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Transcript
Immunity to microbes (mechanisms of defense against bacterial infections) Goal To understand basic principles of defense against infections induced by: bacteria - extracellular - intracellular viruses parasites - protozoa - helmints fungi Important features of defense against infectious agents Mediated by the mechanisms of both innate and adaptive immunity Specialization of the immune system allows optimal response to each type of microbe Establishment, course and outcome of infection depend on ability of pathogen to evade or resist immune response Tissue injury and disease are often result of immune response to pathogens Bacteria Unicellular prokaryotes Survive and replicate: - outside cell (extracellular bacteria) - inside cell (intracellular bacteria) Induce disease by: - induction of inflammation - production of toxins Extracellular bacteria Replicate outside cell (in circulation, tissues and lumens) Induce inflammation (often with pus formation) - e.g. staphylococci and streptococci Produce toxins: - exotoxins (diphteria, tetanus...) - endotoxin (LPS) Mechanisms of defense against extracellular bacteria Mechanisms of innate immunity - complement activation by alterative and lectin pathway - phagocytosis (neutrophils and macrophages) - inflammation (induction of TNF, IL-1, chemokines etc.) Complement activation by alterative and lectin pathway Phagocytosis and killing of microbes Pathogen recognition Phagocytosis and killing of microbes Zipping of membrane around microbe Phagocytosis and killing of microbes Ingestion of microbe Phagocytosis and killing of microbes Fusion of phagosome with lysosome Phagocytosis and killing of microbes Phagocyte activation Phagocytosis and killing of microbes Killing of microbe Inflammation Mechanisms of defense against extracellular bacteria Mechanisms of adaptive immunity Humoral immunity B cells and antibodies - complement activation by clasical pathway (IgG and IgM) - neutralization of toxins (IgG and IgA) - opsonization and phagocytosis (IgG) CD4+ helper T cells Mechanisms of defense against extracellular bacteria (B cells) Neutralization of toxins Opsonization and phagocytosis Mechanisms of defense against extracellular bacteria Mechanisms of adaptive immunity Humoral immunity B cells and antibodies - complement activation by clasical pathway(IgG and IgM) - neutralization of toxins (IgG and IgA) - opsonization and phagocytosis (IgG) CD4+ helper T cells - B cell help (various citokines) - macrophage activation (IFN-γ) – TH1 - neutrophil activation (IL-17) – TH17 - induction of inflammation (TNF) Naïve Naivna CD4+T TH1 IFN- Macrophage stimulation TH2 IL-4 IL-5 Eosinophil stimulation TH17 IL-17A Neutrophil stimulation Naïve Naivna CD4+T TH1 Defence against intracellular pathogens TH2 Defence against helmints TH17 Defence against some extracellular bacteria and fungi Mechanisms of defense against extracellular bacteria Mehanisms of immune evasion - polysaccharide capsule (S. pneumoniae...) Mechanisms of defense against extracellular bacteria Mehanisms of immune evasion - polysaccharide capsule (S. pneumoniae...) - genetic variation of surface antigens (Neisseria sp, E. coli...) - inhibition of complement activation (many bacteria) - production of IgA proteases (Neisseria sp., S. pyogenes...) Mechanisms of defense against extracellular bacteria Injurious effects of immune response - inflammation (SIRS, septic shock) - superantigens (S. aureus, S. pyogenes...) Mechanism of superantigen action T-cell Activation of 5-20% T cells Massive cytokine production Antigen-presenting cell Mechanisms of defense against extracellular bacteria Injurious effects of immune response - inflammation (SIRS, septic shock) - superantigens (S. aureus, S. pyogenes...) - “molecular mimicry” (S. pyogenes and Rheumatic fever) Intracellular bacteria Survive and replicate in cells Enter cells via receptors or phagocytosis Escape from antibody, complement etc. Induce chronic infections Facultative intracellular (e.g. Mycobacterium sp.) Strict intracellular (Chlamydia and Ricketsia) Intracellular bacteria Mechanisms of defense against intracellular bacteria Mechanisms of innate immunity - phagocytosis (inefficient unless stimulated) - NK cells (production of IFN-γ and stimulation of macrophages) Stimulation of macrophages by NK cells Mechanisms of defense against intracellular bacteria Mechanisms of adaptive immunity Cell-mediated immunity CD4+ helper T cells (TH1) - B-cell help to produce opsonizing antibodies (IFN-γ) - macrophage activation (IFN-γ) – TH1 - induction of inflammation (TNF) CD8+ cytotoxic T cells Macrophage activation by TH1 cells Mechanisms of defense against intracellular bacteria Mechanisms of aquired immunity Cell mediated immunity CD4+ helper T-cells (TH1) - Support of B-cells to produce opsonizing antibodies (IFN-γ) - Macrophage activation (IFN-γ) – TH1 - Induction of inflammation (TNF) CD8+ cytotoxic T-cells - destruction of infected cells (containing bacteria in cytoplasm) Cooperation between CD4+ and CD8+ T-cells in elimination of intracellular bacteria Mechanisms of defense against intracellular bacteria Mechanisms of defense against intracellular bacteria Mehanisms of immune evasion - inhibition of phagolysosome formation (M. tuberculosis...) Mechanism of immune evasion by Mycobacteria Mechanisms of defense against intracellular bacteria Mehanisms of immune evasion - inhibition of phagolysosome formation (M. tuberculosis...) - escape from phagolysosome (L. monocytogenes....) - inhibition of ROS i NO (M. leprae...) Mechanisms of defense against intracellular bacteria Injurious effects of immune response -chronic inflammation (DTH) and granuloma formation (tuberculosis) Thanks for your attention! Questions?