Lec. 2 - Innate immune system

The innate immune system begins with the physical barriers. There are a total of 7. List them and give a short answer as to why or what part that allows it to be a line of defense.

1. Skin: dermis (outer layer), epidermis (has WBCs)

2. Microbiota: Natural skin dwelling microbes that fight other microbes

3. Secretions: has antimicrobial proteins

4. Mucosal membranes: Surfactants bind to microbes → marks for phagocytosis & lysozymes in tears/saliva kill g+ bacteria

5. Respiratory tract: coughing & sneezing

6. Digestive tract: acidity in stomach kills microbes

7. Genitourinary tract: urine flushes and slightly acidic

There are multiple pattern recognition receptors on macrophages, dendritic cells, neutrophils, eosinophils, monocytes, mast cells, T cells, and epithelial cells. List the different types of pattern receptors that exist. (Hint* 4)

• Toll-like receptors (TLRs)

• C-type lectin receptors (CLRs)

• Retinoic acid-inducible gene…receptors (RLRs)

• Nucleotide-binding olgo (NOD)-like receptors (NLRs)

What two things do pattern recognition receptors (PRRs) look for? Provide a brief description of what they look for.

1. Pathogen-associated molecular patterns (PAMPs): infectious particles

2. Damage-associated molecular patterns (DAMPs): stress/damage particles

One PRR is the toll-like receptor (TLR). How many are usually found in humans? Explain where they can be found on/in the cell and why.

• 10 in humans

• TLRs are in the cell: b/c viruses in the cell will then trigger the TLR to produce a “help” response via cytokine

• TLRs are on cell surface: It can trigger the adaptive immune system

What 3 cells are commonly found to have TLRs?

• Monocytes

• Macrophages

• Dendritic cells

Another pattern recognition receptor (PRR) is a CLR. What does this stand for and what does it target? Where is it located in/on the cell?

• C-type lectin receptor

• Targets the Carbohydrates in fungal cell walls

• Outside the cell

Another pattern recognition receptor (PRR) are the RLRs. What does this stand for and what does it target? Where is it located in/on the cell? What cells do these receptors recruit?

• Retinoic acid - inducible gene - 1 - like recep. (RIG-1)

• Targets viral RNAs in the cell

• Internally

• Cytotoxic T cells and NK cells

Another pattern recognition receptor are the NLRs. What does this stand for and what do they target? Where are they located in/on the cell?

• Nucleotide-binding (NOD-like) receptors

• Targets bacterial cell walls and protozoans

• Located internally

What do acute-phase reactants respond to and what do they help with? What do they release?

• responds to tissue damage and limit neutrophil damage in skin

• Releases opsonin’s to allow contact between microbes and phagocytosis

What are the 7 acute-phase reactants and their function?

1. C-reactive protein: opsonization & Complete activation

2. Serum Amyloid (A): Activation of monocytes & macro

3. Alpha1-antitrypsin: Protease inhibitor

4. Fibrinogen: Clot formation

5. Haptoglobin: Binds hemoglobin

6. Ceruloplasmin: Binds copper & oxidizes iron

7. Complement C3: opsonization, lysis

What are the 5 symptoms of injury?

• redness/erythema (rubor)

• swelling/edema (tumor)

• Heat (calor)

• Pain (dolor)

• Loss of function (functio lasea)

Explain the 3 main stages of injury and give a brief description of what is released during them.

1. Injury leads to release of histamine → vasodilation (red/heat)

2. Vasodilation leads to dilation & clotting → swelling/pain

3. Chemokines released by macros/DCs/mast cells recruit neutrophils (phagocytes) → cells squeezing through skin to injury is called Diapedesis

What phagocytes are attracted to sites of inflammation?

• Dendritic cells

• macrophages/monocytes

• neutrophils

What are the steps to phagocytosis? Starting with microbe attraction (why are they phagocytosed) (~4 steps)

1. Microbe coated in opsonin attracts phagocytic cell

2. Phagocyte engulfs microbe into phagosome

3. lysosome fuses with phagosome to create phagolysosome and destroys microbe via granules/digestion enzymes

4. Phagocytic cell excretes unneeded things.

What are the two ways the phagocytic cell kills a microbe (internally)?

1. Upon entrance into phagolysosome, pH alters and activates lytic enzymes (due to O2 dependence)

2. Free radicals create an oxidative burst as they burst the microbe by stealing electrons.

What do NK cells produce to recruit what type of cell?

Produces cytokines to recruit T cells

What two ways can an NK cell detect a target cell and how does it kill it?

1. Missing/altered MHC 1: will activate the NK cell b/c likelihood of it being infected or stressed is high.

2. Antibody-dependent cell-mediated cytotoxicity (ADCC): Antibody will attach to infected cell (due to recognition of infectious particles) and NK cell will recognize antibody.

How it kills: NK cell uses perforins to create holes in cell and then shoots granulocytes through perforins.