Flashcards in L3 Deck (29)
1
How does neisseria gonorrhoeae evade immunity?
Prevents cell sloughing (mucous/skin)
By ↑adhesion molecules
Esp @ vagina
2
How does pneumococcus evade immunity?
Resists phagocytosis
3
How does staphylococci evade immunity?
Resistance to ROS once phagocytosed
Makes catalase - breaks Hperoxide into water
4
How does streptococcus evade immunity?
Resists alternative complement pathway activation
Blocks C3 binding
5
How does pseufomonas evade immunity?
Resists antimicrobial peptides
6
What defect results in Chronic Granulomatous Disease?
NADPH defect
Can't made O2 --> superoxide
Can't make HPeroxide for phago-lysosomes
7
What defect results in Chediak Higashi syndrome?
MPO defect
Abnormal fusion of phagosome w/ lysosome
8
What defect results in leukocyte adhesion deficiency (LAD)?
Faulty CD18
Neutrophils & monocytes can't attach to endothelium for diapedesis
9
What complement deficiency leads to increased Neisseria infection?
CD8
Can't form MAC
Neisseria are especially susceptible to killing by MAC
10
What kinds of infections are common with IRAK4 deficiency?
= defect in TLR signaling - don't get enough inflammation to kill pathogen
Recurrent (Gram+) bacterial infections
11
What 2 receptors need to be activated for macrophages to be both microbicidal and tumoricidal?
LPS + TLR4
INF gamma + INF gamma receptor
12
Explain the 4 steps from O2 --> water that can happen to get ROS inside phago-lysosomes.
O2 + NADPH --> superoxide
Superoxide + superoxide dismutase --> HPeroxide
HPeroxide + MPO --> halide ion insertion into pathogen membrane
HPeroxide + catalase --> H2O
13
What cells secrete TNF? What are the effects?
Secreted
- Macrophages
- T cells
Action
- Inflam & coag of endothelium
- Neutrophils
- Fever
- Make acute phase reactants
- Possible apoptosis
14
What cells secrete IL1? What is IL1's effect?
Secreted:
- Macrophages
- Endothelium
Actions:
- Inflam & coag endothelium
- Fever
- Make acute phase reactants via IL6
15
What cells secrete chemokines? What is chemokines effects?
Secreted:
- Macrophages
- Endothelium
- T cells
Actions:
- Migration & activation WBCs
16
What cells secrete IL12? Actions?
Secreted:
- Macrophages
- Dendritic cells
Actions:
- IFN-gamma from NK & T cells
- Th1 differentiation
17
What cells secrete IFN gamma? Actions?
Secreted:
- NK cells
- T cells
Actions:
- Macrophage activation
- ↑Abs
18
What cells secrete IFN alpha vs beta? Actions?
Secreted:
- IFN alpha: macrophages
- IFN beta: fibroblasts
Actions:
1. All cells into antiviral state
2. ↑MHC1
3. NK cells ON
19
What cells secrete IL10? Actions?
Secreted:
- Macrophages
- Th2
Actions:
- Inhibit IL12 production from macrophages
- ↓MHC2 & costimulator receptors from macrophage membrane
20
What cells secrete IL6? Actions?
Secreted:
- Macrophages
- Endothelium
- T cells
Actions
- ↑acute phase reactants: C reactive protein & MBL
- ↑Abs from B cells
21
What cells secrete IL15? Actions?
From macrophages
Actions:
- NK & T cell proliferation
22
What cells secrete IL18? Actions?
From macrophages
↑IFN-gamma from NK & T cells
23
What are the 2 signaling pathways for TLR4?
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
24
What is the other PRR that can activate the TRIF/IR3 signaling pathway?
TRL3
25
Describe the structure of TLRs.
Leucine rich repeat C arm
1 alpha helix transmembrane domain
TIR domain = toll/IL
26
What is the role of acute phase reactants? Where are they made? Which cytokine increases the production of APR?
Turn off inflammation
IL6 --> made @ liver
Simultaneously turning on inflammation while already working to limit it
27
When LPS binds macrophages, what are the 3 resulting actions?
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
28
Name the general steps of PRR signal transduction cascade.
1. PAMP + PRR
2. + adapter
3. + kinase --> phosphorylate downstream proteins
4. Proteins bind DNA to ↑transcription
Outcome = inflam response
29