CTL-mediated cytotoxicity

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Within the scientific discipline of toxicology, Cytotoxic T lymphocytes (CTLs) are generated by immune activation of cytotoxic T cells (Tc cells). They are generally CD8+, which makes them MHC class I restricted. CTLs are able to eliminate most cells in the body since most nucleated cells express class I MHC molecules. The CTL-mediated immune system can be divided into two phases. In the first phase, functional effector CTLs are generated from naive Tc cells through activation and differentiation. In the second phase, affector CTLs destroy target cells by recognizing the antigen-MHC class I complex.

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Phase 1

In phase one, effector CTLs are generated from CTL precursors. The CTL precursors include naive Tc cells since they are incapable of killing target cells. After a precursor cell has been activated, it can then differentiate into a functional CTL with cytotoxic activity. There are three sequential signals that are required to complete this process.

First, there is TCR recognition of the peptide-MHC class I complex. This step allows the cell to become licensed to an antigen-presenting cell.

Second, a costimulatory signal is transmitted by the interaction between CD28 and B7 of the precursor cell and the licensed antigen-presenting cell.

Last, a signal is induced by the interaction between IL-2 and the high-affinity IL-2 receptor. This results in proliferation and differentiation of the antigen-activated precursor cell into a functional effector CTL.

Phase 2

In phase two, the now functional effector CTLs destroy the target cells. This can be done in two ways. These pathways are the cytotoxic protein pathway and the Fas ligand pathway. Apoptosis is the primary mechanism for both of these pathways.

Cytotoxic protein pathway

One pathway is the cytotoxic protein pathway. In this pathway perforins and granzymes are taken up by the target cell. In this pathway, the perforins facilitate the entry of granule contents into the cell. The granzymes then activate the endogenous apoptosis pathway, which induces cell death without necrosis. This leaves packages of fragmented DNA material from the target cell for the macrophages to dispose of.

Fas ligand pathway

The other pathway is the Fas ligand pathway. In this pathway, a Fas ligand (FasL) on the CTL binds to Fas receptor (FasR) on the target cell. This pathway is independent of granzymes. Instead it involves Interleukin-1β converting enzyme (ICE; also known as Caspase 1) activation, which is similar to granzyme B. This ultimately leads to DNA fragmentation.

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T cell White blood cells of the immune system

A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface.

Cytotoxic T cell T cell that kills infected, damaged or cancerous cells

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.

T helper cell Type of immune cell

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 immune system, particularly in the adaptive immune system. As their name suggests, they "help" the activity of other immune cells by releasing cytokines, small protein mediators that alter the behavior of target cells that express receptors for those cytokines. These cells help to polarize the immune response into the appropriate kind depending on the nature of the immunological insult (virus vs. extracellular bacterium vs. intracellular bacterium vs. helminth vs. fungus vs. protist). They are generally 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.

Natural killer cell Type of cytotoxic lymphocyte

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 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.

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.

Granzyme B (GrB) is a serine protease most commonly found in the granules of natural killer cells and cytotoxic T cells. It is secreted by these cells along with the pore forming protein perforin to mediate apoptosis in target cells.

Adaptive immune system Subsystem of the immune system that is composed of specialized, systemic cells and processes

The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system is one of the two main immunity strategies found in vertebrates.

Alloimmunity is an immune response to nonself antigens from members of the same species, which are called alloantigens or isoantigens. Two major types of alloantigens are blood group antigens and histocompatibility antigens. In alloimmunity, the body creates antibodies against the alloantigens, attacking transfused blood, allotransplanted tissue, and even the fetus in some cases. Alloimmune (isoimmune) response results in graft rejection, which is manifested as deterioration or complete loss of graft function. In contrast, autoimmunity is an immune response to the self's own antigens. Alloimmunization (isoimmunization) is the process of becoming alloimmune, that is, developing the relevant antibodies for the first time.

Antigen-presenting cell Cell that displays antigen bound by MHC proteins on its surface

An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T-cells.

MHC class I Protein of the immune system

MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on platelets, but not on red blood cells. Their function is to display peptide fragments of proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein. Because MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called cytosolic or endogenous pathway.

Fas ligand

Fas ligand is a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. Its binding with its receptor induces apoptosis. Fas ligand/receptor interactions play an important role in the regulation of the immune system and the progression of cancer.

T-cell receptor Protein complex on the surface of T cells that recognises antigens

The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen peptides is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen peptide and many antigen peptides are recognized by the same TCR.

Immunological synapse Interface between lymphocyte and target cell

In immunology, an immunological synapse is the interface between an antigen-presenting cell or target cell and a lymphocyte such as a T/B cell or Natural Killer cell. The interface was originally named after the neuronal synapse, with which it shares the main structural pattern. An immunological synapse consists of molecules involved in T cell activation, which compose typical patterns—activation clusters. Immunological synapses are the subject of much ongoing research.

Antigen presentation Vital immune process that is essential for T cell immune response triggering

Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment, now bound to the major histocompatibility complex (MHC), is transported to the surface of the cell, a process known as presentation, where it can be recognized by a T-cell receptor. If there has been an infection with viruses or bacteria, the cell will present an endogenous or exogenous peptide fragment derived from the antigen by MHC molecules. There are two types of MHC molecules which differ in the behaviour of the antigens: MHC class I molecules (MHC-I) bind peptides from the cell cytosol, while peptides generated in the endocytic vesicles after internalisation are bound to MHC class II (MHC-II). Cellular membranes separate these two cellular environments - intracellular and extracellular. Each T cell can only recognize tens to hundreds of copies of a unique sequence of a single peptide among thousands of other peptides presented on the same cell, because an MHC molecule in one cell can bind to quite a large range of peptides. Predicting which antigens will be presented to the immune system by a certain MHC/HLA type is difficult, but the technology involved is improving.

Fas receptor

The Fas receptor, also known as Fas, FasR, apoptosis antigen 1, cluster of differentiation 95 (CD95) or tumor necrosis factor receptor superfamily member 6 (TNFRSF6), is a protein that in humans is encoded by the FAS gene. Fas was first identified using a monoclonal antibody generated by immunizing mice with the FS-7 cell line. Thus, the name Fas is derived from FS-7-associated surface antigen.

Interferon type II

A sole member makes up the type II interferons (IFNs) that is called IFN-γ (gamma). Mature IFN-γ is an anti-parallel homodimer, which binds to the IFN-γ receptor (IFNGR) complex to elicit a signal within its target cell. IFNGR is made up of two subunits each of molecules designated IFNGR1 and IFNGR2.

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.

Centre dimmunologie de Marseille-Luminy

The Centre d’Immunologie de Marseille-Luminy (CIML) was founded in 1976 and has been described by AERES, an independent evaluation agency, as "without doubt one of the best immunology centers of excellence in Europe". The CIML addresses all areas of contemporary immunology; it is located in Marseille in the South of France.

In the immune system, veto cells are white blood cells that have a selective immunomodulation properties. Veto cells were first described in 1979 as cells that “can prevent generation of cytotoxic lymphocytes by normal spleen cells against self-antigens”. Hence, veto cells delete T cells that recognize the veto cells.

Jürg Tschopp was a Swiss biochemist, known for his research on apoptosis and the immunology of inflammation. His greatest achievement was perhaps his team's discovery and scientific description of the inflammasome.

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