Lecture 3: Innate Immunity II

Question 1

What happens in the innate immune detection of non-self?

Answer 1

1. Pathogen Associated Molecular Patterns (PAMP), which are common to many microbes, binds and is identified by the Germline-encoded Pattern Recognition Receptors (PRR) located in the innate immune cell.
2. Activation of immune responses, such as inflammation

Question 2

Examples of PAMPS that are essential microbial structures

Answer 2

1. Bacterial Lipopolysaccharide- present on many bacteria.
2. Glycoproteins- bacterial glycoproteins have terminal mannose residues, mammalian ones have terminal sialic acid or N-acetylgalactosamine
3. Double-stranded RNA- common to many viruses
4. Unmethylated CpG DNA- common to bacteria

Question 3

Characteristics of PRR

Answer 3

1. Detection of non-self structures
2. Ubiquitous, either as a circulating molecule or through expression on innate immune cells
3. Rapidly triggers potent antimicrobial responses

Question 4

What is a PRR?

Answer 4

Innate immune receptors that detect conserved, essential microbial features.

Question 5

Active PRRs drive )_________.

Answer 5

Inflammation

Question 6

Inflammation

Answer 6

mobilization of immune cells to sites of infection

Question 7

Toll-like receptors are major pattern recognition receptor family. Give an example

Answer 7

Toll knockout in fruit flies leads to uncontrolled infection by fungus

Question 8

Toll-like receptors (TLRs) are ______ for PAMPs

Answer 8

PRRs

Question 9

Each Toll-like receptor (TLR) has a distinct ______ and _____, and each initiates a particular ____________.

Answer 9

location and ligands
signaling pathway

Question 10

How does PRRs differ in structure/function?

Answer 10

• some PRRs are Phagocytic receptors
• some PRRs are not Phagocytic receptors but stimulate the activation of immune cells.

Question 11

Pathogens can change rapidly. Give an example of this

Answer 11

there are 30,000 known coronaviruses

Question 12

What is the reason why there are many PRRs?

Answer 12

There are many types of pathogens and it is important to have a recognition system that can recognize any form of any pathogen. That’s why there’s so many PRRs.

Question 12

Pathogens are disadvantaged by having small _____ and at least some _______(low variation) components: that are targets of PRRs

Answer 12

genomes, conserved

Question 12

Where do PRRs reside?

Answer 12

cell surface

Question 13

What do PRRs do or where do they function?

Answer 13

• function in endosomes
• surveil the cytoplasm
• surveil for intact PAMPs, degraded PAMPs, and PAMPs that are never outside of the cell

Question 14

Where do PRRs get expressed?

Answer 14

PRRs are variously expressed on, or in all leukocytes and boundary cells (endothelium and epithelium), and especially in phagocytic cells.

Question 15

Almost all TLR signaling leads to the production of ______ and/or _______, which are both transcription factors.

Answer 15

IRFs and or/ NF-κB

Question 16

IRF

Answer 16

• interferon response factors
• anti-viral response

Question 17

NF-κB

Answer 17

turns on many immune response gene

Question 18

RIG-like receptors (RLRs) include ________ and ________ which are related cytoplasmic sensors of viruses.

Answer 18

RIG-I and MDA5

Question 19

what do RLRs have in common (or similarity) with TLRs?

Answer 19

signaling pathways

Question 20

RLR dependent signaling can amplify _____ signaling

Answer 20

TLR

Question 21

Results of PRR signaling

Answer 21

• production of Type I interferon (IFN-I). IFN-I augments innate and adaptive immunity.
• production of various pro-inflammatory cytokines
• induces many other immune response genes

Question 22

Importance of PRR Innate Immune Signaling

Answer 22

1. Speed- TLR signaling is “on” within minutes of detecting microbial PAMP. Initial activation of adaptive immune responses requires days.
2. Economy- A limited number of TLR (approx. 10 members in humans, fish have 22+) can detect large numbers of different pathogens.
3. Amplification- A localized detection of microbes can result in activation of large, systemic responses.

Question 23

Why are there so many types of, and redundancy in, pattern recognition?

Answer 23

1. To overcome attempts by microbes to evade one or more PRRs.
2. Having multiple PRRs that can detect different common features of the same microbe enhances the chance the microbe is detected.
3. Cross-talk in signaling pathways induced by different PRRs allows for better control over the type or degree of response.