Major Functions Of The Immune System – 2 The main functions of the immune system The immune system belongs to the main homeostatic mechanisms Protection – recognition and protection against pathogenic microorganisms and their toxins Self-tolerance – recognition of own tissues and maintenance of tolerance to them Immune maintenance – identification and elimination of old, damaged and others . altered cells
3 Antigen (immunogen) * a substance that the immune system recognizes and reacts to * usually proteins or polysaccharides (lipids and nucleic acids only together with proteins or polysaccharides) * Molecules <5 kDa cannot cause an immune response, optimal size of molecules of antigen to initiate an immune response is about 40 kDa * autoantigen – antigen obtained from the body itself * exoantigen – foreign substance from the external environment allergen – exoantigen that can cause a pathological (allergic) immune response in sensitive individuals
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4 Haptens * small molecules capable of inducing a specific immune response only when bound to a macromolecular transporter (individual haptens are not immunogenic) * usually drugs (eg, penicillin antibiotics, hydralazine)
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Antigen-antibody interaction * The antibody binding site (paratope) forms non-covalent complexes with the corresponding part on the antigen molecule (epitope) * Involved: hydrogen bonds, electrostatic and hydrophobic interactions, van der Waals forces * the antigen- complex antibody is reversible
6 types of antigens according to antigen presentation 1) thymus-dependent antigens * most often, usually Ag protein * for an antigen-specific humoral immune response, it is necessary to cooperate with TH lymphocytes (or the response is not effective enough ) * help is implemented in the form of cytokines produced by TH lymphocytes
7 types of antigens according to antigen presentation 2) thymus-independent antigens * a small number of antigens can stimulate antibody production directly without the participation of T lymphocytes * these are mainly bacterial polysaccharides, lipopolysaccharides and polymeric forms of proteins ( e.g. Haemophilus, Str. pneumoniae)
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Superantigens * stimulate lymphocytes polyclonally and en masse * massive activation of T lymphocytes can cause shock * eg. bacterial toxins (Staph.aureus, Str.pyogenes, Pseud.aeruginosa)
9 Sequestered antigens * autoantigens that are normally hidden from the immune system and therefore unknown (e.g., lens of the eye, testes, brain) * if “exposed” by an injury, can trigger an immune response (one of the processes of the theory autoimmune)
Components of the immune system * Lymphoid tissues and organs * Cells of the immune system * Molecules of the immune system
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Lymphoid tissues and organs * are connected to other organs and tissues by a lymphoid and vascular network Primary lymphoid tissues and organs * bone marrow, thymus gland * site of maturation and differentiation of immunocompetent cells * immature lymphocytes here acquire their antigenic specificity
Secondary lymphoid tissues and organs * site of meeting of immunocompetent cells with the spleen Ag – unlike lymph nodes they filter the blood and fix the presented antigens lymph nodes and their organized accumulations (tonsils, appendix, Peyer’s patches in the intestine) – filter the lymph and retain existing antigens MALT (mucus-associated lymphoid tissue) – diffuse lymphatic tissue whose main function is to capture antigens that penetrate through the mucous membrane
Immune system cells * Red and white blood cell evolution starts in yolk sac, then hematopoiesis travels to fetal liver and spleen (3-7 months gestation), main hematopoietic function is bone marrow * all blood cells originate up from the pluripotent stem. cell (CD 34) * stem cells self-renew and persist throughout life * hematopoiesis is regulated by cytokines secreted by bone marrow stromal cells, activated TH cells, and macrophages
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Non-specific * non-adaptive, innate * evolutionarily older * immune mechanisms * no immunological memory * in the presence of pathogens respond quickly, within minutes (based on pre-prepared molecules and cells) * cellular component – phagocytes (some are APC), Humoral NK cells – complement, interferons, lectins and other serum proteins
Specific * adaptive, antigen-specific * evolutionarily younger immune mechanisms * have immunological memory * a complete specific immune response develops over several days or even weeks * cellular component – humoral T lymphocytes (TCR) – antibodies
21 Function and structure of the mucosal and skin immune system Mucous membranes and skin are in constant contact with the external environment, where about 80% of immunocompetent cells accumulate. The skin is a barrier against mechanical, physical and chemical damage and against the penetration of microorganisms on the human surface of about 1.5 m2. area of about 400 m2
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22 Natural non-immune defense mechanisms Intact skin and mucous membranes and non-immune defense mechanisms are important to protect the body against infections. mechanical – movement of cilia, flow of air in the respiratory tract or flow of fluid in the urinary tract chemical – fatty acids in the skin; lysozyme in saliva, tears and sweat; antibacterial defensins, acidic pH in the stomach and urine of microbes – non-pathogenic microflora
23 Structure of the Mucosal Immune System MALT (Mucosal Associated Lymphoid Tissue) BALT (Bronchial Associated Lymphoid Tissue) GALT (Intestine Associated Lymphoid Tissue) NALT (Nasal Associated Lymphoid Tissue) o-MALT (Organized) – consists of lymphoid follicles in the mucosa, tonsils and adenoids, appendix, Peyer’s patches d-MALT (diffuse) – composed of leukocytes diffusely distributed in the lamina propria (T and B lymphocytes, macrophages, neutrophils, eosinophils and mast cells)
Humoral immune mechanisms of the mucosal system sIgA *(secretory immunoglobulin A) * the most significant mucosal immunoglobulin, in breast milk * transcytosis – IgA is transported across the epithelium using the transport Fc receptor (poly-Ig receptor), on the luminal side there is a cleavage of IgA with a part of the receptor called the secretory component, which protects IgA from intestinal proteases can trigger an immune response
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SIgM * secretory immunoglobulin M * applies to neonates and in case of selective IgA deficiency * more prone to degradation by intestinal proteases * neutralizing antigens on mucosal surfaces IgG * enters the mucosa by diffusion * especially applicable in the lower respiratory tract
Induction of mucosal immune response * M cells – specialized enterocytes that ensure the transport of Ag (endocytic Ag from the environment) are in close contact with lymphocytes and APC * Mucosal immunization stimulates the production of TH2 and TH3 lymphocytes and IgA.
29 Inflammation * This is a summary of the physiological reactions to a violation of the integrity of the body, which ensures protection from infection of damaged areas, localization of damage and healing. * The first signs about the development of inflammatory reactions come from mast cells, phagocytes and substances released from damaged cells and components of intracellular substances.
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30 Local response to inflammation – increased vascular permeability (vasoactive amines, complement components C3a, C5a, leukotrienes, swelling at the site of inflammation) – increased expression of adhesion molecules on the endothelium – activation of coagulation, fibrinolytic, kinin and complement – influence of local nerve endings (prostaglandins, pain) – temperature changes (IL-1, IL-6, TNF, prostaglandins)
31 Systemic response to inflammation – depends on the extent of damage and duration of local inflammation – fever (anti-inflammatory cytokines TNF, IL-1, IFN ; stimulates the thermoregulatory center of the hypothalamus) – mobilization of tissue metabolism – induction of the expression of Hsp (heat) – shock proteins; act as chaperones) – production of acute phase proteins (CRP, SAP, C3, C4; opsonization and complement activation)
Increased synthesis of certain serum transport proteins (ceruloplasmin, transferrin) in the liver – increased synthesis of protease inhibitors (α-macroglobulin) – leukocytosis Septic shock – massive penetration of microorganisms into the blood ( TNF) Anaphylactic shock – degranulation of basophils and activating allergen complement
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Removal of cells damaged by phagocytes – activation of fibroplastic mechanisms – activation of angiogenesis – tissue regeneration and remodeling
35 Phagocytosis = ability to absorb particles from the environment Professional phagocytes * cells that provide protection by the phagocytosis mechanism * Neutrophil and eosinophilic granulocytes, monocytes and macrophages granulocytes – protection against extracellular pathogens that may play effector functions (MHCpg is not immediately expressed by neutrophils other than APC) macrophages – their own removal of apoptotic cells, protection against certain intracellular parasites, fully functional after cytokine (IFNg, TNF) activation
36 Intersection of phagocytes in damaged and infected tissues 7% neutrophils and peripheral phagocytes 93% neutrophils and phagocytes in bone marrow * this proportion changes due to inflammatory cytokines and bacterial products * phagocytes are recruited to the endothelium at the site of injury (due to adhesion molecules, the expression of inflammatory cytokines is higher) * the first interaction slows down the movement of neutrophils, called rolling,
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38 * then there is a stronger binding between endothelial cells and leukocytes and further penetration between endothelial cells into the tissue – diapedesis, extravasation * phagocytes are targeted to the site of inflammation by chemokines (IL-8, MIP-1a and b, MCP-1, RANTES, C3a, C5a , bacterial products…), whose receptors are phagocytes
39 Phagocyte receptors PAMPs – “pathogen-associated molecular pattern” structures located on the surface of microorganisms but not on their own intact cells * mannose receptor * galactose receptor * CD14 (binds bacterial LPS)
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