complexed with MHC class-ii molecules. They then release lymphokines which activate macrophages, enabling them to kill intracellular pathogens. Cytotoxic T cells recognize antigen on the surface of infected cells, in association with MHC class-i molecules, secrete lymphokines and destroy the cells. Antigenic stimulus that induces & that do not induces CMI are given below: 1. The nature of antigenic stimulus is important in the induction of CMI. 2. It is developed best following infections with intracellular pathogens. 3. Killed vaccines and other non-living antigens do not induce CMI unless administered with adjuvants. 4. Only T cell dependent antigens lead to CMI.

8 Question No. 8 of Which cell type secretes various soluble mediators called as lymphokines? Question #8 (A) Activated macrophages (B) T-cytotoxic cells (C) T-helper cells (D) All of the above Activated macrophages are the effector cells in the CMI response to various microorganisms. Cytotoxic T-cells are involved in killing of virally infected target cells by direct cell lysis. C. Correct! T-helper cells secrete various soluble mediators called lymphokines. Only T-helper cells secrete lymphokines. T-helper cells secrete various soluble mediators called lymphokines. This happens when primed T-helpers are stimulated by surface bound foreign antigen plus MHC class II antigen. This leads to T-cell proliferation and secretion of a battery of lymphokines which leads to the destruction of virally infected target cell. It has been found that T-helper clones can be divided into two types: T-helper I (T H 1) makes IL-2 and IFNγ T-helper II (T H 2) makes IL-4, IL-5, IL-6 Both T H 1 & T H 2 cells secrete IL-3 & colony stimulating factor. T H 1, but not the T H 2 cells are alleged to mediate delayed type of hypersensitivity.

9 Question No. 9 of Natural killer (NK) cells become super killers in response to which cytokine? Question #9 (A) IL- 1 (B) IL- 2 (C) IL- 3 (D) None of the above NK cells secrete the cytokine IL-1. B. Correct! Natural killer cells in response to IL-2 become super killers. The lymphokine IL-3, produced by T-helper cells, causes NK cells to secrete interferon. IL-2 is involved in making NK cells as super killer cells. Natural Killer (NK) cells are large granular lymphocytes that carry the cell surface markers CD56 & CD2. 85% of the NK population lacks all other conventional T & B cell markers. NK cells posses both anti-tumor & anti-microbial activity. NK cells do not require prior exposure to antigen to become cytotoxic & their activity is not MHC restricted. NK cells secrete the cytokine IL-1 and in response to IL-2, they become super killers. Interferon also augments killing by NK cells. The lymphokine IL-3, produced by T-helper cells, causes NK cells to secrete interferon, which then functions in an autocrine manner to further enhance NK cell activity. NK cells attach to their target cells by a receptor in a calcium independent manner. Once the NK cells are activated, they require calcium for lysis. NK cells cause lysis of the target cell by releasing cytotoxic factors capable of forming pores in the target cell membrane. These pore forming molecules are termed perforins. The main targets of NK cells are tumor cells & certain virally infected cells.

10 Question No. 10 of The T cytotoxic cells recognize antigen in conjunction with which class of MHC molecule? Question #10 (A) MHC I (B) MHC II (C) Both MHC I & II (D) None of the above A. Correct! The T cytotoxic cells recognize antigen in conjunction with MHC class I molecules. T-helpers are stimulated by surface bound foreign antigen plus MHC class II antigen. Both the MHC molecules are not required by T cytotoxic cells. It is already known that the T cytotoxic cells recognize antigen in conjunction with MHC class I molecules. Cytotoxic T-cells kill virally infected target cells by direct cell lysis. For lysis to occur, the target cell must carry both the same viral antigen & the same MHC class I antigens as the cells that originally induced the proliferation of T cytotoxic cells as shown in the above figure. The T cytotoxic cells recognize antigen in conjunction with MHC class I molecules, are stimulated by T-helper/inducer cells & then turn cytotoxic. The MHC class I antigens appear to be ideal recognition antigens triggering cytotoxic T-cells because they are present on almost all cells. T-cells have a wide repertoire of target cells against which they can mediate their killing action, this happens just after a few hours of viruses infecting cells & before the viruses can replicate in the cell.

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