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

6. Virus infected cell Macrophage containing bacteria B cell presenting specific antigen Cytotoxins Perforin Granzyme Cytokines FasL IFNγ TNF-β TNF-α Activation IFNγ GM-CSF TNF-α CD40L FasL Cytokines IL-3 GM-CSF IL-10 TGFβ Eotaxin Activation IL-4 IL-5 CD40L Cytokines IL-3 TNF-β IL-2 EFFECTOR T LYMPHOCYTES Effector T cells interact with and act on antigen presenting cells Effector T cells secrete cytokines and cytotoxins

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

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

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

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

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

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

13. Th1 DC Φ IFNγ Th2B IL - 4 B7 expression  antigen presentation Germinal center formation Affinity maturation Isotype switch Memory B cell generation B7 expression  antigen presentation MHC-II expression  antigen presentation Mature dendritic cell Activated macrophage SUBSETS OF HELPER T LYMPHOCYTES COLLABORATE WITH DIFFERENT PROFESSIONAL ANTIGEN PRESENTING CELLS CD40 CD40L

14. EFFECTOR FUNCTIONS OF TH1 CELLS

15. Granulomas develop when intracellular pathogens resist elimination

16. TH2 functions

17. Th2 cells stimulate the proliferation and differentiation of naive B cells

18. 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

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

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

21. Cytotoxic T-cells

22. PRIMING OF CD8+ CYTOTOXIC T CELLS

23. CD28 CD8+ Tc B7 CD4+ Th CD40L ACTIVATION IL-2 PRIMING OF CD8+ CYTOTOXIC T CELLS 1.Dendritic cells with high B7 expression activate CD8+ T cells directly 2.Dendritic cells activate CD4+ T cells, which in turn enhance the co-stimulatory activity of dendritic cells 3.Activated CD4+ T cells secrete cytokines (IL-2), which directly acts on activated CD8+ T cell

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

26. PHYSIOLOGICAL AND PATHOLOGIC CELL DEATH Apoptotic signal Cell demage

27. Healthy cellNecrotic cell Apoptotic cell Late apoptotic cell APOPTOSIS AND NECROSIS HIGHLY REGULATED PROCESS 1.Induction 2.Excecution Mitochondrial function  * Activation of caspases Electron transzport  * Serine protease,calpain, proteasome Oxidative phosphorylateion  * Redox potential ATP synthesis  * DNA degradation (endonuclease)

28. MECHANISM OF CELLULAR KILLING BY CD8+ CYTOTOXIC T LYMPHOCYTES CD8+ T CELLTARGET CELL H 2 O, Ca++, ions Granzyme Polymerized perforin APOPTÓZIS Proteoglycans CYTOKINE RELEASE

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

30. MECHANISMS OF FAS RECEPTOR – MEDIATED PROGRAMED CELL DEATH

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

33. TCR CD4 Naive CD4+ T cell Th0 blaszt TCR CD4 TCRTh1 Intracelluláris patogén Gyulladás Tc aktiváció IgG1 & IgG3 ellenanyag ADCC, opszonizáció Komplement aktiváció TCR CD4 Th2 Extracelluláris patogén Soksejtek parazita Szekretoros IgA IgE, allergia TCR CD4 Treg Th1 gátlás Tolerancia fenntartása KLONÁLIS OSZTÓDÁS DIFFERENCIÁCIÓEPIGENETIKAI VÁLTOZÁS, MEMÓRIA VÁLTOZÁS, MEMÓRIA KÖLCSÖNHATÁSAKTIVÁCIÓINSTRUKCIÓ Th17 Extracelluláris patogén Gyulladás Autoimmun betegségek Allergia TCR CD4 EFFEKTOR SEGÍTŐ T SEJTEK DC

34. TCR + CD4 + CD28 + CD25 + Th1 T-bet CCR1 CCR5 CXCR3 CD45RB lo IL-12Rα LAG3 Th2 GATA3 CCR4 CCR3 CXCR4 CD45RB high IL-1R CD30 Th17 RORγt IL-23R CCR6 CD127 IL-7Rα ↓ CTLA4 B7 ligand GITR CD25 IL-2RαTreg FoxP3 EFFEKTOR T LIMFOCITÁK JELLELMZŐ MOLEKULÁI