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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. - PowerPoint PPT Presentation
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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
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
Symbiotic Associations
Examples
Cleaner Shrimp/Zebra Moray Eel
Mutualism
Examples
Oxpecker bird /Rhinoceros
Mutualism
Examples
Parasitism
Braconid wasp/ Tomato hornworm
Firmicutes/ Human skin
Comensalism
Examples
Examples
Mycorrhizae/Plants
Mutualism
Examples
Commensalism
Escherichia /Human intestine
The Normal Microbiota
Resident microbiota
Transient microbiota
Why?How?
Why? Metabolic rate
Gastrointestinal function
Specific and quantitative aspects of immune function
Biochemical homeostasis
Influence on host–parasite relationships
Metabolic Rate
Carbohydrates and Complex Lipids
Vitamins: Biotin, Folate
Ions: Mg2+, Ca2+, Fe3+
Gastrointestinal Function
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
The Present and the Future..
Damage to the HostDirect or Indirect
Toxins
Anthrax
Botulinum
Shiga
Proteins
Lipopolysaccharides
Direct
Damage to the HostIndirect
• Associated to Inflammation
Neisseria gonorrhoeae
• Associated to Adaptive Immunity
Glomerulonephritis
Rheumatic fever
Exotoxins
Endotoxins
Toxins• 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
Exotoxins (A/B Toxins)
A: TOXIC
B: Binds to surface
Attachment and Entry A) Direct : Formation of a pore
Geny B, 2006, Biol Cell
Attachment and Entry A) Receptor-Mediator Endocytosis
Exotoxins are proteins….
•Heat / Acid labile•Proteolytic enzymes•Catalysis (High biological activity)•Specificity• The host can generate antibodies against them: production of toxoids and antitoxins
What are some characteristics of enzymes that the host can take advantage to avoid their
detrimental effect?
Where? •Neurotoxins
•Enterotoxins
•Cytotoxins
Membrane-damaging toxins •Hemolysins : Form pores Avoid phagocytosis
•Phospholypases: Hydrolize phopholipids
Superantigens
Endotoxins• Lipopolysaccharide• Integral part of the outer membrane Gram (-)• No efficient toxoids
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.
Mechanism1. 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 neutrophil chemotaxis 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.