20.6: Chemical Defenses - Cytokines
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- Ying Liu
- City College of San Francisco
Learning Objectives
- Distinguish the three classes of cytokines
- Describe the actions of inflammation-eliciting mediators
Cytokines
Cytokines are soluble proteins that act as communication signals between cells. In a nonspecific innate immune response, various cytokines may be released to stimulate production of chemical mediators or other cell functions, such as cell proliferation, cell differentiation, inhibition of cell division, apoptosis, and chemotaxis.
When a cytokine binds to its target receptor, the effect can vary widely depending on the type of cytokine and the type of cell or receptor to which it has bound. The function of a particular cytokine can be described as autocrine, paracrine, or endocrine (Figure \(\PageIndex{3}\)). In autocrine function, the same cell that releases the cytokine is the recipient of the signal; in other words, autocrine function is a form of self-stimulation by a cell. In contrast, paracrine function involves the release of cytokines from one cell to other nearby cells, stimulating some response from the recipient cells. Last, endocrine function occurs when cells release cytokines into the bloodstream to be carried to target cells much farther away.
Three important classes of cytokines are the interleukins, chemokines, and interferons. The interleukins were originally thought to be produced only by leukocytes (white blood cells) and to only stimulate leukocytes, thus the reasons for their name. Although interleukins are involved in modulating almost every function of the immune system, their role in the body is not restricted to immunity. Interleukins are also produced by and stimulate a variety of cells unrelated to immune defenses.
The chemokines are chemotactic factors that recruit leukocytes to sites of infection, tissue damage, and inflammation. In contrast to more general chemotactic factors, like complement factor C5a, chemokines are very specific in the subsets of leukocytes they recruit.
Interferons are a diverse group of immune signaling molecules and are especially important in our defense against viruses. Type I interferons (interferon-α and interferon-β) are produced and released by cells infected with virus. These interferons stimulate nearby cells to stop production of mRNA, destroy RNA already produced, and reduce protein synthesis. These cellular changes inhibit viral replication and production of mature virus, slowing the spread of the virus. Type I interferons also stimulate various immune cells involved in viral clearance to more aggressively attack virus-infected cells. Type II interferon (interferon-γ) is an important activator of immune cells (Figure \(\PageIndex{4}\)).
Query \(\PageIndex{1}\)
Inflammation-Eliciting Mediators
Many of the chemical mediators discussed in this section contribute in some way to inflammation and fever, which are nonspecific immune responses discussed in more detail in Inflammation and Fever . Cytokines stimulate the production of acute-phase proteins such as C-reactive protein and mannose-binding lectin in the liver. These acute-phase proteins act as opsonins, activating complement cascades through the lectin pathway.
Some cytokines also bind mast cells and basophils, inducing them to release histamine, a proinflammatory compound. Histamine receptors are found on a variety of cells and mediate proinflammatory events, such as bronchoconstriction (tightening of the airways) and smooth muscle contraction.
In addition to histamine , mast cells may release other chemical mediators, such as leukotrienes. Leukotrienes are lipid-based proinflammatory mediators that are produced from the metabolism of arachidonic acid in the cell membrane of leukocytes and tissue cells. Compared with the proinflammatory effects of histamine, those of leukotrienes are more potent and longer lasting. Together, these chemical mediators can induce coughing, vomiting, and diarrhea, which serve to expel pathogens from the body.
Certain cytokines also stimulate the production of prostaglandins , chemical mediators that promote the inflammatory effects of kinins and histamines. Prostaglandins can also help to set the body temperature higher, leading to fever, which promotes the activities of white blood cells and slightly inhibits the growth of pathogenic microbes (see Inflammation and Fever ).
Another inflammatory mediator, bradykinin , contributes to edema, which occurs when fluids and leukocytes leak out of the bloodstream and into tissues. It binds to receptors on cells in the capillary walls, causing the capillaries to dilate and become more permeable to fluids.
Table \(\PageIndex{3}\) provides a summary of the chemical defenses discussed in this section.
| Defense | Examples | Function |
|---|---|---|
| Chemicals and enzymes in body fluids | Sebum from sebaceous glands | Provides oil barrier protecting hair follicle pores from pathogens |
| Oleic acid from sebum and skin microbiota | Lowers pH to inhibit pathogens | |
| Lysozyme in secretions | Kills bacteria by attacking cell wall | |
| Acid in stomach, urine, and vagina | Inhibits or kills bacteria | |
| Digestive enzymes and bile | Kill bacteria | |
| Lactoferrin and transferrin | Bind and sequester iron, inhibiting bacterial growth | |
| Surfactant in lungs | Kills bacteria | |
| Antimicrobial peptides | Defensins, bacteriocins, dermicidin, cathelicidin, histatins, | Kill bacteria by attacking membranes or interfering with cell functions |
| Plasma protein mediators | Acute-phase proteins (C-reactive protein, serum amyloid A, ferritin, fibrinogen, transferrin, and mannose-binding lectin) | Inhibit the growth of bacteria and assist in the trapping and killing of bacteria |
| Complements C3b and C4b | Opsonization of pathogens to aid phagocytosis | |
| Complement C5a | Chemoattractant for phagocytes | |
| Complements C3a and C5a | Proinflammatory anaphylatoxins | |
| Cytokines | Interleukins | Stimulate and modulate most functions of immune system |
| Chemokines | Recruit white blood cells to infected area | |
| Interferons | Alert cells to viral infection, induce apoptosis of virus-infected cells, induce antiviral defenses in infected and nearby uninfected cells, stimulate immune cells to attack virus-infected cells | |
| Inflammation-eliciting mediators | Histamine | Promotes vasodilation, bronchoconstriction, smooth muscle contraction, increased secretion and mucus production |
| Leukotrienes | Promote inflammation; stronger and longer lasting than histamine | |
| Prostaglandins | Promote inflammation and fever | |
| Bradykinin | Increases vasodilation and vascular permeability, leading to edema |
Key Concepts and Summary
- Cytokines are proteins that facilitate various nonspecific responses by innate immune cells, including production of other chemical mediators, cell proliferation, cell death, and differentiation.
- Cytokines play a key role in the inflammatory response, triggering production of inflammation-eliciting mediators such as acute-phase proteins, histamine , leukotrienes, prostaglandins , and bradykinin .