L2 Flashcards
What is the PAMP for gram negative bacteria? What is the PRR?
PAMP = LPS PRR = TLR4
You usually think of innate activating adaptive. How can the reverse occur?
Adaptive produces cytokines
Cytokines feedback onto innate cells to make their function more potent
(Forward rxn: innate produces cytokines that activate adaptive)
Describe what happens if there is a defect in innate immunity only. Vs. adaptive immunity only.
W/o innate: can't stop antigen replication Why? - Lacking/defective cells - Lacking/block of chemokine gradient W/o adaptive: can't clear infection
What is desiccation?
Barrier innate fxn
Skin & mucus membranes sloughing off layers that have trapped pathogens
What is the fxn of transferrin & lactoferrin?
Bind free Fe in blood so pathogen’s can’t use it
Fe = vital for pathogen survival/toxin production
Innate immune fxn
What are host derived antimicrobial peptides? Where are the found - cellular and tissue levels?
Small - cationic proteins
Antimicrobial activity b/c cause membrane lysis
IN myeloid cells (innate cells)
OM mucosal surfaces
What is the active molecule in defensins? How do they work?
Specific type of host derived antimicrobial peptide
CYSTEINE rich
= antibiotic against bacteria, fungi, viruses, etc
Mechanism:
- Insert directly into microbe membrane –> osmotic rupture
Where are defensins produced?
Paneth cells @ intestinal crypts
What is IFN alpha/beta? Where is it made? What is its fxn?
Interferon = cytokine
Made by activated immune cells & infected host cells
Fxn:
- Protects uninfected cells
- ↑MHC # w/ antigen –> ↑macrophage activity
- Activates NK
Compare the initiating structures for classical vs mannose binding pathways of complement activation.
Classical
1. Ab binds pathogen (adaptive immunity tie)
2. C1 complex binds the Fc region of Ab
Mannose
- Mannose binding lectin has parallel structure to Ab
1. MBL binds mannose sugar on bacteria membrane –> complement activation
Which bacteria is very susceptible to MAC attack? Aka which bacteria is a big problem if you’re lacking MAC?
Neisseria bacteria
What are the 2 ways complement increases inflammation?
- ↑vascular perm - fluid out of vessels –> tissues
2. ↑WBC diapedesis into tissues
What is microbial antagonism as seen in the gut?
Commensal bacteria compete for nutrients vs pathogens
Stimulates innate innate system via interactions w/ gut epithelium –> tonic inflammation –> preventative (probiotics)
What does a monocyte look like on histo?
Kidney shaped nucleus
What GF pushes a hematopoeitic stem cell towards neutrophil?
G-CSF = granulocyte colony stimulating factor
What GF pushes a hematopoeitic stem cell towards monocyte?
M-CSF - macrophage colony stimulating factor
Name the steps of diapedesis and the relevant molecules.
Tissue residing WBCs send out alarmins & chemokines
- Tethering - selectins
- Activation - chemokines
- Binding of chemokine 7TM receptors
- Cytoskeleton changes to move WBC - Adhesion - integrin
- Transendothelial migration
What cells respond to tissue chemokines first? Second?
1st = neutrophils - degraulate to kill pathogen 2nd = monocytes --> macrophages - clean up
What does it mean that macrophages demonstrate plasticity?
Can de-differentiate and re-differentiate
Response to varying stimuli
What is classical macrophage activation?
Inactive macrophage binds inflam cytokines & TLR agonists - Ex: bind IFN-gamma AND LPS Activated macrophage makes: 1. Pro-inflam cytokines 2. ↑MHC 2 to present bound TLR agonist 3. ↑NO = respiratory burst
What are the overall goals of classical macrophage activation?
Microbicidial - NO
Tissue/cellular damage - NO
Inflammation - pro-inflamm cytokines
DTH - delayed type hypersensitivity
What is alternative macrophage activation?
Inactive macrophage binds cytokines from Th2 cells (helper T w/ goal inflam) or infected macrophages
- Ex: IL4, IL13
Activated macrophage:
1. ↑MHC 2
2. Eat antigen
3. Release IL4/3 to feedback and sustain macrophage’s own activity
What are the overall goals of alternative macrophage activation?
Humoral immunity
Allergic (!) and anti-parasite responses
Wound repair (!) and tissue remodeling
If you bind a 7 TMD receptor, what is the functional outcome?
Migration into tissues via integrin & cytoskeleton changes
If you bind a toll-like or mannose receptor, what is the functional outcome?
Killing of microbes via cytokines, ROS or phagocytosis
