Cytokines Flashcards
Which cytokines act in the innate immune response?
IL 12
IFN-y
TNF alpha
IL-1
(see image below)
Which cytokines act in the adaptive immune response?
IL 2
IL 4
IL 5
IFNY-y
IL 12
(see image below)
Some basic functions of cytokines include ___ (one cytokine can act on different cell types to induce different responses), and ___ (some cytokines can have elicit the same responses as others through their own receptors)
Examples of cytokines that demonstrate redundancy are IL6, ___ and ___, the actions of which all result in phagocytosis, complement activation, adaptive immune response activation, decreased bug replication/increased antigen processing + immune response specificity
Some basic functions of cytokines include pleiotropism: (one cytokine can act on different cell types to induce different responses), and redundancy (some cytokines can have elicit the same responses as others through their own receptors)
Examples of cytokines that demonstrate redundancy are IL6, TNFalpha and IL-1 beta, the actions of which all result in phagocytosis, complement activation, adaptive immune response activation, decreased bug replication/increased antigen processing + immune response specificity
Using IFN-y and TNF, explain the difference between synergy and antagonism
Synergy: when two(+) cytokines work together to induce a greater response (esp IFN-y and TNF synergy to increase expression of MHC1 >> important for upregulating CD8+ T cells)
Antagonism: the cytokines work against each other/produce opposite effects
Also, there can be cytokine cascades (one cytokine is activated by another which activates another and so on >> important in highly inflammatory disease states like sepsis)
(see image below)
Describe the general mechanism of action of cytokines in the innate immune response
Basically, DCs recognize microbes and secrete IL12 >> activates NK cells >> NK cells secrete IFN-y >> IFN-y activates macrophages >> macrophages secrete other cytokines that have various downstream effects, primarily inflammation
The cytokines that drive hematopoiesis include Granulocyte-monocyte colony stimulating factor, ___ and ___
The cytokines that drive hematopoiesis include Granulocyte-monocyte colony stimulating factor (GM-CSF), M-CSF and GCSF
Describe the mechanism of cytokine signaling (hint: JAK-STAT signaling)
Essentially, cytokine signaling happens thru receptor tyrosine kinases (here, its JAKs)
**recall JAK signaling: binding of a ligand results in autophosphorylation of the receptor >> recruitment of STATs >> translocation of STATs to nucleus >> binding of STATs to sequence in promoter >> gene transcription**
The following cytokine receptor families share which common structural component?:
IL2 receptor family
GM-CSF receptor family
IL6 receptor family
What is the significance of cytokine receptors sharing structural components?
(see image below)
The sharing of receptor components can lead to the redundancy of cytokine signaling
The functions of TNF-a at low concentrations include ___
At ___ concentrations, TNF signaling leads to systemic effects such as fever (PGE2 induction), acute phase reactant production, leukocyte recruitment from bone marrow
At high concentrations, TNF signaling leads to ___
TNF alpha’s actions are dose dependent:
@ low concentrations, TNF signaling = local inflammation + leukocyte diapedesis
@ moderate concentrations, TNF signaling = systemic effects: fever (PGE2 induction), acute phase reactant production, leukocyte recruitment from bone marrow
@ high concentrations, TNF signaling = organ failure (decreased CO, thrombosis, hypoglycemia etc)
In response to gram negative bacterial infection, __ and __ are released early by the macrophage whereas ___ is released later
In response to gram negative bacterial infection, TNF-a and IL-1 are released early by the macrophage whereas IL-12 is released later
(see image below) **note the synergistic effects of early TNF and IL1 release**
Describe the difference between osteoarthritis and rheumatoid arthritis
Difference between RA and osteoarthritis: swelling in synovial membranes in RA but not in OA; in OA, there’s thinned cartilage and bones rub together (not the case in RA)
RA is more inflammation drive
(see image below)
In RA, there’s interaction between ___ and macrophages in the ___, and the major cell types in synovial fluid are ___. All the actions of all these cells can contribute to cartilage thinning and ultimately bone damage
In RA, there’s interaction between T lymphocytes and macrophages in the pannus, and the major cell types in synovial fluid are neutrophils. All the actions of all these cells can contribute to cartilage thinning and ultimately bone damage
The main cytokines involved in RA __ and __, which have what downstream effects?
The main cytokines involved are IL-1 and TNF-a which induce chondrocytes/synoviocytes to release collagenase and other neutral proteases that breakdown cartilage, and osteoclasts that chew up bone
The combined effects of IL1 and TNF-a signaling in RA include ___
IL1 acting alone leads to increased __ and osteoclast activation, as well as upregulation of ___ factors
TNF-a acting alone leads to increased ___ and ___
(see image below)
How was the RA drug Enbrel made and how does it work?
Enbrel: took piece of TNF receptor and Fc region of IgG1 and fused them to increase its half life in circulation
Briefly describe IL1 receptor signaling
IL1 binds to the Type I IL1 receptor >> recruitment of IL1R accessory protein >> dimerization of IL1R and AcP >> recruitment of MyD88 adaptor protein >> activation of downstream NF-KB signaling
Describe how the IL1 receptor antagonist prevents IL1 signaling
An example drug that is an IL1 receptor antagonist is __. How does this drug differ from biological IL1ra and how does it work?
IL1 receptor antagonist binds to the IL1 receptor and prevents dimerization of the receptor with the accessory protein >> no recruitment of MyD88 >> no NF-KB signaling
Kineret
(Kineret can’t stand MyD88 so she faked being endogenous IL-Rantagonist so she could block MyD88 from dimerizing with IL1R)
How does the inflammasome get activated in gout?
What are Cryopyrin periodic syndromes (CAPS)? An example of such a disorder is ___
In gout, monosodium urate crystals activate the inflammasome, which activates caspase 1. Caspase 1 then cleaves pro-IL 1 beta to mature IL-1 beta, which is pro-inflammatory
People with Cryopyrin periodic syndromes (CAPS) have an overactive inflammasome so they have an accumulation of IL1b
Muckle Wells Syndrome
**note that Cryopyrin = NALP3** - the mutation is a gain of function mutation
What is the significance of IL-12 to the adaptive and innate immune responses?
What are the consequences of too much IL12?
IL12 gene therapy can be used in the treatment of ___ (hint: type of cancer involving brain astrocytes)
IL-12 is often considered the cytokine that bridges the innate and adaptive immune responses
If there’s too much IL12, that leads to tissue damage
Glioblastoma
Besides being a hematopoietic factor, G-CSF increases neutrophil function by enhancing chemotaxis, ___, increasing cytotoxic killing and ___
Besides being a hematopoietic factor, G-CSF increases neutrophil function by enhancing chemotaxis, enhancing phagocytosis, increasing cytotoxic killing and improved responsiveness to antigen
What are the functions of Interferons alpha and beta?
IFN a and b signaling leads to upregulation of ___ and ___, and downregulation of IL12
(see image below)
Upregulation of IL10 and FcR
Downregulation of IL12
Some of the diseases treated by IFN a and b include SARS, MS, ___, ___ and ___
Some of the diseases treated by IFN a and b include SARS, MS, Hep B and C, Hairy Cell Leukemia and Malignant melanoma
