1. 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. PGE 2, TGF , Prostaglandins IL-10 sIL-1R

2. Immunopathology Virus-bacterium synergistic pathology Sepsis and Endotoxemia Molecular mimicry Superantigens

3. 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,

4. Sepsis and Endotoxemia Proinflammatory cytokines: TNF , IFN , IL-1, IL-6, IL-8, IFN , IFN  C5a Neutropenia Soluble cytokine receptors (TNF-R, IL-1R)

5. Molecular Mimicry Chlamydia - heart Campylobacter - Guillan-Barre’ syndrome

6. Superantigens S. aureus enterotoxins causing food poisoning, vomiting & diarrhea (SEA, SEB).  Lymphocyte proliferation  Cytokine production Toxic shock syndrome.

7. 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

8. Mechanisms of Immune Evasion I: Camouflage Capsule formation S aureus protein A Sialic acid LPS O protein S aureus coagulase M bacterium granuloma formation

9. 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

10. 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

11. 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

12. 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

13. Viral Mechanisms of Immune Evasion III Immune Cell Function >CTL cytolysis e.g. HSV >T H depletion e.g. HIV >Immunosuppression e.g. measles, EBV

14. 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.

15. Infection and Pathogenesis Colonization (Benign or asymptomatic)  Infection   Disease (Pathogenesis)  Clinical or Subclinical

16. Requisites for Successful Growth Attachment Nutrition Survival from host defence Transmission

17. 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

18. Bacterial Virulence Factors I: Colonization Adherence: Capsules, Pili, adhesins Penetration: e.g. invasins Host gene modification.

19. 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

20. Pili (Fimbriae) Composed of subunits of pilin. Promote adherence to other bacteria or host. Synonyms: adhesins, lectins, evasins, aggressins. Fragile, often replaced.

21. Bacterial Pathogenesis Toxic byproducts of bacterial growth e.g. acids, gas, proteases Toxins >Endotoxins e.g. LPS >Exotoxins Immunopathogenesis e.g. Chlamydia, treponemes (syphilis), Borrelia (Lyme disease)

22. Endotoxins: Lipopolysaccharide Fever Leukopenia, followed by leukocytosis Complement activation Thrombocytopenia Coagulation Decreased blood circulation Shock Death

23. Exotoxins AB. e.g. Shigella dysenteriae, C. tetani, V. cholerae. Cell Membrane Disruption. e.g. C. perfringens Superantigens. e.g. S. aureus

24. Exotoxins I: AB (i)

25. Exotoxins I:AB (ii)

26. Exotoxins I: AB (iii)