Biochemistry Quiz 6 Flashcards
What are cytokines?
-small proteins
-control growth/activity of immune system cells
-roles in immunity, inflammation and hematopoiesis
What cells do cytokines target?
-macrophage
-B cells
-effector T cells
-tumor cells
-plasma cells
What are the types of cytokines?
-Interleukin 1
-Chemokines
-Hematoprotein
-Interferons
-Interleukin 17
What are some of the cellular effects of Cytokines?
-pleiotropic (affect many different cells and receptors with different outcomes)
-redundant (different cytokines have the same effect)
-Cascade effect (stimulate production of other cytokines)
What are interleukins?
-secrete and act on leukoctyes
-regulate growth/differentiation of hematopoietic cells
What are Chemokines?
-cell migration (during development, immune response, inflammation and cancer)
-Chemokine receptors are GPCRs
What are TNFs (Tumor Necrosis Factor)?
-released upon infection by macrophages (causes inflammation)
-ribbon structure
What are Interferons?
-regulate signaling in cells that are infected
“interfere” with viral replication
-helical structure, three types (I,II, and III)
What are the 6 types of cytokine receptors?
-Immunoglobulin (Ig) family (IL-1 and IL-18)
-Hemopoietic Growth Factor (type 1) (IL-2 and IL-6)
-Interferon (type 2) (IFN B and Y)
-Tumor necrosis factors (type 3) (TNF cytokines, CD40, CD27, CD30)
-G Protein-coupled receptors
-Interleukin-17 receptor (IL-17R) family (A-E)
What are chemokines?
-subset of cytokines that direct migration of leukocytes to regions of infected tissue
-signal through GPCRs
-chemoattractant
What is the concept of cross-reactivity?
-one cytokine receptor can recognize multiple different ligands
What is role in cytokine signaling?
-Macrophage release of chemokines induces leukocyte migration
What are the three types of Leukocytes?
-Granulocytes (innate immunity)
-Monocytes (innate immunity)
-Lymphocytes (adaptive immunity)
What is the role of CXCL8?
-recruits neutrophils (granulocyte; innate) from the blood and guides them to the infected tissue
What is the role of TNFa?
-in the TNF receptor family
receptors: TNFR1 (expressed on most cell types; pro-inflammatory and apoptotic) TNFR2 (endothelial, epithelial and some immune cells; anti-inflammaotry and promotes cell survival and proliferation)
-released by lymphocytes and monocytes when infection is detected
-can induce fever, apoptosis and inflammation
What do cytokines that recognize the gamma chain do?
-activate three major signaling pathways that promote cellular survival and proliferation
-PI3K/Akt pathway (anti-apoptotic)
-JAK-STAT pathway
-RAS-MAPK pathway
-serve as critical regulators of development, survival, proliferation, differentiation and/or function of multiple immune cell types
What does the IL-6 signaling pathway do?
-important for T-cell differentiation and proliferation; B cell differentiation into plasma cells
-stimulates acute-phase protein synthesis, survival, proliferation, production of neutrophils, regulates inflammation
What are some drugs against the IL-6 receptor?
TOCILIZUMAB and SARILUMAB, SILTUXIMAB
-antibodies that are against IL-6
What are some qualities associated with IL-1?
-IL-1a and IL-1B forms
-master regulator of inflammation in innate immune response
-drugs developed against it (anakinra; Canakinumab; Rilonacept)
What are some qualities associated with IL-17?
-pro-inflammatory immune responses; beneficial against infection from bacteria and fungi
-drug against it (Secukinumab)
What are some qualities associated with Heterotrimeric G-proteins that couple to GPCRs
-three subunits (alpha, beta, gamma)
-Ga has GTPase activity
Ga can dissociate from By complex which stimulates/represses a particular effector protein
What are the 4 types of a-subunits?
ai- inhibitory (inhibits cAMP)
as- stimulatory (increases cAMP)
aq- Phospholipase C
a12- Rho GEFs (activates Rho-family GTPases)
What happens in GPCR signal termination?
- Phosphorylation by G protein-coupled receptor kinases (GRK)
- Binding of B-arrestin - desensitization
- Recruitment to Clathrin-coated pits - internalization
- Recycling or degradation
- arrestin can also mediate intracellular signaling
What does Adenylate cyclase do?
-catalyzes conversion of ATP to cAMP
-part of Gs and Gi and cAMP-mediated signaling
cAMP is a second messenger with numerous signaling roles
