Innate Receptors and Signaling Overview

PRR

PRR

recognizes PAMPs, MAMPs, and DAMPs

Toll-like receptors

TLRs, can be homo or heterodimer and cytoplasmic or membrane bound

Membrane-bound TLRs

TLR4/4, 2/1, 2/6, 5/5, 11/11, 12/12

Cytoplasmic TLRs

TLR 4/4, 3/3, 7/7, 8/8, 9/9

Myd88 and TRIF

adapter proteins in TLR signaling

C-type lectin receptor

CLRs, similar ITAMs and mechanism to B cell receptors

NOD-like receptors

Leucine rich hook like TLRs, 3 subtypes

CARD

domain of NLRC subtype

PYD

domain of NLRP subtype

BIR

domain of NLRB subtype

Inflammasome

induces immune response, esp. inflammation, and activates cytokines

NLR, ASC, Capsase-1

components of inflammasome

RIG-1-like Receptors

RLRs, bind viral RNA inside of infected cells

cGAS, STING, ALR

new receptors for transcription factor activators (NFKB, have to do with cancer)

Paneth cells

cells that constantly produce a/b defensins (mostly alpha) in the intestinal epithelia

Dendritic and NK

cells that produce antimicrobial peptides (when activated)

Type 1 interferon

produced when internal TLRs encounter antigen, bind to cause 4 different mechanisms with ISG (interferon stimulate genes)

Protein kinase R

activated by dsRNA to stop translation with type 1 interferons

Oligo(A) synthetase

activated by dsDNA to activate RNase with type 1 interferons

Mx proteins

inhibit viral assembly and transcription with type 1 interferons

IFIT proteins

inhibit translation with type 1 interferons

IL-1, TNFa, and IL-6

cytokines produced by intracellular PRRs

IL-1

activated before secretion, in alpha or beta form, forms positive feedback loop with its own PRR, slowly activates IL-10

IL-10

activated by accumulation of IL-1 to suppress inflammation at high concentration

TNF

cytokine pathway leads either to apoptosis or inflammation induction

Chemokines

attract neutrophils in innate response

inducible nitric oxide sythase

iNOS

cyclo-oxygenase 2

COX2, arachidonic acid activated to prostaglandins (help with inflammation)

Reactive oxygen species

ROS, bind DNA to cause damage, has to do with radiotherapy in cancer and antioxidants

actin filaments

used to extend pseudopodia around pathogen when PRR is activated

Phagosome

vesicle that bacteria is phagocytosed into

Lysosome

has low pH (4.5) and digestive enzymes, binds phagosome to kill microbes

pH, anti-microbial peptides, granules

3 ways digestion occurs for pathogens

NADPH oxidase

has to do with ROS and NOS production to kill cells

Mannose receptor

CLR that binds mannans (bacteria, fungi, parasites)

SR-A

scavenger receptor that binds lipopolysaccharide, lipoteichoic acid (bacteria)

SR-B

scavenger receptor that binds lipopolysaccharide, lipopeptides, diacylglycerides (bacteria), and beta-glucans (fungi)

Mannose-binding lectin

deficiencies cause a lot of diseases, but helps with tuberculosis

C1q

opsonin recognized by CR1 receptor

C-reactive protein

CRP, binds bacteria and has high antibody affinity

Homeobox genes

regulate development and body position during development

Christaine Nusslein-Volhard

scientist that won nobel prize for homeobox research

Toll gene

gene in flies that removes immune function when mutated

Septic shock

organ failure due to bacteria (gram -) infection without TLRs