Transcript 9 memory
RECEPTORS AND CELL-SURFACE MOLECULES OF MACROPHAGES TLR4 + CD14 Scavenger receptor Mannose receptor MHCI TLR – pattern recognition Rs FcRI (CD64) Ag + IgG complex FcRII (CD32) FcRIII (CD16) LFA1 (CD11a/CD18) MHCII Mϕ CR1 (CD35) CR3 (CD11b/CD18) ! ! ! Anti-viral immune response Type I INTERFERONs vírus IFN és IFN ! ! 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 KINETICS OF VARIOUS ANTI-VIRAL MECHANISMS IFNα/β, IL-12 Cytotoxic T cells Antibody level/activity NK cells Complement vírustiter VIRUS TITER 1 2 3 4 5 6 7 8 9 10 11 12 13 na pok days 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 some elderly got sick re-infected, but 1. Life long protection against some viruses exists 2. Maintenance of memory does not require the sustained or intermitting presence of the virus 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 communication - developes in several days - specific - has memory Humoral immunity Cellular immunity ! ! ! 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 ! Antigen recognition by specific BCR induces clonal expansion and differentiation of the sepcific B cells. Plasma cells, antibody production A n ti g e n 2.Differen tiation Activation of specific B cells 1. Clonal expansion A n ti g e n MEMORY B CELLS A n ti g e n ! A n ti g e n A n ti g e n B cell memory is provided by: Memory B cells proliferation and differentiation to the GC reaction again plasma cell upon re-activation or entry to and Long-lived plasma cells Plasma cells generated during GC reaction migrate to bone marrow and survive for years, producing antibody Much of circulating IgG is produced by long-lived plasma cells, provides initial protection ! Ig. Concentration Repeated immunization Szekunder ’lasyecondary resp IgG IgA IgE primer response IgM IgM primary response against B antigen 5 „A” antig é n 10 15 20 25 „A” és „B” antigén 30 napok days ! NEUTRALIZATION PRODUCTION OF IMMUNOGLOBULINS BEFORE BIRTH AFTER BIRTH breast milk IgA 100% (adult) maternal IgG IgM IgG IgA 0 3 month 6 9 1 2 3 4 5 adult year IMMUNOLOGICAL MEMORY – B CELLS SUMMARY Germinal Center reaction • B cell proliferation • Somatic hypermutation • Affinity maturation Memory B cells B B FDC B FDC B • 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 T B B B BB B BB B B B T B plasma cell B – T cell collaboration Plasma cells Provides serological memory by pre-existing neutralizing Abs to pathogens and/or toxins T-CELL MEMORY Central memory cells Effector memory cells ! T cell memory: Quicker response Increase in the number of responding cells ! 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 5 10 15 20 25 30 Days Days Effector T Naive T AICD Citokines/Cytotoxicity Central memory T PERIPHERAL LYMPHOID ORGANS Effector memory T PERIPHERAL TISSUES Skin dermis, gut lamina propria, alveolar space Tissue-specific migration Effector T Effector T Cytokines/cytotoxicity Citokines/cytotoxicity ANTIGEN/SITE OF INFECTION IMMUNOLOGICAL MEMORY MEDIATED BY T LYMPHOCY Naive T cell Effector T cell cytokine production cytotoxicity Central Memory T cell Effector T cell • 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 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 2X107 Maintained by cytokines: IL-7, IL-15 2X105 Functional differences between lymphoid tcm cells and tissue-resident TEM cells Proliferation cytotoxicity killing Woodland DL & Kohlmeier JR 2009 Nat Rev 9:153 AGE THYMUS PERIPHERY M E N M A O I R V Y E IMMUNOLOGICAL EXPERIENCE A TERMÉSZETES ÉS SZERZETT IMMUNITÁS EGYÜTTMŰKÖDÉSE IDŐBEN Active and passive immunization Active: generates memory response Passive: ensure the protection by premade antibodies (the adaptive immune system of the person is not activated) ! ! PASSZÍV IMMUNIZÁLÁS mouse monoclonal antibodies immunization humanized mouse monoclonal antibodies immunization PROTECTED SUBJECT serum antibody ENDANGERED SUBJECT Human immunoglobulin transgenic mouse human monoclonal antibodies This is a case of PASSIVE IMMUNIZATION Immune system is not activated prompt effect temporary protection/effect Immunoglobulin degradation Active and passive immunization protection Time-span active passive slow (2 weeks) long (years) immediate protection passive active injection time short !! ! 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 PRODUCTION OF IMMUNOGLOBULINS BEFORE BIRTH AFTER BIRTH breast milk IgA 100% (adult) maternal IgG IgM IgG IgA 0 3 month 6 9 1 2 3 4 5 adult year Pathological consequences of placental transport of IgG (hemolytic disease of the newborn) anti-Rh IgM Passive anti-D IgG Immunization Active Host itself produce antibodies and cells biotic artificial Passive preformed antibodies are imported to the host biotic artificial 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