1. Antiinfection immunity

2. Relationship between host and microorganism microorganisms - commensal - potential pathogens - pathogenic microorganisms - microorganisms can cause damage to the body by direct mechanisms (toxins, cytopathic effect), or indirect, which initiate harmful immune reactions In defense against various microorganisms are, despite a predominant type of immune response, involved all elements of nonspecific and specific immunity.

3. Use of receptors on host cells as a gateway of infection CD4 - HIV, herpesvirus7 CD21 (CR2) - EBV CD71 - hepatitis B virus CD81 - hepatitis C virus  1 integrins - Yersinia, pathogenic E. coli  3 integrins - Borrelia

4. Mechanisms of microorganisms escape before defense system - conceal the cells, integration into the genome and the persistence in the latent form (herpes viruses, retroviruses) - variability of surface molecules (influenza, HIV...) - suppression of MHC gp expression in infected cells (adenoviruses, herpes viruses) - suppression of Ag presentation (blocking cleavage antigen)

5. - suppression of inflammatory response by production of virus analogues of cytokines or their inhibitors - inhibition of complement by production of protective proteins (herpes), secretion of proteases, which inactivate C3a and C5a, cell wall protects against membranolytic effect of complement - cleavage of blocking sIgA antibodies - the use of cytokines produced by the host to create an optimal environment (TNF stimulates HIV replication)

6. - integration of the host's own molecules into the microbial wall (borrelia burgdorferi) - antigenic mimicry - surface structure mimic the structure of the host organism cells - inhibition of phagocytosis, inhibition of fusion phagosome with lysosomes; escape from phagosome to the cytoplasm, inhibition of acid pH inside phagolysosome - production of antagonistic peptides (hepatitis B virus, HIV)

7. Defense against extracellular bacteria - gram-negative, gram-positive cocci, bacilli - for their elimination is necessary opsonization (C3b, lectins, antibodies...) - neutrophilic granulocytes are chemotactic attracting to the site of the infection (C5a, C3a and chemotactic products of bacteria) - absorbed bacteria are destroyed by the microbicidal systems (products NADP-H oxidase, hydrolytic enzymes and bactericidal substances in lysosomes) - phagocytes production of proinflammatory cytokines (IL-1, IL-6, TNF) that induce an increase in temperature, metabolic response of the organism and synthesis of acute phase proteins

8. - in later stages of infection are stimulated antigen-specific mechanisms - plasma cells initially produce IgM isotype after isotype switching produce IgG1 and IgA (opsonization) - sIgA protect against intestinal and respiratory infections by bacteria - bacteria with a polysaccharide capsule may cause T-independent IgM antibody production (after the establishment to the bacteria activate the classical complement path) - after infection persist IgG, IgA (protective effect), and memory T and B lymphocytes

10. - in the defense against bacterial toxins apply neutralizing antibodies (Clostridium tetani and botulinum...) - "indirect toxins - bacterial Lipopolysaccharide (LPS) stimulates big number of monocytes to release TNF, which can cause septic shock - extracellular bacterial infections are especially at risk individuals with disorders in the function of phagocytes, complement and antibody production

11. Defense against intracellular bacteria and molds - intracellular parasitism is given by the ability of microorganisms to escape microbicidal mechanisms of phagocytes - mycobacteria, some yeasts and molds - macrophages, which absorbed them, produce IL-12 → T H 1 differentiation, production of IFN  and membrane TNF → activation of macrophages and induction of iNOS - plasma cells under the influence of IFN  produce IgG2, immune complexes containing IgG2 bind to Fc receptors on macrophages and thus stimulate - in the defense against intracelular parasites, which escape from phagolysosomes apply T C lymphocytes - intracellular microorganisms infections are at risk individuals with certain disorders of phagocytes and defects of T lymphocytes

12. Defense against viruses - interferons - in infected cells is induced production of IFN  and IFN  (prevents viral replication and in uninfected cells cause the anti-virus status); IFN  stimulates the conversion to activated macrophages (iNOS) - NK cells - ADCC (Antibody-dependent cell-mediated cytotoxicity) = cytotoxic reaction depends on the antibodies; the NK-lymphocyte recognizes cell opsonized with IgG by stimulation Fc receptor CD16 and then activate cytotoxic mechanisms (degranulation) - infected macrophages produce IL-12 (a strong activator of NK cells) - in the defense against cytopathic viruses mostly applied antibodies: - sIgA inhibit mucosal adhesion of viruses (defense against respiratory viruses and enteroviruses) - neutralizing IgG and IgM antibodies activate the classical way of complement, which is capable of some viruses lysis - IgA and IgG derived in viral infection have a preventive effect in secondary infection

13. - effector T C lymphocytes destroy infected cells in direct contact (granzym/perforin; FasL) and by produced cytokines (lymfotoxin) - some viruses after infection integrate into the host genome, where persist for years (varicella zoster, EBV, papillomavirus) - by these infections are at risk individuals with T lymphocyte immunodeficiency and with combined immune disorders - increased susceptibility to herpes infections in individuals with dysfunction of NK cells.

14. Defense against protozoa parasites - defense against protozoa parasites is similar to bacteria - extracellular parasites - antibodies - intracellular parasites - T H 1 lymphocytes and activated macrophages

15. Defense against multicelular parasites - contact of mast cells, basophils and eosinophils with parasite antigens - T H 2 stimulation under the influence of IL-4 (mast cells and other APC stimulated by parasite) - T H 2 stimulate B cells with BCR-specific parasite antigens - isotype switching under the influence of IL-4 in IgE - IgE bind to Fc  RI on mast cells and basophils (antigen-specific receptors) - establish of multivalent antigen (multicellular parasite) using the IgE to highafinity Fc receptor for IgE (Fc  RI)

16. - aggregation of several molecules Fc  RI - initiate mast cell degranulation (cytoplasmic granules mergers with the surface membrane and release their contents) - activation of arachidonic acid metabolism (leukotriene C4, prostaglandin PGD2) - amplification of inflammatory responses - start of production of cytokines (TNF, TGF , IL-4, 5,6...) by mast - in later stages are activated T H 1 and are produced antibodies of other classes - eosinophils fagocyte complexes of parasitic particles with IgE via their receptors for IgE - eosinophils use against parasites extracellular bactericidal substances released from granules (eosinophil cationic protein, protease)

18. Possibilities of the therapeutic effect on the immune system

19. Causal treatment a) stem cell transplantation - for serious congenital disorders of the immune system (some lymphoproliferative and myeloproliferative disorders) - complications: infectious complications Graft-versus-host - obtaining stem cells - the collection from shovel hip bone - from umbilical cord blood - from peripheral blood after stimulation with GM-CSF

20. b) gene therapy - with a suitable expression vector is introduced functional gene (to replace dysfunctional gen) into the lymphocytes or stem cells - used as a treatment for some cases of SCID

21. Substitution treatment - autologous stem cell transplantation following chemotherapy and radiotherapy - treatment with intravenous immunoglobulin (derived from plasma of blood donors) - substitution of C1 inhibitor for hereditary angioedema - substitution of erythropoietin in patients with chronic renal failure - substitution of G-CSF in agranulocytosis

22. Non-specific immunomodulation therapy Immunomodulation = medical procedure to adjust the disrupted immune function a) non-specific immunosuppressive therapy nonspecific = affects not only autoreactive and aloreactive lymphocytes, but also other components of immunity (risk of reduction antiinfectious and anti-tumor immunity) - used for treatment of autoimmune diseases, severe allergic conditions and for organ transplantation

23. corticosteroids - anti-inflammatory, immunosuppressive effects - blocking the activity of transcription factors (AP-1, NF  B) - suppress the expression of genes (IL-2, IL-1, phospholipase A, MHCgpII, adhesion molecules) - inhibition of histamine release from basophil - higher concentrations induce apoptosis immunosuppressants affecting the metabolism of DNA - cyclophosphamide - methotrexate immunosuppressant selectively inhibiting T lymphocyte - cyclosporin A (inhibits the expression of IL-2 and IL-2R in activated T lymphocytes) - monoclonal antibody anti-CD3 (immunosuppression after transplantation, treatment of rejection crises)

24. b) anti-inflammatory and antiallergic treatment nonsteroidal anti-inflammatory drugs antihistamines - blocking H1 receptor - reduce the expression of adhesion molecules - reduce the secretion of histamine... inhibitors of inflammatory cytokine - receptor antagonist for IL-1 - monoclonal antibodies against TNF - thalidomide (TNF inhibitor)

25. c) non-specific immunostimulant therapy imunostimulancia - stimulate the immune system synthetic immunomodulators - Methisoprinol (Isoprinosine) - used in viral infections with more severe or relapsing course bacterial extracts and lysates - Broncho-Vaxom - prevention of recurrent respiratory tract infections - Ribomunyl products of the immune system - IL-2 - renal adenocarcinoma - IFN , IFN  - viral hepatitis, some leukemia - Erythropoietin - G-CSF, GM-CSF - neutropenia

26. Antigen-specific immunomodulatory therapy specific immunomodulation = induce an immune response or tolerance against a specific antigen a) active immunization = use of antigen to induce an immune response that can later protect against a pathogen bearing the antigen (or antigen like him) - immunization vaccines made from inactivated or attenuated microorganisms or their antigens (polysaccharide capsule, toxins) - creates long-term immunity - activate cellular and antibody immunity - administration of antigen injectable, oral - prophylaxis - risk of causing infection or anaphylactic reactions

27. Active immunization DTP (diphtheria, tetanus, Pertussis) Haemophilus influenzae Neisseria meningitidis Pneumococci BCG (Bacillus Calmette-Guérin) MMR (measles, mumps, rubella) Poliomyelitis Hepatitis A, B experimentally implementing specific vaccination against cancer

28. b) passive immunization - natural - transfer of maternal antibodies in fetal blood - therapeutically - the use of animal antibodies against various toxins (snake toxins, tetanus toxin, botulinum toxin) - prophylaxis - the human immunoglobulin from immunized individuals (hepatitis A, rabies, tetanus) - Anti-RhD antibodies - preventing maternal immunization with RhD + fetus - provides a temporary (3 weeks) specific humoral immunity - the risk of inducing anaphylactic reactions

29. c) specific immunosuppression = induction of tolerance against a specific antigen the clinical studies: - induction of tolerance by oral administration of antigen - allergen immunotherapy (pollen, insect poisons)

30. THANK YOU FOR ATTENTION