Cell-mediated immunity

Immunofluorescence micrograph of threecytotoxic T cells(outer three) surrounding a cancer cell. Lytic granules (red) are secreted at the contact site, killing the target. Cytotoxic T cells are powerful agents of cellular immunity.

Cellular immunity,also known ascell-mediated immunity,is animmune responsethat does not rely on the production ofantibodies.Rather, cell-mediated immunity is the activation ofphagocytes,antigen-specificcytotoxic T-lymphocytes,and the release of variouscytokinesin response to anantigen.

History

In the late 19th centuryHippocratic traditionmedicine system, the immune system was imagined into two branches:humoral immunity,for which the protective function of immunization could be found in the humor (cell-freebodily fluidorserum) andcellular immunity,for which the protective function of immunization was associated with cells.CD4cells orhelper T cellsprovide protection against differentpathogens.Naive T cells,which are immature T cells that have yet to encounter anantigen,are converted into activated effectorT cellsafter encounteringantigen-presenting cells(APCs). These APCs, such asmacrophages,dendritic cells,andB cellsin some circumstances, load antigenic peptides onto themajor histocompatibility complex(MHC) of the cell, in turn presenting thepeptideto receptors on T cells. The most important of these APCs are highly specialized dendritic cells; conceivably operating solely to ingest and present antigens.Activated effector T cells can be placed into three functioning classes, detectingpeptideantigens originating from various types ofpathogen:The first class being 1)Cytotoxic T cells,which kill infected target cells byapoptosiswithout using cytokines, 2)T_h1 cells,which primarily function to activate macrophages, and 3)T_h2 cells,which primarily function to stimulateB cellsinto producingantibodies.

In another ideology, theinnate immune systemand theadaptive immune systemeach comprise bothhumoraland cell-mediated components. Some cell-mediated components of the innate immune system include myeloidphagocytes,innate lymphoid cells (NK cells) andintraepithelial lymphocytes.

Synopsis

Cellular immunity protects the body through:

• T-cell mediated immunity or T-cell immunity: activating antigen-specificcytotoxic T cellsthat are able to induceapoptosisin body cells displayingepitopesof foreign antigen on their surface, such asvirus-infected cells, cells withintracellular bacteria,andcancercells displayingtumorantigens;
• Macrophageandnatural killer cellaction: enabling the destruction of pathogens via recognition andsecretionof cytotoxic granules (for natural killer cells)and phagocytosis (for macrophages);and
• Stimulating cells to secrete a variety ofcytokinesthat influence the function of other cells involved in adaptive immune responses and innate immune responses.

Cell-mediated immunity is directed primarily atmicrobesthat survive inphagocytesand microbes that infect non-phagocytic cells. It is most effective in removingvirus-infected cells,but also participates in defending againstfungi,protozoans,cancers,and intracellular bacteria. It also plays a major role intransplant rejection.

Type 1 immunity is directed primarily atviruses,bacteria,andprotozoaand is responsible for activatingmacrophages,turning them into potent effector cells. This is achieved by the secretion ofinterferon gammaandTNF.

Overview

CD4⁺T-helper cellsmay be differentiated into two main categories:

1. T_H1 cells which produceinterferon gammaandlymphotoxin Alpha,
2. T_H2 cells which produceIL-4,IL-5,andIL-13.

A third category calledT helper 17 cells(T_H17) were also discovered which are named after their secretion ofInterleukin 17.

CD8⁺cytotoxic T-cellsmay also be categorized as:

1. T_c1 cells,
2. T_c2 cells.

Similarly to CD4⁺T_Hcells, a third category called T_C17 were discovered that also secrete IL-17.

As for theILCs,they^{[Clarification needed.]}may be classified into three main categories

1. ILC1which secrete type 1 cytokines,
2. ILC2which secrete type 2 cytokines,
3. ILC3which secrete type 17 cytokines.

Development of cells

All type 1 cells begin their development from thecommon lymphoid progenitor(CLp) which then differentiates to become the common innate lymphoid progenitor (CILp) and the t-cell progenitor (Tp) through the process oflymphopoiesis.

Common innate lymphoid progenitors may then be differentiated into a natural killer progenitor (NKp) or a common helper like innate lymphoid progenitor (CHILp). NKp cells may then be induced to differentiate intonatural killer cellsbyIL-15.CHILp cells may be induced to differentiate intoILC1cells byIL-15,intoILC2cells byIL-7orILC3cells byIL-7as well.

T-cell progenitors may differentiate into naïve CD8⁺cells or naïve CD4⁺cells. Naïve CD8⁺cells may then further differentiate into T_C1 cells uponIL-12exposure, [IL-4] can induce the differentiation into T_C2 cells andIL-1orIL-23can induce the differentiation into T_C17 cells. Naïve CD4⁺cells may differentiate into T_H1 cells uponIL-12exposure, T_H2 uponIL-4exposure or T_H17 uponIL-1orIL-23exposure.

Type 1 immunity

Type 1 immunity makes use of the type 1 subset for each of these cell types. By secretinginterferon gammaandTNF,T_H1, T_C1, and group 1 ILCS activate macrophages, converting them to potent effector cells. It provides defense against intracellularbacteria,protozoa,andviruses.It is also responsible forinflammationandautoimmunitywith diseases such asrheumatoid arthritis,multiple sclerosis,andinflammatory bowel diseaseall being implicated in type 1 immunity. Type 1 immunity consists of these cells:

• CD4+ T_H1 cells
• CD8⁺cytotoxic T cells (T_c1)
• T-Bet⁺interferon gammaproducing group 1 ILCs(ILC1 and Natural killer cells)

CD4⁺T_H1 Cells

It has been found in bothmiceandhumansthat the signature cytokines for these cells areinterferon gammaandlymphotoxin Alpha.The main cytokine for differentiation into T_H1 cells is IL-12 which is produced bydendritic cellsin response to the activation ofpattern recognition receptors.T-betis a distinctivetranscription factorof T_H1 cells. T_H1 cells are also characterized by the expression of chemokine receptors which allow their movement to sites of inflammation. The mainchemokine receptorson these cells areCXCR3AandCCR5.Epithelial cellsandkeratinocytesare able to recruit T_H1 cells to sites of infection by releasing the chemokinesCXCL9,CXCL10andCXCL11in response tointerferon gamma.Additionally,interferon gammasecreted by these cells seems to be important in downregulatingtight junctionsin the epithelial barrier.

CD8⁺T_C1 Cells

These cells generally produceinterferon gamma.Interferon gamma andIL-12promote differentiation toward T_C1 cells.T-betactivation is required for both interferon gamma and cytolytic potential.CCR5andCXCR3are the main chemokine receptors for this cell.

Group 1 ILCs

Groups 1 ILCs are defined to includeILCsexpressing the transcription factorT-betand were originally thought to only includenatural killer cells.Recently, there have been a large amount of NKp46⁺cells that express certain master [transcription factor]s that allow them to be designated as a distinct lineage of natural killer cells termed ILC1s. ILC1s are characterized by the ability to produceinterferon gamma,TNF,GM-CSFandIL-2in response to cytokine stimulation but have low or no cytotoxic ability.

See also

• Immune system
• Humoral immunity(vs. cell-mediated immunity)
• Immunity

References

Bibliography

• Cell-mediated immunity(Encyclopædia Britannica)
• Chapter 8:T Cell-Mediated ImmunityImmunobiology: The Immune System in Health and Disease. 5th edition.
• [1]The 3 major types of innate and adaptive cell-mediated effector immunity
• functions%20in%20steady-state%20homeostasis%20and%20during%20immune%20challenge.Innate lymphocytes-lineage, localization and timing of differentiation

Further reading

• Cell-Mediated Immunity. Murphy
• Cell-mediated immunity: How T cells recognize and respond to foreign antigens