Cytokines of adaptive immunity Flashcards
IL-2
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
what produces IL-2
CD4+ T cells (T helper cells)
what activates IL-2
Antigen presentation and costimulators
What are the cytokines of the TH2 subset
IL-2
what is CD8+
cytotoxic cells
destroy cells
IL-4
of the TH2 subset
stimulates differentation of CD4 to TH2
inhibits TH1 differentiation
defense against helminthic or arthropod infection (mast cells and eosinophils)
when do allergies occur
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)
Systemic activities of IL-4
Allergies
Fibrosis
How does IL-4 and IL-13 stimulate fibrosis?
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
why do we want fibrosis with parasites?
collagen deposition helps to isolate the parasite so they can’t release toxins and damage tissues
what makes IL-4
TH2 subset
Mast cells
IL-5
Functions:
- Activator of eosinophils
- stimulates B cells to proliferate and produce IgA
Why is it important for IL-5 to stimulate B cells to produce IgA
Because IgA is mostly responsible for mucosal immunity
often parasites are associated with mucosal surfaces
what produces IL-5
TH2
activated mast cells
IL-13
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)
what produces IL-13
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
Where are receptors for IL-13
B cells mononuclear phagocytes Dendritic cells Eosinophils Basophils Endothelial cells Bronchial epithelial NOT IN T CELLS
Clinical application of IL-13
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
IFN-gamma
macrophage activating cytokine
TH1 subset
produced in response to presence of intracellular microbes
what produces IFN-gamma
CD4+ T cells (TH1 subset)
CD8+ T cells
NK cells
what stimulates production of IFN-gamma
IL-12
How does the body kill microbes in the cytoplasm of cells?
CD8+ (cytotoxic killer cell) actually kills the entire infected cell
macrophage undergoes apoptosis
How does the body kill microbes contained in vesicles inside the cell?
Macrophages are stimulated by IFN-gamma, which induces Reactive oxygen and NO within lysosomes to destroy microbes
whenever we have a TH1 type of reaction we want to reduce eosinophilic reaction. How is this done?
IFN-gamma inhibits IgE
Functions of IFN-gamma
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)
What stimulates IL-12
whenever cell surface markers are found on cells
IL-12 then goes on to stimulate TH1 subset–> producing IFN-gamma
TGF-Beta
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)
what produces TGF-beta
Antigen-stimulated T cells
LPS-activated phagocytes
Regulatory T cells
what is opsonization
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)
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?
macrophages
which are produced by TH2 subset
what is innate response to a virus
IL-12–> leads to activation of TH1 helper cells producing IFN-gamma
Type I interferons
what if the innate response doesn’t clear up virus or extracellular infection….
after TH1 response, then switch response to TH2
this is long-term response
TH2 pathway lead to fibrotic response from macrophages and fibroblasts
Classical response to innate and TH1 responses of macrophages do….
antigen presentation
phagocytosis
induction of NO synthase–> assisting in inflammatory process and recruitment
Macrophages alternatively activated do what…
Induce fibrosis
expresses arginase–> inhibit NO synthase
no longer properly do phagocytosis
inhibit TH1 cell response
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?
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
Myofibroblasts
produce alpha-smooth muscle actin
this causes constriction in the lungs
