cytokines copy Flashcards
(45 cards)
Define pleiotropism
Ability of 1 cytokine to have many functions
Define redundancy
More than 1 cytokine with the same function
Define synergism
2 cytokines acting together to enhance a biological effect
Ex. IL-4 and IL-13 promote class switching in B cells to make IgE
Define antagonism
2 cytokines oppose each other’s effects
Ex: IL-4 favors Th2 response while IFN-gamma favors Th1 response
Describe the local and systemic effects of cytokines
Autocrine: acts on same cell which secreted itParacrine: acts on nearby cellsEndocrine: goes systemic and acts on distant cells
List the cytokines involved in innate immunity
IL-1
TNF-alpha
IL-6
IL-8
Which signaling pathway does IL-1 and TNF-alpha activate?
NF-KB
Name 2 principal cellular responses to TNF-alpha
- Gene transcription: production of IL-1/TNF-alpha, inflammatory mediators and ROS
- Apoptosis: Fas/FasL death via Caspase 8
What is the main source of TNF-alpha?
activated macrophages
What other stimuli can activate the pathway stimulated by IL-1/TNF-alpha?
PAMPs like LPS or peptidoglycans stimulate the NF-KB pathway resulting in IL-1/TNF-alpha production and local inflammation
Describe the local and systemic effects of TNF-alpha.
Local: -leukocyte recruitment via increased adhesion molecule expression on endo cells-self-amplifying cascade-eicosanoid synthesis via activation of phospholipase A2 and AA pathway
Moderate systemic:-pyrogen: PG synthesis by hypothalamus-stimulate hepatocytes to make acute phase proteins-cachexia-bone marrow stimulation–> increased prod of leukocytes
Massive systemic:-hypotension via decreased myocardial contraction and decreased vascular smooth muscle tone- activation of coagulation–> thrombosisAKA toxic shock!
Name 2 differences b/t IL-1 and TNF-alpha.
- IL-1 does NOT induce apoptosis
2. IL-1 has 3 subtypes…IL-1alpha is preformed in keratinocytes
What are the principle products of the pathway stimulated by IL-1/TNF-alpha?
- IL-1/TNF-alpha…self-amplifying
- ROS…antimicrobial defense
- eicosanoids via activation of phospholipase A2
- Bcl-2…inhibitor of Caspase 8 and apoptosis
How does UV light cause inflammation in the skin?
IL-1alpha is pre-formed and active in keratinocytes–> UV light damages keratinocytes–> release of IL-1alpha–> leukocyte recruitment via increased adhesion molecules and self-amplifying cascade
How does a sunburn make you not feel well?
Massive amounts of IL-1alpha are released from keratinocytes–> systemic circulation–> pyrogen (hypothalamus), acute phase response (liver) and cachexia
Give 2 specific mechanisms of action by which glucocorticoids suppress proinflammatory effects of IL-1/TNF-alpha.
- promote synthesis of IkBalpha= inhibitor of NF-KBIkBalpha dimerizes NF-KB–> sequestering it in cytolplasm–> prevents translocation to nucleus and gene transcription
- upregulate IL-1RA–> competes w/ IL-1alpha/beta for IL-1 rececptor
Describe the 3 forms of IL-1.
IL-1alpha
IL-1beta
IL-1RA
Which form of IL-1 is active when made?
IL-1alpha
Which form of IL-1 requires enzymatic activation?
IL-1beta
Which form of IL-1 is counter regulatory?
IL-1RA
Explain how keratinocytes upregulate the innate immune system.
keratinocytes express PRR (pattern recognition receptors) like TLRs, mannose receptors, C-type lectins
These receptors recognize PAMPs (pathogen associated molecular patterns) such as LPS, bacterial peptidoglycans, bacterial DNA, viral DNA.
Upon activation–> secretion of ILs, chemokines, antimicrobial peptides (beta-defensins, cathelicidins)
Keratinocytes can also be induced to express MHC II and present Ag
Give a broad definition of the following: 1. interleukins 2. interferons 3. tumor necrosis factor 4. growth factors 5. chemokines
- IL: cytokines regulating actions b/t lymphocytes and other WBCs
- IFN: glycoproteins synthesized in response to viral infection
- TNF: cytokines from MO/T cells involved in apoptosis and inflammation
- growth factors: group of cytokines which stimulate cell growth and proliferation
- chemokines: subset of cytokines which mediate chemotaxis; aid in wound healing
Which cells are responsible for IL-1 production?
IL-1alpha: keratinocytes
IL-1beta:
- MO
- dendritic cells
- T/B/NK cells
- endo cells
- fibroblasts
Describe the Jak-STAT pathway.
- binding of cytokine to receptor
- dimerization of transmembrane portions of receptor
- phosphorylation of JAK proteins
- phosphorylation of STAT proteins
- dissociation of STAT from JAK
- STAT relocates to nucleus
- act as transcription factors and induce gene expression