Lecture 3, Innate Immunity

Question 1

What barrier is the first line of defense when a pathogen tries to enter our bodies?

Answer 1

Epithelium

Question 2

What produces denfensins, and what do they do?

Answer 2

• Epithelial cells

- Use electrostatic interactions to enter lipid bilayer of pathogen -> permeabilization -> cell death

Question 3

In a word, what’s the end result of the innate response?

Answer 3

Inflammation

Question 4

What are the 4 main sx of inflammation?

Answer 4

• Rubor (redness)
• Calor (heat)
• Tumor (swelling)
• Dolor (pain)

Question 5

What types of things are happening to the inflamed site of the body?

Answer 5

• Alteration of blood flow
• Increased vascular permeability
• Infiltration of white cells into area of reaction

Question 6

In a word, what major category of cells is involved in the innate response?

Answer 6

Granulocytes

Question 7

List some details of the 2 ways macrophages and neutrophils counter threats

Answer 7

Phagocytosis
- Particle uptake + employ receptors to enhance uptake of pathogens
- Receptor can bind PAMPS, complement and AB
Mediator production
- Cytokines and Chemokines
- Hydrolases
- Reactive oxygen and nitrogen species

Question 8

What’s the difference b/w cytokines and chemokines?

Answer 8

• Cytokines: cause differentiation, proliferation, or death of other cells
• Chemokines: strictly recruit other types of cells

Question 9

In the innate response, what receptor detects the “danger” signal?
What specifically does it detect?

Answer 9

Pattern recognition receptor (PRR) detects “danger” signal

- Patterns!

Question 10

*What’s the difference b/w the DAMPs and PAMPs that the PRR is detecting?

Answer 10

• PAMPs: Pathogen Associated Molecular Pattern (foreign)

- DAMPs: Damage Associated Molecular Pattern (endogenous)

Question 11

What occurs after a PRR binds a DAMP/PAMP?

*What large macromolecular structure forms to mediate this?

Answer 11

Leads to expression of proinflamatory cytokines and antimicrobial proteins
- Inflamasome

Question 12

What are the 4 different classes of PRRs? (which are intra and which are extracellular?)

Answer 12

• Toll-like receptors (extracellular)
• C-type lectin receptors (extracellular)
• NOD-like receptors (intracellular)
• Rig-I-like receptors (intracellular)

Question 13

What is mannose-binding lectin?

What organ produces it?

Answer 13

A soluble acute phase protein (like CRP) that’s produced by the liver (in response to IL-1, IL-6, TNFa) that binds mannose residues on pathogens, thus acting as an opsinin or complement activator

Question 14

What are the 3 pw’s that lead to generation of C3 convertase during complement activation?

Answer 14

• Lectin pw
• Classical pw
• Alternative pw

Question 15

*What does C3 convertase make and what are the 3 effects that can occur?

Answer 15

Makes C3b (bound to microbial surface), C3a (soluble)

1. Recruit phagocytic cells to site of infection (C3a)
2. Phagocytes engulf C3b-bound pathogen
3. Membrane-attack complex (MAC) forms -> cell lysis

Question 16

What 5 cells have phagocytic abilities?

Answer 16

Monocytes, Neutrophils, Eosionophils, Macrophages, Dendritic cells (doesn’t destroy)

Question 17

What are the 2 classes of DCs?

Answer 17

Myeloid and lymphoid

Question 18

Class II MHC is primarily used to present __________ antigens while Class I MHC molecules are major presenter of __________ antigens

Answer 18

• Exogenous

- Endogenous (peptides generated w/in the cells)

Question 19

In what 3 ways do innate lymphoid (ILCs) cells differ from T/B cells?

Answer 19

(1) Absence of RAG gene—no DNA rearrangement
(2) Lack of myeloid cells/DCs marker
(3) lymphoid morphology.

Question 20

What set of cells distinguishes the innate from adaptive immune systems?

Answer 20

Macrophages

Question 21

Define opsonization, simply.

Answer 21

The coating of particles by molecules that enhance recognition by phagocytes

Question 22

The final common path for pro-inflammatory activation is _____.
How is this commonly induced (simple, general mech).

Answer 22

NFkappaB

- PAMP binds PRR on immune cell.

Question 23

Activation of transcription factor NF-kB activates genes encoding pro-inflammatory cytokines. One of the most important factors is IL-1 beta. Generation of IL-1beta also requires activation of a protein complex called ____________.

Answer 23

Inflamemasome

Question 24

The inflamemasome’s function is to activate a protease called ____________, which cleaves precursor of what inflammatory cytokine to the mature form?

Answer 24

Caspase I

- IL-1beta

Question 25

Name the 3 types of ILCs.

Answer 25

1. Type I (such as NK cells and NKT cells)
2. Type II cells
3. Type III cells

Question 26

What cytokines to type I ILC cells produce and why? (not sure if important)

Answer 26

Pro-inflammatory cytokines such as IFN-gamma and activates DCs.

Question 27

What cytokines to type II ILC cells produce and why? (not sure if important)

Answer 27

IL-4 and help maturation of DCs

Question 28

What cytokines to type III ILC cells produce and why? (not sure if important)

Answer 28

IL-17 which helps recruitment of neutrophils and production of anti-microbial peptides