Cytokines Flashcards
Growth factors
Stimulators of hematopoiesis that regulate immature leukocyte growth and differentiation
drive terminal differentiation of hematopoietic progenitors
e.g. granulocyte-colony stimulating factor (G-CSF; MP-CSF, oncostatin M; IL-3
Interleukins
mediators and regulators of lymphocytes and leukocytes
regualtors of both innate and adaptive functions of other immune cells
diverse in structure and function
e.g. IL-2, IL-6, IL-8, IL-10, IL-12, TNF-a
Interferons
mediators and regulators of antiviral and innate immunity
activate intracellular processes that inhibit viral replication
also key regulators of MP activity and tolerance of developing fetus
expressed in response to immune stimulation
e.g. IFN-g, IFN-a, IFN-b
Chemokines
Separate group from cytokines
chemoattractants - regulate directed movement of immune cells from the blood into tissues
MIP-1a, IL-8, RANTES, MCP-2
IFN-a/B (=Type 1 IFN)
Consists of a family of glycoproteins
involved in antiviral activity
released from virus infected cells of all types (T cells, MPs, and fibroblasts are primary sources)
can accelerate differentiation of B cells (influencing Ab response to specific Ags)
multiple genes code for this
Increases expression of class I MHC molecules on infected and neighboring cells, lysis by CTLs
act on neighboring cells to activate enzymes to slow replication (=induction of antiviral state)
activate NK cells to kill virally infected cells (via same mechanisms as CTLs)
IFN-g
produced mainly by Th and NK cells
most important activator of MPs
increase MP microbicidal activity
stops MP migration
activates pro inflammatory cytokine gene expression
augments phagocytosis
increases anti-tumor and antibacterial processes
upregulates MHC expression (and Ag presentation)
influences production of Ig isotypes (isotype switching to osponizing Abs)
stimulates neutrophil respiratory burts
activates vascular endothelial cell adhesion molecule expression
Colony stimulating factors
promote terminal differentiation of omnipotent or polypotent progenitor cells
many are expressed in certain tissues
all show altered expression during inflammation
IL-1
principal regulator of host inflammatory response
produced by several cell types (MPs, epith. cells)
exist in 2 forms IL-1a and IL-1B (have overlapping activity)
activates T cell proliferation during Ag presentation
induces expression of IL-6 by hepatocytes and MPs
initiates acute phase reactant production by hepatocytes
acts on hypothalamus to cause fever
synergizes IL-2 to regulate B cell proliferation
Overall, works on:
CNS to induce fever and sleepiness
Vascular endothelia: adhesion molecule expression, IFN synthesis, acute phase ptn expression
IL-2
produced by activated TH-1
causes autocrine proliferation of T cells
regulates proliferation of B cells (in coop w/IL-1)
Augments Ig synthesis
stimulates CTL and Nk cell activity against tumors
Enhances MP function
Primary growth factor for T cell proliferation
Naive T cells that recognize an Ag on the surface of an APC responds to IL-2 by undergoing a burst of replication prior to terminal differentiation to effector cells
IL-6
produced by activates MPs, T cells, fibroblasts, and stromal cells of the bone marrow
induces IL-2 expression and IL-2R expression by T cells
promotes CD8+ T cell differentiation and activatio
cofactors with IL-1 for IgM synthesis
cofactors with IL-5 for IgA synthesis
**induces acute phase protein expression by hepatocytes
**endogenous pyrogen which acts on the hypothalamus to cause fever
IL-12
critical cytokine for influencing differentiation of naive T cells toward TH1 pathway
produced by dendritic cells and MPs
has several subunits synthesized at different rates
activates NK cells to secrete IFN-g
b/c IL-12 impacts TH1 vs. TH2 balance, it is important for determining the type of IR that predominates
TNF-a
most important and powerful cytokine
principle mediator of endotoxic shock (G- sepsis)
produced by activated MPs and NK cells
kills cells (good and bad)
immunocyte activation (stims production of cytokines by other cells)
acute phase reactant expression
elicits fever
regulates hematopoiesis
activates vascular endothelial cell adhesion molecule & IL-1 expression
induces cytokine cascades
causative agent of cachexia
MPS: decreased proliferation, terminal differentiation, increased phagocytosis, ROS products, adhesion molecule expression, IL-1, IL-6, IL-12, production, GM-CSF secretion
Activates vascular endothelium to begin process of extravasation
induces loval protective effects, but can cause damage when released in excess or systemically (can cause organ failure, death)
has 2 difft receptors which can be shed during IR
IL-4 & IL-10
principal regulators of humoral IR
produced by TH2 cells
activated mast cells rel. IL-4 from stored vesicles
anti-inflammatory
T cells: promote growth of TH2 cells, enhanced proliferation, production of TH2 cytokines, inhibition of TH1 differentiation
MPs: inhibits activation
Chemokines
families of small cytokines
regulate the migration of immunce cells into inflammatory loci
produced by phagocytic cells, T cells, endothelial cells, fibroblasts
induced by a variety of stimuli during inflammation
divided into 4 classes based on AA sequence: C, CC, CXC, CXXXC
species variation in some chemokine genes (mice lack IL-8)
G-CSF
colony-stimulating factor
drives differentiation of neutrophils, eosinophils
