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Immunology/ Pharmacy students Adaptive Immunity Lecture 6 Dr. Mohammad Odibate

Immunology/ Pharmacy students Adaptive Immunity Lecture 6 Dr. Mohammad Odibate Department of Microbiology and immunology Faculty of Medicine, Mu’tah University. Objectives. The definition and the importance of the adaptive immunity

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Immunology/ Pharmacy students Adaptive Immunity Lecture 6 Dr. Mohammad Odibate

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  1. Immunology/ Pharmacy students • Adaptive Immunity • Lecture 6 Dr. Mohammad Odibate Department of Microbiology and immunology Faculty of Medicine, Mu’tah University

  2. Objectives • The definition and the importanceof the adaptive immunity • Understanding the arms of the adaptive immunity: • Humoral immunity • Cell-mediated immunity • The importance of T- helper cells in communicating and activating immune cells • Function and mechanism of action of TH1 & TH2 cells • Function and mechanism of action of T cytotoxic cells

  3. ? APC ? ? T B

  4. Introduction innate immunity adaptive (acquired) immunity TLR2 TLR3 TLR1 TLR4 BCR TCR APC B cell T cell Why acquired immunity? Pathogen-specific receptors are already encoded in the germline Why adaptive immunity?

  5. Introduction Triggering of adaptive immunity Adaptive immunity is triggered when an infection eludes the innate defense mechanisms (eg. viral) and generates a threshold dose of antigen

  6. Introduction Initiation of innate and acquired immunity Inflammation Antigens Chemical signals Complement Neutrophils Defensins APC Lysozymes Macrophages Vasodilatation Dendritic cells Innate immune response Mast cells The initial step in triggering adaptive immunity To the secondary lymphoid organs

  7. Adaptive Immunity APC What will happen inside the lymph node?

  8. T lymphocytes TH1 TH TCR+ CD4+ T Helper cells (TH) Recognized MHC2 TH2 Tc TCR+ CD8+ T cytotoxic cells (Tc) Recognized MHC1

  9. What will happen inside the lymph node? Activation of B lymphocytes Activation of T lymphocytes TH1 TH2 T cytotoxic lymphocytes (TCL) Humoral immunity Cell mediated immunity

  10. Adaptive Immunity Activation of naïve T lymphocytes DC displayed Ag of extracellular pathogens its surface by MHC 2 displayed Viral or intracellular bacterial By MHC1 CTL naïve T cell TH1 TH2 Activation and proliferation Differentiation Cell mediated immunity Humoral immunity

  11. Adaptive Immunity What determines the naïve T cell differentiation into Th1? Viral components Viral components TLR IL-12 TLR

  12. Adaptive Immunity What determines the naïve T cell differentiation into Th2? Extracellular pathogens Extracellular pathogens TLR IL-4

  13. Humoral Arm of Adaptive Immunity

  14. Humoral Immunity Phagocytic cells Neutrophil Dendritic cell Phagolysosome Ag complexed with MHC class 2 To the blood circulation

  15. Humoral Immunity In the lymph node, dendritic cell Start presenting Ag to naïve T cells until Finding one T cell with specific TCR For the displayed Ag Dendritic cell CD4 TCR naïve T cell Clonal selection naïve T cell naïve T cell naïve T cell

  16. Humoral Immunity The binding between TCR, MHC2 , and CD4 activated the Differentiation and proliferation of naïve T cell Into Th2 lymphocyte IL-4 IL-2 IL-4 IL-4 IL-4 IL-5 Differentiation IL-5 naïve T cell IL-5 Clonal expansion TH2 cell TH2 TH2 TH2 TH2

  17. Humoral Immunity Phagocytic cells Neutrophil Dendritic cell Ag complexed with MHC class 2 To the blood circulation

  18. Humoral Immunity The free antigens that were released from neutrophils will activate naïve B cells Neutrophil Reaching lymph node via lymph BCR B cell B cell B cell Clonal selection

  19. Humoral Immunity Antigen binding to the BCR will activate the IL-4R gene expression IL-4 IL-4R IL-4 IL-4 IL-5 IL-5 IL-4 will activate B cell proliferation IL-5 B cell B cell B cell B cell Clonal expansion IL-5 will activate B cell differentiation into plasma cells B cell TH2 TH2 TH2 TH2

  20. Humoral Immunity The produced antibodies will be released into blood circulation and reaching the Inflammatory site to start working there through • Opsonization • Complement activation • Neutralization viruses • bacteria, and toxins • Agglutination

  21. Cellular immunity vs. Humoral immunity Extracellular pathogens Intracellular pathogens Virus or intracellular bacteria Complement & antibodies are ineffective in fighting intracellular pathogens X The body can defend itself against the extracellular pathogens by complement, antibodies Humoral immunity Cellular immunity is activated

  22. Cellular Arm of Adaptive Immunity

  23. Cellular immunity Types Macrophage activation by TH1 cells CD8+ cytotoxic T lymphocytes (CTLs) mediated cell lysis immunity independent of antibody and subsequent destruction of cells bearing the antigen dependent the secretion by T cells of cytokines that enhance the ability of phagocytes to eliminate the phagocytized pathogens

  24. All nucleated ells can express MHC1 APC can express both MHC1 & MHC2

  25. Cellular immunity CD8+ cytotoxic T lymphocytes (CTLs) mediated cell lysis Virally infected APC Viral antigens Damaged cellular debris containing Viral antigens By phagocytosis CTL MHC2 Virus MHC1 Naïve T cell with specific TCR for the Displayed Ag Activation naïve T cell CTL with TCR specific for the displayed Ag

  26. Cellular immunity CD8+ cytotoxic T lymphocytes (CTLs) mediated cell lysis Virally infected APC Viral antigens 2 Damaged cellular debris containing Viral antigens By phagocytosis CTL Virus MHC1 IL-2 naïve T cell Proliferation and differentiation

  27. Cellular immunity CD8+ cytotoxic T lymphocytes (CTLs) mediated cell lysis IL-2 CTL CTL CTL CTL CTL CTL CTL CTL CTL CTL CTL CTL CTL Effector CTL cells Memory CTL cells naïve T cell

  28. Cellular immunity CD8+ cytotoxic T lymphocytes (CTLs) mediated cell lysis Effector CTL cells They leave lymph node to start circulating in blood until finding cells infected with the virus and expressed the same displayed by APC the blood circulation CTL CTL CTL CTL CTL CTL • CTL releases types of cytolytic granules: • Perforin: pore forming protein • Granzymes: serine proteases

  29. Cellular immunity CTLs mediate cell lysis of virally infected cells CTL

  30. Cellular immunity CD8+ cytotoxic T lymphocytes (CTLs) mediated cell lysis Memory CTL cells CTL CTL CTL CTL CTL CTL In the secondary exposure to the same virus memory CTL will recognize the infected cell and they start mitosis and eventually killing the virus before spreading and the appearance of symptoms

  31. Cellular immunity CD4 & CD8 T lymphocytes

  32. The importance of memory T & B cells Primary immune response Secondary immune response Naïve T or B cells with specific TCR For the displayed Ag on APC APC APC Memory cells Requires more time to find the T cell with specific TCR less time required to find T cell with specific TCR

  33. Innate vs. Adaptive Immunity

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