Defense against Defense against

extracellular pathogensextracellular pathogens

Defence against extracellular pathogensDefence against extracellular pathogens

bacteria (gram-negative, gram-positive cocci, bacilli), bacteria (gram-negative, gram-positive cocci, bacilli),

unicellular parasitesunicellular parasites

complementcomplement activation stimulated by bacterial cell activation stimulated by bacterial cell

wallwall

phagocytosis by neutrophil granulocytesphagocytosis by neutrophil granulocytes

opsonizationopsonization (C3b, lectins, antibodies ...) enhance (C3b, lectins, antibodies ...) enhance

phagocytosisphagocytosis

OpsonisationOpsonisation

Phagocytes are attracted to the site of infection by Phagocytes are attracted to the site of infection by

chemotactic substances (C5a, C3a and chemotactic chemotactic substances (C5a, C3a and chemotactic

products of bacteria)products of bacteria)

absorbed bacteria are destroyed by the microbicidal absorbed bacteria are destroyed by the microbicidal

systems systems

(products of NADP-H oxidase, hydrolytic enzymes and (products of NADP-H oxidase, hydrolytic enzymes and

bactericidal substances in lysosomes) bactericidal substances in lysosomes)

phagocytes produce proinflammatory cytokines phagocytes produce proinflammatory cytokines

(IL-1, IL-6, TNF) that induce an increase in (IL-1, IL-6, TNF) that induce an increase in

temperature, metabolic response of the organism and temperature, metabolic response of the organism and

synthesis of acute phase proteinssynthesis of acute phase proteins

PhagocytosisPhagocytosis

in later stages of infection are stimulated antigen-in later stages of infection are stimulated antigen-

specific mechanisms specific mechanisms

plasma cells initially plasma cells initially produce IgMproduce IgM isotype after isotype after

isotype switching produce isotype switching produce IgG1IgG1 and and IgAIgA

(opsonization) (opsonization)

sIgA protect against intestinal and respiratory sIgA protect against intestinal and respiratory

infections by bacteria infections by bacteria

bacteria with a polysaccharide capsule may cause bacteria with a polysaccharide capsule may cause

T-independent IgM antibody production (after the T-independent IgM antibody production (after the

establishment to the bacteria activate the classical establishment to the bacteria activate the classical

complement path) complement path)

after infection persist IgG, IgA (protective effect) after infection persist IgG, IgA (protective effect) and memory T and B lymphocytes and memory T and B lymphocytes

in the defense against bacterial toxins apply in the defense against bacterial toxins apply neutralizing antibodies (Clostridium tetani and neutralizing antibodies (Clostridium tetani and botulinum ...) botulinum ...)

"indirect toxins - bacterial Lipopolysaccharide "indirect toxins - bacterial Lipopolysaccharide (LPS) stimulates big number of monocytes to (LPS) stimulates big number of monocytes to release TNF, which can cause septic shock release TNF, which can cause septic shock

extracellular bacterial infections are especially at extracellular bacterial infections are especially at risk individuals with disorders in the function of risk individuals with disorders in the function of phagocytes, complement and antibody phagocytes, complement and antibody production production

Defense against Defense against

intracellular pathogensintracellular pathogens

Defense against intracellular Defense against intracellular pathogenspathogens

bacteria, fungi and unicellular parasites bacteria, fungi and unicellular parasites

intracellular parasites are resistant to the intracellular parasites are resistant to the

microbicidal mechanisms of phagocytes microbicidal mechanisms of phagocytes

macrophagesmacrophages, which absorbed them, produce IL-12 → , which absorbed them, produce IL-12 →

TTHH11 differentiation, production of IFN differentiation, production of IFN and membrane and membrane

TNF → activation of macrophages and induction of TNF → activation of macrophages and induction of

iNOS iNOS

Defense against intracellular Defense against intracellular pathogenspathogens

in the defense against intracelular parasites, in the defense against intracelular parasites, which escape from phagolysosomes apply which escape from phagolysosomes apply TTCC lymphocyteslymphocytes

intracellular microorganisms infections are at risk intracellular microorganisms infections are at risk individuals with certain disorders of phagocytes individuals with certain disorders of phagocytes and defects of T lymphocytes and defects of T lymphocytes

Defense against intracellular Defense against intracellular pathogenspathogens

Anti-viral defenseAnti-viral defense

Anti-viral defenceAnti-viral defence

interferonsinterferons - in infected cells is induced - in infected cells is induced

production of IFNproduction of IFN and IFN and IFN (prevents viral (prevents viral

replication and in uninfected cells cause the replication and in uninfected cells cause the

anti-virus status); IFNanti-virus status); IFN stimulates the stimulates the

conversion to activated macrophages (iNOS)conversion to activated macrophages (iNOS)

IFNIFN and IFN and IFNinduce proliferation ofinduce proliferation ofNK NK

cellscells

Anti-viral defence - interferonsAnti-viral defence - interferons

NK cellsNK cells - ADCC - ADCC (Antibody-dependent cell- (Antibody-dependent cell-

mediated cytotoxicity) = cytotoxic reaction mediated cytotoxicity) = cytotoxic reaction

depends on the antibodies; the NK-lymphocyte depends on the antibodies; the NK-lymphocyte

recognizes cell opsonized with IgG by stimulation recognizes cell opsonized with IgG by stimulation

Fc receptor CD16 and then activate cytotoxic Fc receptor CD16 and then activate cytotoxic

mechanisms (degranulation)mechanisms (degranulation)

infected macrophages produce infected macrophages produce IL-12IL-12 (a strong (a strong

activator of NK cells) activator of NK cells)

NK cell activationNK cell activation

in the defense against cytopathic viruses mostly in the defense against cytopathic viruses mostly applied applied antibodiesantibodies::

sIgAsIgA inhibit mucosal adhesion of viruses inhibit mucosal adhesion of viruses (defense against respiratory viruses and (defense against respiratory viruses and enteroviruses) enteroviruses)

neutralizing neutralizing IgGIgG and and IgMIgM antibodies antibodies activate activate the classical way of complement, which is the classical way of complement, which is capable capable of some viruses lysisof some viruses lysis

IgA IgA and and IgGIgG derived in viral infection have derived in viral infection have a preventive effect in secondary infection a preventive effect in secondary infection

Anti-viral defence - antibodiesAnti-viral defence - antibodies

effector effector TTCC lymphocytes lymphocytes destroy infected cells in destroy infected cells in direct contact (granzym/perforin; FasL) and by direct contact (granzym/perforin; FasL) and by produced cytokines (lymfotoxin) produced cytokines (lymfotoxin)

some viruses after infection integrate into the host some viruses after infection integrate into the host genome, where persist for years (varicella zoster, genome, where persist for years (varicella zoster, EBV, papillomavirus) EBV, papillomavirus)

by these infections are at risk individuals with T by these infections are at risk individuals with T lymphocyte lymphocyte immunodeficiency and with combined immune immunodeficiency and with combined immune disorders disorders

increased susceptibility to herpes infections in increased susceptibility to herpes infections in individuals with dysfunction of NK cellsindividuals with dysfunction of NK cells

Anti-viral defence – NK cells and Tc lymphocytesAnti-viral defence – NK cells and Tc lymphocytes

Defense against Defense against

multicellular parasitesmulticellular parasites

Defense against multicellular parasitesDefense against multicellular parasites

IgE, mast cells, basophils and eosinophilsIgE, mast cells, basophils and eosinophils

TTHH2 stimulation under the influence of IL-4 (mast 2 stimulation under the influence of IL-4 (mast cells and other APC stimulated by parasite)cells and other APC stimulated by parasite)

TTHH2 stimulate B cells with BCR-specific parasite 2 stimulate B cells with BCR-specific parasite antigensantigens

isotype switching under the influence of IL-4 to isotype switching under the influence of IL-4 to IgEIgE

IgE bind to FcIgE bind to FcRI on mast cells and basophils RI on mast cells and basophils („antigen-specific receptors“)(„antigen-specific receptors“)

establish of multivalent antigen (multicellular establish of multivalent antigen (multicellular parasite) using the IgE to highafinity Fc receptor parasite) using the IgE to highafinity Fc receptor for IgE (Fcfor IgE (FcRI) aggregation of several molecules RI) aggregation of several molecules FcFcRI RI

initiate mast cell degranulation (cytoplasmic initiate mast cell degranulation (cytoplasmic granules mergers with the surface membrane and granules mergers with the surface membrane and release release hydrolytic enzymes, proteoglycans, biogenic hydrolytic enzymes, proteoglycans, biogenic amines (histamine, serotonin)amines (histamine, serotonin)

activation of arachidonic acid metabolism activation of arachidonic acid metabolism (leukotriene C4, prostaglandin PGD2) - (leukotriene C4, prostaglandin PGD2) - amplification of inflammatory responsesamplification of inflammatory responses

cytokine production by mast cell (TNF, TGFcytokine production by mast cell (TNF, TGF, IL-4, , IL-4, 5,6 ...)5,6 ...)

Mast cell activationMast cell activation

Activation of mast cellActivation of mast cell

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

in later stages are activated Tin later stages are activated THH1 and are 1 and are produced antibodies of other classesproduced antibodies of other classes

eosinophilseosinophils fagocyte complexes of parasitic fagocyte complexes of parasitic

particles with IgE via their receptors for IgE particles with IgE via their receptors for IgE

eosinophils use against parasites extracellular eosinophils use against parasites extracellular bactericidal substances released from granules bactericidal substances released from granules (eosinophil cationic protein, protease) (eosinophil cationic protein, protease)

Defense against multicellular parasites - Defense against multicellular parasites - eosinophilseosinophils