cytokines Flashcards
What are two receptors generated by somatic recombination?
TCR and Ig
What are 3 examples of germ line encoded receptors?
PRRs, cytokine receptors and MHC
What are PAMPs and where are they found?
What are PRRs and where are they found
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
Which cells express PRRs?
Innate immune cells–macrophages, NK cells, neutrophils
PAMP:PRR interaction activates which signaling pathway? And induces gene expression of what factors? (general)
NFkB; pro-inflammatory (cytokines, chemokines, etc)
What 3 main cytokines are produced in initial inflammatory response? (in response to pathogen encounter; PAMP:PRR)
Which 2 are responsible for inducing fever?
TNFalpha, IL1, IL6; TNFalpha and IL1
What distinguishes a chemokine from a cytokine?
chemotaxis–promote migration of leukocytes into an infected site.
Function in a cell-contact INDEPENDENT manner
What factors influence neutrophil extravasation? (cytokines)
TNFalpha, IL1, chemokines
How do chemokines aid neutrophil extravasation?
activates integrins on neutrophil cell surface to aid Attachment and adhesion to endothelial cells as they’re rolling
What cytokines do Macrophages and Th cells secrete that induces proliferation and migration of neutrophils?
G-CSF and GM-CSF (granulocyte colony stimulating factor)
What is the function of IL-8 and which cells secrete it?
chemotactic for circulating PMNs and secreted by macrophages, endothelial/epithelial cells, airway smooth muscle cells.
Can PRRs be found intracellularly?
Yes, some are located on the endosomal membrane and bind PAMPs such as microbial nucleic acids, CpG dinucleotides
What are the four stages of PMN extravasation?
Rolling, Integrin activation by chemokines, stable adhesion/binding, and migration through the endothelium
T-cell activation leads to what as a result of intracellular signaling? (expression of 2 surface molecules and one very general process)
CD40L, expression of (high affinity) IL2 receptor (CD25), DNA synthesis
What cytokine is responsible for providing autocrine, cell contact INDEPENDENT, Pro-proliferative feedback to Th cell?
IL-2
Cyclosporin A blocks production of which cytokine?
IL-2
Which APC produced cytokines cause differentiation of each
THnaive–>Th1
THnaive–>Treg
THnaive–>Th2
IL-12
IL-10/TGFB
no cytokines (default)
What cytokines do Th1 cells produce and what is effect?
secrete IFNy. Autocrine signal for Th1 prol., activate macrophages, promote class switching to IgG2a, SUPPRESS Th2 development
What cytokines do Th2 cells produce and what is effect?
IL-4: prol of Th2 cells, suppress Th1, class switch to IgG1 IL-5: class switch to IgA, promote eosinophilia
What cytokines do Tregs cells produce and what is effect?
TGFb and IL-10: autocrine signal for further treg development
What combination of cytokines promotes Th17 cell differentiation/proliferation?
What cytokines do Th17 cells secrete?
TGFB, IL-6, IL-23
IL-17, IL-22
What Th cell subsetl is FoxP3 associated with?
Tregs
What is Alum/Alhydrogel? What cytokines expression does it promote?
only FDA approved vaccine adjuvant. Promotes expression of IL4 which in turn promotes TH2 development and antibody production
Which Th cell cytokines cause the following class switching? IgM IgG1/3 IgE IgA
default
IFNy
IL-4
IL-5, (TGFB from mucosal )
Helminths opsonized with IgE antibody bind Fc (FceR1) receptors on which cell type?
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)
What molecules are released in the granules of granulocytes?
Histamine, Prostaglandin D2, Leukotriene C4
All pro-inflammatory
Antibody-directed phagocytosis is dependent on which FCR:Ab interaction?
FcyRI (on macrophages) with IgG bound to pathogen
Antibody-directed cytotoxicity is dependent on which FCR:Ab interaction?
FcyRIIIA (aka CD16, on NK cells) with IgG bound to virus-infected or cancer cell
Which cytokines are associated with CTL and NK cell cytotoxicity (defense against viruses)?
IFN alpha and beta
IFN alpha induces an antiviral state in all cells, and up regulates MHC class 1 expression
Which cytokines secreted by MACROPHAGES cause NK cell proliferation?
IL-15 and IL-18
Which inflammatory mediators released by granulocytes affect vasodilation and bronchoconstriction?
Histamine and Prostaglandin and Leukotrienes all cause bronchoconstriction
Prostaglandin acts as a vasodilator in smooth muscle
