L2

Question 1

What is the PAMP for gram negative bacteria? What is the PRR?

Answer 1

PAMP = LPS
PRR = TLR4

Question 2

You usually think of innate activating adaptive. How can the reverse occur?

Answer 2

Adaptive produces cytokines
Cytokines feedback onto innate cells to make their function more potent
(Forward rxn: innate produces cytokines that activate adaptive)

Question 3

Describe what happens if there is a defect in innate immunity only. Vs. adaptive immunity only.

Answer 3

W/o innate: can't stop antigen replication 
Why?
- Lacking/defective cells
- Lacking/block of chemokine gradient
W/o adaptive: can't clear infection

Question 4

What is desiccation?

Answer 4

Barrier innate fxn

Skin & mucus membranes sloughing off layers that have trapped pathogens

Question 5

What is the fxn of transferrin & lactoferrin?

Answer 5

Bind free Fe in blood so pathogen’s can’t use it
Fe = vital for pathogen survival/toxin production
Innate immune fxn

Question 6

What are host derived antimicrobial peptides? Where are the found - cellular and tissue levels?

Answer 6

Small - cationic proteins
Antimicrobial activity b/c cause membrane lysis
IN myeloid cells (innate cells)
OM mucosal surfaces

Question 7

What is the active molecule in defensins? How do they work?

Answer 7

Specific type of host derived antimicrobial peptide
CYSTEINE rich
= antibiotic against bacteria, fungi, viruses, etc
Mechanism:
- Insert directly into microbe membrane –> osmotic rupture

Question 8

Where are defensins produced?

Answer 8

Paneth cells @ intestinal crypts

Question 9

What is IFN alpha/beta? Where is it made? What is its fxn?

Answer 9

Interferon = cytokine
Made by activated immune cells & infected host cells
Fxn:
- Protects uninfected cells
- ↑MHC # w/ antigen –> ↑macrophage activity
- Activates NK

Question 10

Compare the initiating structures for classical vs mannose binding pathways of complement activation.

Answer 10

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

Question 11

Which bacteria is very susceptible to MAC attack? Aka which bacteria is a big problem if you’re lacking MAC?

Answer 11

Neisseria bacteria

Question 12

What are the 2 ways complement increases inflammation?

Answer 12

1. ↑vascular perm - fluid out of vessels –> tissues

2. ↑WBC diapedesis into tissues

Question 13

What is microbial antagonism as seen in the gut?

Answer 13

Commensal bacteria compete for nutrients vs pathogens

Stimulates innate innate system via interactions w/ gut epithelium –> tonic inflammation –> preventative (probiotics)

Question 14

What does a monocyte look like on histo?

Answer 14

Kidney shaped nucleus

Question 15

What GF pushes a hematopoeitic stem cell towards neutrophil?

Answer 15

G-CSF = granulocyte colony stimulating factor

Question 16

What GF pushes a hematopoeitic stem cell towards monocyte?

Answer 16

M-CSF - macrophage colony stimulating factor

Question 17

Name the steps of diapedesis and the relevant molecules.

Answer 17

Tissue residing WBCs send out alarmins & chemokines

1. Tethering - selectins
2. Activation - chemokines
   - Binding of chemokine 7TM receptors
   - Cytoskeleton changes to move WBC
3. Adhesion - integrin
4. Transendothelial migration

Question 18

What cells respond to tissue chemokines first? Second?

Answer 18

1st = neutrophils - degraulate to kill pathogen
2nd = monocytes --> macrophages - clean up

Question 19

What does it mean that macrophages demonstrate plasticity?

Answer 19

Can de-differentiate and re-differentiate

Response to varying stimuli

Question 20

What is classical macrophage activation?

Answer 20

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

Question 21

What are the overall goals of classical macrophage activation?

Answer 21

Microbicidial - NO
Tissue/cellular damage - NO
Inflammation - pro-inflamm cytokines
DTH - delayed type hypersensitivity

Question 22

What is alternative macrophage activation?

Answer 22

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

Question 23

What are the overall goals of alternative macrophage activation?

Answer 23

Humoral immunity
Allergic (!) and anti-parasite responses
Wound repair (!) and tissue remodeling

Question 24

If you bind a 7 TMD receptor, what is the functional outcome?

Answer 24

Migration into tissues via integrin & cytoskeleton changes

Question 25

If you bind a toll-like or mannose receptor, what is the functional outcome?

Answer 25

Killing of microbes via cytokines, ROS or phagocytosis