Regulating the immune responses: role of cytokines and chemokines Flashcards
Give examples of cytokines involved in specific lineages
Multipotential haematopoietic stem cell -> GM-CSF Mast cell -> SCF, G-CSF, GM-CSF, IL-6 Myeloblast -> GM-CSF Erythrocyte -> EPO Megakaryocyte -> TPO, IL-11 T-lymphocyte -> IL-2 Monocyte -> GM-CSF Eosinophil -> IL-5, GM-CSF Basophil + neutrophil -> G-CSF, GM-CSF
What are the anti-viral mediators?
Interferons interfere with viral replication:
IFN-alpha (made by lymphocytes)
IFN-beta (made by fibroblasts)
IFN-gamma (made by lymphocytes & NK cells) -> very poor antiviral molecule.
What are the immune activators?
Lymphocyte-activating cytokines (IL-1)
T cell growth factors (IL-2, -7, -9, -15 share co-receptor)
Macrophage-activating cytokines (IFN-gamma)
What are cytotoxins?
Products of activated lymphocytes or macrophages that can kill tumour cells -> TNF-alpha
What is X-linked SCID (severe combined immunodeficiency) caused by?
Mutation of one receptor that’s a common signalling component of IL-2, IL-4, IL-7 receptors
What are the cardinal signs of inflammation and what are they caused by?
Heat, swelling, redness, pain, tissue damage Inflammatory cytokines (IL-1, IL-6, TNF) on vascular endothelium or via production of prostaglandins or chemokines.
What are the TNF-mediated diseases?
Rheumatoid arthritis
Inflammatory bowel disease
septic shock, multiple organ failure, respiratory distress syndrome, graft-versus-host rejection, diabetes, pulmonary fibrosis.
Which cytokine is important in allergic diseases?
Th2
What are the T cell subsets and their roles?
Naive CD4:
Th1 -> IFN-gamma -> inflammation
Th2 -> IL-4, 5, 9, 13 -> allergy, anti-inflammation
Th17 -> IL-17 -> inflammation
Treg -> IL-10, inhibit activity of other T cells -> anti-inflammatory.
What is the role of cytokines?
Homing + migration of cells of immune system -> role in development
Which cell does MCP-1 attract?
Monocyte
Which cell does IL-8 attract?
Neutrophil
What are the actions of macrophages once they encounter bacteria in tissues?
Macrophages are triggered to release cytokines -> increase permeability of blood vessels -> fluid + proteins pass into tissues, produce chemokines that direct migration of neutrophils to site of infection.
stickiness of endothelial cells of blood vessels is changed, so cells adhere to blood vessel wall + crawl through it. 1st neutrophils + then monocytes enter tissue from blood vessel.
accumulation of fluid + cells at site of infection causes inflammation. neutrophils + macrophages are principal inflammatory cells. Later, activated lymphocytes may also contribute to inflammation.
What is the effect of the cytokine CCL-2 and which molecules is it made by?
Th1 cytokines, causes macrophages to accumulate at site of infection
Outline the therapeutic use of cytokines?
IFN-gamma -> macrophage activation
IFN-beta (MS) “immunomodulation”
Host defence:
IL-2 -> melanoma, renal cell carcinoma
IFN-alpha -> hairy cell leukemia, Kaposi, viral hepatitis
Haemopoiesis:
GM-CSF -> myelo-reconstitution following bone marrow transplant, chemotherapy-induced neutropenia
G-CSF -> chemotherapy-induced neutropenia
IL-11 -> thrombocytopenia in oncology
EPO -> anaemia
Pathogenesis
Anti-TNF + sTNFR -> Crohn’s, UC, psoriasis
IL-1Ra -> rheumatoid arthritis, CAPS.
Anti-IL-6, IL-6R -> rheumatoid arthritis
Anti-IL-17, -12, -23 -> psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s.
Anti-IL-5 -> Reslizumab, Mepolizumab for asthma + eosinophilic granulomatosis.
Anti-IL-4R -> Dupilumab for eczema
