#8 Mechanisms of Host Defense Against Infections Part 1

Question 1

Bacterial infection: what happens upon entry?

Answer 1

The surface lipopolysaccharide may activate:

1. “alternative complement pathway”
   OR
2. Mannan-binding “lectin” pathway → bacterial lysis

Question 2

What does C-reactive protein bind?

Answer 2

Bacterial coat polysaccharides

(Mannan-binding lectin binds lipopolysaccharide)- Bacteria that express mannose→bind mannose-binding lectin→activates complement via lectin pathway

Question 3

What does mast cell degranulation enhance?

Answer 3

Blood flow

Question 4

What can activate neutrophils adhering to vein wall?

Answer 4

Chemokines (IL-8) and C5a and bacterial products

Question 5

What attracts neutrophils to infection site? (chemotaxis)

Answer 5

FMLP, C5a, IL-8

Question 6

What causes swollen lymph nodes?

Answer 6

Trapped lymphocytes (enter directly from blood)

DC’s enter LN and move to germinal center

Question 7

Early antibacterial Ab production is of what class?

Answer 7

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

Question 8

2 mechanisms of pathogenic extracellular bacteria

Answer 8

1. Inflammation

2. Toxin production

Question 9

Bacterial toxins are divided into 2 groups:

Answer 9

Endotoxins (bacteria cell walls)

Exotoxins: secreted by bacteria

Question 10

Endotoxin (LPS): gram -

Answer 10

Potent activator of Mφ, Dcs, endothelial cells

Question 11

What are some exotoxins that are cytotoxic?

Answer 11

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)

Question 12

What activates the complement alternative pathway (innative immunity)?

Answer 12

Peptidoglycans (gram +) and LPS (gram -)

Question 13

What do C3a and C5a do?

Answer 13

C3a and C5a recruit and activate leukocytes

Stim. inflammatory response

Question 14

What Ab does the Classical pathway (complement-innate) require?

Answer 14

IgM or IgG → C2+C4

Question 15

What does the MBL pathway (complement-innate) need?

mannose-binding lectin

Answer 15

Does not use C1

MBP binds →MASPs activated→C2+C4

Question 16

What does the Alternative pathway (complement-innate) need?

Answer 16

C3b + [Factor B/D] → C3 convertase → C5 convertase → C5 → MAC

(Properdin stabilizes convertases)

Question 17

What does C3b do?

Answer 17

C3b→MAC→lysis

OR

C3b→recognized by phagocyte→phagocytosis

Question 18

What do neutrophils and Mφ use to recognize bacteria?

Answer 18

Mannose receptors/scavenger receptors → EXTRAcellular bacteria

Fc receptor/complement receptors(CR1-CR4) → opsonized bacteria

Question 19

What do TLRs stimulate?

Answer 19

Microbicidal activities (via ROI and NO)

Question 20

What causes apoptosis or necrosis?

Answer 20

Peroxynitrite (ONOO-)

Question 21

What is resistant to phagocytosis?

Answer 21

Pneumococcus, Neisseria meningitidis

Question 22

Many bacteria can inhibit complement activation?

Answer 22

True

Question 23

What bacteria use evasion technique: scavenging of ROS?

Answer 23

Catalase-positive staphylococci

Question 24

IgG and Phagocytosis

Answer 24

1. IgG binds microbe
2. Fc receptors bind (phagocyte)
3. Fc receptor activates phagocyte
4. Phagocytosis
5. Killing of microbe

Question 25

What do Mφ and neutrophils express receptors for?

Answer 25

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)

Question 26

Strategies to evade immunity

Answer 26

1. Antigenic variation: alter surface proteins
2. Inhibition of complement
3. Resistance to phagocytosis: interfere with complement activation, inject anti-phagocytic effectors into cell
4. Scavenging ROI: deactivate the peroxide radicals