User:Nxxxdine/Cell-mediated immunity

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Edit summaries Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Instead, it involves the activation of various immune cells, including macrophages, natural killer cells, and cytotoxic T-lymphocytes (T cells), to fight against pathogens, and the release of various cytokines in response to an antigen.

History
In the late 19th century, within the Hippocratic tradition of medicine, the immune system was categorized into two branches: humoral immunity and cellular immunity. '''Humoral immunity, involving B cells and antibody production, was linked to protective immunization in bodily fluids or serum. On the other hand, cellular immunity was associated with protection provided by cells.''' This classification relied on the belief that CD4 cells or helper T cells are crucial for coordinating immune responses against various pathogens. Naive T cells undergo conversion into activated effector T cells upon encountering antigen-presenting cells (APCs), such as macrophages, dendritic cells, and B-cells presenting antigenic peptides to receptors on T-cells through loading onto major histocompatibility complex molecules. The most specialized antigen-presenting cells are dendritic cells, which play a crucial role in ingesting and presenting antigens. Activated effector T-cells can be categorized into three functional classes based on their response to different types of pathogens. The first class includes cytotoxic T cells, which are responsible for killing infected target cells through apoptosis without using cytokines. The second class includes Th1 cells, which primarily function to activate macrophages. The third class includes Th2 cells, which primarily function to stimulate B cells in producing antibodies.

Another school of thought describes the existence of both the innate and adaptive immune systems, each having humoral and cell-mediated elements. The cell-mediated components of the innate immune system encompass myeloid phagocytes, innate lymphoid cells (NK cells), and intraepithelial lymphocytes.

Synopsis
Cellular immunity protects the body through:


 * T-cell mediated immunity, also known as T-cell immunity, involves the activation of specific cytotoxic T cells that can trigger programmed cell death (apoptosis) in body cells presenting epitopes of foreign antigens. This includes virus-infected cells, those containing intracellular bacteria, and cancer cells displaying tumor antigens;
 * Additionally, it facilitates pathogen destruction through macrophage and natural killer cell activity by recognizing and releasing cytotoxic granules (in the case of natural killer cells) and engulfing pathogens (for macrophages) ; and
 * This immune response stimulates the secretion of various cytokines that impact the functioning of other cells participating in both adaptive and innate immune responses.

Cell-mediated immune response is primarily targeted at microorganisms that can survive inside phagocytes and those that infect non-phagocytic cells. This form of immunity eradicates cells infected with a virus, and also contributes to the defense against fungi, protozoans, cancers, and intracellular bacteria. Moreover, it plays a significant role in rejecting transplanted tissues.

Type 1 immunity is a type of immunity that involves a subset of immune cells that produce type 1 cytokines which include interferon gamma and TNF. This type of immunity targets viruses, bacteria, and protozoa, activating macrophages and converting them into potent effector cells via the release of interferon gamma and TNF.

Overview
CD4+ T-helper cells may be differentiated into two main categories:[5]


 * 1) TH1 cells which produce interferon gamma and lymphotoxin alpha,
 * 2) TH2 cells which produce IL-4, IL-5, and IL-13.

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 categorized as:


 * 1) Tc1 cells,
 * 2) Tc2 cells.

Similarly to CD4+ TH cells, a third category called TC17 were discovered that also secrete IL-17.

As for the ILCs, they may be classified into three main categories[5]


 * 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. '''This process is important in the development of T-cells for the formation of a functional immune system. During lymphopoiesis, hematopoietic stem cells in the bone marrow give rise to common lyphoid progenitors, which eventually differentiates into various types of lymphocytes, including T-cells, B-cells, and natural killer cells.'''

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.[5][6]

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
Type 1 immunity is mediated by the type 1 subset within 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
 * CD8+ cytotoxic T cells (Tc1)
 * T-Bet+ interferon gamma producing group 1 ILCs(ILC1 and Natural killer cells)

CD4+ TH1 Cells

Interferon gamma and lymphotoxin alpha are identified as the signature cytokines for these cells in both mice and humans. 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 specific transcription factor that plays a key role in regulating the function of TH1 cells, which are important components of the immune system. TH1 cells express chemokine receptors such as CXCR3A and CCR5, which enable their migration to inflamed areas. Epithelial cells and keratinocytes promote the recruitment of TH1 cells to infection sites by secreting chemokines like CXCL9, CXCL10, and CXCL11 in response to interferon gamma."T-bet is a specific transcription factor that plays a key role in regulating the function of TH1 cells.". Additionally, interferon gamma secreted by these cells seems to be important in downregulating tight junctions in the epithelial barrier.

CD8+TC1 Cells

CD8+ TC1 cells are a subset of cytotoxic T-cells that are involved in type 1 immunity. These cells typically produce interferon gamma, which along with IL-12, promotes differentiation towards TC1 cells. Activation of T-bet is necessary for both interferon gamma production and cytolytic potential. CCR5 and CXCR3 serve as the primary chemokine receptors for this cell type.

Group 1 ILCs

ILC1s are defined to include cells expressing the transcription factor T-bet and were initially believed to only consist of natural killer cells. However, there has been a significant number of NKp46 cells that express specific master transcription factors, categorizing them as a distinct lineage termed ILC1s. These cells have the ability to produce interferon gamma, TNF, GM-CSF, and IL-2 in response to cytokine stimulation but demonstrate low or no cytotoxic abilities.