1. CELL-MEDIATED IMMUNITY RAHUL KUMAR LOHANA 2K16/MB/50 INSTITUTE OF MICROBIOLOGY UNIVERSITY OF SINDH, JAMSHORO

2. CELL – MEDIATED IMMUNITY  INTRODUCTION: The type of immune response where the defense cells itself are involved rather than the secretion of immunoglobulins or antibodies. Take action against those antigen that can cross humoral immunity These antigen have ability to enter inside the host cell, known as intracellular antigens. The defense cells of this type of immunity includes T lymphocytes Helper T lymphocyte (T H cell) Cytotoxic T lymphocyte (T C cell) In addition to these, it also involves macrophages and natural killer (N.K) cell, these cell support cell-mediated immunity. Rahul Kumar 2

3.  FUNCTIONS Elimination of intracellular pathogens. Elimination of tumor or cancer cells.  PATHWAYS OF IMMUNE RESPONSE A. Antigen-specific: It involve the action of T lymphocytes. Secretes cytokines specifically to the target cell. Rahul Kumar 3 Tc-cell T H- cell CD-4 TCR CD-8 TCR

4. B. Antigen-non-specific: It involves the action of NK cell and macrophages. NK cell same as Tc-cell secretes cytokines but target tumor or cancer cell non-specifically. Macrophages accelerate phagocytosis. Rahul Kumar 4 MACROPHAGES NK CELLS

5. MECHANISM OF IMMUNE RESPONSE  Recognition The first step cell-mediated immune response is the recognition of intracellular antigen by T lymphocytes. A. Antigen presenting cells (APCs): T lymphocytes cannot recognize antigens directly but they requires presenting of antigens by host cell. These presenter cell are called antigen presenting cells (APCs). APCs includes dendritic cells, B-cell and phagocytes such as macrophages. Among these, dendritic cells are the most important APCs than the rest. Rahul Kumar 5 MACROPHAGES DENDRITIC CELLSB- CELL

6. B. Major histocompatibility complex (MHC): These are glycoprotein compounds, helps in cell-cell recognition. Present the peptide fragment of antigens to the T lymphocytes. Also known as human leukocyte antigen (HLA). There are two types of MHC molecules: I. Class-I MHC molecule : Present peptide fragment of endogenous antigen (replicate inside the cell) to CD8+ Tc-cell. Found on all nucleated cells. II. Class-II MHC molecule: Present peptide fragment of exogenous antigen (enter in the cell from environment) to CD4+ T H -cell. CD stands for cluster of difference. Rahul Kumar 6

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8.  Activation After recognition, the second step is the activation the defense cells. A. Helper T cells (T H -cell): When CD4 of T H -cell bound to class II MHC molecule, APC secrets specific cytokines, such intreleukin-1 (IL-1), which activates helper T cells. Interleukin-1 causes the naive T cell to secrete other cytokines, including interleukin-2 ( IL-2 ), which stimulates cell division of that T cell and others activated by the APCs. The result is the production of a clone of antigen-specific activated T cells. Some of these mature into memory T cells and await a future encounter with the same epitope. Some T H cells mature into helper T1 (T H 1 ) cells, activates Tc-cell, and infected macrophages. Other mature into helper T2 ( T H 2 ) cells. T H 2 cells “help” in the activation of humoral immunity, this phenomena is called co- stimulation. Rahul Kumar 8

9. B. Cytotoxic T cells: Tc-cell, after recognition of antigen, depended upon helper T cells to get activated. Helper T1 (T H 1 ) cells release a cytokine, interleukine-1 to activate Tc-cell. Tc-cell then release interlrukine-2 to make clone of itself. Completely activated Tc-cell are called CTLs. Rahul Kumar 9

10. SUMMARIZED ACTIVATION PHASE Rahul Kumar 10

11.  RESPONSE OF DEFENSE CELL A. Role of activated B-cell: In response to T H 2-cell, B-cells launch humoral immunity. T H 2-cell binds to MHC-II molecule of B-cells and release a cytokine. B-cells, then proliferate and differentiate into plasma and memory cells. Effector plasma cells release antibodies or immunoglobulins, but this against specific endogenous antigen. These endogenous antigens responded by antibodies are known as T-depended antigens, requires the service of T H 2-cell. Rahul Kumar 11

12. Humoral Response Rahul Kumar 12

13. B. Role of activated Macrophage: Macrophages routinely perform phagocytosis, non-specifically in innate immune response. However, some microbes survives even after being phagocytose. T H -cell then activate those infected macrophages by releasing cytokines. The activation of macrophages s similar as of B-cells, but this time T H 1-cell binds to MHC-II molecule. T H 1 cells stimulate lysosome fusion in these cells, resulting in the destruction of the bacterial invaders. Rahul Kumar 13

14. Response of Macrophages Rahul Kumar 14

15. C. Role of Cytotoxic T cells (Tc-cell): Tc-cell play important roll in immunity against endogenous antigen such as virus. After activation, the CTLs leave the lymphoid tissue and enter the lymph and blood vessels. The CTLs bind to the MHC-I/ peptide on the virus infected cell surface and release a number of active substances. Perforins, lethal proteins cause cytolysis of target cell. Granzymes, enter the target cell and trigger apoptosis. Rahul Kumar 15

16. Natural killer cells NK cell are types of lymphatic cell provide immunity in non-specific manner. Have influence on both innate and adaptive immunity. Take action against tumor and virus S Some viruses have evolved mechanisms to circumvent the action of cytotoxic T cells. NK- cell express non- TCR related receptors called Killer Inhibitory receptors (KIRs). Virus infected and tumor cell have reduced MHC-I molecules. Thus when such cell encounter NK-cells they fail to effectively engage these KIRs. Therefore becomes susceptible to NK-cells-mediated cytotoxicity. Rahul Kumar 16

17.  KILLING: is achieved same as by Tc-cells, the released of various cytotoxic molecules.  Perforin, cause pores in the membrane of target cell leading to its lysis.  Granzymes: enter the target cell cause apoptosis (programed cell death) of the target cell by enhanced fragmentation of its DNA. Rahul Kumar 17

18. SUMMARIZED ADAPTIVE IMMUNITY Rahul Kumar 18

19.  REFERENCES :  Immunology by Janis Kuby  Microbiology (a human perspective) by Nester Anderson Roberts Nester  Microbiology, Principals and Explorations by Jacquelyn G. Black  Fundamentals of Microbiology by I. Edward Alcamo Rahul Kumar 19

20. THE END Rahul Kumar 20