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Transcript
SITE OF REPLICATION EXTRACELLULAR Interstitial spaces Blood, lymph Bronchial, Gastrointestinal lumen Viruses Bacteria Protozoa Fungi Worms INTRACELLULAR Epithelial surfaces Neisseria gonorrhoeae Worms Mycoplasma Streptococcus pneumoniae Vibrio cholerae Escherichia coli Candida albicans Helicobacter pylori Cytoplasmic Viruses Chlamydia ssp. Richettsia ssp. Listeria monocytogenes Protozoa Vesicular Mycobacteria Salmonella typhimurium Seishmania spp. Listeria ssp. Trypanosoma spp. Legionella pneumophila Cryptococcus neoformans Histoplasma Yersinia pestis PROTECTIVE IMMUNITY Antibodies Complement Phagocytosis Neutralization IgA type Antibodies Anti-microbial peptides Cytotoxic T cells NK cells T cell and NK celldependent macrophage activation THE SITE OF PATHOGEN DEGRADATION DETERMINES THE TYPE OF IMMUNE RESPONSES PATHOGEN TYPE PROCESSING RESPONSE Extracellular ANTIBODY PRODUCTION Acidic vesicles MHCII Neutralization Complement activation Phagocytosis MHC II binding CD4+ T cells B-se jt Intravesicular KILLING BACTERIA OF PARASITE IN VESICLES Acidic vesicles MHCII MHC II binding Intracellular killing CD4+ T cells Th1 Cytosolic MHCI Cytoplasm MHC I binding MHC II binding CD8+ T cells CD4+ T cells MHCII NK KILLING OF INFECTED CELL Extracellular killing ANTIBODY PRODUCTION THE IMMUNE RESPONSE TO EXTRACELLULAR BACTERIA Polysaccharide capsule Exotoxins – secreted by bacteria - Cytotoxicity of various mechanisms - Inhibition of various cellular functions - Induction of cytokines pathology, septic shock Endotoxins – released by phagocytic cells - Cell wall – Gram (-) rods LPS Gram (+) cocci glycan EVASION OF THE IMMUNE RESPONSE TO STREPTOCOCCI B Lymphocyte Bacterium 12 hrs 6x1010 Bacteria Toxin S. pneumoniae in the lung ESCAPE High carbohydrate variability Competition of strains ~90 serotypes Serotype-specific Ab response Opsonization Fibrin mesh in fluid with PMN's at the area of acute inflammation. It is this fluid collection that produces the "tumor" or swelling aspect of acute inflammation. The vasculitis shown here demonstrates the destruction that can accompany the acute inflammatory process and the interplay with the coagulation mechanism. The arterial wall is undergoing necrosis, and there is thrombus formation in the lumen. Edema with inflammation is not trivial at all: Marked laryngeal edema such that the airway is narrowed. This is life-threatening. Thus, fluid collections can be serious depending upon their location. A purulent exudate is seen beneath the meninges in the brain of this patient with acute meningitis from Streptococcus pneumoniae infection. The exudate obscures the sulci. Acute bronchopneumonia of the lung This tissue gram stain of an acute pneumonia demonstrates gram positive cocci that have been eaten by the numerous PMN's exuded into the alveolar space. Opsonins such as IgG and C3b facilitate the attachment of PMN's to offending agents such as bacteria so that the PMN's can phagocytose them. Neutrophilic alveolar exudate with PMN The patient had a "productive" cough because of large amounts of purulent sputum. Numerous neutrophils fill the alveoli in this case of acute bronchopneumonia in a patient with a high fever. Pseudomonas aeruginosa was cultured from sputum. Dilated capillaries in the alveolar walls from vasodilation with the acute inflammatory process. CONSEQUENCES OF SKIN DAMAGE INFLAMMATION IN CONNECTIVE TISSUE THE IMMUNE RESPONSE AGAINST EXTRACELLULAR BACTERIA Complement-mediated lysis T-INDEPENDENT IgM/IgG antibody + Complement Bacterial killing Plasma level plasma B CR1 CR3macrophage LPS FcR TNF-α IC IL-1β IL-6 1 2 3 4 5 INNATE IMMUNITY hours Helper T-cell activation IgM IgG switch MECHANISMS OF PROTECTION INNATE IMMUNITY Complement activation Gram (+) Gram (-) peptidoglycan LPS Mannose + MBL alternative pathway alternative pathway lectin pathway Phagocytosis Antibody and complement mediated opsonization Inflammation LPS Peptidoglycan TLR macrophage activation TLR macrophage activation ACQUIRED IMMUNITY Humoral immune response Targets: cell wall antigens and toxins T-independent T-dependent cell wall polysaccharide bacterial protein isotype switch inflammation macrophage activation ESCAPE MECHANISMS - overcome complement activation ANTIBODY MEDIATED EFFECTOR FUNCTIONS SPECIFIC ANTIBODY Bacterial toxin Bacteria in interstitium Bacteria in plasma Toxin receptor Neutralization Opsonization Complement activation COMPLEMENT Neutralization Phagocytosis Phagocytosis and lysis EVASION MECHANISMS OF EXTRACELLULAR BACTERIA Proteins to increase adhesion Bordetella pertussis Inhibition of phagocytosis S.aureus, Str. pneumoniae, Antigenic variants Neisseria gonorrhoeae (pilin) Inhibition of complement-dependent cell lysis Str. pyogenes M-protein Sialic acid rich capsule inhibits activation of the alternative complement pathway A reaktív oxigén gyökök lekötése Katalase pozitív staphylococci Degradation of IgA antibodies Neisseria, H. influenzae GENERAL SUPPRESSION OF THE IMMUNE RESPONSE SUBVERSION OF THE IMMUNE SYSTEM BY EXTRACELLULAR BACTERIA Superantigens of staphylococci – staphylococcal enterotoxins (SE) PROFESSIONAL APC 2 2 – toxic shock syndrom toxin-1 (TSST-1) Simultaneous binding to MHC class II and TCR -chain irrespective of peptide binding specificity Mimic specific antigen 1 1 Induce massive but ineffective T-cell activation and proliferation in the absence of specific peptide 2 – 20% of CD4+ T-cells, which are not specific for the bacteria but share V get activated and develop to effector T-lymphocytes Over production of cytokines – IL-1, IL-2, TNF-α T cell Systemic toxicity – sepsis/septicemia Suppression of adaptive immunity by apoptosis Sepsis/Septicemia TNF-α→platelet activating factor by endothelial cells→clotting, blockage restricts plasma leakage & spread of infection Infection of blood – Sepsis Sysemic edema, decreased blood volume, collapse of vessels Disseminated intravascular coagulation, multiple organ failure