HRR: innate immunity

Question 1

Name three characteristics that distinguish the innate and adaptive immune
responses

Answer 1

The innate immune system is fast and has no memory, while the adaptive immune system is slower but has memory and gets stronger with subsequent responses

Question 2

What does the innate immune system recognize for activation?

Answer 2

PAMPS and DAMPS via pattern recognition receptors; many receptors can detect the same pathogen, and the same receptor can detect many different pathogens

Question 3

What are the two broad categories of innate immune response?

Answer 3

Inflammation and anti-viral defense

Question 4

Peptidoglycans, terminal mannose, flagellin, double stranded RNA, and unmethylated CG rich oligonucleotides are examples of…

Answer 4

PAMPs

Question 5

HMGB1 and extracellular ATP released from damaged mitochondria are examples of…

Answer 5

DAMPs

Question 6

What are the 3 things associated with acute inflammation

Answer 6

Complement, phagocytic cells, and cytokines

Question 7

In general, where are PRR’s found?

Answer 7

PRR’s can be found on the cell surface, in endosomal membranes, and in cytosol

Question 8

What are the 5 types of pattern recognition receptors?

Answer 8

1.toll-like receptors
2.NOD-like receptors
3.Inflammasomes
4.Cytosolic RNA and DNA sensors
5.Circulating receptors in the blood

Question 9

Toll-like receptors 3,7,8, and 9: where they are and what they do

Answer 9

They’re found on endosomal membranes and activate an antiviral defense

Question 10

PAMP binding in membrane TLR initiates the production of ___, and PAMP binding in endosomal TLR initiates the production of___

Answer 10

transcription factors NF-kb; IRF-3

Question 11

What does NF-kb do?

Answer 11

NF-kb will start the inflammatory process and stimulate adaptive immunity

Question 12

What does IRF-3 do

Answer 12

IRF-3 produces interferons and activates the antiviral state

Question 13

Describe NOD-like receptors

Answer 13

Cytosolic receptors that recognize PAMPs and DAMPs. They can be found in phagocytes and mucosal epithelial cells. They’re associated with the inflammatory pathway

Question 14

Explain what an inflammasome is, and what it is composed of

Answer 14

Inflammasomes has an ultimate goal of secreting IL1-beta. It is composed of NLRP3, adaptors, and caspase-1

Question 15

Describe how inflammasomes lead to secretion of IL-1beta

Answer 15

o NF-kb is formed and translocase to the nucleus to turn on the pro-IL1-beta gene

o Pro-IL1-beta exits the nucleus

o An inflammasome composed of NLRP3, adaptors, and caspases cleaves the pro-IL1-beta into IL-1beta.

o IL1-beta can exit the cell and lead to acute inflammation

Question 16

What are RIG-like receptors? what do they induce?

Answer 16

A cytosolic RNA sensor. They recognize viral RNA by their length or lack of methyl cap; they induce type 1 interferon production

Question 17

Describe cytosolic DNA sensors: what they do and what they induce

Answer 17

Recognize microbial dsDNA in the cytosol and induce type 1 interferon production as well as autophagy

Question 18

Describe the pathway used by cytosolic DNA sensors

Answer 18

o cGAS floating in the cytoplasm binds to DNA in the cytoplasm

o cGAS forms cyclic dinucleotides that bind to STING

o STING’s kinase (TBK1) phosphorylates IRF3, releasing it from the complex

o IRF3 translocates to the nucleus and induces the antiviral response

Question 19

What are the two PRR’s circulating in the blood

Answer 19

complement and acute phase proteins

Question 20

Name mechanisms by which the epithelium of the skin prevents the entry of
microbes.

Answer 20

Providing a physical barrier, killing microbes via defensins and cathelicidins, and killing microbes via intraepithelial lymphocytes

Question 21

List differences between monocytes and neutrophils, the primary phagocytes of innate immunity

Answer 21

Neutrophils: short lived and fast. They’re released from bone marrow during acute phase response

Monocytes: longer lived. They migrate to tissues in response to inflammation

Question 22

Which chemicals are produced by neutrophils and monocytes respectively?

Answer 22

ROS; NO

Question 23

Which phagocyte makes cytokines?

Answer 23

monocytes

Question 24

Describe the functions of dendritic cells

Answer 24

They produce pro-inflammatory cytokines and migrate to lymph nodes to present antigens

Question 25

Describe the functions of mast cells

Answer 25

The release vasoactive amines, proteolytic enzymes, and cytokines (TNF). They increase mucous production and leaky vessels

Question 26

What two things are associated with antiviral defense?

Answer 26

NK cells and type I interferons

Question 27

Describe natural killer cells: what they do, what they secrete/activate

Answer 27

They eliminate intracellular pathogens. They recognize infected or stressed cells and secrete IFN-gamma to activate macrophages and release granules to induce apoptosis

Question 28

Describe activating and inhibitory NK cell receptors

Answer 28

NK cell activating receptors: recognize patterns associated with stressed, infected, or malignant cells. This alone with no presence of the inhibitory receptor will activate the NK cell. Inhibitory NK receptors recognize class I MHC, which are ‘self’ molecules on human cells. This combined with the activating receptor keeps the NK cell from turning on.

Question 29

Describe interferon I and the antiviral defense

Answer 29

They are found on most cells and are either made by dendritic cells (IFN-a) or fibroblasts (IFN-b). a virus present in a cell induces interferons. they activate OAS and PKR, which shuts down protein synthesis in the particular cell and leads to no viral production

Question 30

Briefly describe complement

Answer 30

They’re synthesized largely in the liver and are distributed throughout the blood and lymph. They directly destroy microbes and generate signals that indicate an attack has happened.

Question 31

What are the 3 mechanisms for initiating complement activation?

Answer 31

Alternate: microbe-based Classical: antibody-based Lectin: mannose binding lectin

Question 32

Explain the three complement activation cascades to C5, and the common cascade from C5-C9

Answer 32

All 3 mechanisms cleave C3 into C3a and C3b via a unique C3 convertase. C3a will act as a signaling molecule. C3b binds to microbes, initiating cleavage of C5 into C5a and C5b. C5b will bind to the microbe and initiate the assembly of complement and C6-9

Question 33

Name functions of C3a, C3b, and C5a

Answer 33

C3a: degranulate mast cells C3b: increase phagocytosis C5a: degranulate mast cells and recruit neutrophils

Question 34

Name the acute phase proteins circulating in the blood

Answer 34

Complement, collectins, c-reactive protein

Question 35

How do cytokines act?

Answer 35

Autocrine or paracrine methods

Question 36

What are chemokines?

Answer 36

Subset of cytokines that stimulate and direct leukocyte migration

Question 37

What does IL-10 do?

Answer 37

Is an antagonist for IL-1 receptor and has anti-inflammatory activity.

Question 38

Explain the purpose and general mechanism of the innate immune system stimulation of adaptive immune responses

Answer 38

Various elements in the innate immune system act as costimulatory molecules, acting as the second required signal for the active immune system.