Bloque 7: Cytokines Flashcards
Functions and general properties of cytokines
Functions:
- Hematopoyesis
- Induce lymphocyte growth and differentiation
- Activation of effector cells for pathogen clearance
General properties:
- In physiological conditions, they are produced in a brief and self-limited manner
- Pleiotropism: One cytokine may have different effects. Ej: IL-4 participates in IgE synthesis, differentiation of CD4 T cells into Th2 cells or macrophages inhibition
- Redundancy: A same effect can be produced by different cytokines (backup mechanism). Seen in the fact that IL-2, IL-4 and IL-5 participate in B cell proliferation
- Cytokines may coordinate different signal cascades due to the effect on cytokine synthesis (IFN-gamma provoques the synthesis of IL-12) or effect on cytokine action (IFN-gamma and TNF have a synergic interaction while IFN-gamma and IL-10 have opposite actions)
- Their actions can be local or systemic
- They bind to specific receptors to achieve their effects with high affinity
There are external factors regulating the expression of cytokine receptors and by so, they controle cytokine actions
Examples of cytokines and their main functions
IL-1: Multiple actions related to inflammation, fever and acute phase proteins synthesis
IL-2: Activation, proliferation and differentiation of T cells. B cell proliferation
IL-3: Hematopoyesis
IL-4: B-cell proliferation, synthesis of IgE and Th2 cells differentiation
IL-5: Eosinophil and B cells proliferation
IL-6: Multiple actions related to inflammation, fever and acute phase proteins synthesis. It can be used as cancer therapy in order to generate a “cytokine storm”.
IL-7: Hematopoyesis
IL-8: Chemotaxis of neutrophils and T cells
IL-9: Improves mast cells activity
IL-10: Main macrophage suppressor
IL-11: Hematopoyesis
IL-12: NK cells activation and Th1 differentiation. Main mediator of innate immunity against intracellular pathogens
IL-13: Inhibits cytokine production by macrophages. Induces B cell’s growth and differentiation
TNF-alpha:They recognise lipopolysaccharides produced by gram negative bacteria. In local infections they activate neutrophils and monocytes whereas in systemic ones they may cause fever, inflammation or even a septic shock
IFN-gamma: Macrophages activation, differentiation of Th1 cells
G-CFS: Hematopoyesis
Cytokines related to hematopoyesis
IL-3
G-CFS
IL-7
IL-11
Cytokines mediating immune and innate response
Innate immunity cytokines are mainly TNF-alpha, IL-1, IL-12, IFN-alpha and IFN-beta. They are produced by dendritic cells, macrophages and natural killer cells after being stimulated by bacterial lipopolysaccharides and viral nucleic acids. These cytokines are the main mediators of innate immunity and inflammation but in order to be able to perform their functions, they must reach high levels. They can either act in local or systemic levels and are related to systemic diseases such as septic shock. These cytokines can be inhibited by corticoid administration.
- IL-1: Multiple actions related to inflammation, fever and acute phase proteins synthesis
- IL-12: NK cells activation and Th1 differentiation. It is the main mediator of innate immunity against intracellular pathogens.
- TNF-alpha: They recognise lipopolysaccharides produced by gram negative bacteria. In local infections they activate neutrophils and monocytes whereas in systemic ones they may cause fever, inflammation or even a septic shock
- IFN-alpha and IFN-beta: Early innate antiviral immune response. They prepare the cell to inhibit viral replication and upregulate MHC-I expression.
On the other hand, the main cytokines present in adaptive immunity are IL-2, IL-4 and IFN-gamma. They are mainly produced by T cells after an antigenic peptide is presented to them. Their main functions are lymphocyte differentiation and growth and activation of effector cells. Adaptive immune cytokines act locally, and they are usually undetectable in serum. These cytokines may be inhibited by cyclosporine and FK-506.
- IL-2: Activation, proliferation and differentiation of T cells. B cell and NK cell proliferation
- IL-4: B-cell proliferation, synthesis of IgE and Th2 cells differentiation
- IFN-gamma: Macrophages activation, differentiation of Th1 cells
