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Host-Microbe Interactions

Host-Microbe Interactions. Numbers. The total number of microbes that colonize the surface of an adult body is 10 times greater than the total number of human cells Human genome encodes for 223 proteins with significant homology to bacterial but not eukaryotic proteins. Symbiotic Associations.

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Host-Microbe Interactions

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  1. Host-Microbe Interactions

  2. Numbers • The total number of microbes that colonize the surface of an adult body is 10 times greater than the total number of human cells • Human genome encodes for 223 proteins with significant homology to bacterial but not eukaryotic proteins

  3. Symbiotic Associations • Symbiosis: Relation between 2 different species • Mutualism: both partners benefit • Commensalism: one partner benefits, other is unharmed • Parasitism: one organism benefits at expense of other

  4. Examples • Mutualism • Cleaner Shrimp/Zebra Moray Eel

  5. Examples • Mutualism • Oxpecker bird /Rhinoceros

  6. Examples • Parasitism • Braconid wasp/ Tomato hornworm

  7. Examples • Comensalism • Firmicutes/ Human skin

  8. Examples • Mutualism • Mycorrhizae/Plants

  9. Examples • Commensalism • Escherichia /Human intestine

  10. The Normal Microbiota • Resident microbiota • Transient microbiota • Why? • How?

  11. Why? • Metabolic rate • Gastrointestinal function • Specific and quantitative aspects of immune function • Biochemical homeostasis • Influence on host–parasite relationships

  12. Metabolic Rate • Carbohydrates and Complex Lipids • Ions: Mg2+, Ca2+, Fe3+ • Vitamins: Biotin, Folate

  13. Gastrointestinal Function

  14. Immune Function • Gut mucosa. Lacking normal microbiota leads to smaller Peyers Patches, lower intraepithelial lymphocytes and lower secretion of IgA • Regulate the expression of the TLRs: differentiate pathogens and commensals • Allergies: Presence of certain bacteria stimulates the • T cells. Some microorganism are also responsible for the development of dendritic cells. Overall problem is no block of IgE production

  15. The Present and the Future..

  16. Damage to the Host • Direct or Indirect • Direct • Toxins • Proteins • Anthrax • Botulinum • Shiga • Lipopolysaccharides

  17. Damage to the Host • Indirect • Associated to Inflammation • Neisseriagonorrhoeae • Associated to Adaptive Immunity • Glomerulonephritis • Rheumatic fever

  18. Toxins • Exotoxins • Endotoxins • Soluble Proteins/Polypeptides • Usually secreted by bacteria • Act on site or at site removed from bacterial growth • Gram (+) and Gram (-) • Cell associated substances • Structural components of bacteria • Location: Outer membrane Gram (-) • Released from growing bacteria or lysis/ effect of an atibiotic

  19. Exotoxins (A/B Toxins) • A: TOXIC • B: Binds to surface

  20. Attachment and Entry • A) Direct : Formation of a pore • Geny B, 2006, Biol Cell

  21. Attachment and Entry • A) Receptor-Mediator Endocytosis

  22. Exotoxins are proteins…. • What are some characteristics of enzymes that • the host can take advantage to avoid their detrimental effect? • Heat / Acid labile • Proteolytic enzymes • Catalysis (High biological activity) • Specificity • The host can generate antibodies against them: • production of toxoids and antitoxins

  23. Where? • Neurotoxins • Enterotoxins • Cytotoxins

  24. Membrane-damaging toxins • Hemolysins : Form pores • Avoid phagocytosis • Phospholypases: Hydrolizephopholipids

  25. Superantigens

  26. Endotoxins • Lipopolysaccharide • Integral part of the outer membrane Gram (-) • No efficient toxoids

  27. Structure of LPS • Phosphorylated N-acetylglucosamine (NAG) dimer with 6 or 7 fatty acids (FA) attached. • All FA in Lipid A are saturated. Some FA are attached directly to the NAG dimer and others are esterified to the 3-hydroxy fatty acids that are characteristically present.

  28. Mechanism 1. Production of cytokines. IL and TNF activates macrophages to enhanced phagocytosis and cytotoxicity. 2. Activation of the complement cascade. C3a and C5a cause histamine release (leading to vasodilation) and affect neutrophilchemotaxis and accumulation. 3. Activation of the coagulation cascade.  Initial activation of Hageman factor (blood-clotting Factor XII)  can activate several humoral systems : a. coagulation: Leads to internal bleedingb. activation of the complement alternative pathway c. plasmin activation which leads to fibrinolysis and hemorrhaging. d. kinin activation releases bradykinins and other vasoactive peptides which causes hypotension. 

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