Host Defense: Antimicrobial Peptides

Question 1

The Lederberg Experiment found?

Answer 1

Many mutations are random, not directed → penicillin-bacteria were there before they met penicillin

Question 2

2 types of antimicrobial peptides

Answer 2

1. PMN

2. Neutrophils

Question 3

2 types of AMPs

Answer 3

1. Cathelicidins

2. Defensins

Question 4

Effector host defense peptides

Answer 4

Very diverse, very species-specific

Kill microbes and have host-defense activities

Question 5

2 porcine cathelicidins

Answer 5

1. PR-39 (proline rich)

2. PG 1-5 (protegrin)

Question 6

2 bovine cathelicidins

Answer 6

1. Bac-5
2. Bac-7

(Bac = bactenecins)

Question 7

Human cathelicidin

Answer 7

LL-37I

Question 8

Porcine beta defensin

Answer 8

pBD-1 (porcine beta defensin)

Question 9

3 bovine beta defensins

Answer 9

1. TAP (tracheal antimicrobial peptide)
2. LAP (lingual antimicrobial peptide)
3. EBD (enteric beta densin)

Question 10

Human alpha defensin

Answer 10

Human neutrophil peptide 3

Question 11

Monkey zeta (or theta) defensin

Answer 11

Rhesus TD-1

Question 12

3 mini-defensins

Answer 12

1. Retrocyclin (human)
2. Rhesus TD-1 (monkey)
3. Protegrin-1 (pig)

Question 13

Defensins form?

Answer 13

Pores

Question 14

Defensins are categoried on?

Answer 14

Common patterns of cysteine residues

Question 15

Human alpha-defensins found in?

Answer 15

1. Neutrophils
2. Intestinal crypt cells (Paneth)
3. Urogenital tract

Question 16

Beta-defensins have what type of antimicrobial spectrum?

Answer 16

Broad antimicrobial spectrum

Question 17

Theta-defensin

Answer 17

Present in Old-World monkeys; pseudogene in humans, chimps and gorillas

Question 18

Host-defense peptides are?

Answer 18

Naturally occurring antibiotics → functional in innate immunity

Question 19

Host-defense peptide functions

Answer 19

1. Protect from invasion by broad range of microorganisms: bacteria, fungi, viruses and metazoan parasites
2. Interact with other host-defense systems that complement their roles as antibiotics

Question 20

Host-defense peptide mechanisms of action

Answer 20

1. Pore-forming
2. LPS-binding
3. Interference with microbe’s intracellular metabolism

Question 21

Host-defense peptide structure and binding

Answer 21

Amphipathic structure, bind tightly to anionic bacterial sufaces

Question 22

Why is it difficult for microbes to develop resistance to host-defense peptides?

Answer 22

Very difficult to change microbes’ cell-surface biochemistry

Question 23

Future directions in host-defense peptide research

Answer 23

1. Understand their physiologic significance
2. Understand AMP regulation mechanisms
3. Develop constructs and vectors for AMP drug delivery
4. Understand structure/function relationships of AMPs
5. Understand how peptides interact with rest of immune system
6. Develop clinical uses

Question 24

Beta-defensins are chemotactic

Answer 24

1. Dendritic cells

2. T cells

Question 25

Beta-defensins activate?

Answer 25

1. Mast cells

2. Monocyte expression of IL-1 and TNF-alpha