Immune Recognition I: Innate Receptors

Question 1

what are innate receptors called?

Answer 1

pattern recognition receptors or PRRs

Question 2

what are the three main categories of receptors of the innate system?

Answer 2

1. transmembrane receptors on immune cells
2. secreted proteins
3. cytoplasmic receptors that are in almost all cells

Question 3

There are 4 types of receptors in the transmembrane category. Name one.

Answer 3

1. Toll-like receptors
2. mannose or glucan receptors
3. receptors for bacT cell walls
4. receptors that bind complement system components
5. scavenger receptors that take up macromolecules with a negative surface charge

Question 4

The secreted proteins category of receptors have two functions…

Answer 4

1. bind microbes and tag them for phagocytosis (lectins and complement)
2. direct anti-microbial function (defensins)

Question 5

The cytoplasmic receptor class of receptors includes what?

Answer 5

“nucleotide-binding domain, leucine-rich repeat containing” (NLRs) that bind microbial compounds and stress-associated self molecules and activate response

Question 6

what is the fxn of the complement system?

Answer 6

recognize and eliminate extracellular microorganisms and promote host inflammatory responses

Question 7

what is the central biochemical event?

Answer 7

proteolytic cleavage of C3 –> C3a + C3b which then activate two effector response pathways

Question 8

what does C3a do?

Answer 8

acute inflammatory response:

vasoactive effects, chemo-attractant for phagocytes

Question 9

what does C3b do?

Answer 9

covalently attaches to microbe

promotes uptake by phagocytes and initiates deposition of pore-forming complex

Question 10

What are the three pathways that activate complement cascade leading to C3 cleavage?

Answer 10

1. alternative pathway
2. lectin pathway
3. classical pathway

Question 11

describe the alternative pathway

Answer 11

complement proteases directly activated by factors on surface of microbe resulting in cascade that cleaves C3

Question 12

describe lectin pathway

Answer 12

plasma protein mannose-binding lectin binds high mannose proteoglycans that initiates the proteolytic cleavage cascade

Question 13

describe the classical pathway

Answer 13

CRP or certain antibody types bind surface of microbe, a complement component called C1q recruited to surface of microbe.

C1q (stxally similar to MBL leads to C3 cleavage

Question 14

what are the three effector mechanisms

Answer 14

1. anaphylatoxins
2. opsonization
3. MAC formation

Question 15

describe anaphylatoxins

Answer 15

low MW fragments from C3, C4, C5 (a versions)

smooth muscle contraction
histamine release from mast cells, enhanced vascular permeability
chemo-attractants for phagocytic cells

Question 16

describe opsonization

Answer 16

C3b covalently attaches to microbe

microphages and neutrophils recognize C3b and phagocytose

Question 17

Describe MAC formation

Answer 17

Membrane attack complex

after C3b attaches, cascade continues and 5 different proteins come together to produce a pore-forming unit that lyses bacT

Question 18

What pathways protect our own cells from complement system?

Answer 18

Factor H and Factor I

cell surface complement-destabilizing proteins

Question 19

what are factor H and factor I

Answer 19

plasma protein that cleave C3b from cell surface

factor H binds sialic acid so it coats mammalian cells and keeps C3b from binding

Question 20

what do cell surface complement-destabilizing proteins do?

Answer 20

mammalian cells express cell surface decay-accelerating factor (DAF) and membrane cofactor protein (MCP) that cleave C3b that bind to cell surface

Question 21

List as many Toll-like Receptor ligands as you can

Answer 21

lipopeptides
lipteichoic acid
lipopolysaccharide
dsRNA (viral)
ssRNA (viral)
ssRNA  (viral)
unmethylated CpG-rich DNA
GPI
flagellin
zymosan

Question 22

Relationship between cell type and type of TLR?

Answer 22

Different cell types have different TLRs

a NK cells will have TLRs for viral recognition, a macrophage will ahve TLR for bacteria

Question 23

two cellular locations of TLR?

Answer 23

plasma membrane

endosomes

Question 24

relationship between TLR location and its target?

Answer 24

if its in the endosome, then the target is intracellular (ssRNA, unmethylated DNA, dsRNA)

If it is in the plasma membrane then extracellular (lipopolysaccharide, flagellin, GPI, lipopeptides, lipoteichoic acid, zymosan)

Question 25

Give an example of TLR co-operation

Answer 25

TLR4 recognizes LPS from G- bacT…

monocytes and macrophages express CD14 that has high affinity for LPS…

CD14 binds LPS, but must come together with TLR4 and MD2 inorder to stimulate intracellular signaling

Question 26

how does TLR co-operation affect sensitivity?

Answer 26

monocytes and macrophages are highly sensitive to low concentrations of LPS but dendritic cells, mast cells, eosinophils (which do not express CD14) are less sensitive.

Question 27

How do intracellular signals get transmitted?

Answer 27

adaptor protein acts as bridge to signaling cascades

ultimately, a protein is translocated to nucleus (i.e. NFkB) which is a trx factor that induces inflammation/cytokines/other p

There is an alternative that leads to IRF3 which has different targets than NFkB…innate defense mechanisms…protect against viral infection