Cytokines and Their Receptors Flashcards
what are the three ways cytokines act?
- autocrine
- paracrine
- endocrine
what does pleiotropic activity mean?
one cytokine induces different biological effects depending on target cells
what does redundant activity mean?
two cytokines mediate similar effects on the target cells
what does synergy effect mean?
the combined effect of two cytokines is greater than the additive effect
what is the antagonistic effect?
inhibition of one cytokines effect by another’s actions
what is the cascade effect?
a cytokine induces other cells to produce additional cytokines
what cytokines are unique to T helper 1 subset?
IFN-gamma, lymphotoxin (TNFB)
what cytokines are unique to T helper 2 subset?
IL-4, IL-5, IL-10 and IL-13
which cytokines induce inflammation?
IL-1B, TNF-a, and IL-6
which cytokines suppress inflammation?
TGFB
which chemokine effects lymphocyte movement and how?
IL-8 induces adhesion molecules on leukocytes and endothelial cells
what do adhesion molecules function as?
a co-stimulatory molecule on antigen presenting cells to activate MHC class II restricted T cells and in association with the MHC class I to activate cytotoxic T cells
what important role do adhesion molecules play when expressed on epithelium?
diapedesis
what are the four families of adhesion molecules ?
- selectins
- integrins
- immunoglobulin like adhesion molecules
- cadherins
what induces adhesion molecules?
cytokines
what are selectins?
adhesion molecules that bind to carbohydrates, adhere weakly and mediate the rolling and thumbling
what are integrins?
adhesion molecules that mediate interactions between cells and the extracellular matrix that are used for arrest and adhesion
what are immunoglobulin like adhesion molecules?
intracellular adhesion molecule 1 (ICAM 1) on endothelium plays an important roll in trans-endothelial migration of leukocytes
what are cadherins?
involved in embryonic development, tumor metastasis
describe the interleukin 1 family
important inflammatory mediators
describe class 1 (hematopoietin) cytokine family
exhibit striking sequence and functional diversity
describe class 2 (interferon) cytokine family
important roles in antiviral responses and important modulators of immune response
describe the tumor necrosis factor family
either soluble or membrane bound and involved in immune system development, effector functions and homeostasis
describe the interleukin-17 family
function to promote neutrophil accumulation and activation and are pro-inflammatory
describe the chemokine family
all serve chemoattractant function
what is the function of erythropoietin ?
red blood cell production
what is the function of granulocyte macrophage colony stimulating factor (GM-CSF)?
stimulation of diverse set of granulocyte macrophage colonies
what is the function of granulocyte colony stimulating factor (G-CSF)?
granulocyte stimulation
what is the function of macrophage colony stimulating factor (M-CSF)?
macrophage stimulation
what is the function of interleukin-3?
granulocyte, macrophage, eosinophil, megakaryocyte and erythroid colony formation
what is the function of interleukin-2?
T-cell proliferation
what are the common cytokine receptor subunits and what do they recognize?
- gamma c: interleukin 2,4,7,9,15, and 12
- beta c: interleukin 3 and 5 and GM-CSF
- gp130: interleukin 6, 11 and 27, LIF, OSM, CNTF
the action of IL-2 is controlled by binding affinity to what?
IL-2 receptor aka CD25
where is the IL-2 receptor expressed?
antigen activated T cells
what are the three peptides of an IL-2 receptor?
- IL-2R alpha
- IL-2R beta
- IL-2R gamma-c
which peptides bind IL-2 with low, medium and high affinity?
- low: IL-2R gamma c MONOMER
- intermediate low: IL-2R beta and IL-2R gamma c DIMER
- High: IL-2R alpha, IL-2R beta and IL-2R gamma c TRIMERIC
what do high levels of IL-2 favor?
development of the effector T cells
what do low levels of IL-2 favor?
promotes differentiation of memory T cells
what does IL-2 inhibit the differentiation of?
TH-17 and TFH cells
what are the effects and indications for the IFN-alpha cytokine?
- EFFECTS: antiproliferative and antiviral
- INDICATIONS: chronic hepatitis C infection, AIDS related Kaposi’s sarcoma and hairy cell leukemia
what are the effects and indications for the IFN-gamma cytokine?
- EFFECTS: immunostimulatory and antiviral
- INDICATIONS: control of infection in chronic granulomatous disease
what are the effects and indications for the IL-2 cytokine?
- EFFECTS: immunostimulatory
- INDICATIONS: renal cell carcinoma and metastatic melanoma
what are the effects and indications for the erythropoietin cytokine?
- EFFECTS: stimulates erythropoiesis
- INDICATIONS: anemia associated with chronic renal failure
what are the effects and indications for the G-CSF cytokine?
- EFFECTS: stimulates granulocyte production
- INDICATIONS: reversal of neutropenia after chemotherapy, radiation therapy or both
what are the effects and indications for the GM-CSF cytokine?
- EFFECTS: stimulates granulocyte and monocyte/macrophage production
- INDICATIONS: reversal of neutropenia after chemotherapy, radiation therapy or both
what are the effects and indications for the Basiliximab antibody?
- EFFECTS: anti-IL-2 receptor
- INDICATIONS: prevention of acute organ rejection in kidney transplant patients
what are the effects and indications for the Cetuximab antibody?
-EFFECTS: anti-epidermal growth factor receptor
- INDICATIONS: solid organ tumors refractory to standard treatments
what are the effects and indications for the Daclizumab antibody?
- EFFECTS: anti-IL-2 receptor
- INDICATIONS: prevention of acute organ rejection in kidney transplant patients
what are the effects and indications for the Adalimumab antibody?
- EFFECTS: anti-TNF-alpha
- INDICATIONS: moderate to severe Rheumatoid arthritis refractory to standard treatments
how does Entanercept act as a receptor decoy in rheumatoid arthritis?
a biologic drug that acts as a “fake” TNF-α receptor, preventing TNF-α from causing inflammation
