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8 th lecture

8 th lecture. The collaborations between innate and adaptive immunity. Antibody types and functions. THE EFFECTS OF B CELLS ON THE INNATE ARM OF THE IMMUNE SYSTEM (HUMMORAL IMMUNITY). A nti g en b inding. Complement b inding s ite. Binding to Fc r eceptors. Placental t ransfer.

felicia-baxter
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8 th lecture

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  1. 8th lecture The collaborations between innate and adaptive immunity. Antibody types and functions.

  2. THE EFFECTS OF B CELLS ON THE INNATE ARM OF THE IMMUNE SYSTEM (HUMMORAL IMMUNITY)

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

  4. VARIABILITY IN THE CONSTANT REGION HEAVY AND LIGHT CHAINS DETERMINES THE CLASS OF IMMUNOGLOBULIN Isotype Sequence variability of H/L-chain constant regions Sequence variability of H/L-chain constant regions

  5. ! HUMAN IMMUNOGLOBULIN CLASSESEncoded by different structural gene segments (Isotypes) ! Heavy chain types: Light chain types: • kappa (κ) • lambda (λ) FcγR (gamma) can only bind IgG immunoglobulins FcαR (alpha) can only bind IgA immunoglobulins FcεR (epsilon) can only bind IgE immunoglobulins 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

  6. Different cells express different Fc receptors on their surface • Expression of Fc receptors on the surface of cells is relatively constant (INFγ macrophages) • Fc receptors are activated not from a free antibody but by antibody-antigen complex • Antibodies of different isotypes activate different cells and have different effector functions

  7. ISOTYPE SWITCHING

  8. MAIN CHARACTERISTICS OF IMMUNOGLOBULIN ISOTYPES

  9. B CELL ACTIVATION AND THE GERMINAL CENTER Somatic mutation Affinity maturation Isotype switching Memory The progress of these germinal center reactions depend on T cell signals!

  10. 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

  11. Antigenbinding Complement binding site Binding to Fc receptors Placental transfer TRANSPORT PROCESSES INVOLVING THE Fc RECEPTORS Poly Ig receptors for IgA transport across the epithelium to the mucosal surface Neonatal Fcγ receptor for transport of maternal IgG across the placenta FcγRn on the placenta facilitate the transfer of maternal IgG to the fetus’s circulation, recognizing the constant region of IgGs

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

  13. EFFECTOR FUNCTIONS OF ANTIBODIES Antibody-mediated immune responses • Opsonization • Neutralization • Complement fixation • ADCC

  14. ANTIBODY EFFECTOR FUNCTIONS OPSONIZATION

  15. ANTIBODY EFFECTOR FUNCTIONS NEUTRALIZATION

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

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

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

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

  20. THE EFFECTS OF T CELLS ON THE INNATE ARM OF THE IMMUNE SYSTEM

  21. MACROPHAGES

  22. ! 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)

  23. EXTRACELLULAR PATHOGEN PHAGOCYTOSIS AND KILLING

  24. KILLING THROUGH LYSOSOMAL ENZYMES, OXYGEN AND NITROGEN SPECIES

  25. Activation of macrophages

  26. Inflammatory cytokines Antimicrobial substances IL-12 IL-18 Th1 cell NK cell activation IFNg Inactivation IL-10 T cell APC Activation of macrophages Inflammatory cytokines Leukocyte recruitment TNF IL-6 IL-12 Microorganism IL-13 Th 2 cell IL-4 Alternative activation: Mannose receptor – endocytosis Th2 chemokines NOS inhibition Tissue regeneration

  27. THE LOCATION OF INNATE AND ADAPTIVE INTERACTIONS

  28. KINETICS OF AN IMMUNE RESPONSE AGAINST PATHOGENS

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