Immune systemImmune system

J. Ochotná

The main functions of the immune The main functions of the immune systemsystem

Immune system belongs to the basic homeostatic Immune system belongs to the basic homeostatic mechanisms mechanisms

DefenseDefense - identification and protection against pathogenic - identification and protection against pathogenic microorganisms and their toxinsmicroorganisms and their toxins

AutotoleranceAutotolerance – recognition of own tissues and keeping – recognition of own tissues and keeping tolerance to themtolerance to them

Immune surveillanceImmune surveillance - identifying and removing the old , - identifying and removing the old ,

damaged and otherwise changed cellsdamaged and otherwise changed cells

Antigen (immunogen)Antigen (immunogen)

** substance that the immune system recognizes and substance that the immune system recognizes and

responds to it responds to it

** usually proteins or polysaccharides (lipids and nucleic usually proteins or polysaccharides (lipids and nucleic

acids only in the combination with proteins or acids only in the combination with proteins or polysaccharides) polysaccharides)

** Molecules <5 kDa can´t trigger an immune response, Molecules <5 kDa can´t trigger an immune response,

the optimal size of the antigen molecules to initiate the optimal size of the antigen molecules to initiate immune response is about 40 kDa immune response is about 40 kDa

** autoantigen autoantigen - antigen derived from his own body- antigen derived from his own body

** exoantigenexoantigen - alien substance from the external environment - alien substance from the external environment

allergen - exoantigen that in susceptible individuals may allergen - exoantigen that in susceptible individuals may cause pathological (allergic) immune response cause pathological (allergic) immune response

Haptens Haptens

** small molecules, that are able to induce specific small molecules, that are able to induce specific

immune response only immune response only after the establishment after the establishment to the macromolecular carrier to the macromolecular carrier (separate haptens are not immunogenic) (separate haptens are not immunogenic)

** typically drugs (eg penicillin antibiotics, hydralazin) typically drugs (eg penicillin antibiotics, hydralazin)

Interaction antigen – antibodyInteraction antigen – antibody

* Binding site of antibody Binding site of antibody ((paratopparatop))

form non-covalent complexes with form non-covalent complexes with the corresponding part on antigen the corresponding part on antigen molecule molecule ((epitopeepitope))

** participation: the hydrogen bonds, electrostatic participation: the hydrogen bonds, electrostatic

and hydrophobic interactions, van der Waals forces and hydrophobic interactions, van der Waals forces

** antigen-antibody complex is reversible antigen-antibody complex is reversible

Types of antigens according to Types of antigens according to antigen presentationantigen presentation

1) thymus dependent antigens1) thymus dependent antigens

* more frequently, mostly protein Agmore frequently, mostly protein Ag

** for specific humoral immune response to antigen for specific humoral immune response to antigen

is necessary to cooperate with T is necessary to cooperate with THH lymphocytes lymphocytes

(or response isn´t enough effective) (or response isn´t enough effective)

** assistance implemented in the form of cytokines assistance implemented in the form of cytokines

produced by T produced by THH lymphocytes lymphocytes

Types of antigens according to Types of antigens according to antigen presentationantigen presentation

2) thymus independent antigens2) thymus independent antigens

* in a small number of antigens can be induced antibodies in a small number of antigens can be induced antibodies

production directly without the participation of T lymphocytes production directly without the participation of T lymphocytes

** this are mainly a bacterial polysaccharides, this are mainly a bacterial polysaccharides,

lipopolysaccharides and polymer forms of proteins lipopolysaccharides and polymer forms of proteins (e.g. Haemophilus, Str.pneumoniae) (e.g. Haemophilus, Str.pneumoniae)

SuperantigensSuperantigens

* stimulate lymphocytesa stimulate lymphocytesa

polyclonaly and massively polyclonaly and massively

** massive activation of T lymphocytes massive activation of T lymphocytes

can cause shock can cause shock

** e.g. bacterial toxins (Staph.aureus, Str.pyogenes, e.g. bacterial toxins (Staph.aureus, Str.pyogenes,

Pseud.aeruginosa) Pseud.aeruginosa)

Sequestered antigensSequestered antigens

* autoantigens that are normallyautoantigens that are normally hidden from the immune hidden from the immune

system and therefore unknow (e.g. the lens of the eye , system and therefore unknow (e.g. the lens of the eye , testes,brain) testes,brain)

** if they are "uncovered" by demage, can induce the if they are "uncovered" by demage, can induce the

immune response (one of the theories of autoimmune immune response (one of the theories of autoimmune processes) processes)

Components of the immune Components of the immune systemsystem

Components of the immune Components of the immune systemsystem

** Lymphoid tissues and organs Lymphoid tissues and organs

** Cells of the immune system Cells of the immune system

** Molecules of the immune system Molecules of the immune system

Lymphoid tissues and organsLymphoid tissues and organs

** are linked with the other organs and tissues by network are linked with the other organs and tissues by network

of lymphatic and blood vessels of lymphatic and blood vessels

Primary lymphoid tissues and organsPrimary lymphoid tissues and organs

** bone marrow, thymusbone marrow, thymus

** place of maturation and differentiation of immunocompetent place of maturation and differentiation of immunocompetent

cells cells

** immature lymphocytes acquire here their antigenic specificity immature lymphocytes acquire here their antigenic specificity

Secondary lymphoid tissues and organsSecondary lymphoid tissues and organs

* * meeting place of immunocompetent cells with Agmeeting place of immunocompetent cells with Ag

spleenspleen - in contrast to the lymph nodes filter the blood and - in contrast to the lymph nodes filter the blood and captures presented antigenscaptures presented antigens

lymph nodeslymph nodes and their organized clusters (tonsils, and their organized clusters (tonsils, appendix, Peyer patches in the intestine) - filter lymph and appendix, Peyer patches in the intestine) - filter lymph and capture present antigens capture present antigens MALT MALT (mucous associated lymphoid tissue) - diffuse (mucous associated lymphoid tissue) - diffuse lymphatic tissue, the main role is capture of antigens that lymphatic tissue, the main role is capture of antigens that penetrate through the mucous membranepenetrate through the mucous membrane

Cells of the immune systemCells of the immune system

** development of red and white blood cells begin at yolk development of red and white blood cells begin at yolk

sack, then haematopoiesis travels to fetal liver sack, then haematopoiesis travels to fetal liver and spleen (3 to 7 month gestation), the main and spleen (3 to 7 month gestation), the main hematopoietic function has hematopoietic function has bone marrowbone marrow

** all blood cells arise from a pluripotent stem cell (CD 34) all blood cells arise from a pluripotent stem cell (CD 34)

** stem cells self-renew and maintain throughout life stem cells self-renew and maintain throughout life

** haematopoiesis is regulated by cytokines that are haematopoiesis is regulated by cytokines that are

secreted by bone marrow stromal cells, activated T secreted by bone marrow stromal cells, activated THH cells cells

and macrophages and macrophages

Immune mechanismsImmune mechanisms

Nonspecific immune mechanismsNonspecific immune mechanisms

** non-adaptive, innate non-adaptive, innate

** evolutionarily older evolutionarily older

** no immunological memory no immunological memory

** in the presence of pathogens react quickly, in minutes in the presence of pathogens react quickly, in minutes

(based on molecules and cells which are in the body (based on molecules and cells which are in the body prepared in advance) prepared in advance)

** component cellular - phagocytes (some are APC), NK cells component cellular - phagocytes (some are APC), NK cells

humoral - complement, interferons, lectins humoral - complement, interferons, lectins and other serum proteins and other serum proteins

Specific immune mechanismsSpecific immune mechanisms

** adaptive, antigen-specific adaptive, antigen-specific

** evolutionarily youngerevolutionarily younger

** have immunological memoryhave immunological memory

** development of a full-specific immune response takes development of a full-specific immune response takes

several days even weeks several days even weeks

** component cellular - T lymphocytes (TCR) component cellular - T lymphocytes (TCR)

humoral - antibodies humoral - antibodies

PhagocytosisPhagocytosis

PhagocytosisPhagocytosis= ability to absorb particles from the surroundings= ability to absorb particles from the surroundings

Professional phagocytesProfessional phagocytes

** cells, which provide defenses by mechanism of phagocytosis cells, which provide defenses by mechanism of phagocytosis

** neutrophilic and eosinophilic granulocytes, monocytes neutrophilic and eosinophilic granulocytes, monocytes

and macrophages and macrophages

granulocytesgranulocytes - defense against extracellular pathogens - defense against extracellular pathogens - able to perform effector functions immediately - able to perform effector functions immediately - neutrophils don´t express MHCgpII (not APC) - neutrophils don´t express MHCgpII (not APC)

macrophagesmacrophages - removal of own apoptotic cells, - removal of own apoptotic cells, defense against certain intracellular parasites defense against certain intracellular parasites - fully functional after activation by cytokines - fully functional after activation by cytokines (IFN (IFN, TNF), TNF)

The intersection of phagocytesThe intersection of phagocytesin damaged and infected tissuesin damaged and infected tissues 7% of peripheral neutrophils and phagocytes7% of peripheral neutrophils and phagocytes93% neutrophils and phagocytes in the bone marrow93% neutrophils and phagocytes in the bone marrow

** this ratio changes due to inflammatory cytokines this ratio changes due to inflammatory cytokines

and bacterial products and bacterial products

** in place of damage are captured phagocytes in place of damage are captured phagocytes

to endothelium (due to inflammatory cytokine expression to endothelium (due to inflammatory cytokine expression of of adhesion moleculesadhesion molecules is higher) is higher)

** the first is interactions slows the movement of neutrophils the first is interactions slows the movement of neutrophils

- called - called rolingroling,,

** then there is a stronger link between endothelial then there is a stronger link between endothelial

cells and leukocytes and subsequent penetration between cells and leukocytes and subsequent penetration between endothelial cells to the tissue - endothelial cells to the tissue - diapedesis , extravasationdiapedesis , extravasation

** phagocytes are directed to the site of inflammation by phagocytes are directed to the site of inflammation by

chemokineschemokines (IL-8, MIP-1 (IL-8, MIP-1 and and, MCP-1, RANTES, , MCP-1, RANTES, C3a, C5a, bacterial products ...), C3a, C5a, bacterial products ...), for which phagocytes have receptors for which phagocytes have receptors

Receptors on phagocytesReceptors on phagocytes

PAMPsPAMPs - "pathogen associated molecular patterns„- "pathogen associated molecular patterns„ - structures that are located on the surface of - structures that are located on the surface of microorganisms, but not on their own intact cells microorganisms, but not on their own intact cells

* * mannose receptormannose receptor* * galactose receptorgalactose receptor* * CD14CD14 (binds bacterial LPS) (binds bacterial LPS)* receptors of * receptors of TLRTLR group (binds bacterial lipoproteins, group (binds bacterial lipoproteins, lipopolysaccharides, bacterial DNA) lipopolysaccharides, bacterial DNA)* * scavenger receptorsscavenger receptors (bind phospholipids on the surface (bind phospholipids on the surface of apoptotic cells) of apoptotic cells)

Opsonization - process, which increases the efficiency - process, which increases the efficiency of foreign particles phagocytosis of foreign particles phagocytosis - the establishment of opsonins (IgG, IgA, - the establishment of opsonins (IgG, IgA, C3b, MBL, fibronectin, fibrinogen, CRP, C3b, MBL, fibronectin, fibrinogen, CRP, SAP) on the surface of foreign particles SAP) on the surface of foreign particles

* * Fc receptorsFc receptors on phagocytes (recognize antibodies linked on phagocytes (recognize antibodies linked to surface of micro-organism) to surface of micro-organism)

* * complement receptorscomplement receptors (for binding C3b) (for binding C3b)

Liquidation of absorbed organismLiquidation of absorbed organism* fusion of fagosome with lysosomesfusion of fagosome with lysosomes lysosomes contains - bactericidal substances (defensins) - hydrolytic enzymes (cathepsin, lysozyme) - liquid with a pH of 4-5

* activation of membrane NADPH oxidaseactivation of membrane NADPH oxidase after activation after activation of Fc receptors and complement receptors, which leads of Fc receptors and complement receptors, which leads to to respiratory (oxidative) flashrespiratory (oxidative) flash, when arise , when arise reactive oxygen reactive oxygen intermediatesintermediates (superoxid radical O (superoxid radical O22-, singlet oxygen, hydrogen -, singlet oxygen, hydrogen

peroxide, hydroxyl radical), which damage the structure of peroxide, hydroxyl radical), which damage the structure of biopolymers, enzymes and DNA of microorganisms; biopolymers, enzymes and DNA of microorganisms; enzyme myeloperoxidaseenzyme myeloperoxidase catalyses the reaction of Hcatalyses the reaction of H22OO2 2 withwith ClCl--

to form chlornan anions (ClO-) to form chlornan anions (ClO-)* production of nitric oxide (NO)production of nitric oxide (NO) -macrophages produce NO after macrophages produce NO after activation with cytokines (IFN activation with cytokines (IFN, TNF) that are produced by T, TNF) that are produced by THH1 1

lymphocytes, NO liquidate intracellular parasites of macrophages lymphocytes, NO liquidate intracellular parasites of macrophages

Secretory products of phagocytesSecretory products of phagocytes

* IL-1, 6, TNF (systemic response to inflammation)* IL-1, 6, TNF (systemic response to inflammation)

* IL-8 (chemokine)* IL-8 (chemokine)

* IL-3, GM-CSF (control haematopoiesis)* IL-3, GM-CSF (control haematopoiesis)

* TGF* TGF, TGF, TGF (helping healing of tissues) (helping healing of tissues)

* metabolic products of arachidonic acid (prostaglandins, * metabolic products of arachidonic acid (prostaglandins, prostacyclin, leukotrienes and thromboxanes prostacyclin, leukotrienes and thromboxanes

ComplementComplement

ComplementComplement

* * system of about 30 serum and membrane proteins system of about 30 serum and membrane proteins (humoral component of nonspecific immunity) (humoral component of nonspecific immunity)

* * complement components in serum are present in inactive formcomplement components in serum are present in inactive form

* * complement activation has cascade charactercomplement activation has cascade character

* * complement proteins are synthesized in the liver, less by tissue complement proteins are synthesized in the liver, less by tissue macrophages and fibroblasts macrophages and fibroblasts

* * the main complement componentsthe main complement components: C1-C9 (C3 is the central : C1-C9 (C3 is the central component) component)

* * other complement componentsother complement components: factor B, factor D, factor P: factor B, factor D, factor P

* * regulatory proteinsregulatory proteins: C1 - inhibitor, factor I, factor H, DAF, MCP, : C1 - inhibitor, factor I, factor H, DAF, MCP, CR1, CD59 (protektin) inactivator of anafylatoxin CR1, CD59 (protektin) inactivator of anafylatoxin

Function of complementFunction of complement

* * OpsonizationOpsonization (C3b) (C3b)

* * ChemotaxisChemotaxis (C3a, C5a) (C3a, C5a)

* * Osmotic lysisOsmotic lysis (MAC C5b-C9) (MAC C5b-C9)

* * AnafylatoxinsAnafylatoxins (C3a, C4a, C5a) (C3a, C4a, C5a)

Complement activationComplement activation

* Alternative pathway* Alternative pathway

* Clasial pathway* Clasial pathway

* Lektin pathway* Lektin pathway

An alternative pathwayAn alternative pathway

* C3 component of complement rarely spontaneously breaks * C3 component of complement rarely spontaneously breaks into C3b and C3a into C3b and C3a* C3b can covalently bind on the surface of microorganism * C3b can covalently bind on the surface of microorganism * to bound C3b join a factor B, which is cleaved by factor D * to bound C3b join a factor B, which is cleaved by factor D to Ba and Bb, resulting complex C3bBb is stabilized by to Ba and Bb, resulting complex C3bBb is stabilized by factor P and functions as an factor P and functions as an alternative C3 convertasealternative C3 convertase* C3 convertase cleaves C3 to C3a (chemotactic for * C3 convertase cleaves C3 to C3a (chemotactic for phagocytes) and C3b, which binds to the surface of the phagocytes) and C3b, which binds to the surface of the microorganism (opsonization), or gives rise to other microorganism (opsonization), or gives rise to other C3 convertases C3 convertases* from some C3 convertases form C3bBbC3b that act as* from some C3 convertases form C3bBbC3b that act as an an alternative C5 convertasealternative C5 convertase, which cleaves C5 to C5a , which cleaves C5 to C5a (chemotaxis) and C5b (starts terminal lytic phase) (chemotaxis) and C5b (starts terminal lytic phase)

Classical pathwayClassical pathway

* Can be initiated by antibodies (IgG, not by IgG4; IgM)* Can be initiated by antibodies (IgG, not by IgG4; IgM) or so-called pentraxins (CRP, SAP - acute phase or so-called pentraxins (CRP, SAP - acute phase proteins) proteins)* after binding of antibodies to the bacteria surface, there is * after binding of antibodies to the bacteria surface, there is

a change in its conformation and C1 protein can bind a change in its conformation and C1 protein can bind * C1 have to bind to the 2 molecules of antibodies, change * C1 have to bind to the 2 molecules of antibodies, change their conformation and get proteolytic activity - will cleave their conformation and get proteolytic activity - will cleave proteins C4 and C2 proteins C4 and C2* fragments C4b and C2a bind to the surface of organism * fragments C4b and C2a bind to the surface of organism and create the and create the classic C3 convertaseclassic C3 convertase (C4bC2a), which (C4bC2a), which cleaves C3 to C3a and C3b cleaves C3 to C3a and C3b* then creates a * then creates a classic C5 convertaseclassic C5 convertase (C4bC2aC3b) that (C4bC2aC3b) that cleaves C5 to C5a and C5b cleaves C5 to C5a and C5b

Lektin pathwayLektin pathway

* is initiated by serum mannose binding lectin (MBL)* is initiated by serum mannose binding lectin (MBL)

* MBL binds to carbohydrate structures on the surface* MBL binds to carbohydrate structures on the surface of some microbes, after the bindins starts cleave C4 of some microbes, after the bindins starts cleave C4 and C2 and C2

* this way is similar to the classical way* this way is similar to the classical way

Terminal (lytic) phase of the Terminal (lytic) phase of the complement cascadecomplement cascade

C5b fragments creates a complex with C6, C7 and C8, the C5b fragments creates a complex with C6, C7 and C8, the complex dive into the lipid membrane of the cell and attached complex dive into the lipid membrane of the cell and attached to it into a circle 13-18 molecules of C9, thus create in the to it into a circle 13-18 molecules of C9, thus create in the membrane pores and cell can lysis (G-bacteria, protozoans, membrane pores and cell can lysis (G-bacteria, protozoans, some viruses). some viruses).

Most microorganisms is to this lytic effect of complement Most microorganisms is to this lytic effect of complement resistant (protection by cell wall).resistant (protection by cell wall).

Regulation of complement and Regulation of complement and protection of own cellsprotection of own cells

Activation of complement cascade is controlled by the plasma Activation of complement cascade is controlled by the plasma and membrane inhibitors.and membrane inhibitors.

* * C1 inhibitorC1 inhibitor

* * DAFDAF (decay-accelerating protein)-degradation of C3 convertase (decay-accelerating protein)-degradation of C3 convertase

* * factor I, MCPfactor I, MCP (membrane cofactor protein), (membrane cofactor protein), CR1, factor HCR1, factor H – – C3b cleavage C3b cleavage

* * CD 59CD 59 (protectin) - prevents the polymerization of C9 (protectin) - prevents the polymerization of C9

* * inactivator of anafylatoxininactivator of anafylatoxin - inactivates anafylatoxins (C3a, - inactivates anafylatoxins (C3a, C4a, C5a) C4a, C5a)

Complement receptorsComplement receptors

* Bind fragments of complement components* Bind fragments of complement components

CR1CR1 - on various cells - on various cells - removing of immunecomplexes - removing of immunecomplexes

CR2CR2 - on B lymphocytes and FDC - on B lymphocytes and FDC - activation of B cells - activation of B cells

CR3, CR4CR3, CR4 - on phagocytes - on phagocytes - participation in opsonization, adhesion - participation in opsonization, adhesion

NK cellsNK cells

InterferonsInterferons

NK cellsNK cells Part of antigen non-specific mechanisms Part of antigen non-specific mechanisms (innate) (innate)

They do not have antigen-specific receptors They do not have antigen-specific receptors

Recognize cells that have abnormally low Recognize cells that have abnormally low MHCgpI MHCgpI expression (some tumor and virus infected cells) expression (some tumor and virus infected cells)

They are able to kill quickly - without prior They are able to kill quickly - without prior stimulation, proliferation and differentiation stimulation, proliferation and differentiation

Activators of NK cells - IFNActivators of NK cells - IFN, IFN, IFN

Activating receptorsActivating receptors - Some surface lectins, - Some surface lectins, Fc receptor CD16 Fc receptor CD16 ADCCADCC (antibody-dependent cellular cytotoxicity) NK cells (antibody-dependent cellular cytotoxicity) NK cells recognize cell opsonized IgG antibody through the Fc recognize cell opsonized IgG antibody through the Fc receptor CD16, this leads to the activation of cytotoxic receptor CD16, this leads to the activation of cytotoxic mechanisms (NK degranulation) mechanisms (NK degranulation)

Inhibitory receptorsInhibitory receptors - Signals provided through these - Signals provided through these receptors inhibit the cytotoxic mechanisms (recognize receptors inhibit the cytotoxic mechanisms (recognize MHC gpI)MHC gpI)

Imunoglobulin familyImunoglobulin family - KIR (killer - KIR (killer

inhibitor receptors)inhibitor receptors) C-type lektin familyC-type lektin family - eg CD94/NKG2 - eg CD94/NKG2

NK cells receptorsNK cells receptors

NK cell cytotoxic mechanismsNK cell cytotoxic mechanisms

The resulting reaction of NK cell after meeting The resulting reaction of NK cell after meeting with another cell depends on which signal prevail, with another cell depends on which signal prevail, whether activating or inhibitory signals whether activating or inhibitory signals

Cytotoxic granulesCytotoxic granules contain perforin and contain perforin and granzyme (perforin creates pores in the granzyme (perforin creates pores in the cytoplasmic membrane of target cells, in some cytoplasmic membrane of target cells, in some cases may cause osmotic lysis of the target cell, cases may cause osmotic lysis of the target cell, formed pores in the cell receiving granzymes, formed pores in the cell receiving granzymes, that cause the target cell to die by that cause the target cell to die by apoptosisapoptosis. .

Fas ligandFas ligand (FasL) - which binds to the apoptotic (FasL) - which binds to the apoptotic receptor Fas (CD95) presented on the surface of receptor Fas (CD95) presented on the surface of many different cellsmany different cells

TNFTNF

InterferonsInterferons Belongs to the humoral component of non-specific Belongs to the humoral component of non-specific

mechanismsmechanisms IFNIFN - produced by virus infected lymphocytes, - produced by virus infected lymphocytes,

monocytes and macrophagesmonocytes and macrophages IFNIFN - produced by virus-infected fibroblasts and - produced by virus-infected fibroblasts and

epithelial cellsepithelial cells IFNIFN and IFN and IFN- bind to receptors on the surface of - bind to receptors on the surface of

infected and healthy cells and induce in them an infected and healthy cells and induce in them an antiviral state (synthesis of enzymes that block antiviral state (synthesis of enzymes that block viral replication in the cell) viral replication in the cell)

IFNIFN - produced by T - produced by THH1 cells, has regulatory 1 cells, has regulatory function, activates macrophages and stimulates the function, activates macrophages and stimulates the expression of MHCgpexpression of MHCgp

Basophils and mast cells Basophils and mast cells

and their importance in and their importance in

immune responsesimmune responses

Mast cellsMast cells

Mucosal mast cellsMucosal mast cells - in the mucous - in the mucous membranes of respiratory and membranes of respiratory and gastrointestinal tract, participate in gastrointestinal tract, participate in parasitosis and allergy parasitosis and allergy

CConnective tissue mast cellsonnective tissue mast cells - the - the connective tissue, in parasitosis and connective tissue, in parasitosis and allergy are not participating allergy are not participating

Mast cell functionsMast cell functions

Defense against parasitic infectionsDefense against parasitic infections

In pathological circumstances, responsible for the In pathological circumstances, responsible for the early type of hypersensitivity (immunopathological early type of hypersensitivity (immunopathological reaction typeI)reaction typeI)

Apply during inflammation, in angiogenesis, in Apply during inflammation, in angiogenesis, in tissue remodeling tissue remodeling

Regulation of immune responseRegulation of immune response

Mast cell activation Mast cell activation

Mast cells can be stimulated to degranulate:Mast cells can be stimulated to degranulate:

cross-linking of IgE Fc receptorscross-linking of IgE Fc receptors

anafylatoxinsanafylatoxins (C3a, C4a, C5a) (C3a, C4a, C5a)

by direct injuryby direct injury (opioids, alcohols, and (opioids, alcohols, and

certain antibiotics)certain antibiotics)

Mast cell activation by cross-Mast cell activation by cross-linking of IgE Fc receptorslinking of IgE Fc receptors

Establishing of multivalent antigen (multicellular parasite) Establishing of multivalent antigen (multicellular parasite) to IgE linked to highaffinnity to IgE linked to highaffinnity Fc receptor for IgEFc receptor for IgE (Fc (FcRI) RI)

Aggregation of several molecules FcAggregation of several molecules FcRI RI

Initiate mast cell degranulation (cytoplasmic granules Initiate mast cell degranulation (cytoplasmic granules mergers with the surface membrane and release their mergers with the surface membrane and release their contents) contents)

Activation of arachidonic acid metabolism (leukotriene C4, Activation of arachidonic acid metabolism (leukotriene C4, prostaglandin D2) prostaglandin D2)

Start of production of cytokines (TNF, TGFStart of production of cytokines (TNF, TGF, IL-4, 5,6 ...) , IL-4, 5,6 ...)

Activation schema of mast cellActivation schema of mast cell

Secretory products of mast cellsSecretory products of mast cells

Cytoplasmatic granulesCytoplasmatic granules: hydrolytic enzymes, : hydrolytic enzymes, proteoglycans (heparin, chondroitin sulphate), biogenic proteoglycans (heparin, chondroitin sulphate), biogenic amines (histamine, serotonin) amines (histamine, serotonin)

Histamine causes vasodilation, increased vascular Histamine causes vasodilation, increased vascular permeability, erythema, edema, itching, contraction of permeability, erythema, edema, itching, contraction of bronchial smooth muscle, increases intestinal peristalsis, bronchial smooth muscle, increases intestinal peristalsis, increased mucus secretion of mucosal glands in the increased mucus secretion of mucosal glands in the respiratory tract and GIT (helps eliminate the parasite) respiratory tract and GIT (helps eliminate the parasite)

Arachidonic acid metabolitesArachidonic acid metabolites (leukotriene C4, (leukotriene C4, prostaglandin D2) prostaglandin D2)

Cytokines Cytokines (TNF, TGF (TNF, TGF , IL-4, 5,6 ...), IL-4, 5,6 ...)

The role of mast cells in development of The role of mast cells in development of allergyallergy

BasophilsBasophils

Differentiate from myeloid precursor Differentiate from myeloid precursor

They are considered to be the circulating form of They are considered to be the circulating form of mast mast

Receptor equipment, containing granules, the Receptor equipment, containing granules, the mechanisms of stimulation and functions are very mechanisms of stimulation and functions are very similar to mast cellssimilar to mast cells

They are responsible for the emergence of They are responsible for the emergence of anaphylactic shock anaphylactic shock