Lecture 5: Receptors of Innate Immunity

What are the main receptors involved in innate immunity?

PRRs

What do PRRs bind to?

PAMP

• common biochemical structures expressed by microbes

• many are CRITICAL to pathogen survival and thus SHARED among families of related microorganisms

*****PRRs survey ALL MAJOR CELLULAR COMPARTMENTS for pathogens: What type of PAMPS are Plasma membrane PRRs (outward facing censor) activated by/ do they bind?

EXTRACELLULAR PATHOGENS

*****PRRs survey ALL MAJOR CELLULAR COMPARTMENTS for pathogens: What type of PAMPS are PRRs found INSIDE the cell (outward facing censor) activated by/ do they bind?

• particles released by ENDOCYTOSED or PHAGOCYTOSED pathogens

• Or they Detect CYTOPLASMIC bacteria

• NUCLEIC ACIDS from REPLICATING VIRUSES

*****do EXTRA or INTRA cellular PRRs detect tissue/Cellular damage?

BOTH intra + Extra cellular PRRs detect tissue/cellular damage

***Dead and dying cells (tissue/cellular damage) releases what?

• Hint: like PAMPs

DAMPs

• Damage associated Molecular particles

*****How are DAMPs different from PAMPs?

DAMPs = Our OWN molecules that PRRs recognize where as PAMPs = molecules from a Pathogen

*****What 8 types of cells express PRRs?

1. Monocytes

2. Macrophages

3. Granulocytes

4. DCs

5. some B cells

6. Some T cells

7. NK

8. ILC3 cells

******PRRs exist in specific cellular LOCATIONS, unique and overlapping effects follow after ligand binding. The innate immune system has evolved to recognize cellular threats found in both EXTRA + INTRA cellular compartments

• List the 6 types of PRRs

• Where are they each located

1. TLR (toll-like receptors) - On the plasma membrane + Endosomal membrane

2. NLR (Nod-like receptors) - in the Cytosol close to the endosomes

3. CLRs (C-type lectin receptors - Exclusively on the plasma membrane only

4. ALR (AIM-like receptors) - located in the Cytosol

5. RIG-I-like Receptors - Located in the cytosol close to the mitochondrial membrane

6. cGAS/STING receptors - in the cytosol close to the ER

*****Where does ALL SIGNALING (that results from PRR activation) occur?

in the CYTOSOL

******PRRs exist in specific cellular LOCATIONS, unique and overlapping effects follow after ligand binding. The innate immune system has evolved to recognize cellular threats found in both EXTRA + INTRA cellular compartments

• List the LIGANDS of the 6 types of PRRs

• aka WHERE (intra or extra cell) and nucleic acids or not

1. TLR = EXTRA + INTRA(endosomal) ligands

2. NLR = EXTRA + INTRA ligands

3. CLRs = EXTRA ligands only

4. ALR - CYTOSOLIC NUCLEIC ACIDS (DNA + RNA)

5. RIG like = CYTOSOLIC RNA

6. cGAS/STING = CYTOSOLIC DNA

*****Other than on IMMUNE CELLS where else are PRRs commonly found?

Non-immune cells that are commonly exposed to pathogens

• Epithelial skin

• Mucosal + Glandular

• Endothelial line blood vessels

• Fibroblasts + other stromal support cells in tissue

************_______ PRRs that sense _______ _____ _____ are expressed by MOST CELLS OF THE BODY

CYTOSOLIC PRRs that sense VIRAL NUCLEIC ACIDS are expressed by most cells of the body

*****PRRs binding to PAMPs results in the activation of intracellular signalling leading to:

• WHAT 3 things?

1. Generation of proinflammatory cytokines + chemokines

2. Production of anti-viral factors (Type 1 Interferon)

3. Activation of cellular antimicrobial responses including phagocytosis + the synthesis of antimicrobial proteins

Transcriptional factors are turned on to gear to a anti-viral/bacterial profile