L3

Question 1

How does neisseria gonorrhoeae evade immunity?

Answer 1

Prevents cell sloughing (mucous/skin)
By ↑adhesion molecules
Esp @ vagina

Question 2

How does pneumococcus evade immunity?

Answer 2

Resists phagocytosis

Question 3

How does staphylococci evade immunity?

Answer 3

Resistance to ROS once phagocytosed

Makes catalase - breaks Hperoxide into water

Question 4

How does streptococcus evade immunity?

Answer 4

Resists alternative complement pathway activation

Blocks C3 binding

Question 5

How does pseufomonas evade immunity?

Answer 5

Resists antimicrobial peptides

Question 6

What defect results in Chronic Granulomatous Disease?

Answer 6

NADPH defect
Can’t made O2 –> superoxide
Can’t make HPeroxide for phago-lysosomes

Question 7

What defect results in Chediak Higashi syndrome?

Answer 7

MPO defect

Abnormal fusion of phagosome w/ lysosome

Question 8

What defect results in leukocyte adhesion deficiency (LAD)?

Answer 8

Faulty CD18

Neutrophils & monocytes can’t attach to endothelium for diapedesis

Question 9

What complement deficiency leads to increased Neisseria infection?

Answer 9

CD8
Can’t form MAC
Neisseria are especially susceptible to killing by MAC

Question 10

What kinds of infections are common with IRAK4 deficiency?

Answer 10

= defect in TLR signaling - don’t get enough inflammation to kill pathogen
Recurrent (Gram+) bacterial infections

Question 11

What 2 receptors need to be activated for macrophages to be both microbicidal and tumoricidal?

Answer 11

LPS + TLR4

INF gamma + INF gamma receptor

Question 12

Explain the 4 steps from O2 –> water that can happen to get ROS inside phago-lysosomes.

Answer 12

O2 + NADPH –> superoxide
Superoxide + superoxide dismutase –> HPeroxide
HPeroxide + MPO –> halide ion insertion into pathogen membrane
HPeroxide + catalase –> H2O

Question 13

What cells secrete TNF? What are the effects?

Answer 13

Secreted
- Macrophages
- T cells
Action
- Inflam & coag of endothelium
- Neutrophils
- Fever
- Make acute phase reactants
- Possible apoptosis

Question 14

What cells secrete IL1? What is IL1’s effect?

Answer 14

Secreted:
- Macrophages
- Endothelium 
Actions:
- Inflam & coag endothelium
- Fever
- Make acute phase reactants via IL6

Question 15

What cells secrete chemokines? What is chemokines effects?

Answer 15

Secreted:
- Macrophages
- Endothelium 
- T cells
Actions:
- Migration & activation WBCs

Question 16

What cells secrete IL12? Actions?

Answer 16

Secreted:
- Macrophages
- Dendritic cells
Actions:
- IFN-gamma from NK & T cells
- Th1 differentiation

Question 17

What cells secrete IFN gamma? Actions?

Answer 17

Secreted:
- NK cells
- T cells
Actions:
- Macrophage activation
- ↑Abs

Question 18

What cells secrete IFN alpha vs beta? Actions?

Answer 18

Secreted:
- IFN alpha: macrophages
- IFN beta: fibroblasts 
Actions:
1. All cells into antiviral state
2. ↑MHC1
3. NK cells ON

Question 19

What cells secrete IL10? Actions?

Answer 19

Secreted:
- Macrophages
- Th2
Actions:
- Inhibit IL12 production from macrophages
- ↓MHC2 & costimulator receptors from macrophage membrane

Question 20

What cells secrete IL6? Actions?

Answer 20

Secreted:
- Macrophages
- Endothelium 
- T cells
Actions
- ↑acute phase reactants: C reactive protein & MBL 
- ↑Abs from B cells

Question 21

What cells secrete IL15? Actions?

Answer 21

From macrophages
Actions:
- NK & T cell proliferation

Question 22

What cells secrete IL18? Actions?

Answer 22

From macrophages

↑IFN-gamma from NK & T cells

Question 23

What are the 2 signaling pathways for TLR4?

Answer 23

Small differences in receptor conformation with each different ligand bound

1. MyD88 adapter –> NF kappa B TF –> transcribe inflam cytokines
2. Internalize TLR4+antigen –> TRIF adapter –> IR3 TF –> type 1 IFs

Question 24

What is the other PRR that can activate the TRIF/IR3 signaling pathway?

Answer 24

TRL3

Question 25

Describe the structure of TLRs.

Answer 25

Leucine rich repeat C arm 1 alpha helix transmembrane domain TIR domain = toll/IL

Question 26

What is the role of acute phase reactants? Where are they made? Which cytokine increases the production of APR?

Answer 26

Turn off inflammation IL6 --> made @ liver Simultaneously turning on inflammation while already working to limit it

Question 27

When LPS binds macrophages, what are the 3 resulting actions?

Answer 27

1. Lipid metabolites - modulate vessel tightness/edema 2. Cytokines/chemokines - IFN-gamma that feeds back on macrophage to increase macro activity 3. ROS All need to be balanced Dysregulation - (gram neg sepsis) circulatory collage, organ failure, shock, death

Question 28

Name the general steps of PRR signal transduction cascade.

Answer 28

1. PAMP + PRR 2. + adapter 3. + kinase --> phosphorylate downstream proteins 4. Proteins bind DNA to ↑transcription Outcome = inflam response

Question 29

What is the PAMP for gram+ bacteria? What PRR do they bind?

Answer 29

``` PAMP = peptidoglycan & lipoproteins PRR = TLR2 ```