http://uia.fnplzen.cz/ J. Ochotná * autoantigen * * - antigen derived from his own body exoantigen - alien substance from the external environment allergen - exoantigen that in susceptible individuals may cause pathological (allergic) immune response Secondary lymphoid tissues and organs Fagosome fusion with lysosomes * bactericidal substances (defensins) * hydrolytic enzymes (cathepsin, lysozyme) * liquid with a pH of 4-5 activation of membrane NADPH oxidase * activation of Fc receptors and complement receptors leads to respiratory (oxidative) flash * oxygen intermediates (superoxid radical O2-, singlet oxygen, hydrogen peroxide, hydroxyl radical) → damage of the pathogen production of nitric oxide (NO) * macrophages produce NO after activation with cytokines (IFNg, TNF) that are produced by TH1 lymphocytes * NO liquidate intracellular parasites of macrophages lymphoid cells which belon to innate immune mechanisms kill cells which have abnormally low MHCgpI expression (some tumor and virus infected cells) have similar cytotoxic mechanisms as Tc NK cells activators - IFNa, IFNb NK cells receptors Activating receptors - Some surface lectins, Fc receptor CD16 ADCC (antibody-dependent cellular cytotoxicity) NK cells recognize cell opsonized with IgG antibodies by the Fc receptor CD16, this leads to the activation of cytotoxic mechanisms (NK degranulation) Inhibitory receptors - recognize MHC gpI Imunoglobulin family - KIR (killer cell immunoglobulin like receptors) C-type lektin family - eg CD94/NKG2 The resulting reaction of NK cell after meeting with another cell depends on which signal prevail, whether activating or inhibitory signals Cytotoxic granules contain perforin and granzyme (perforin creates pores in the cytoplasmic membrane of target cells, in some cases may cause osmotic lysis of the target cell, formed pores in the cell receiving granzymes, that cause the target cell to die by apoptosis. Fas ligand (FasL) - which binds to the apoptotic receptor Fas (CD95) presented on the surface of many different cells TNFa NK cell activates in target cell apoptosis Belongs to the humoral component of non-specific mechanisms IFNa - produced by virus infected lymphocytes, monocytes and macrophages IFNb - produced by virus-infected fibroblasts and epithelial cells IFNa and IFNb - bind to receptors on the surface of infected and healthy cells and induce in them an antiviral state (synthesis of enzymes that block viral replication in the cell) IFNg - produced by TH1 cells, has regulatory function, activates macrophages and stimulates the expression of MHCgp Mucosal mast cells - in the mucous membranes of respiratory and gastrointestinal tract, participate in parasitosis and allergy Connective tissue mast cells - the connective tissue, in parasitosis and allergy are not participating Defense against parasitic infections In pathological circumstances, responsible for the early type of hypersensitivity (immunopathological reaction typeI) Apply during inflammation, in angiogenesis, in tissue remodeling Regulation of immune response Mast cells degranulation can be stimulated by: cross-linking of IgE Fc receptors anafylatoxins (C3a, C4a, C5a) TLR Establishing of multivalent antigen (multicellular parasite) to IgE linked to highaffinnity Fc receptor for IgE (FcRI) Aggregation of several molecules FcRI Initiate mast cell degranulation (cytoplasmic granules mergers with the surface membrane and release their contents) Activation of arachidonic acid metabolism (leukotriene C4, prostaglandin D2) Production of cytokines (TNF, TGF , IL-4, 5,6 ...) Cytoplasmatic granules: hydrolytic enzymes, heparin, chondroitin sulphate, histamine, serotonin Histamine causes vasodilation, increased vascular permeability, erythema, edema, itching, contraction of bronchial smooth muscle, increases intestinal peristalsis, increased mucus secretion of mucosal glands in the respiratory tract and GIT (helps eliminate the parasite) Arachidonic acid metabolites (leukotriene C4, prostaglandin D2) Cytokines (TNF, TGF b, IL-4, 5,6 ...) Differentiate from myeloid precursor They are considered to be the circulating form of mast cells Receptor equipment, containing granules, the mechanisms of stimulation and functions are very similar to mast cells They are responsible for the emergence of anaphylactic shock