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Cell-mediated immunity
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Cellular immunity, also known as cell-mediated
immunity, is an immune response that does not rely on
the production of antibodies. Rather, cell-mediated
immunity is the activation of phagocytes, antigen-specific
cytotoxic ‘T-lymphocytes, and the release of various
cytokines in response to an antigen.)
History
In the late 19th century Hippocratic tradition medicine
system, the immune system was imagined into two
branches: humoral immunity, for which the protective oo coli Lyicgranules (od) are somreted
function of immunization could be found in the humor 3 tho contact sito, king tho target, Cytotoxic
(cell-free bodily fluid or serum) and cellular immunity, fT cells are powerful agents of cellular
for which the protective function of immunization was immunity
associated with cells. CD4 cells or helper T cells provide
protection against different pathogens. Naive T cells,
which are immature T cells that have yet to encounter an antigen, are converted into activated effector
Immunofluorescence micrograph of three
ytotoxic T cells (outer three) surrounding a
T cells after encountering antigen-presenting cells (APCs). These APCs, such as macrophages,
dendritic cells, and B cells in some circumstances, load antigenic peptides onto the major
histocompatibility complex (MHC) of the cell, in turn presenting the peptide to 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, detecting peptide antigens originating from various types of pathogen: The first class being 1)
Cytotoxic T cells, which kill infected target cells by apoptosis without using cytokines, 2) T,1 cells,
which primarily function to activate macrophages, and 3) T,2 cells, which primarily function to
stimulate B cells into producing antibodies.4)
In another ideology, the innate immune system and the adaptive immune system each comprise both
humoral and cell-mediated components. Some cell-mediated components of the innate immune
system include myeloid phagocytes, innate lymphoid cells (NK cells) and intraepithelial
lymphocytes.(2)
Synopsis
Cellular immunity protects the body through:
= T-cell mediated immunity or T-cell immunity: activating antigen-specific cytotoxic T cells that are
able to induce apoptosis in body cells displaying epitopes of foreign antigen on their surface, such
as virus-infected cells, cells with intracellular bacteria, and cancer cells displaying tumor antigens;= Macrophage and natural killer cell action: enabling the destruction of pathogens via recognition
and secretion of cytotoxic granules (for natural killer cells)!3) and phagocytosis (for
macrophages);!4] and
= Stimulating cells to secrete a variety of cytokines that influence the function of other cells involved
in adaptive immune responses and innate immune responses _!Sll4]
Cell-mediated immunity is directed primarily at microbes that survive in phagocytes and microbes
that infect non-phagocytic cells. It is most effective in removing virus-infected cells, but also
participates in defending against fungi, protozoans, cancers, and intracellular bacteria. It also plays a
major role in transplant rejection,
Type 1 immunity is directed primarily at viruses, bacteria, and protozoa and is responsible for
activating macrophages, turning them into potent effector cells. This is achieved by the secretion of
interferon gamma and TNF.
Overview
CD4* T-helper cells may be differentiated into two main categories:!5]
4. Tut cells which produce interferon gamma and lymphotoxin alpha,
2, Ty2 cells which produce IL-4, IL-5, and IL-13.
A third category called T helper 17 cells (Ty17) were also discovered which are named after their
secretion of Interleukin 17.
CD8* cytotoxic T-cells may also be categorized as:!5)
1. Te1 cells,
2. T,2 cells.
Similarly to CD4* Ty cells, a third category called To17 were discovered that also secrete IL-17.
As for the ILCs, they/larication needed] may be classified into three main categories!)
1. ILC1 which secrete type 1 cytokines,
2. ILC2 which secrete type 2 cytokines,
3. ILC3 which secrete type 17 cytokines.
Development of cells
All type 1 cells begin their development from the common lymphoid progenitor (CLp) which then
differentiates to become the common innate lymphoid progenitor (CILp) and the t-cell progenitor
(Tp) through the process of lymphopoiesis.{51(61
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 into natural killer cells by IL-15. CHILp cells may be induced to differentiate into TLC1
cells by IL-15, into ILC2 cells by IL-7 or ILC3 cells by IL-7 as well. (SIl61T-cell progenitors may differentiate into naive CD8* cells or naive CD4* cells. Naive CD8* cells may
then further differentiate into Tc1 cells upon IL-12 exposure, [IL-4] can induce the differentiation into
Te2 cells and IL-1 or IL-23 can induce the differentiation into Tc17 cells. Naive CD4* cells may
differentiate into Ty cells upon IL-12 exposure, Ty2 upon IL-4 exposure or Ty17 upon IL-1 or IL-23
exposure l5Il6]
Type 1 immunity
Type 1 immunity makes use of the type 1 subset for each of these cell types. By secreting interferon
gamma and TNF, Ty1, Tc1, and group 1 ILCS activate macrophages, converting them to potent
effector cells. It provides defense against intracellular bacteria, protozoa, and viruses. It is also
responsible for inflammation and autoimmunity with diseases such as rheumatoid arthritis, multiple
sclerosis, and inflammatory bowel disease all being implicated in type 1 immunity. Type 1 immunity
consists of these cells:{51
= CD4+ Tit cells
= CD8°* cytotoxic T cells (T,1)
= T-Bet* interferon gamma producing group 1 ILCs(ILC1 and Natural killer cells)
CD4* Ty1 Cells
It has been found in both mice and humans that the signature cytokines for these cells are interferon
gamma and lymphotoxin alpha. The main cytokine for differentiation into Ty1 cells is IL-12 which is
produced by dendritic cells in response to the activation of pattern recognition receptors. T-bet is a
distinctive transcription factor of Tjz1 cells. Ty1 cells are also characterized by the expression of
chemokine receptors which allow their movement to sites of inflammation. The main chemokine
receptors on these cells are CXCR3A and CCR5. Epithelial cells and keratinocytes are able to recruit
Ty1 cells to sites of infection by releasing the chemokines CXCL9, CXCL1o and CXCLi1 in response to
interferon gamma. Additionally, interferon gamma secreted by these cells seems to be important in
downregulating tight junctions in the epithelial barrier.{5)
CD8* Te1 Cells
These cells generally produce interferon gamma. Interferon gamma and IL-12 promote differentiation
toward Tot cells. T-bet activation is required for both interferon gamma and cytolytic potential. CCR5
and CXCR3 are the main chemokine receptors for this cell.{5]
Group 1 ILCs
Groups 1 ILCs are defined to include ILCs expressing the transcription factor T-bet and were
originally thought to only include natural 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 adistinct lineage of natural killer cells termed ILCis. ILC1s are characterized by the ability to produce
interferon gamma, TNF, GM-CSF and IL-2 in response to cytokine stimulation but have low or no
cytotoxic ability..5}
See also
= Immune system
= Humoral immunity (vs. cell-mediated immunity)
= Immunity
References
1. Ross Russell, Amy L; Dryden, Matthew S; Pinto, Ashwin A; Lovett, Joanna K (2018-10-03). "Lyme
disease: diagnosis and management” (htips://dx.doi.org/10,1136/practneurol-2018-001998).
Practical Neurology. 18 (6): 455-464. doi:10.1136/practneurol-2018-001998 (https://doi.org/10.113
6%2F practneurol-2018-001998). ISSN 1474-7758 (https://www.worldcat.orglissn/1474-7758).
PMID 30282764 (https://pubmed.ncbi.nim.nih.gov/30282764). S2CID 52915054 (https://api.sema
nticscholar.org/CorpuslD:52915054).
2. Romo, MR; Pérez-Martinez, D; Ferrer, CC (2016). "Innate immunity in vertebrates: an overview"
(https://www.nebi.nlm.nih.govipme/articles/PMC4863567). Immunology. 148 (2): 125-139
doi:10.1111/imm. 12597 (https://doi.org/10,1111%2Fimm.12597). PMC 4863567 (https://www.ncbi,
nim.nih.govipme/articles/PMC 4863567). PMID 26878338 (https://pubmed.ncbi.nlm.nih.gov/26878
338). S2CID 35251844 (https://api.semanticscholar. org/CorpusID:35251844).
3. Eissmann, Philipp. "Natural Killer Cells" (https://www.immunology.org/public-information/bitesized-i
mmunology/cells/natural-killer-cells). British Society for Immunology. Retrieved 8 November 2018
4, Saldana, José, "Macrophages" (https:/Awww.immunology.org/public-information/bitesized-immunol
ogy/cells/macrophages). British Society for Immunology. Retrieved 8 November 2018.
5. Annunziato, F; Romagnani, C; Romagnani, S (March 2015). "The 3 major types of innate and
adaptive cell-mediated effector immunity” (https://doi.org/10.1016%2F},jaci.2014.11.001). The
Journal of Allergy and Clinical immunology. 135 (3): 626-35, doi:10.1016/jaci.2014.11.001 (http
si/idoi.org/10.1016%2Fj,jaci.2014,11,001). PMID 25528359 (https://pubmed.nebi.nim.nih.gov/2552
8359).
6. Kansler, Emily R.; Li, Ming O. (July 2019). "Innate lymphocytes—lineage, localization and timing
of differentiation" (https://www. nebi.nim.nih.gov/pmc/articles/PMC6804950). Cellular & Molecular
Immunology. 16 (7): 627-633. doi:10.1038/s41423-019-0211-7 (https://doi.org/10.1038%2Fs4142
3-019-0211-7). PMC 6804950 (https://www.ncbi.nim.nih. gov/pmelarticles/PMC6804950).
PMID 30804475 (https://pubmed. ncbi.nim.nih.gov/30804475).
Bibliography
= Cell-mediated immunity (https://www.britannica.com/science/cell-mediated-immunity)
(Encyclopzedia Britannica)
= Chapter 8:T Cell-Mediated Immunity (https:/www.ncbi.nim.nih.gov/books/NBK10762/)
Immunobiology: The Immune System in Health and Disease. 5th edition.
= [4] (https://pubmed.ncbi.nim.nih.gov/25528359/) The 3 major types of innate and adaptive cell-
mediated effector immunity
= functions%20in%20steady-state%20homeostasis%20and%20during%20immune%20challenge.
(https://pubmed.ncbi.nim.nih.gov/30804475/#:~:text=Innate%20lymphocytes-lineage, %20localizati0n%20and%20timing%200f%20differentiation%20Innate,) Innate lymphocytes-lineage,
localization and timing of differentiation
Further reading
= Cell-Mediated Immunity. Murphy (https://link. springer.com/chapter/10.1007/978-3-662-10373-9_3)
= Cell-mediated immunity: How T cells recognize and respond to foreign antigens (htips:/web.archi
ve.org/web/20130507 192352/http://missinglink.ucsf.edu/lm/immunology_module/prologue/objectiv
es/obj07.html)
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