#8 Mechanisms of Host Defense Against Infections Part 1 Flashcards
Bacterial infection: what happens upon entry?
The surface lipopolysaccharide may activate:
- “alternative complement pathway”
OR - Mannan-binding “lectin” pathway → bacterial lysis
What does C-reactive protein bind?
Bacterial coat polysaccharides
(Mannan-binding lectin binds lipopolysaccharide)- Bacteria that express mannose→bind mannose-binding lectin→activates complement via lectin pathway
What does mast cell degranulation enhance?
Blood flow
What can activate neutrophils adhering to vein wall?
Chemokines (IL-8) and C5a and bacterial products
What attracts neutrophils to infection site? (chemotaxis)
FMLP, C5a, IL-8
What causes swollen lymph nodes?
Trapped lymphocytes (enter directly from blood)
DC’s enter LN and move to germinal center
Early antibacterial Ab production is of what class?
IgM (affinity is helped by the 5 adhesion sites on the IgM). Thus it’s a good complement activator and opsonin → bacteria lysed by complement
2 mechanisms of pathogenic extracellular bacteria
- Inflammation
2. Toxin production
Bacterial toxins are divided into 2 groups:
Endotoxins (bacteria cell walls)
Exotoxins: secreted by bacteria
Endotoxin (LPS): gram -
Potent activator of Mφ, Dcs, endothelial cells
What are some exotoxins that are cytotoxic?
Diptheria toxin: shuts down protein synthesis in infected cells
Cholera toxin: interferes with ion/water transport
Tetanus toxin: Inhibits neuromuscular transmission
(Other exotoxins can cause disease)
What activates the complement alternative pathway (innative immunity)?
Peptidoglycans (gram +) and LPS (gram -)
What do C3a and C5a do?
C3a and C5a recruit and activate leukocytes
Stim. inflammatory response
What Ab does the Classical pathway (complement-innate) require?
IgM or IgG → C2+C4
What does the MBL pathway (complement-innate) need?
mannose-binding lectin
Does not use C1
MBP binds →MASPs activated→C2+C4
What does the Alternative pathway (complement-innate) need?
C3b + [Factor B/D] → C3 convertase → C5 convertase → C5 → MAC
(Properdin stabilizes convertases)
What does C3b do?
C3b→MAC→lysis
OR
C3b→recognized by phagocyte→phagocytosis
What do neutrophils and Mφ use to recognize bacteria?
Mannose receptors/scavenger receptors → EXTRAcellular bacteria
Fc receptor/complement receptors(CR1-CR4) → opsonized bacteria
What do TLRs stimulate?
Microbicidal activities (via ROI and NO)
What causes apoptosis or necrosis?
Peroxynitrite (ONOO-)
What is resistant to phagocytosis?
Pneumococcus, Neisseria meningitidis
Many bacteria can inhibit complement activation?
True
What bacteria use evasion technique: scavenging of ROS?
Catalase-positive staphylococci
IgG and Phagocytosis
- IgG binds microbe
- Fc receptors bind (phagocyte)
- Fc receptor activates phagocyte
- Phagocytosis
- Killing of microbe
What do Mφ and neutrophils express receptors for?
IgG(FcγRI) and IgA (FcαRI). Ab binds Ag and forms complex→phagocytes remove complexes via FcγRI and FcαRI
Exceptions:
Mast cells, eosinophils, basophils use FcεRI→binds IgE (no Ag needed)
Strategies to evade immunity
- Antigenic variation: alter surface proteins
- Inhibition of complement
- Resistance to phagocytosis: interfere with complement activation, inject anti-phagocytic effectors into cell
- Scavenging ROI: deactivate the peroxide radicals
