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THE COLLABORATIONS BETWEEN INNATE AND ADAPTIVE IMMUNITY. ANTIBODY TYPES AND FUNCTIONS.

THE COLLABORATIONS BETWEEN INNATE AND ADAPTIVE IMMUNITY. ANTIBODY TYPES AND FUNCTIONS. 8 th week Public Health BSc 2014. limited specificity immediate reaction does not improve no memory. highly specific develops in several days improves after exposure has memory.

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THE COLLABORATIONS BETWEEN INNATE AND ADAPTIVE IMMUNITY. ANTIBODY TYPES AND FUNCTIONS.

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  1. THE COLLABORATIONS BETWEEN INNATE AND ADAPTIVE IMMUNITY. ANTIBODY TYPES AND FUNCTIONS. 8thweekPublic Health BSc 2014

  2. limited specificity • immediate reaction • does not improve • no memory • highly specific • develops in several days • improves after exposure • has memory

  3. THE EFFECTS OF ANTIGEN PRESENTING CELLS ON THE ADAPTIVEARM OF THE IMMUNE SYSTEM

  4. THE LOCATION OF INNATE AND ADAPTIVE CELL INTERACTIONS

  5. THE EFFECTS OF TCELLS ON THE INNATE ARM OF THE IMMUNE SYSTEM

  6. 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)

  7. KILLING THROUGH LYSOSOMAL ENZYMES, OXYGEN AND NITROGEN SPECIES

  8. Activation of macrophages

  9. THE EFFECTS OF BCELLS ON THE INNATE ARM OF THE IMMUNE SYSTEM

  10. EFFECTOR FUNCTIONS OF ANTIBODIES Antibody-mediated immune responses • NEUTRALIZATION • OPSONIZATION • opsonizedphagocytosis (IgG) • ADCC (NK cell-mediatedkilling) (IgG) • mast cell degranulation (IgE) • COMPLEMENT ACTIVATION

  11. Antigenbinding Complement binding site Binding to Fc receptors Placental transfer THE CONSTANT REGION OF AN ANTIBODY CAN BIND TOFc RECEPTORS (FcR) FcR activation occurs when the antibody forms a complex with an antigen

  12. Opsonization facilitate and accelerate the recognition of the pathogens by phagocytes Phagocytes must express receptors for the opsonins: IgG  FcγRI C3b  CR1 • Main opsonins: • ANTIBODIES • Complement molecules • Acute-phase proteins (CRP, SAP)

  13. 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)

  14. ANTIBODY EFFECTOR FUNCTIONS ANTIBODY-DEPENDENT CELL CYTOTOXICITY Antibodies target virus infected cells, flagging them for the recognition by natural killer (NK) cells

  15. IgE • most importantisotypeagainsthelminths • triggers ADCC byeosinophils • mastcellscarryhighaffinityFcεreceptors • samemechanisminallergicreactions

  16. HUMAN IMMUNOGLOBULIN CLASSESEncodedbydifferentheavychainconstantgenesegments Heavy chain types: IgG - gamma (γ) heavy chains IgM - mu (μ) heavy chains IgA - alpha (α) heavy chains IgD - delta (δ) heavy chains IgE - epsilon (ε) heavy chains

  17. GC reaction: • proliferation (clonal expansion) of activated B cells • affinity maturation (stronger binding to epitopes) • isotype switch (different effector functions) • memory B cell formation (from improved clones) • Only by the help of Th cells!

  18. ISOTYPE SWITCH • heavychainconstantgenesegmentsaredevided • alwaystheclosesttothevariabledomain is expressed (firstalwaysIgM) • theswitch is drivenbythecytokinesproducedbyhelper (CD4+) T cells

  19. 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 ISOTYPE SWITCHING IS T-DEPENDENT B cell proliferation, differentiation and isotype switching

  20. IgAtransporttomucosalsurfaces and body secretions Poly Ig receptors for IgA transport across the epithelium to the mucosal surface • additionalhelpforthenaturalbarriers of our body – defense of theepithelialsurfaces • mainlyneutralization

  21. NATURAL PASSIVE IMMUNIZATION

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

  23. EFFECTOR FUNCTIONS OF ANTIBODIES Antibody-mediated immune responses • NEUTRALIZATION • OPSONIZATION • opsonizedphagocytosis (IgG) • ADCC (NK cell-mediatedkilling) (IgG) • mast cell degranulation (IgE) • COMPLEMENT ACTIVATION

  24. ANTIBODY EFFECTOR FUNCTIONS COMPLEMENT FIXATION Binding of complement protein 1 to IgG or IgM immunoglobulins on a bacterial surface

  25. ANTIBODY EFFECTOR FUNCTIONS COMPLEMENT FIXATION Complement 1 protein and the immunoglobulin bound to the bacteria cause the binding of more complement proteins

  26. ANTIBODY EFFECTOR FUNCTIONS COMPLEMENT FIXATION More complement proteins are recruited leading to the death of the extracellular pathogen (bacteria) by forming pores in it

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