14 March wk 3-A Flashcards
What is the cytokine profile for a TH-1 immune response and how is it related to leprosy?
TH-1 response is a cell-mediated response that involves IL-2, 12 and IFN-gamma.
In leprosy, the initial response that is necessary for the elimination of the pathogen is a TH-1 response. This activates the phagocytes and macrophages needed to destroy the bacteria. A strong response leads to Tuberculoid type leprosy and a positive skin test. A weak response leads to Lepromatous leprosy and a negative skin test.
What is the function of helper T-cells?
These cells are essential in the adaptive immune system. They regulate the immune response by releasing cytokines, activating macrophages, causing growth and replication of cytotoxic T-cells, B cell antibody class switching and other immune regulation.
What is the function of TH-1 helper T-cells?
Primary function is defense against intracellular bacteria and protozoa.
Triggered by IL-12,2
Effector cytokine is IFN-gamma
Effector cells are macrophages (activated by IFN-gamma), Cytotoxic T-cells, IgG B cells
Over-activation of this pathway leads to Type IV hypersensitivity reactions
What is the function of TH-2 helper T-cells?
Host immunity against extracellular pathogens like helminths.
Triggered by IL-4
Effector cytokines: IL-4,5,9,10,13
Effector cells: eosinophils, basophils, mast cells, B cells
Causes production of IgE antibodies leading to release of histamine, serotonin, leukotrienes causing responses related to Type I hypersensitivity like asthma.
Describe Basophils, their role, location, and activation.
Basophils are granulocytes, have a bilobed nucleus (when visible)
Granules contain histamine and heparin
They respond to bound IgE which is related to allergies and ectoparasite infections like ticks as well as other parasitic infections
Similar to the mast cell in contents and function except unlike mast cells it is mostly found in the blood, but can be recruited to the tissues when needed
Thought to be one of the major sources of IL-4 which signals the production of IgE and is a major contributing factor to the development of allergies
Mnemonic for IL-1-6 function
HOT T-bone stEAK IL-1: fever IL-2: stimulates T-cells IL-3: stimulates bone marrow IL-4: stimulates IgE IL-5: IgA IL-6: aKute phase protein production
What cytokines come from macrophages and what is their function?
IL-1: fever, acute inflammation
IL-6: fever, acute phase proteins
IL-8: chemotactic factor for neutrophils “clean up on aisle 8”
IL-12: induces differentiation of T-cells into Th1 cells, activates NK cells
TNF-alpha: Mediates septic shock, activates endothelium, causes WBC recruitment, vascular leak, cachexia in malignancy
What cytokines are produced by all T-cells and what is their function?
IL-2: stimulates growth of helper, cytotoxic and regulatory T cells and NK cells
IL-3: support and differentiation of bone marrow stem cells, functions like GM-CSF
What cytokines are produced just by Th1 cells and what is their function?
IFN-gamma: secreted also by NK cells, in response to IL-12 from macrophages, stimulates macrophages to kill phagocytosed pathogens, inhibits differentiation of Th2 cells, also activates NK cells to kill virus infected cells, increases MHC expression and antigen presentation by all cells
What cytokines are produced by Th2 cells?
IL-4: induces differentiation of T cells into Th2 cells, growth of B cells, enhances class switching to IgE and IgG IL-5: growth of B cells, class switching to IgA, growth of eosinophils IL-10: attenuates inflammatory response, decreases expression of MHC II and Th1 cytokines, inhibits macrophages and dendritic cells, TGF-beta and IL-10 both atTENuate the immune response
Explain pathogenesis of TSS
Caused by the toxins from Staph aureus called TSST
This is a superantigen that activates a lot of T cells causing a cytokine storm of IL-1,2 and TNF-alpha that lead to shock, and skin findings that look like a sunburn, and multiorgan failure
Describe the signaling pathway for insulin
Insulin Receptor (IR) is a 4-part protein with two alpha portions outside the cell and two beta portions inside the cell. When insulin binds, the tyrosine kinase inside the cell causes autophosphorylation that then creates insulin receptor substrates 1 & 2 (IRS-1&2). These are the signaling molecules that then activate the PI3K and the RAS/MAPK pathways for growth and glycogen/lipid/protein synthesis.
How do TNF-alpha, glucocorticoids, catecholamines, and glucagon affect insulin sensitivity?
These molecules cause a serine phosphorylation of the insulin receptor and prevent the downstream signaling. Threonine phosphorylation of the receptor can have similar effects.
Explain the relationship between fructose-2,6-bisphosphate and glucose metabolism
Fructose-2,6-bisphosphate is an important regulatory molecule for glucose metabolism. It helps control the balance between gluconeogenesis and glycolysis.
When there are high levels of fructose-6-phosphate and the presence of insulin, the enzyme PFK-2 produces fructose-2,6-bisphosphate which in turn enhances the function of PFK-1 and promotes glycolysis while also inhibiting fructose-1,6-bisphosphatase which moves molecules in the gluconeogenesis direction.
When glucagon is high, it promotes the inverse function of PFK-2 and reduces the amount fructose-2,6-bisphosphate and thereby promotes gluconeogenesis by disinhibiting fructose-1,6-bisphosphatase.
What should be ruled out in a patient with depression before treatment with an antidepressant?
Patients with depression should be screened for mania to rule out bipolar disorder because treatment with an antidepressant can lead to treatment-induced mania.
If a depressed patient responds faster than normal to treatment it may be due to an induced episode of mania and the patient is actually bipolar.
