Cytokines of adaptive immunity

Question 1

IL-2

Answer 1

TH2 subset

mediates growth, survival and differentiation of T lymphocytes by exerting anti-apoptotic function by activating Bcl-2 (mitochondria surface)

induces synthesis of cyclins and induces degradation of p27 (cdK inhibitor so can’t slow down cell cycle)

necessary for survival of Reg t cells

stimulates NK cells

Stimulates Ab production

Question 2

what produces IL-2

Answer 2

CD4+ T cells (T helper cells)

Question 3

what activates IL-2

Answer 3

Antigen presentation and costimulators

Question 4

What are the cytokines of the TH2 subset

Answer 4

IL-2

Question 5

what is CD8+

Answer 5

cytotoxic cells

destroy cells

Question 6

IL-4

Answer 6

of the TH2 subset

stimulates differentation of CD4 to TH2
inhibits TH1 differentiation

defense against helminthic or arthropod infection (mast cells and eosinophils)

Question 7

when do allergies occur

Answer 7

When IL-4 stimulates IgE production

IgE then goes on to help eosinophils and mast cells degranulate in the ABSENCE of a microorganism (so happening unusually)

Question 8

Systemic activities of IL-4

Answer 8

Allergies

Fibrosis

Question 9

How does IL-4 and IL-13 stimulate fibrosis?

Answer 9

induces arginase expression in macrophages

arginase diminishes activity of NO synthase

NO synthase promotes extravasation/inflammation normally

so decreased level of this will promote “wound healing” type of response –> leading to fibrosis

Question 10

why do we want fibrosis with parasites?

Answer 10

collagen deposition helps to isolate the parasite so they can’t release toxins and damage tissues

Question 11

what makes IL-4

Answer 11

TH2 subset

Mast cells

Question 12

IL-5

Answer 12

Functions:

• Activator of eosinophils
• stimulates B cells to proliferate and produce IgA

Question 13

Why is it important for IL-5 to stimulate B cells to produce IgA

Answer 13

Because IgA is mostly responsible for mucosal immunity

often parasites are associated with mucosal surfaces

Question 14

what produces IL-5

Answer 14

TH2

activated mast cells

Question 15

IL-13

Answer 15

TH2 subset cytokine
has shared effects with IL-4

this is the chemical signal that allows us to get somatic tissues to respond to our TH2 response
(promotes extravasation)

Question 16

what produces IL-13

Answer 16

CD4+ T helper cells (TH2)

can also be produced by (minor contribution):

• NK cells and TH1 cells during early phase allergic response
• basophils and eosinophils

Question 17

Where are receptors for IL-13

Answer 17

B cells
mononuclear phagocytes
Dendritic cells
Eosinophils
Basophils
Endothelial cells
Bronchial epithelial
NOT IN T CELLS

Question 18

Clinical application of IL-13

Answer 18

Promotes Fibrosis

• arginase
• induces TGF-beta
• chronic asthma (one receptor is on bronchial epithelial)

Induces mucus production
-bronchial epithelia

Induces IgE class switching in B cells

Induces inflammation

• extravasation
• VCAM-1 on endothelial cells

Question 19

IFN-gamma

Answer 19

macrophage activating cytokine

TH1 subset

produced in response to presence of intracellular microbes

Question 20

what produces IFN-gamma

Answer 20

CD4+ T cells (TH1 subset)

CD8+ T cells

NK cells

Question 21

what stimulates production of IFN-gamma

Answer 21

IL-12

Question 22

How does the body kill microbes in the cytoplasm of cells?

Answer 22

CD8+ (cytotoxic killer cell) actually kills the entire infected cell

macrophage undergoes apoptosis

Question 23

How does the body kill microbes contained in vesicles inside the cell?

Answer 23

Macrophages are stimulated by IFN-gamma, which induces Reactive oxygen and NO within lysosomes to destroy microbes

Question 24

whenever we have a TH1 type of reaction we want to reduce eosinophilic reaction. How is this done?

Answer 24

IFN-gamma inhibits IgE

Question 25

Functions of IFN-gamma

Answer 25

Promotes TH1 differentiation (with IL-12) Promotes B cells to switch to IgG - activates complement - activates phagocytes to opsonize microbes - inhibits IgE (no more eosinophil) Stimulates antigen processing on APC's -induce MHCI and II expression Promotes extravasation (TNF)

Question 26

What stimulates IL-12

Answer 26

whenever cell surface markers are found on cells IL-12 then goes on to stimulate TH1 subset--> producing IFN-gamma

Question 27

TGF-Beta

Answer 27

Activity dependent of timing and whether or not its systemic or local Inhibits proliferation of lymphocytes and leukocytes Counteracts the effects of inflammatory cytokines on neutrophils and endothelial Stimulates healing (fibrosis, angiogenesis) Stimulates B cells to produce IgA (mucosal immunity)

Question 28

what produces TGF-beta

Answer 28

Antigen-stimulated T cells LPS-activated phagocytes Regulatory T cells

Question 29

what is opsonization

Answer 29

a pathogen is marked for ingestion and destruction usually involves the binding of an opsonin (antibody) to a receptor on the pathogens cell membrane this attracts phagocytes which then bind and eat up the pathogen can also happen with IgG where the pathogen does not need to be ingested/phagocytosed, rather IgG triggers a release of lysis products from the immune effector cell (macrophage, eosinohpil, NK cell, etc)

Question 30

Case study--> positive intracellular virus infection. liver biopsy reveals chronic inflammation and fibrotic tissue changes which cell type is most likely responsible for the deposition of collagen?

Answer 30

macrophages which are produced by TH2 subset

Question 31

what is innate response to a virus

Answer 31

IL-12--> leads to activation of TH1 helper cells producing IFN-gamma Type I interferons

Question 32

what if the innate response doesn't clear up virus or extracellular infection....

Answer 32

after TH1 response, then switch response to TH2 this is long-term response TH2 pathway lead to fibrotic response from macrophages and fibroblasts

Question 33

Classical response to innate and TH1 responses of macrophages do....

Answer 33

antigen presentation phagocytosis induction of NO synthase--> assisting in inflammatory process and recruitment

Question 34

Macrophages alternatively activated do what...

Answer 34

Induce fibrosis expresses arginase--> inhibit NO synthase no longer properly do phagocytosis inhibit TH1 cell response

Question 35

``` Case study 9 year old history of allergies/asthma physician--> the persistence of an initial infectious stimulus may have skewed the tissue's response towards fibrosis/mucus production/inflammation through extravasation/myofibroblasts what cytokine is involved? ```

Answer 35

IL-13 first you have your initial stimulus which is seen as persistent infectious agent transition to TH2 cytokine response Secondary stimulus then exacerbates fibrotic response

Question 36

Myofibroblasts

Answer 36

produce alpha-smooth muscle actin this causes constriction in the lungs