Cell-mediated immunity is an immune response that does not involve 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.[ citation needed ]
In the late 19th century Hippocratic tradition medicine 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-free bodily fluid or serum) and cellular immunity, for which the protective function of immunization was 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 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) Th1 cells, which primarily function to activate macrophages, and 3) Th2 cells, which primarily function to stimulate B cells into producing antibodies.
In another ideology, the innate immune system and the adaptive immune system each comprise both humoral and cell-mediated components.[ citation needed ]
Cellular immunity protects the body through:
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.
CD4+ T-helper cells may be differentiated into two main categories:
A third category called T helper 17 cells (TH17) were also discovered which are named after their secretion of Interleukin 17.
CD8+ cytotoxic T-cells may also be differentiated into two main categories:
Similarly to CD4+ TH cells, a third category called TC17 were discovered that also secretes Interleukin 17.
As for the ILCs, they may be differentiated into three main categories
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.
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 ILC1 cells by IL-15, into ILC2 cells by IL-7 or ILC3 cells by IL-7 as well.
T-cell progenitors may differentiate into naïve CD8+ cells or naïve CD4+ cells. Naïve CD8+ cells may then further differentiate into TC1 cells upon IL-12 exposure,, [IL-4] can induce the differentiation into TC2 cells and IL-1 or IL-23 can induce the differentiation into TC17 cells. Naïve CD4+ cells may differentiate into TH1 cells upon IL-12 exposure, TH2 upon IL-4 exposure or TH17 upon IL-1 or IL-23 exposure.
Type 1 immunity makes use of the type 1 subset for each of these cell types. By secreting interferon gamma and TNF, TH1, 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:
CD4+ TH1 Cells
It has been found in both mice and humans that the signature cytokines for these cells is interferon gamma and lymphotoxin alpha. The main cytokine for differentiation into TH1 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 TH1 cells. TH1 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 TH1 cells to sights of infection by releasing the chemokines CXCL9, CXCL10 and CXCL11 in response to interferon gamma. Additionally, interferon gamma secreted by these cells seems to be important in downregulating tight junctions in the epithelial barrier.
CD8+ TC1 Cells
These cells generally produce interferon gamma. Interferon gamma and IL-12 promote differentiation toward TC1 cells. T-bet activation is required for both interferon gamma and cytolytic potential. CCR5 and CXCR3 are the main chemokine receptors for this cell.
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 a dinstinct lineage of natural killer cells termed ILC1s. 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.
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways.
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4.
Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cell and other intracellular pathogens acting at around 3 days after infection, and respond to tumor formation. Typically, immune cells detect the major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release, causing the death of the infected cell by lysis or apoptosis. NK cells are unique, however, as they have the ability to recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of MHC class 1. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.
Interleukins (ILs) are a group of cytokines that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related proteins.
Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation. IL-12 belongs to the family of interleukin-12. IL-12 family is unique in comprising the only heterodimeric cytokines, which includes IL-12, IL-23, IL-27 and IL-35. Despite sharing many structural features and molecular partners, they mediate surprisingly diverse functional effects.
Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin, and by others as a product of antigen-stimulated lymphocytes. It was also shown to be produced in human lymphocytes. or tuberculin-sensitized mouse peritoneal lymphocytes challenged with Mantoux test (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus. Those reports also contained the basic observation underlying the now widely employed IFN-γ release assay used to test for tuberculosis. In humans, the IFN-γ protein is encoded by the IFNG gene.
Lymphopoiesis (lĭm'fō-poi-ē'sĭs) is the generation of lymphocytes, one of the five types of white blood cell (WBC). It is more formally known as lymphoid hematopoiesis.
Chemokine ligand 9 (CXCL9) is a small cytokine belonging to the CXC chemokine family that is also known as monokine induced by gamma interferon (MIG). The CXCL9 is one of the chemokine which plays role to induce chemotaxis, promote differentiation and multiplication of leukocytes, and cause tissue extravasation.
Interferon type II is a family of interferons involved in immune system regulation. There is only one member of type II interferons (IFNs), known as IFN-γ. IFN-γ is a cytokine which binds to the type II IFN receptor, or the IFN-γ receptor(IFNGR), to elicit a signal within its target cell. Through cell signaling, IFN-γ plays a role in regulating the immune response of its target cell. A key signaling pathway that is activated by type II IFN is the JAK-STAT signaling pathway. IFN-γ plays an important role in both innate and adaptive immunity. Type II IFN is primarily secreted by adaptive immune cells, more specifically CD4+ T helper 1 (Th1) cells, natural killer (NK) cells, and CD8+ cytotoxic T cells. The expression of type II IFN is upregulated and downregulated by cytokines. By activating signaling pathways in cells such as macrophages, B cells, and CD8+ cytotoxic T cells, it is able to promote inflammation, antiviral or antibacterial activity, and cell proliferation and differentiation. Type II IFN is serologically different from interferon type 1, binds to different receptors, and is encoded by a separate chromosomal locus. Type II IFN has played a role in the development of cancer immunotherapy treatments due to its ability to prevent tumor growth.
Understanding of the antitumor immunity role of CD4+ T cells has grown substantially since the late 1990s. CD4+ T cells (mature T-helper cells) play an important role in modulating immune responses to pathogens and tumor cells, and are important in orchestrating overall immune responses.
Gamma delta T cells are T cells that have a distinctive T-cell receptor (TCR) on their surface. Most T cells are αβ T cells with TCR composed of two glycoprotein chains called α (alpha) and β (beta) TCR chains. In contrast, gamma delta (γδ) T cells have a TCR that is made up of one γ (gamma) chain and one δ (delta) chain. This group of T cells is usually less common than αβ T cells, but are at their highest abundance in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs).
The following outline is provided as an overview of and topical guide to immunology:
Type IV hypersensitivity, often called delayed-type hypersensitivity, is a type of hypersensitivity reaction that takes several days to develop. Unlike the other types, it is not humoral but rather is a type of cell-mediated response. This response involves the interaction of T cells, monocytes, and macrophages.
The pluripotency of biological compounds describes the ability of certain substances to produce several distinct biological responses. Pluripotent is also described as something that has no fixed developmental potential, as in being able to differentiate into different cell types in the case of pluripotent stem cells.
Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and natural killer cells. Many of these cells recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that binds self and foreign lipids and glycolipids. They constitute only approximately 1% of all peripheral blood T cells. Natural killer T cells should neither be confused with natural killer cells nor killer T cells.
Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells, derived from common lymphoid progenitors (CLPs). In response to pathogenic tissue damage, ILCs contribute to immunity via the secretion of signalling molecules, and the regulation of both innate and adaptive immune cells. ILCs are primarily tissue resident cells, found in both lymphoid, and non- lymphoid tissues, and rarely in the blood. They are particularly abundant at mucosal surfaces, playing a key role in mucosal immunity and homeostasis. Characteristics allowing their differentiation from other immune cells include the regular lymphoid morphology, absence of rearranged antigen receptors found on T cells and B cells, and phenotypic markers usually present on myeloid or dendritic cells.
Immunology is the study of the immune system during health and disease. Below is a list of immunology-related articles.
Immunoediting is a dynamic process that consists of immunosurveillance and tumor progression. It describes the relation between the tumor cells and the immune system. It is made up of three phases: elimination, equilibrium, and escape.
ILC2 cells, or type 2 innate lymphoid cells are a type of innate lymphoid cell. Not to be confused with the ILC. They are derived from common lymphoid progenitor and belong to the lymphoid lineage. These cells lack antigen specific B or T cell receptor because of the lack of recombination activating gene. ILC2s produce type 2 cytokines and are involved in responses to helminths, allergens, some viruses, such as influenza virus and cancer.
Type 3 innate lymphoid cells (ILC3) are immune cells from the lymphoid lineage that are part of the innate immune system. These cells participate in innate mechanisms on mucous membranes, contributing to tissue homeostasis, host-commensal mutualism and pathogen clearance. They are part of a heterogeneous group of innate lymphoid cells, which is traditionally divided into three subsets based on their expression of master transcription factors as well as secreted effector cytokines - ILC1, ILC2 and ILC3.