1 / 38

Cell Mediated Immunity

Cell Mediated Immunity. By. Dr. Emad AbdElhameed Morad. Lecturer of Medical Microbiology and Immunology. Host defense against extracellular microbes is mediated by antibody, complement. When the microbe invades the host cell, the cell mediated immunity will take action.

jeremy-good
Download Presentation

Cell Mediated Immunity

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Cell Mediated Immunity By Dr. Emad AbdElhameed Morad Lecturer of Medical Microbiology and Immunology

  2. Host defense against extracellular microbes is mediated by antibody, complement. • When the microbe invades the host cell, the cell mediated immunity will take action. Dr. Emad AbdElhameed Morad

  3. So cell mediated immunity plays a role in: Dr. Emad AbdElhameed Morad

  4. Resistance to intracellular infections. • Resistance to fungi & protozoa. • Resistance to tumors. Dr. Emad AbdElhameed Morad

  5. Cell mediated immunity is harmful in: Dr. Emad AbdElhameed Morad

  6. Hypersensitivity type IV • Graft rejection • Autoimmune diseases Dr. Emad AbdElhameed Morad

  7. Characters of cell mediated immunity Dr. Emad AbdElhameed Morad

  8. It is mediated by T lymphocytes, NK, macrophages cells and their cytokines. • First, macrophages present antigens via MHC to T helper (TH) lymphocytes. Dr. Emad AbdElhameed Morad

  9. Activated T helper cells release cytokines which will: • Activate CD8 cytotoxic lymphocytes. • Activate NK cells. • Attract and activate macrophages • Stimulate B cells to differentiate into plasma cells to secrete antigen specific antibodies. Dr. Emad AbdElhameed Morad

  10. Phases of cell mediated immunity Dr. Emad AbdElhameed Morad

  11. 1- Antigen processing and presentation. 2- Activation of T lymphocytes. 3- Activation of macrophages. Dr. Emad AbdElhameed Morad

  12. 1- Antigen processing and presentation (MHC restriction) Dr. Emad AbdElhameed Morad

  13. Exogenous proteins are internalized into vesicles inside APCs then degraded to peptides inside the endosomes. Then peptides will bind with MHC class II inside endosomes. Finally this peptide MHC complex is transported to the surface of APC to be presented to CD4 T helper cells. Dr. Emad AbdElhameed Morad

  14. Endogenous proteins (viruses & tumor cells & graft cells) are synthesized in the cytosol of nucleated cells. Proteins are then degraded in the proteasome into peptides. These peptides will combine with MHC class I in the rough endoplasmic reticulum. Finally the complex is transported to the surface of APC to be presented to CD8 T cytotoxic cells. Dr. Emad AbdElhameed Morad

  15. 2- Activation of T lymphocytes Dr. Emad AbdElhameed Morad

  16. Three signals are required for activation of T lymphocytes: • The first signal is: recognition of antigenic peptide MHC complex on APC by T cell receptor (TCR) CD3 complex. CD3 acts as signal transduction molecule. Dr. Emad AbdElhameed Morad

  17. The second is : costimulatory signals Dr. Emad AbdElhameed Morad

  18. CD 28 on T cells and B7 on APC N.B. CTLA-4 molecule is similar to CD28 but opposite function (turn off immunity) N.B. Without this interaction, anergy occurs (functional unresponsiveness) Dr. Emad AbdElhameed Morad

  19. CD40L on T cells and CD40 on APCs N.B. This interaction is important in immunoglobulin class switching. • CD 2 on T cells and LFA 3 on APC • LFA 1 on T cells and ICAM 1 on APC Dr. Emad AbdElhameed Morad

  20. (The first and second signals for T cell activation) Dr. Emad AbdElhameed Morad

  21. The third signal is: • IL 1 which is produced from APC and activates both APCs and T helper cells. • IL 2 produced from T helper cells that will auto-activate them. Dr. Emad AbdElhameed Morad

  22. All the above mentioned signals will activate T helper cells that will proliferate and differentiate into antigen specific effector cells. • Some of activated T helper cells become memory cells to provide secondary immune response. • Activated T helper (TH0) cells will become either TH1 or TH2 according to the stimulating cytokine. Dr. Emad AbdElhameed Morad

  23. (T cell subsets) Dr. Emad AbdElhameed Morad

  24. TH1 cells will differentiate under influence of IL12and control cell mediated immunity by secreting the following cytokines: 1- IL2that activates CD8 T cytotoxic cells that will kill target cells. * IL2will also stimulate NK cells that resembles CD8 T cells but with no MHC restriction. 2- IFN-γthat will cause activation and recruitment of macrophages (delayed hypersensitivity) + Suppression of TH2 Dr. Emad AbdElhameed Morad

  25. 3- Tumor necrosis factor beta (TNF-β) • TH2 cells differentiate under the influence of IL4 and will control humoral immunity by secreting the following cytokines: • IL2, IL4, IL5, IL6, IL10, IL13 • IL4 and IL10 will suppress TH1 cells • Both TH1 and TH2 cells secrete IL3 and GM-CSF Dr. Emad AbdElhameed Morad

  26. (Scheme of cell mediated immunity) Dr. Emad AbdElhameed Morad

  27. Mechanisms of activation of cytotoxic T lymphocytes (CTLs) and target cell killing Dr. Emad AbdElhameed Morad

  28. Cytotoxic T lymphocytes (CTLs) become activated in response to two signals: 1-Recognition of peptide MHC complex class I on the surface of target cells. 2-IL 2 which is produced from TH1 cells. After activation, CTLS kill target cells by: Dr. Emad AbdElhameed Morad

  29. 1- Cytotoxic T lymphocytes (CTLs) release perforinsto create pores in the cell wall of target cells through which granzymeswill enter in the cytoplasm to induce apoptosis of target cells. 2- On activation, CTLs will express Fas ligand (FasL) that binds Fas protein on target cells. The result is degradation of target cell DNA. Dr. Emad AbdElhameed Morad

  30. (Cytotoxic T cell activation and target cell killing) Dr. Emad AbdElhameed Morad

  31. 3- Activation of macrophages and delayed hypersensitivity Dr. Emad AbdElhameed Morad

  32. TH1 cells secrete IFN-γwhich will attract and activate macrophages. • Macrophages will infiltrate the site of infection causing delayed type hypersensitivity. • Macrophages will kill the infected cells by several mechanisms. Dr. Emad AbdElhameed Morad

  33. Polyclonal activation of lymphocytes Dr. Emad AbdElhameed Morad

  34. When a specific antigen enters the body, only a specific clone of lymphocytes will proliferate and differentiate in response to that antigen (Monoclonal activation). • Some molecules have been discovered which stimulate non specifically many clones of lymphocytes (Polyclonal activation). Dr. Emad AbdElhameed Morad

  35. Examples of these molecules are: 1- Phyto-hemagglutinin (PHA)and concanavalin (CONA) are polyclonal T lymphocytes activators. 2- Pokeweed mitogen (PWM) and Epstein Barr virus are polyclonal B lymphocytes activators. Dr. Emad AbdElhameed Morad

  36. 3- Endotoxin is polyclonal T and B cell activator. 4-Superantigens • They are antigens that activate multiple clones of T lymphocytes. • Examples:S. aureus toxic shock syndrome toxin, enterotoxin and gp 120 of HIV Dr. Emad AbdElhameed Morad

  37. Dr. Emad AbdElhameed Morad

  38. (Ordinary antigens andsuperantigens) Dr. Emad AbdElhameed Morad

More Related