Definition and role of cytokines
Cytokines are low-molecular-weight regulatory proteins or glycoproteins secreted by cells of the immune system and other body cells in response to various stimuli. Cytokines serve as the primary language of intercellular communication: through them, cells transmit information about the body's state to one another, much like humans exchange information using words.
When a pathogen enters the body, such as Mycobacterium tuberculosis or a virus, innate immunity cells are the first to recognize it and begin producing cytokines. These molecules inform other cells about the nature of the threat and direct the development of the immune response: intracellular pathogens activate type 1 T helper cells and cytotoxic T lymphocytes, whereas extracellular pathogens activate other arms of adaptive immunity.
Main functions of cytokines
- Initiation and regulation of the inflammatory response;
- Activation of adhesion molecule expression on the endothelium and facilitation of leukocyte migration from blood vessels into tissues (the stage preceding phagocytosis);
- Activation of inflammatory effector cells;
- Regulation of local and systemic manifestations of inflammation;
- Determination of the type of adaptive immune response.
Properties of cytokines
- Pleiotropy — a single cytokine acts on multiple target cells (macrophages, neutrophils, eosinophils, etc.);
- Functional convergence (redundancy) — different cytokines are capable of performing similar functions, such as stimulating cell migration to the site of inflammation;
- Production polymorphism — a single cell in response to a single stimulus can produce multiple different cytokines with diverse effects.
The biological effects of cytokines on the target cell include proliferation, differentiation, maintenance of survival, induction of apoptosis or necrosis, as well as cell migration along a chemokine gradient.
Classification by biological effect
- Interleukins (IL) — signaling molecules between leukocytes (IL-1, IL-2, IL-6, IL-10, etc.);
- Tumor necrosis factors (TNF) — cytokines with cytotoxic and regulatory activity, for example, TNF-α;
- Interferons — IFN-α and IFN-β (type I), IFN-γ (type II); provide the antiviral status of the cell;
- Colony-stimulating factors and growth factors — for example, GM-CSF (granulocyte-macrophage colony-stimulating factor), which stimulates the red bone marrow to produce monocytes; fibroblast, endothelial, and epidermal growth factors;
- Chemokines — provide chemotaxis; designated according to the structure of cysteine residues (CC, CXC, etc.).
Classification by role in inflammation
Pro-inflammatory cytokines: IL-1, IL-6, IL-8, IFN-γ, TNF-α. IL-1, IL-6, TNF-α, and IFN-γ are of particular importance to memorize.
Anti-inflammatory cytokines: the key representative is IL-10, which suppresses the development of the inflammatory response.
Cytokine receptors and signaling pathways
Cytokines exert their effects through specific receptors on the cell surface. Ligand binding activates intracellular cascades whose endpoints are transcription factors in the nucleus.
- IL-1 receptor family — immunoglobulin-like domains; trigger the classical NF-κB pathway via adapter molecules;
- Type I (heterodimeric) and type II (homodimeric) receptors for hemopoietins, most interleukins, and interferons — activate the JAK-STAT pathway;
- TNF receptor family — trimeric; trigger the classical and alternative NF-κB pathways, as well as the induction of apoptosis via "death receptors";
- Growth factor receptors (EGF, PDGF, VEGF, M-CSF) possess intrinsic tyrosine kinase activity and activate MAP kinase cascades;
- TGF-β receptors — dimers of dimers with intrinsic serine-threonine kinase activity; trigger the SMAD pathway;
- Chemokine receptors — seven-transmembrane rhodopsin-like proteins coupled with a G protein; cause cell polarization and movement along a chemokine gradient.
Key points
- Cytokines are the universal language of intercellular communication in the immune system;
- Three key properties: pleiotropy, functional convergence, and production polymorphism;
- Main groups: interleukins, TNF, interferons, colony-stimulating factors, growth factors, and chemokines;
- Main pro-inflammatory cytokines are IL-1, IL-6, TNF-α, IFN-γ; the primary anti-inflammatory one is IL-10;
- Most interleukins and interferons transmit signals via the JAK-STAT pathway;
- IL-1 and TNF receptors activate the NF-κB pathway; growth factor receptors activate MAP kinases; TGF-β activates SMAD;
- Chemokine receptors are seven-transmembrane, coupled with a G protein, and ensure directed cell migration;
- The type of cytokine response determines the subsequent direction of adaptive immunity.