Flashcards in L3 Deck (29)
How does neisseria gonorrhoeae evade immunity?
Prevents cell sloughing (mucous/skin)
By ↑adhesion molecules
Esp @ vagina
How does pneumococcus evade immunity?
How does staphylococci evade immunity?
Resistance to ROS once phagocytosed
Makes catalase - breaks Hperoxide into water
How does streptococcus evade immunity?
Resists alternative complement pathway activation
Blocks C3 binding
How does pseufomonas evade immunity?
Resists antimicrobial peptides
What defect results in Chronic Granulomatous Disease?
Can't made O2 --> superoxide
Can't make HPeroxide for phago-lysosomes
What defect results in Chediak Higashi syndrome?
Abnormal fusion of phagosome w/ lysosome
What defect results in leukocyte adhesion deficiency (LAD)?
Neutrophils & monocytes can't attach to endothelium for diapedesis
What complement deficiency leads to increased Neisseria infection?
Can't form MAC
Neisseria are especially susceptible to killing by MAC
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
What 2 receptors need to be activated for macrophages to be both microbicidal and tumoricidal?
LPS + TLR4
INF gamma + INF gamma receptor
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
What cells secrete TNF? What are the effects?
- T cells
- Inflam & coag of endothelium
- Make acute phase reactants
- Possible apoptosis
What cells secrete IL1? What is IL1's effect?
- Inflam & coag endothelium
- Make acute phase reactants via IL6
What cells secrete chemokines? What is chemokines effects?
- T cells
- Migration & activation WBCs
What cells secrete IL12? Actions?
- Dendritic cells
- IFN-gamma from NK & T cells
- Th1 differentiation
What cells secrete IFN gamma? Actions?
- NK cells
- T cells
- Macrophage activation
What cells secrete IFN alpha vs beta? Actions?
- IFN alpha: macrophages
- IFN beta: fibroblasts
1. All cells into antiviral state
3. NK cells ON
What cells secrete IL10? Actions?
- Inhibit IL12 production from macrophages
- ↓MHC2 & costimulator receptors from macrophage membrane
What cells secrete IL6? Actions?
- T cells
- ↑acute phase reactants: C reactive protein & MBL
- ↑Abs from B cells
What cells secrete IL15? Actions?
- NK & T cell proliferation
What cells secrete IL18? Actions?
↑IFN-gamma from NK & T cells
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
What is the other PRR that can activate the TRIF/IR3 signaling pathway?
Describe the structure of TLRs.
Leucine rich repeat C arm
1 alpha helix transmembrane domain
TIR domain = toll/IL
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
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
All need to be balanced
Dysregulation - (gram neg sepsis) circulatory collage, organ failure, shock, death
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