RECEPTORS AND CELL - SURFACE MOLECULES OF MACROPHAGES

1. ! RECEPTORS AND CELL-SURFACE MOLECULES OF MACROPHAGES ! TLR4 + CD14 Scavenger receptor Mannose receptor MHCI TLR – pattern recognition Rs FcRI (CD64) Ag + IgG complex FcRII (CD32) MHCII Mϕ FcRIII (CD16) CR1 (CD35) LFA1 (CD11a/CD18) CR3 (CD11b/CD18)

4. ! Anti-viral immune response Type I INTERFERONs vírus IFN és IFN !

5. ! Anti-viral immune response Defense: Innate Immunity: – type I interferons(INFα, β) – NK cells Adaptive immunity B cells – antibody-mediated neutralization T cells --- cytotoxic T cells, cytokines

6. KINETICS OF VARIOUS ANTI-VIRAL MECHANISMS IFNα/β, IL-12 NK cells Cytotoxic T cells Antibody Complement level/activity VIRUS TITER days

7. IMMUNOLOGICAL MEMORY Inhabitants: 46 000 Area: 1 400 km2 • 1781: Measles epidemics in the Faroe islands • after the epidemics the island has remained measles free for 65 years • 1846: Another epidemics • Those, who were elder than 65 years and were sick in 1781 were not re-infected, but some elderly got sick • Life long protection against some viruses exists • Maintenance of memory does not require the sustained or intermitting presence of the virus

8. ! ! THE TWO ARMS OF THE IMMUNE SYSTEM Differentiation between harmless and harmful impacts DETECTION OF STRESS AND DANGER SIGNALS INNATE IMMUNITY Differentiation between self and non-self structures Antigen-specific recognition ADAPTIVE IMMUNITY Neutralization and elimination of foreign and harmful structures EXECUTIVE FUNCTIONS COORDINATED AND REGULATED ACTIONS INNATE IMMUNITY • immediate reaction • not antigen-specific • no memory ADAPTIVE IMMUNITY • developes in several days • specific • has memory communication Humoral immunity Cellular immunity

9. ! ! B cell memory: Quicker response Increase in the number of specific B cells The amounts of antibody are biger Higher affinity antibodies (‘more specific’) Isotype switch In case of T dependent B cell activation

10. ! Antigen recognition by specific BCR induces clonal expansion and differentiation of the sepcific B cells. Activation of specific B cells 1. Clonalexpansion MEMORY B CELLS Plasma cells, antibody production 2.Differentiation

12. B cell memory is provided by: Memory B cells proliferation and differentiation to plasma cell upon re-activation or entry to the GC reaction again and Long-lived plasma cells Plasma cells generated during GCreaction migrate to bone marrow and survive for years, producing antibodyMuch of circulating IgG is produced by long-lived plasma cells, provides initial protection

14. ! Repeated immunization primary response against B antigen days

15. !

16. NEUTRALIZATION

17. PRODUCTION OF IMMUNOGLOBULINS

18. B B B B B B B B B B IMMUNOLOGICAL MEMORY – B CELLS SUMMARY Germinal Center reaction • B cell proliferation • Somatic hypermutation • Affinity maturation Memory B cells • Perviously activated • Passed through affinity maturation • Present in the circulation • proliferation and differentiation to plasma cell upon re-activation or entry to the GC reaction again Plasma cells Provides serological memory by pre-existing neutralizing Abs to pathogens and/or toxins B B FDC B FDC B T B plasma cell B – T cellcollaboration T B

19. T-CELL MEMORY Central memory cells Effector memory cells

20. ! ! T cell memory: Quicker response Increase in the number of responding cells

22. DEVELOPMENT OF CELLULAR MEMORY Negative regulation of the immune system AICD Activation Induced Cell Death DIFFERENTIATION Naive lymphocytes Memory Az antigen-specific cell number Secondary effector T cells Primary effector cells EXPANSION AICD MEMORY Days

23. Central memory T PERIPHERAL LYMPHOID ORGANS Effector T Citokines/cytotoxicity Naive T Effector T AICD Citokines/Cytotoxicity Effector memory T PERIPHERAL TISSUES Skin dermis, gut lamina propria, alveolar space Tissue-specific migration Effector T Cytokines/cytotoxicity ANTIGEN/SITE OF INFECTION

24. IMMUNOLOGICAL MEMORY MEDIATED BY T LYMPHOCYTES Naive T cell Effector T cell 2X107 cytokine production cytotoxicity Central Memory T cell Effector T cell Maintained by cytokines: IL-7, IL-15 • Previously activated, partially differentiated cell type • Circulating CCR7+ cells in blood, lymphoid tissues • High proliferation rate induced by activation signals • Rapid differentiation to effector cells 2X105 Effector Memory T cell Effector T cell • Previously activated, partially differentiated cell type • Closest to the effector state • Circulating CCR7- cells in blood and tissues • Slow proliferation, rapid effector functions

25. Functional differences between lymphoid tcm cells and tissue-resident TEM cells Proliferation Cytotoxicity cytotoxicity killing Woodland DL & Kohlmeier JR 2009 Nat Rev 9:153

26. AGE THYMUS PERIPHERY M E M O R Y N A I V E IMMUNOLOGICAL EXPERIENCE

27. A TERMÉSZETES ÉS SZERZETT IMMUNITÁS EGYÜTTMŰKÖDÉSE IDŐBEN

28. Active and passive immunization

29. Active: generates memory response Passive: ensure the protection by premade antibodies (the adaptive immune system of the person is not activated)

30. ! !

31. mouse monoclonal antibodies immunization humanized mouse monoclonal antibodies immunization Human immunoglobulin transgenic mouse human monoclonal antibodies ENDANGERED SUBJECT PASSZÍV IMMUNIZÁLÁS PROTECTED SUBJECT serum antibody This is a case of PASSIVE IMMUNIZATION Immune system is not activated prompt effect temporary protection/effect Immunoglobulin degradation

32. Active and passive immunization activepassive protection slowimmediate (2 weeks) Time-span longshort (years) ! ! passive protection active injection time

34. ! Anti-viral immune response Defense: Innate Immunity: – type I interferons(INFα, β) – NK cells Adaptive immunity B cells – antibody-mediated neutralization T cells --- cytotoxic T cells, cytokines

35. PRODUCTION OF IMMUNOGLOBULINS

36. Pathological consequences of placental transport of IgG (hemolytic disease of the newborn) anti-Rh IgM Passive anti-D IgG

37. Immunization Active Passive Host itself produce preformed antibodies antibodies and cells are imported to the host biotic biotic artificial artificial

38. Immunitás Természetes Aktív: betegség, immunizálódás (sorozatos találkozás az adott kórokozóval) Passzív-in utero, placentán át, maternális (anyai IgG, folyamatos, homológ) - születés után, colostrális, anyatej útján IgG, IgA