Lecture 3 - Innate Immunity II

Question 1

PRR

Answer 1

Germline-encoded Pattern Recognition Receptors

Innate immune receptors that detect conserved, essential microbial features (They identify PAMPs and activate immune responses)

Some PRRs are Phagocytic receptors, and some PRRs are NOT phagocytic receptors but stimulate the activation of immune cells

PRRs are expressed on/in all leukocytes and boundary cells (endothelium and epithelium), and in phagocytic cells

(Not found on T cells but found on B cells)

Question 2

PAMP

Answer 2

Pathogen Associated Molecular Patterns

Found on numerous foreign microbes

Question 3

Bacterial Lipopolysaccharide

Answer 3

PAMP present on many bacteria

Question 4

Glycoproteins

Answer 4

Type of PAMP
Bacterial glycoproteins have terminal mannose residues, mammalian ones have terminal sialic acid or N-acetylgalactosamine

Question 5

Double-stranded RNA

Answer 5

PAMP common to many viruses

Question 6

Unmethylated CpG DNA

Answer 6

PAMP common to bacteria

Question 7

PRR characteristics

Answer 7

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

Question 8

Toll-Like Receptors (TLRs)

Answer 8

They are transmembrane PRRs for PAMPs

Consist of:
- Exterior Domain with Leucine-Rich Repeats (LRRs) in the extracellular matrix
- TLR Domain with Box 1, Box 2, and Box 3 in the intracellular matrix

Each TLR has a distinct location & ligands, and initiates a particular signaling pathway

Almost all TLR signaling leads to the production of transcription factors IRFs &/or NF-kappaB

Question 9

TLR1 + TLR2

Answer 9

Surveil for bacterial parasites

Question 10

TLR2 + TLR6

Answer 10

Surveil for gram-positive bacteria and fungus

Question 11

TLR4 + TLR4

Answer 11

Surveil for gram-negative bacteria

Question 12

TLR5 + TLR5(?)

Answer 12

Surveil for flagellated bacteria

Question 13

TLR3

Answer 13

Viral dsRNA

Question 14

TLR7

Answer 14

Viral ssRNA

Question 15

TLR8

Answer 15

Viral ssRNA

Question 16

TLR9

Answer 16

Bacterial DNA elements

Question 17

IRF

Answer 17

interferon response factors
—anti-viral response

A transcription factor turned on by most TLR pathways

Question 18

NF-kappaB

Answer 18

turns on many immune response genes

A transcription factor turned on by most TLR pathways

Question 19

RIG-like receptors (RLRs)

Answer 19

Related cytoplasmic sensors of viruses
eg RIG-I & MDA5

Have signalingpathways similar to TLRs

RLR dependent signaling can amplify TLR signaling

Question 20

Result of PRR signaling

Answer 20

• 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 21

IFN-I

Answer 21

Type I interferon

augments innate and adaptive immunity

Question 22

Importance of PRR Innate Immune Signaling

Answer 22

Speed: TLR signaling is “on” within minutes of detecting microbial PAMP. Initial activation of adaptive immune responses requires days

Economy: A limited number of TLR (approx. 10 members in humans, fish have 22+) can detect large numbers of different pathogens

Amplification: A localized detection of microbes can result in activation of large, systemic responses