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Overview of the Immune System: Defense, Autotolerance, and Immune Mechanisms

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  1. Summary

  2. The main function of the immune system • Defense • Autotolerance • Immune supervision • Antigens • Exoantigeny (allergens, superantigeny ...) • autoantigens • Epitope

  3. Nonspecific immune mechanisms • non-adaptive, congenital • evolutionarily older • respond to the presence of harmful substances quickly • recognize structural features common to many pathogens • absence of immunological memory • components - cellular (phagocytes, NK cells) - humoral (complement, interferons, lectins and other serum proteins)

  4. Specific immune mechanisms • adaptive • evolutionarily younger • antigen specific • Immunological memory • components - humoral (antibody) - cellular (T lymphocytes)

  5. Components of the immune system • lymphoid tissues and organs • cells of the immune system • molecules of the immune system Lymphoid tissues and organs • primary lymphoid organs (bone marrow, thymus) • secondary lymphoid tissues and organs (spleen, lymph nodes and their organized clusters, MALT) • lymphoid organs are connected with other organs and tissues by network of lymphatic and blood vessels

  6. Leukocyte surface molecules • CD nomenclature - a designation surface molecules of leukocytes, a newly described molecules receive serial numbers, some have alternative names associated with their structure or function (eg, CD14- LPS receptor, CD16-FcgRIII ...) • antigen-specific receptors (TCR, BCR) • adhesion molecules (integrins, selectins, adhesion molecules Ig-family) • Fc receptors • complement receptors • cytokines and chemokines receptors • MHC gp. • receptors for microbial components ...

  7. Molecules of the immune system • antigen-specific receptors (TCR, BCR) • antibodies • MHC gp. I. and II. class (HLA) • Fc receptors • adhesion and costimulating molecules • cytokines and their receptors • nonspecific receptor for components of microbial surfaces • complement system

  8. Phagocytes • phagocytosis - absorbing particles from the surroundings • professional phagocytes (neutrophils, eosinophils, monocyte and macrophages) • granulocytes - defense against extracellular pathogens • macrophages - elimination of apoptotic cells, defense against intracellular parasites Receptors of phagocytes • surface lectins - bind microbial glycoproteins and polysaccharides - galactose receptor, manose receptor • CD14 - binds bacterial LPS • TLR - bind bacterial lipopolysaccharides, lipoproteins, DNA • Scavenger-receptors recognize apoptotic cells • Fc receptors • complement receptors

  9. opsonization - Ig                          - complement component                          - serum MBL                          - fibronectin, fibrinogen                          - CRP, serum amyloid P • liquidation of absorbed microorganisms:- lysosomes: bactericidal substances and hydrolytic enzymes - activation of NADPH oxidase - oxidation flash - NO

  10. Mast cells - defense against parasitic infections - in the pathological circumstances are responsible for the early type hypersensitivity

  11. Complement • system of about 30 serum and membrane proteins • main components C1-C9 • cascade activation • MAC (C5b, C6, C7, C8 and C9) • main functions of complement: opsonization (C3b)                                                chemotaxis (C3a, C5a)                                                osmotic lysis (MAC)                                                anafylatoxins (C3a, C4a, C5a)

  12. complement activation: an alternative pathway                                       classical pathway                                       lectine pathway • terminal lytic phase of complement cascade → MAC → pores in the membrane → osmotic cell lysis • regulation of complement and protection of its own cells - using membrane and serum proteins - C1 inhibitor - DAF (decay-accelerating factor) - degradation of C3 convertase- factor I, MCP (membrane cofactor protein), CR1, factor H - cleavage of C3b - CD59 (protectin) - prevents the polymerization of C9

  13. Antigen-specific receptorsTCR- antigen recognition module associated with the CD3 complex- coreceptors CD4, CD8- costimulating receptor CD28BCR- surface immunoglobulin (IgM, IgD) associated with CD79a and CD79b- costimulating receptor CD40- enhanced signaling through CR2 (CD21)

  14. Secreted immunoglobulins • structure: - 2 heavy (H) chains - covalently linked by disulfide bonds- 2 light (L) chains - linkeded to the heavy chains by disulfide bonds • isotypes of immunoglobulins: IgM, IgD, IgG (1-4), IgA (1-2), IgE • functions: opsonisation, neutralisation, activation of complement

  15. - pleiotropic effect - operates in a cascade - cytokine network - cytokine system is redundant effects of cytokines - autocrine - paracrine - endocrine - are known as interleukins (exception: TNF, lymphotoxin, TGF, interferons, CSF and growth factors)

  16. Cell-mediated immune mechanisms

  17. Merry Christmas

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