Cytokines Flashcards
What are the sources if IL-1?
Monocytes, macrophages, dendritic cells, B cells, tumour lines, epithelial cells, endothelial cells.
What are the targets of IL-1?
Th cells, B cells, NK cells, endothelial cells, macrophages, hypothalamus, etc.
What are the stimuli of IL-1?
Bacteria (endotoxins), viruses, fungi (zymosan), parasites, C5a, immune complexes, cytokines (CSF and gamma-IFN), and silica
What are the activities of IL-1 (hint: there are 9)?
Accessory molecules for APC-T cell interactions; acts on T-lymphocytes to produce IL-2; proliferation and differentiation of B cells and enhances antibody production; induces release of y-IFN and CSF; fever via prostaglandin mediated pathway; enhances NK cell activation; ICAM expression on endothelium; chemotactic for macrophages, PMN; acute phase proteins.
What are the source of IL-6?
Macrophages, monocytes, Th2, bone marrow, endothelial cells.
What are the targets of IL-6?
Th cells, B cells, plasma cells, myeloid stem cells, hepatocytes.
What are the activities of IL-6?
Costimulation T cell activation; terminal differentiation of B cells; stimulates antibody secretion; promotes differentiation of myeloid cells (neutrophils and macrophages); acute phase proteins.
What are the genes expressed by Th cells immediately following interaction with antigen?
C-Fos, c-Jun, NFAT, c-Myc, NF-kB.
What are the 6 T cell growth factors?
IL-2, IL-4, IL-7, IL-9, IL-15, IL-21
What are the genes expressed by Th cells early following interaction with antigens?
IFN-y, IL-2 and IL-2 receptor, IL-3, TGF-B, TNF-B, cyclin, IL-4, IL-5, IL-6, c-Myb, GM-CSF, insulin receptor.
What are the genes expressed by Th cells late following interaction with antigens?
HLA-DR and VLA-1 to 5
What is the source of IL-2?
Th cells (Th0 cells and Th1 cells), and Tc cells.
What are the targets of IL-2?
Th cells, Tc cells, NK cells.
What are the activities of IL-2?
Proliferation of T cells, long term growth of T cell clones (no apoptosis), enhances Tc and NK cell activation (enhances cytotoxicity).
What is the general motif of T cell growth factors?
Four helix bundle cytokine.
What are the targets of IL-15?
Th and Tc cells, NK cells, etc.
What are the activities of IL-15?
Recruitment of T cell precursors to thymus, proliferation of T cells, enhances Tc and NK cell activation.
What is the structure and function of the IL-2/IL-15 receptor complex?
IL-2 and IL-15 use both the yc and B chain of the IL-2 receptor and a unique a chain. The a chain confers high affinity binding (also used to present IL-15 in trans). The B and yc chain signal via Jak1 and Jak3 respectively
What are the 3 common features shared by all cytokine receptors?
All have: extracellular domain, single membrane-scanning domain, and a cytoplasmic domain
What are the 5 families of cytokine receptors?
Immunoglobulin superfamily, Class 1 or hematopoietic receptor family, class 2 or interferon receptor family, TNF receptor family, chemokine receptor family.
What are the 3 ligands for the immunoglobulin superfamily receptors?
IL-1, M-CSF, c-Kit
What are the class 1 cytokine receptor (hematopoietic) ligands?
All T cell growth factors (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and dimers (IL-3, IL-5, IL-6, IL-11, IL-12, IL-13, and GM-CSF).
What are the class 2 receptor (interferon) ligands?
IFN-a, IFN-B, IFN-y, and IL-10 (stimulates same receptor as gamma interferon).
What are the TNF receptor ligands?
TNF-a, UNF-B, CD40, FAS, and TRAIL.
What are the chemokine receptor (G coupled receptor) ligands?
IL-8, RANTES, MIP-1, PF4, MCAF, NAP-2, CXCL, XCL, CX3CL, CCL.
What are the 5 features of the Class 1/hematopoietic receptor family?
4 conserved cysteines, conserved WSXWS (Trp-Ser-X-Trp-Ser), heterodi(tri)meric (mostly heterodimeric), alpha (cytokine specific), beta/gamma (signals through JAK-STAT pathway)
What are the hematopoietic receptor subfamilies?
IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-13, IL-15, IL-21 (share IL-2Ryc), GM-CSF (common beta subunits)
What is the common subunit for the IL-6 receptor subfamily?
gp130
What are the 3 receptors in the IL-6 subfamily?
IL-6, IL-11, IL-27 (also includes WSX1).
What are the 3 domains of the IL-12 receptor families?
Cytokine-receptor homology domain, fibronectin-like domain, immunoglobulin-like domain.
What is the subunit that is common within the IL-2 receptor subfamily? What 4 types of IL receptors have this subunit?
y subunit.
IL-2, IL-15, IL-7, and IL-4.
What 2 receptor types act through the JAK-STAT pathway?
Class 1 and Class 2