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This article provides an overview of the immune system, including its main functions, components, and mechanisms. It discusses defense mechanisms, autotolerance, antigen recognition, nonspecific and specific immune mechanisms, lymphoid tissues and organs, leukocyte surface molecules, immune system molecules, phagocytes, mast cells, complement system, and antigen-specific receptors.
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The main function of the immune system • Defense • Autotolerance • Immune supervision • Antigens • Exoantigeny (allergens, superantigeny ...) • autoantigens • Epitope
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)
Specific immune mechanisms • adaptive • evolutionarily younger • antigen specific • Immunological memory • components - humoral (antibody) - cellular (T lymphocytes)
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
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 ...
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
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
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
Mast cells - defense against parasitic infections - in the pathological circumstances are responsible for the early type hypersensitivity
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)
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
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)
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
- 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)