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Effector T-cells, effector T-cell functions

Effector T-cells, effector T-cell functions. Activation of effector T-cells is less dependent on co-receptor signaling. Naive or „resting” T cells… relentless migration and recirculation, LN, lymph, blood… For several month, which is its lifespan.

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Effector T-cells, effector T-cell functions

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  1. Effector T-cells, effector T-cell functions

  2. Activation of effector T-cells is less dependent on co-receptor signaling Naive or „resting” T cells… relentless migration and recirculation, LN, lymph, blood… For several month, which is its lifespan

  3. T-cell activation changes the expression of multiple receptors Integrin VLA-4 enables effector T-cells to home in inflamed tissues

  4. EFFECTOR T LYMPHOCYTES

  5. EFFECTOR T LYMPHOCYTES Effector T cells interact with and act on antigen presenting cells Effector T cells secrete cytokines and cytotoxins

  6. Environmental factors and interactions with APCs initiate distinct differentiation programs in naive T-cells

  7. Virus, bacteria, protozoa, fungi CD8+ cytotoxic T cell NK cell DCΦ IL-12 IL-12 IFNγ IFNγ IL-12 Th1 Th0 Th2 IL-2 IFNγ TNF-β GM-CSF IL-3 IL-4 IL-5 IL-10 IL-13 IL-12 FAVORS POLARIZATION TO TH1-TYPE EFFECTOR T-CELLS

  8. Self tissue, tumor cell Makrofág DC IL-10 IL-10 Th1 Th0 Th2 IL-2 IFNγ TNF-β TNF-α GM-CSF IL-3 IL-4 IL-5 IL-10 IL-13 IL-10 FAVORS POLARIZATION TO Th2 TOLERANCE

  9. Th2 Th1 Th0 Inflammatory cytokines CELLULAR IMMUNE RESPONSE Anti-inflammatory cytokines HUMORAL IMMUNE RESPONSE IL-4, IL-5, IL-6, IL-10 IFNγ, IL-2, TNF-β/LT EFFECTOR CD4+ HELPER T LYMPHOCYTES SECRETE DIFFERENT CYTOKINES IFNγ IL-4

  10. Responses to Mycobacterium leprae are sharply differentiated in tuberculoid and lepromatous leprosy.

  11. POLARIZATION OF HELPER T LYMPHOCYTES IS DIRECTED BY DENDRITIC CELL DERIVED AND AUTOCRINE CYTOKINES AND TRANSCRIPTION FACTORS

  12. SUBSETS OF HELPER T LYMPHOCYTES COLLABORATE WITH DIFFERENT PROFESSIONAL ANTIGEN PRESENTING CELLS Th2 B IL - 4 B7 expression  antigen presentation Germinal center formation Affinity maturation Isotype switch Memory B cell generation CD40L CD40 B7 expression  antigen presentation MHC-II expression  antigen presentation Mature dendritic cell Activated macrophage CD40L CD40 DCΦ Th1 IFNγ

  13. EFFECTOR FUNCTIONS OF TH1 CELLS

  14. Granulomas develop when intracellular pathogens resist elimination

  15. TH2 functions

  16. Th2 cellsstimulatetheproliferation and differentiation of naive B cells

  17. ISOTYPE SWITCH IN ACTIVATED B CELLS IS REGULATED BY HELPER T CELL - DERIVED CYTOKINES • ISOTYPE SWITCH IS INFLUENCED BY • site of antigen entry • tissue microenvironment • nature of professional antigen presenting cells • polarization of helper T lymphocytes

  18. IL-2 IL-4 IL-5 Helper T cell IgM IL-2 IL-4 IL-6 IFNγ IL-2 IL-4 IL-5 IgG IL-5 TGFβ IgA B cell IL-4 IgE REGULATION OF ISOTYPE SWITCH OF B CELLS B cell proliferation and differentiation – isotype switch

  19. Human Ig classes and subclasses Complement activation Classical Alternative FcR binding IgM ++++ ++ - IgG1 ++++ ++ +++ IgG2 + ++ + IgG3 +++ ++ ++++ IgG4 +/- ++ + IgA - +++ +++ IgE - ++ +++ IgD - ++ -

  20. Cytotoxic T-cells

  21. PRIMING OF CD8+ CYTOTOXIC T CELLS

  22. ACTIVATION CD4+ Th CD40L IL-2 B7 CD28 CD8+ Tc PRIMING OF CD8+ CYTOTOXIC T CELLS • Dendritic cells with high B7 expression activate CD8+ T cells directly • Dendritic cells activate CD4+ T cells, which in turn enhance the co-stimulatory activity of dendritic cells • Activated CD4+ T cells secrete cytokines (IL-2), which directly acts on activated CD8+ T cell

  23. KILLING OF INFECTED CELLS BY CTL Recognition by CTLs induces secretion of cytotoxins to the target cell

  24. PHYSIOLOGICAL AND PATHOLOGIC CELL DEATH Apoptotic signal Cell demage

  25. Healthy cell Necrotic cell Late apoptotic cell Apoptotic cell APOPTOSIS AND NECROSIS • HIGHLY REGULATED PROCESS • Induction • Excecution • Mitochondrial function  * Activation of caspases • Electron transzport  * Serine protease,calpain, proteasome • Oxidative phosphorylateion  * Redox potential • ATP synthesis  *DNA degradation (endonuclease)

  26. MECHANISM OF CELLULAR KILLING BY CD8+ CYTOTOXIC T LYMPHOCYTES Proteoglycans H2O, Ca++, ions Polymerized perforin Granzyme APOPTÓZIS CYTOKINE RELEASE CD8+ T CELL TARGET CELL

  27. TNF AND TNF RECEPTOR FAMILY MEMBERS AND THEIR LIGANDS Soluble TNF TNF-α TNF-β/LTα TNFRI TNFRII RECEPTOR TRIMERIZATION LTβ LTα LTβ LTβR Soluble FasL FasL FAS CD40L CD30L CD27L 4-1BBL Ox40L CD40 CD30 CD27 4-1BB Ox40 DEATH DOMAIN

  28. MECHANISMS OF FAS RECEPTOR – MEDIATED PROGRAMED CELL DEATH

  29. CONSEQUENCE OF T CELL-MEDIATED IMMUNE RESPONSES Cytotoxic T lymphocytes recognize virus-infected or tumor cells Activated cytotoxic T-lymphocytes kill virus-infected or tumor cells

  30. Th1 Intracelluláris patogén Gyulladás Tc aktiváció IgG1 & IgG3 ellenanyag ADCC, opszonizáció Komplement aktiváció CD4 TCR Th2 Extracelluláris patogén Soksejtek parazita Szekretoros IgA IgE, allergia CD4 DC TCR CD4 Th17 Extracelluláris patogén Gyulladás Autoimmun betegségek Allergia TCR CD4 TCR Th0 blaszt Treg Th1 gátlás Tolerancia fenntartása CD4 TCR KLONÁLIS OSZTÓDÁS DIFFERENCIÁCIÓ EPIGENETIKAI VÁLTOZÁS, MEMÓRIA EFFEKTOR SEGÍTŐ T SEJTEK Naive CD4+ T cell CD4 TCR KÖLCSÖNHATÁS AKTIVÁCIÓ INSTRUKCIÓ

  31. EFFEKTOR T LIMFOCITÁK JELLELMZŐ MOLEKULÁI CCR1 CCR5 CXCR3 CCR6 T-bet GATA3 RORγt FoxP3 Th17 Th1 CD45RBlo IL-23R IL-12Rα LAG3 CD25 IL-2Rα CD127 IL-7Rα↓ CCR4 CCR3 CXCR4 Th2 Treg CD45RBhigh IL-1R CD30 CTLA4 B7 ligand GITR TCR+ CD4+ CD28+ CD25+

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