Cytokines Overview and Types

Cytokines

• Cytokines are small, secreted, low-molecular-weight proteins that mediate and regulate immunity, inflammation, and hematopoiesis.
• They are produced in response to an immune stimulus.
• Cytokine is a general term for a large group of molecules involved in cell signaling during immune responses.
• All cytokines are proteins; some have attached sugar molecules (glycoproteins).
• They are produced and released by white blood cells and tissue macrophages.
• Over 200 different human cytokines have been identified.

Types of Cytokines

• Originally called lymphokines (produced by lymphocytes)
• Then monokines (secreted by monocytes and macrophages).
• Then interleukins (produced by leukocytes and affect other leukocytes).
• Chemokines are also considered cytokines.
• The term "cytokine" is now a broad term encompassing all these types.
• Key categories of cytokines based on function include: Proinflammatory, Antiinflammatory, Inhibition of Virus Replication, Macrophage-Activating, B Cell-Activating, T Cell-Activating, Eosinophil/Mast Cell-Activating. Specific examples of cytokines within these categories are listed in the provided lecture notes.

Actions of Cytokines

• Autocrine: Affect the same cell that produced them (e.g., IL-2 promotes T-cell growth.)
• Paracrine: Affect nearby cells (e.g., IL-7 from marrow stromal cells promotes B-cell differentiation.)
• Endocrine: Affect distant cells through the bloodstream, (long distance effects.)

Cytokine Families

• Hematopoietic (IL-2, IL-4)
• Interferon (IFN-α, β, γ)
• Tumor necrosis factor family
• Chemokine family

Cytokine Receptors

• Proteins on cell surfaces (specific binding sites for cytokines).
• Crucial for transducing signals from cytokines into target cells
• Important for immune responses, inflammation, and cell growth
• Cytokine binds to alpha subunit, followed by association with the beta subunit. Signal transduction happens via the beta subunit.
• Majority of cytokine receptors are in Class I and Class II families.

Signal Transduction

• Begins with cytokine binding.
• Activates Janus kinase (JAK).
• Phosphorylation of tyrosine.
• Signal transducers and activators of transcription (STAT) binding follows.
• STAT translocation to the cell's DNA initiates transcription of specific target genes.

Main Sets of Cytokines

• Interleukins (IL-1 to IL-37)
• Interferons (IFN-α, β, γ)
• Tumor necrosis factors (TNF-α, TNF-β)
• Growth factors
• Colony stimulating factors
• Chemokines (specific examples like IL-8 are not explicitly listed here)

Interferons (IFNs)

• Signaling proteins produced by virus-infected cells (monocytes & lymphocytes).
• Secreted proteins that are key antiviral proteins.
• Interferes with viral replication (in infected and neighboring cells)
• Warn neighboring cells of viral presence.

Tumor Necrosis Factor (TNF)

• Crucial cytokine regulating immune responses and inflammation.
• Activates immune cells
• Promotes inflammation
• Regulates cell survival and proliferation
• Plays critical role combating infections and tissue damage
• Dysregulation can contribute to autoimmune diseases and cancer.

Transforming Growth Factor Beta (TGF-β)

• Multifunctional cytokine regulating cell proliferation, differentiation, adhesion, and migration.
• Belongs to the transforming growth factor superfamily (includes many other signaling proteins).

Chemokines

• Small proteins signaling molecules in the immune system
• Guide immune cells to specific locations.
• Chemotactic (induce cell migration).
• Recruit neutrophils, monocytes, and lymphocytes to sites of infection, inflammation, and tissue damage.
• Crucial role in mediating inflammation.

Functional Features of Cytokines

• Pleiotropy: one cytokine can have different effects on different cells.
• Redundancy: different cytokines can have the same effects.
• Synergy: cytokines can act together to enhance effects.
• Antagonism: cytokines can oppose each other's effects.
• Cascade effect: cytokines can stimulate the production of other cytokines.
• Influence on cytokine receptors: cytokines can influence the expression and transmodulation of receptors.
• Hematopoiesis: cytokines are crucial in regulating innate and acquired immunity.