Innate Immunity

Question 1

Antibiotic therapy can lead to loss of _____, allowing pathogens to grow out

Answer 1

Commensals

Question 2

What types of pathogens do Toll-Like Receptors help defend against, what cells are they expressed on, and what type of reaction do they induce?

Answer 2

Bacteria, fungi and viruses. On monocytes/macrophages and dendritic cells. Induce inflammation

Question 3

Which receptors are at the PM and which are in the endosome: TLR-2, TLR-3, TLR-4, TLR-7 and TLR-9?

Answer 3

TLR-2 and 4 are at the PM, TLR-3, 7, and 9 are in the endosome

Question 4

What is the major component of gram-negative bacteria outer membranes and what human receptor of the innate immune system recognizes it?

Answer 4

Bacterial lipopolysaccharide, recognized by TLR-4

Question 5

What does TLR-9 recognize?

Answer 5

Unmethylated CpG DNA, a hallmark of bacterial DNA

Question 6

What are the three main receptors in the innate immune system?

Answer 6

Toll-Like Receptors (TLRs), Mannose receptors and RIG-like Receptors (RLRs)

Question 7

What do Rig-Like Receptors (RLRs) recognize?

Answer 7

Viral RNA

Question 8

What two types of molecules do innate immune cells emit and what does each do?

Answer 8

Type I interferons (alpha and beta) - have anti-viral properties, and Pro-inflammatory cytokines and chemokines - attract effector cells

Question 9

Endothelial cells produce chemokines and adhesion molecules to attract monocytes and neutrophils. What stimulates them to do so?

Answer 9

Cytokines from macrophages

Question 10

Name four types of phagocytic cells

Answer 10

Circulating monocytes, resident macrophages, dendritic cells, neutrophils

Question 11

Activation of innate phagocytic cells leads to production of what toxic species?

Answer 11

ROS, NO, and lysosomal proteases

Question 12

Name 5 cytokines produced by innate phagocytic cells, what cell type produces each, and what each does

Answer 12

Type I interferons - any infected cell, is anti-viral, TNFa - Macrophages and DCs, increases vascular permeability, IL-1 - Macrophages and keratinocytes, induces acute phase proteins, IL-6 - Phagocytes, endothelial cells, fibroblasts, release of acute phase proteins, IL-8 (aka CXCL8) - phagocytes, attracts neutrophils

Question 13

TNFa and IL-1 induce expression of what proteins in endothelium to attract inflammatory cells?

Answer 13

P-selectin and E-selectin

Question 14

Binding of what leukocyte protein to what endothelial protein causes extravasation?

Answer 14

Leukocyte LFA-1 binding to endothelial ICAM-1

Question 15

What leads to pus formation at sites of injury?

Answer 15

Neutrophils ingest pathogens and then die, releasing pus

Question 16

NKG2D

Answer 16

A receptor in NK cells which recognizes molecules that resemble MHC class I molecules (expressed on stressed or infected cells)

Question 17

What are two activating receptors for NK cells and what is an inhibiting receptor?

Answer 17

NKG2D and Fc (for IgG or IgE) receptors are activating, MHC class I recognizing receptors are inhibiting

Question 18

What cytokines activate NK cells?

Answer 18

Type I interferons, IFNg, IL-12

Question 19

Where do gamma-delta T cells live and what do they do?

Answer 19

In epithelia and in the gut, they recognize self components that are altered by infection

Question 20

What type of cell recognizes microbial glycolipid antigens and what receptor presents these molecules?

Answer 20

NK T cells (found in epithelia, liver, and lymphoid organs). Presented by CD1

Question 21

B1 Cells

Answer 21

Found in pleural and peritoneal cavities with specificities for common targets in the gut, often polysaccharides. Produce IgM

Question 22

What cytokines in particular produce an acute phase response?

Answer 22

IL-1, IL-6, and TNFa

Question 23

Two important acute phase proteins and what each does

Answer 23

C-reactive protein - binds phosphocholine (on surface of dead or dying cells), and Mannose-binding lectin - recognizes microbial carbohydrates and can coat microbes or activate complement

Question 24

What are four roles of the acute phase response?

Answer 24

Neutrophil mobilization, increase body temperature, protein and energy mobilization, dendritic cell maturation

Question 25

How do complement proteins contribute to B cell activation?

Answer 25

They provide co-stimulation by binding to CD21 (a complement receptor on B cells)

Question 26

What are the four main roles of the innate system in adaptive responses?

Answer 26

Antigen presentation, co-stimulation, cytokine growth and differentiation factors, and effector mechanisms (both humoral and T-mediated)

Question 27

What are two PAMPs that external TLRs recognize

Answer 27

LPS and Flagellin

Question 28

What are the first and second phagocytic responders of the innate immune system?

Answer 28

Macrophages (first) and neutrophils (second)

Question 29

What do dendritic cells produce which serves as an important Signal 3 for T-cells and what other effect does it have?

Answer 29

IL-12, which also pushes the response towards Th1

Question 30

IL-10

Answer 30

Inhibits IL-12 production in macrophages, reduces expression of co-stimulators and MHC Class II. Produced mainly by macrophages and Th2

Question 31

IL-12

Answer 31

Stimulates IFNg synthesis and increase in cytolytic activity from T and NK cells. Pushes response towards TH1. Produced by macrophages, DCs

Question 32

What two innate cells are well known for reciprocal activation and what molecules do they use?

Answer 32

Macrophages can activate NK cells with IL-12, which produce IFNg in response which further activates the macrophage

Question 33

Why is it useful for NK cells to look for MHC Class I on a potential victim cell?

Answer 33

Because viruses often inhibit MHC Class I expression (so if MHC Class I isnt there, cell may be infected)

Question 34

What receptor mediates Antibody-Dependent Cytotoxicity in NK cells and Eosinophils, and in each what Ig does this receptor bind?

Answer 34

Fc receptor. Binds IgG in NK cells, and binds IgE in eosinophils (important for parasitic infection)

Question 35

What type of antigens do B1-B cells respond to?

Answer 35

T-independent antigens (IgM response to very common antigens such as LPS)

Question 36

For Th1 and Th2 responses respectively, which cytokine is most associated with promoting each?

Answer 36

Th1 - IL-12, Th2 - IL-4