Anti-Inflammatory Responses Complement regulatory proteins: e.g. C1 inhibitor, C4 binding protein,...
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Anti-Inflammatory Responses
• Complement regulatory proteins: e.g. C1 inhibitor, C4 binding protein, Factor H, Factor I, complement receptor CR1, decay accelerating factor.
• Acute phase proteins e.g. protease inhibitors, ceruloplasmin.
• PGE2, TGF, Prostaglandins
• IL-10• sIL-1R
Immunopathology
• Virus-bacterium synergistic pathology
• Sepsis and Endotoxemia
• Molecular mimicry
• Superantigens
Virus-Bacterium Synergy
• Enhancement of inflammatory response by bacterial growth, IFN, complement.
• Increased tissue damage by bacterial toxins (cytolysin, LPS)
• Amplification of macrophage reactivity by cytokines, LPS,
Sepsis and Endotoxemia
• Proinflammatory cytokines:TNF, IFN, IL-1, IL-6, IL-8, IFN, IFN
• C5a
• Neutropenia
Soluble cytokine receptors (TNF-R, IL-1R)
Molecular Mimicry
• Chlamydia - heart
• Campylobacter - Guillan-Barre’ syndrome
Superantigens
• S. aureus enterotoxins causing food poisoning, vomiting & diarrhea (SEA, SEB).
Lymphocyte proliferation
Cytokine production• Toxic shock syndrome.
Immune Evasion• Camouflage
• Encapsulation
• Antigenic mimicry
• Antigenic masking
• Antigenic shift
• Latency
• Intracellular replication
• Subversion
• Production of anti-Ig proteases
• Destruction of phagocyte• Inhibition of chemotaxis• Inhibition of phagocytosis• Inhibition of phagolysosome
fusion• Resistance to lysosomal
enzymes• Superantigens
Mechanisms of Immune Evasion I: Camouflage
• Capsule formation
• S aureus protein A
• Sialic acid
• LPS O protein
• S aureus coagulase
• M bacterium granuloma formation
Mechanisms of Immune Evasion III: Anti-Phagocytosis
• Inhibit opsonization (S aureus protein A)• Inhibit chemotaxis• Kill phagocyte (S aureus streptolysin)• Inhibit phagocytosis (S pneumoniae capsule, S pyogenes M protein)• Inhibit lysosomal fusion (M. tuberculosis)• Escape lysosome and grow in cytoplasm (Mycobacteria, Salmonella, S.
aureus)• Block activation by IFN (Mycobacteria)
• Viral envelope glycoproteins
• LPS
Mechanisms of Immune Evasion II: Proteases
• Inhibit opsonization (N gonorrhoeae IgA protease)• Inhibit chemotaxis• Kill phagocyte (S aureus streptolysin)• Inhibit phagocytosis (S pneumoniae capsule, S pyogenes M protein)• Inhibit lysosomal fusion (M. tuberculosis)• Escape lysosome and grow in cytoplasm (Mycobacteria, Salmonella, S.
aureus)• Block activation by IFN (Mycobacteria)
• Viral envelope glycoproteins
• LPS
Viral Mechanisms of Immune Evasion I
• Humoral Response
Latency e.g. HSV, retroviruses Syncytia formation e.g. HSV, VZV, HIV Antigenic variation e.g. HIV Blocking antigen e.g. HBV e Ag Complement decay e.g. HSV
Viral Mechanisms of Immune Evasion II.
• Interferon HBV blocks transcription of IFN EBV synthesizes BRC1, an analogue of
IL-10. Adenovirus RNA - double stranded
duplex blocks interferon antiviral action; early protein binds cl I heavy chain preventing upregulated expression
Viral Mechanisms of Immune Evasion III
• Immune Cell Function CTL cytolysis e.g. HSV TH depletion e.g. HIV
Immunosuppression e.g. measles, EBV
Viral Mechanisms of Immune Evasion IV.
• Antigen Presentation Inhibition of Cl I MHC expression e.g.
Adenovirus, CMV Inactivating peptides e.g. HBV
• Inhibition of Inflammation Blocking of inflammatory cytokines e.g.
Poxviruses, adenovirus.
Infection and Pathogenesis
Colonization (Benign or asymptomatic)
Infection Disease (Pathogenesis)
Clinical or Subclinical
Requisites for Successful Growth
• Attachment
• Nutrition
• Survival from host defence
• Transmission
Virulence Factors
• Factors which promote infection and which contribute to disease
• Studied with mutants
• Are multifactorial
• Consist of: Factors promoting colonization and invasion Factors which are pathogenic
Bacterial Virulence Factors I: Colonization
• Adherence: Capsules, Pili, adhesins
• Penetration: e.g. invasins
• Host gene modification.
Capsules• Present in some gram negative and positive
bacteria.
• May be composed of protein or polysaccharide layers.
• Is poorly antigenic and anti-phagocytic
• Can act as a barrier to toxic hydrophobic molecules such as detergents.
• Can promote adherence to other bacteria or cell surfaces
Pili (Fimbriae)
• Composed of subunits of pilin.
• Promote adherence to other bacteria or host.
• Synonyms: adhesins, lectins, evasins, aggressins.
• Fragile, often replaced.
Bacterial Pathogenesis
• Toxic byproducts of bacterial growthe.g. acids, gas, proteases
• Toxins Endotoxins e.g. LPS Exotoxins
• Immunopathogenesis e.g. Chlamydia, treponemes (syphilis), Borrelia (Lyme disease)
Endotoxins: Lipopolysaccharide
• Fever
• Leukopenia, followed by leukocytosis
• Complement activation
• Thrombocytopenia
• Coagulation
• Decreased blood circulation
• Shock
• Death
Exotoxins
• AB. e.g. Shigella dysenteriae, C. tetani, V. cholerae.
• Cell Membrane Disruption. e.g. C. perfringens
• Superantigens. e.g. S. aureus
Exotoxins I: AB (i)
Exotoxins I:AB (ii)
Exotoxins I: AB (iii)