Immunity against infection Institute of Immunology 2nd Faculty of Medicine Pragu

Immunity against infection Institute of Immunology 2nd Faculty of Medicine Pragu www.phwiki.com

Immunity against infection Institute of Immunology 2nd Faculty of Medicine Pragu

King, Jayme, Meteorologist has reference to this Academic Journal, PHwiki organized this Journal Immunity against infection Institute of Immunology 2nd Faculty of Medicine Prague 5- Motol Janeway’s Immunobiology 8th Edition / Kenneth Murphy Pathogenic microorganisms Parasites Protozoa Helmints Fungi mechanisms of pathogenicity immune escape mechanisms number of pathogens genes regulating immune responses health condition of the host Host-pathogen interaction

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Epithelial barriers against infection Mechanical (intact epithelial surface, longitudinal flow of air or fluid, movements of mucous by cilia) Chemical (skin – fatty acids, enzymes – lysozym in saliva or tears, pepsin in the gut, low pH, anti-bacterial peptides) Microbiological (normal microbiota – competition as long as nutrients, blocking of adhesion, production of anti-microbial substances ) Bordetella pertussis Mucosal immunity defence against invasion of pathogenic microorganisms defence against harmful inflammatory reactions against pathogens, but also against harmless environmental antigens (oral tolerance) 400 m2 Oral tolerance Default response to oral administration of antigens (food) Immune unresponsivness It can be overcome by administration of adjuvants Immune mechanisms of oral tolerance: Active suppression by T regulatory cells producing TGF-, IL-10 Clonal anergy Tolerogenic dendritic cells (CD103+)

Mucosal immune responses MALT (mucosa-associated lymphoid tissue) GALT, BALT, NALT o-MALT (organized, Peyer’s patches, lymphoid follicles, FAE) d-MALT (scattered, effector site, IEL, lamina propria lymfocyty) M-cells IgA IgA IgA binds to a secretory component in addition to is transported by transcytosis to the luminal surface of the epithelium Secretory IgA is resistant to proteolytic enzymes IgA binds unspecifically to bacteria Main function is to neutralize toxins in addition to to block adhesion of pathogens Anti-inflammatory effect (IgA does not activate complement) Sensitive to proteolysis by bacterial proteases (IgA1) (H.influenzae, N.gonorrheae) IgA1 (respiratory tract, serum – 87% monomeric, bone marrow) IgA2 (gastrointestinal tract, dimeric as long as m) production 24 mg/kg/day Immunoglobulin A Development of immune response to pathogens Host cellular receptors serve as portals of entry as long as pathogens mainly viruses (CD4 – HIV; CD21 – EBV) bacteria (CR3 – Mycobacterium, Bordetella; 1-integrins – Yersinia, E.coli)

Innate immunity in defence against pathogens Alternative in addition to lectin pathway of complement activation Production of interferons in addition to cytokines Local inflammatory response Production of acute-phase proteins Phagocytes Antigen-presenting cells (APC) Cytotoxic activity of NK cells T lymphocytes gama/delta B1 lymphocytes CD5+ NK-T lymphocytes Humoral innate immunity Cellular innate immunity Phagocytosis of M.tuberculosis Adaptive immunity in defence against pathogens Antigen-presenting cells (APC) Activation of T in addition to B lymphocytes Functional differentiation of T lymphocytes (Th1, Th2, Th17) Induction of cytotoxic T lymphocytes (CTL) Immunological memory (affinity maturation, memory lymphocytes, long-lasting presentation of immunocomplexes on FDC) Humoral adaptive immunity Cellular adaptive immunity antibodies cytokines Localization of infection in addition to type of immune response

Defence against extracellular bacteria Bacteria producing toxins (C.tetani, C.botulinum, C.diphtheriae) Polysaccharide capsule (Streptococci, Neisseria, Staphylococci) Opsonization – complement, lectin or antibodies Neutralization – antibodies Phagocytosis – neutrophils, macrophages B lymphocytes (IgM), Th2 response (IgA, IgG1) People with defect in phagocytosis, complement in addition to antibody production at risk bacteria with polysaccharide capsule dangerous as long as small children (up to 2y) in addition to people with a defective spleen function, or after splenectomy. Streptococcus pneumoniae Defence against Streptococcus pyogenes primary pathogenic, human is a carrier toxin production neutralization M protein – resistance to phagocytosis opsonization autoimmune-mediated complications: cross-reactivity of antibodies against M protein with host proteins rheumatic fever, glumerulonephritis Semmelweiss – childbed fever antiseptic procedures Defence against intracellular bacteria Intracellular parasites e.g Listeria, Mycobacterium, Brucella Phagocytosis – macrophages Antibodies are inefficient Th1 response (IFN- production to activate macrophages) Th17 response (IL-17 production as long as neutrophils recruitment) Cytotoxic T lymphocytes (Listeria monocytogenes) People with defects of innate in addition to adaptive immunity at risk Pathology: granulomas M. tuberculosis

Defence against viruses Obligatory intracellular parasites Interferons in addition to Neutralizing antibodies Complement activation (virolysis) B lymphocytes a Th2 response Activity of NK cells Th1 response Cytotoxic T lymphocytes (CTL) People with T cell immunodeficiency, combined immunodeficiencies in addition to defect in NK cell function (herpesviruses) at risk Influenza virus HIV Defence against fungi Aspergillus fumigatus C in addition to ida albicans Opportunistic pathogens Neutrophils, macrophages Th1 response (IFN- production to activate macrophages) Th17 response (IL-17 production as long as neutrophils recruitment) Antibodies are inefficient Systemic disease only in immunocompromised individuals Pneumocystis jirovecii (carinii) Defence against protozoan infections Chronic non-symptomatic latent infection Antigenic variation, different developmental stages Intracellular (Plasmodium, Trypanosoma, Leishmania, Toxoplasma) Th1 lymphocytes in addition to activated macrophages Extracellular (Entameba, Giardia, Trichomonas) Antibodies Cytokine milieu determines the outcome of infection (Th1) Clinical manifestation when immune system is compromised or weakend Trypanosoma Trichomonas

Defence against helminths chronic persistent infection (e.g tapeworm, roundworm, pinworms) High morbidity, low mortality reinfection Mastocytes, eosinophils (extracellular bactericidal substances) Th2 response, antibody IgE later Th1 response (macrophages), CTL Pathology: Formation of immunocomplexes Auto-antibodies, granulomas Allergic reactions tapeworm roundworm Immune escape mechanisms of pathogens Antigenic variation (Influenza virus, S.pneumoniae, Trypanosoma) Antigenic mimicry (mimic the structures of host cells) – M protein (the utility of host proteins – T. pallidum, B. burgdorferi) Inhibition of phagocytosis – capsule, protein M (Streptoccoci), toxins Inhibition of complement – (Borrelia burgdorferi – Factor H) Hiding inside the cells – (integration into genom – HIV, latency – herpesviruses) Inhibition of antigen presentation in addition to MHC expression (Mycobacterium, viruses) Secretion of inhibitory factors (IL-10 analogue) or proteolytic enzymes (IgA) Pathogens are not only bad .immunotherapy Derivatives of bacterial cell walls (LPS) Bacterial toxins in addition to their non-toxic variants (cholera toxin) Cytotoxic effects Adjuvants Vectors as long as antigen delivery Attenuated bacterial strains (Listeria, Salmonella) Bacterial toxins in addition to their non-toxic variants with inserted antigenic epitopes (B.pertussis ACT) Immunotoxins containing bacterial toxin bound to an antibody specifically recognizing tumour-associated antigen (C.diphtheriae diphtheria toxin, P. aeruginosa exotoxin A)

Vaccination in the Czech Republic I. II. III. IV. I. II. Infantrix Hexa, Hexavac inactivated viruses in addition to toxins, antigens Prevenar (S. pneumoniae) Polysaccharide antigens Priorix (measels,mumps,rubella) Live attenuated viruses Contraindication imunodeficiency BCG-VACCINE SSI Live attenuated M.bovis BCG Contraindication imunodeficiency Silgard Non-infectious VLP (virus like particles)

King, Jayme Fox 10 News at 9 PM Weekend - KSAZ-TV Meteorologist www.phwiki.com

King, Jayme Meteorologist

King, Jayme is from United States and they belong to Fox 10 News at 9 PM Weekend – KSAZ-TV and they are from  Phoenix, United States got related to this Particular Journal. and King, Jayme deal with the subjects like Meteorology

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