- Outline 5 general characteristics of cytokines
- Autocrine, paracrine and endocrine action
- Redundant: 2 or more cytokines mediate similar functions
- Synergistic: Combined effect of 2 cytokines have promotive effect
- Antagonist: Effect of one cytokine inhibits or offsets the effects of another
- Pleiotropic: One cytokine can have diverse biological activites, often on many cell types
- Cascade induction: The action of one cytokine on a target cell induces that cell to produces one or more other cytokines which in turn induce other target cells to produce other cytokines
- Secretion is a brief-self-limited event: Synthesis is transient via transcriptional activation, mRNA is unstable, never remain stored as preformed molecules
- Bind to specific receptor on target cell molecues: Very high affinity between cytokines and their receptors leading to activation at picomolar concentrations
- Classify cytokines giving examples of each
- Interleukins: Mediators between leukocytes, majority produced by Th cells
- Lymphokines: Produced by lymphocytes
- Monokines: Produced by monocytes
- Interferons: Involved in antiviral responses
- Colony stimulating factors: supports growth of blood cells
- Chemokines: mediates chemotaxis
- Write short notes on growth factors: definition, general characteristics, classification (examples), physiological role
- Secreted glycoproteins that induce proliferation, differentiation and maturation of blood cells in all stages of their development
- Characteristics: soluble, signal by paracrine, endocrine, or autocrine signaling
- TGF-B: Inhibits pro-inflammatory enzymes, repair and remodeling of tissue and bone, growth and diff of embryonic tissue cells and stem cells in post-natal period, antibody class-switching to IgA
- PDGF: potent mitogen for cells of mesenchymal origin (platelets, fibroblasts, smooth muscle cells, glial cells), promotes wound healing
- EGF: stimulates growth of epidermal and epithelial cells
- FGF: angiogenesis, keratinocyte organization and wound healing
- GM-CSF: Mitosis, differentiation and activity of CFU-GM to for granulocytes and monocytes
- M-CSF: Mitosis, differentiation and activity of CFU-M to form macrophages
- G-CSF: Mitosis, differentiation and activity of CFU-G to form mature granulocytes, promotes neutrophil activity
- EPO: Stimulates CFU-E to form erythrocytes
- TPO: Stimulates CFU-Meg to form platelets
- Outline the general physiological role of cytokines
- Pro-inflammatory: IL-6
- Anti-inflammatory: IL-10, TGF-B
- Adaptive immunity: IL-2, IL-5, IL-6
- B-cell growth and differentiation: IL-4
- Proliferation of activated T and B cells: IL-2
- Regulate Hematopoiesis: GM-CSF, G-CSF, M-CSF, IL-2, IL-7
- Pyrogenic activity : IL-1, TNF-a
- Innate antiviral properties: IFN-a
- Mediate tissue repair: FGF, EGF, TGF-B
- Bone resorption: Osteoclast activating factor
- Using examples, describe the specific roles of cytokines in diseased states
- Fever: IL-1, TNF-a
- Shock: IL-1, TNF-a
- Anemia of chronic disease: IL-6
- Granulomas: IFN-y
- Cachexia: TNF-a
- Viral infection: IFN-a
- Helminth infection: IL-4
- Allergic reaction: IL-4, IL-5
- Using examples, outline the therapeutic roles of cytokines (5)
- IFN-a: Hepatitis B,
- IFN-B: Multiple sclerosis
- IFN-y: Chronic granulomatous disease
- TNFa (Adalimumab, Infliximab): IBD, Rheumatoid arthritis, ankylosing spondylitis, psoriasis
- G-CSF (Filgrastim) and GM-CSF (Sargramostim): Leukopenia
- Aldesleukin (IL-2): Renal Cell Carcinoma, Metastatic melanoma
