cytokines

Question 1

What are two receptors generated by somatic recombination?

Answer 1

TCR and Ig

Question 2

What are 3 examples of germ line encoded receptors?

Answer 2

PRRs, cytokine receptors and MHC

Question 3

What are PAMPs and where are they found?

What are PRRs and where are they found

Answer 3

Component of a pathogen. Most pattern associated molecular patterns are derived from bacterial and viral pathogens (some fungal and helminth) and include bacterial cell wall molecules, flagellin, LPS
Receptors on innate immune cells that recognize PAMPs. example: TLRs

Question 4

Which cells express PRRs?

Answer 4

Innate immune cells–macrophages, NK cells, neutrophils

Question 5

PAMP:PRR interaction activates which signaling pathway? And induces gene expression of what factors? (general)

Answer 5

NFkB; pro-inflammatory (cytokines, chemokines, etc)

Question 6

What 3 main cytokines are produced in initial inflammatory response? (in response to pathogen encounter; PAMP:PRR)
Which 2 are responsible for inducing fever?

Answer 6

TNFalpha, IL1, IL6; TNFalpha and IL1

Question 7

What distinguishes a chemokine from a cytokine?

Answer 7

chemotaxis–promote migration of leukocytes into an infected site.
Function in a cell-contact INDEPENDENT manner

Question 8

What factors influence neutrophil extravasation? (cytokines)

Answer 8

TNFalpha, IL1, chemokines

Question 9

How do chemokines aid neutrophil extravasation?

Answer 9

activates integrins on neutrophil cell surface to aid Attachment and adhesion to endothelial cells as they’re rolling

Question 10

What cytokines do Macrophages and Th cells secrete that induces proliferation and migration of neutrophils?

Answer 10

G-CSF and GM-CSF (granulocyte colony stimulating factor)

Question 11

What is the function of IL-8 and which cells secrete it?

Answer 11

chemotactic for circulating PMNs and secreted by macrophages, endothelial/epithelial cells, airway smooth muscle cells.

Question 12

Can PRRs be found intracellularly?

Answer 12

Yes, some are located on the endosomal membrane and bind PAMPs such as microbial nucleic acids, CpG dinucleotides

Question 13

What are the four stages of PMN extravasation?

Answer 13

Rolling, Integrin activation by chemokines, stable adhesion/binding, and migration through the endothelium

Question 14

T-cell activation leads to what as a result of intracellular signaling? (expression of 2 surface molecules and one very general process)

Answer 14

CD40L, expression of (high affinity) IL2 receptor (CD25), DNA synthesis

Question 15

What cytokine is responsible for providing autocrine, cell contact INDEPENDENT, Pro-proliferative feedback to Th cell?

Answer 15

IL-2

Question 16

Cyclosporin A blocks production of which cytokine?

Answer 16

IL-2

Question 17

Which APC produced cytokines cause differentiation of each
THnaive–>Th1
THnaive–>Treg
THnaive–>Th2

Answer 17

IL-12
IL-10/TGFB
no cytokines (default)

Question 18

What cytokines do Th1 cells produce and what is effect?

Answer 18

secrete IFNy. Autocrine signal for Th1 prol., activate macrophages, promote class switching to IgG2a, SUPPRESS Th2 development

Question 19

What cytokines do Th2 cells produce and what is effect?

Answer 19

IL-4: prol of Th2 cells, suppress Th1, class switch to IgG1
IL-5: class switch to IgA, promote eosinophilia

Question 20

What cytokines do Tregs cells produce and what is effect?

Answer 20

TGFb and IL-10: autocrine signal for further treg development

Question 21

What combination of cytokines promotes Th17 cell differentiation/proliferation?
What cytokines do Th17 cells secrete?

Answer 21

TGFB, IL-6, IL-23

IL-17, IL-22

Question 22

What Th cell subsetl is FoxP3 associated with?

Answer 22

Tregs

Question 23

What is Alum/Alhydrogel? What cytokines expression does it promote?

Answer 23

only FDA approved vaccine adjuvant. Promotes expression of IL4 which in turn promotes TH2 development and antibody production

Question 24

Which Th cell cytokines cause the following class switching?
IgM
IgG1/3
IgE
IgA

Answer 24

default
IFNy
IL-4
IL-5, (TGFB from mucosal )

Question 25

Helminths opsonized with IgE antibody bind Fc (FceR1) receptors on which cell type?

Answer 25

Granulocytes (mast cells, basophils, eosinophils) and cause activation and degranulation

In this case it is cell contact dependent, but it CAN be contact-independent (don’t need to know now)

Question 26

What molecules are released in the granules of granulocytes?

Answer 26

Histamine, Prostaglandin D2, Leukotriene C4

All pro-inflammatory

Question 27

Antibody-directed phagocytosis is dependent on which FCR:Ab interaction?

Answer 27

FcyRI (on macrophages) with IgG bound to pathogen

Question 28

Antibody-directed cytotoxicity is dependent on which FCR:Ab interaction?

Answer 28

FcyRIIIA (aka CD16, on NK cells) with IgG bound to virus-infected or cancer cell

Question 29

Which cytokines are associated with CTL and NK cell cytotoxicity (defense against viruses)?

Answer 29

IFN alpha and beta

IFN alpha induces an antiviral state in all cells, and up regulates MHC class 1 expression

Question 30

Which cytokines secreted by MACROPHAGES cause NK cell proliferation?

Answer 30

IL-15 and IL-18

Question 31

Which inflammatory mediators released by granulocytes affect vasodilation and bronchoconstriction?

Answer 31

Histamine and Prostaglandin and Leukotrienes all cause bronchoconstriction

Prostaglandin acts as a vasodilator in smooth muscle