Diebel Innate System Review Q's

Question 1

What are defensins and cathelicidins? What are their modes of action?

Answer 1

Cathelicidins (Cationic Helical bacteriCidal proteIn)

• alpha-helical peptide
• PMNs, mucosal, epithelial cells

Defensins
-beta-strand peptides (+) charge

• *increase cell membrane permeability –> cell death
• *modulate inflammatory response

Question 2

What are defensins and cathelicidins? What are their modes of action?

Answer 2

Cathelicidins (Cationic Helical bacteriCidal proteIn)

• alpha-helical peptide
• PMNs, mucosal, epithelial cells

Defensins
-beta-strand peptides (+) charge

• *increse cell membrane permeability –> cell death
• *modulate inflammatory response

Question 3

TLR1 + TLR2:

Ligand:

Trigger production of:

Answer 3

Triacylated lipoproteins
Peptidoglycans
LPS

Inflammatory Cytokines

Question 4

TLR2 + TLR6:

Ligand:

Trigger production of:

Answer 4

Diacylated lipoproteins

Inflammatory cytokines

Question 5

TLR3:

Ligand:

Trigger production of:

Answer 5

dsRNA
tRNA
siRNA

IC
IFN-beta (via TRIF)

Question 6

TLR4:

Ligand:

Trigger production of:

Answer 6

LPS
Paclitaxel

IC
IFN-beta (via TRAM, TRIF, TIRAP, MyD88, Mal)

Question 7

TLR5:

Ligand:

Trigger production of:

Answer 7

Flagellin

IC (via MyD88)

Question 8

TLR7:

Ligand:

Trigger production of:

Answer 8

ssRNA
Imidazoquinolones
Guanasine analogs

ICs
INF-alpha (via MyD88)

Question 9

TLR8:

Ligand:

Trigger production of:

Answer 9

ssRNA
Imidazoquinolones

ICs
INF-beta (via MyD88)

Question 10

TLR9:

Ligand:

Trigger production of:

Answer 10

CpG DNA

ICs
INF-beta (via MyD88)

Question 11

TLR10:

Ligand:

Trigger production of:

Answer 11

profilin-like proteins

ICs (via MyD88)

Question 12

PMN lineage?

Answer 12

1. IL3 + GM-CSF
2. ” “
3. GM-CSF + G-CSF + IL-3

Question 13

Eosinophil lineage?

Answer 13

1. IL-3 + GM-CSF
2. ” “
3. GM-CSF + IL-3 + IL-5

Question 14

Basophil lineage?

Answer 14

1. IL-3 + GM-CSF
2. ” “
3. GM-CSF + IL-3 + IL-4

Question 15

Monocyte lineage?

Answer 15

1. GM-CSF + IL-3
2. ” “
3. GM-CSF + M-CSF + IL-3

Question 16

IL-5 unique to lineage of which myeloid cell?

Answer 16

Eosinophil

Question 17

IL-4 unique to lineage of which myeloid cells (2)?

Answer 17

Basophils

Dendrites

Question 18

M-CSF unique to lineage of which myeloid cell?

Answer 18

Monocyte

*becomes macrophage once in tissue

Question 19

G-CSF unique to lineage of which myeloid cell?

Answer 19

PMNs (neutrophils)

Question 20

Macrophage lineage?

Answer 20

1. and 2. GM-CSF + IL-3
2. GM-CSF + M-CSF + IL-3 (now a monocyte)
3. M-CSF + GM-CSF

Question 21

Describe the pathway of events involved in the activation of the acute inflammatory response up to the point of the presence of Th1 CD4+ T cells.

Answer 21

1. presents of microbes
2. Tissue damage, complement activation
3. release of inflammatory cytokines
   - TNFalpha
   - IL-1
   - INFgama
4. recruitment of leukocytes

Question 22

Dendrite lineage (from myeloid precursor):

Answer 22

1. and 2. GM-CSF + IL-3
2. GM-CSF + M-CSF + IL-3 (now a monocyte)
3. GM-CSF + IL-4

Question 23

• lack of GM-CSF

- frequent bacterial infx

Answer 23

Congenital neutropenia

Question 24

• inability to produce H2O2 and hypochlorous acid

- inability to kill phagocytosed bacteria

Answer 24

Chronic Granulomatous disease

Question 25

- lack of integrin subunit, common beta chain - inability to recruit innate immune cells to inflammation site - increased susceptibility to bacterial, fungal, and viral infx

Answer 25

Leukocyte adhesion deficiency (LAD)

Question 26

- increased susceptibility to bacterial infx | - reduced ability to remove immunocomplexes

Answer 26

Complement defects (various)

Question 27

- defect in gene LYST (CHS1), a lysosomal trafficking gene that affects lysosomes and melanosomes - increased susceptibility to bacterial infx

Answer 27

Chediak-Higashi Syndrome

Question 28

Describe the pathway of events involved in the activation of the acute inflammatory response up to the point of the presence of Th1 CD4+ T cells.

Answer 28

1. microbe gets past physical barrier 2. Tissue damage, complement activation or TLR on resident macrophage recognizes PAMP/DAMP 3. release of inflammatory cytokines - TNFalpha--> M1 "angry macrophage" - IL-1 - INFgama 4. recruitment of leukocytes - MHC II on APCs