Innate Immunity

Question 1

What are 5 components of innate barriers?

Answer 1

1) Skin
- low pH, high salt, defensins, IgA in sweat

2) Mucous membrane
- blockage of attachment, shedding

3) Tears
- lysozymes

4) Gut
- Acid

5) Commensals
- prevent attachment, produce bacteriocins, maintain epithelial barrier integrity, compete for nutrients

Question 2

What are the 4 components of innate immunity?

Answer 2

1) Barriers
2) DAMPs
3) PAMPs
4) Complement activation

Question 3

What are the functions of DAMPs?

Answer 3

DAMPs activate Dendritic cells (B7 exp.)

Question 3

What are some NK cell phenotypes?

Answer 3

CD3-, NKp46+, CD2+, CD56+ (human), CD49b+ (murine)

Question 4

What are the functions of NK cells?

Answer 4

1) Anti-viral (NK before T cells)
2) Anti-tumour, esp tumour cells w:
- ↓ MHC I exp. (avoid CD8+ T cells)
- NK cell-activating receptor ligand exp. (MIC-A/B, ULB)

Question 5

How do NK cells target viral-infected/tumour cells?

Answer 5

“altered”/absent MHC 1→ cannot stimulate -ve signal (eg. CD94-NKG2) → NK activation → apoptosis

Question 6

What are the functions of PAMPs?

Answer 6

Recognised by PRR on phagocytes
→ phagocytosis
→ cytokine release

Question 7

What are the types of cytokines released and what are their 2 main functions?

Answer 7

1) Type 1 IFNs (INFα/ß): anti-viral
→ activate NK cells IFN-y → activate macrophages (IL-12) → ↑ NK cells (+ve loop)
→ ↑ MHC 1 exp.
→ interfere with viral replication

2) IL-1ß, TNF-α: inflammatory cytokines (acute inflammation)
→ neutrophils chemotaxis
→ ↑ selectins/integrins

Question 8

How is the complement system activated in innate immunity?

Answer 8

Through the alternative pathway (direct binding with microbe PAMPs)

Spontaneous/Ab-independant C3 lysis

Question 9

What are the effects of complement activation?

Answer 9

1) C3→C3a + C3b
2)C3b catalyse→C5→C5a + C5b

a) C3a + C5a → mast cell degranulation
b) C3b → opsonisation → targeted phagocytosis
c) C5a → inflammation
d) C5b + C6-9 → MAC → cell lysis

Question 10

What are some examples of phagocytotic cells?

Answer 10

1) Neutrophils
2) Monocytes
3) Macrophages
4) Dendritic cells

Question 11

What are 2 classes of receptors present on phagocytes that induce phagocytosis of a foreign body?

Answer 11

1) Membrane receptors
- Mannose receptors (to polysaccharides on targets)
- Scavenger receptors (to charged molecules on targets)

2) Opsonin
- FcR
- Complement receptors

Question 12

What are some mechanisms by which a microbe would be killed within a phagocyte?

Answer 12

1) Acidification (bacteriostatic/bactericidal)
2) Toxic oxygen-derivatives (eg. H202, superoxide, singlet oxygen, hydroxyl radical, hypohalite)
3) Nitric oxide
4) Antimicrobial peptides (eg. defensins, cationic proteins)
5) Enzymes (eg. lysozymes, acid hydrolases)

Question 13

How are NK cells activated?

Answer 13

1) Type 1 Interferons (IFN-α/ß)
2) DC & Macrophage-derived cytokines (TNF-α, IL-12)

Question 14

How do NK cells kill target cells?

Answer 14

Non-ADCC activation of NK cells (via eg. MIC-A/B, MUC ligands) → lytic granule release eg. granzyme, perforin)

Question 15

What are the differences between inducible and non-inducible innate immunity?

Answer 15

Non-inducible:
- 0-4hrs
- Skin, mucous, acidity, enzymes, lytic peptides, etc.

Inducible
- 4-96hrs
- Phagocytes, Complements, Nk cells, cytokines, etc.