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© Dirk Biddle
T-cells are lymphocytes which develop from bone marrow progenitors that migrate to the thymus. There are two subpopulations of T-cells and their development in the thymus can be traced by surface markers. Membrane cluster differentiation (CD) antigens are called "markers" to help identify the phenotype of cells that look identical under a microscope - but are functionally distinct. There are over 200 recognised and described markers (x) and their function on the cell membrane is to serve as receptors for antigens, cytokines, or adhesion molecules on other cells. The youngest T-cells have a T-cell receptor (TcR) associated with a protein marker called CD3. In the thymus, these cells then go on to develop both a CD4 glycoprotein and a CD8 glycoprotein marker. These cells are referred to as double positive (ie; CD4+CD8+). Eventually these cells lose either CD4 or CD8 to become one of the functional T-cell subpopulations. T-cells with a CD4 marker are called helper T-cells (TH cells). CD8 marker cells are called cytotoxic T-cells (TC cells). Mature TH and TC cells both retain their CD3 receptors, but they perform very different functions in the immune system. Mature CD3+CD4+CD8– TH cells are associated with helper/inducer activities, and mature CD3+CD4–CD8+ TC cells show cytotoxic/suppressor cell functions.
Importantly, after positive selection and before T-cells leave the medulla of the thymus, they undergo negative selection. That is, those cells whose TcR binds very strongly to complexes of self-peptide and self-major histocompatibility complex (MHC) molecules are destroyed by apoptosis. This process of negative selection is important as it eliminates cells that might otherwise mount an autoimmune attack.
Cytotoxic (TC) cells are immunised T-lymphocytes which can directly destroy appropriate target cells. TC cells bind to antigen fragments (epitopes) presented in the Class I Major Histocompatibility Complex (MHC-1) molecule on the surface of other cells (such as somatic cells infected by a virus) and secrete cytotoxins to destroy virus infected cells or cells transformed by cancer. Except while in transit, viruses work inside of cells, safe from any antibodies that might be present in blood, lymph, and secretions. But early in the process, infected cells display fragments of the viral proteins in their surface MHC molecules. TC cells specific for that antigen will then be able to bind to the infected cell and often will be able to destroy it before it can release a fresh crop of viruses. TC cells are also responsible for tissue rejection in organ transplants or grafts.
A subpopulation of CD8+ Tc cells are known as suppressor/effector T-lymphocytes. These Tc cells act to suppress antibody production or inhibit cellular immune responses. Tc suppressor-effector cells execute the message received from TH1 suppressor-inducer cells.
Helper T-cells, TH1 and TH2 varieties, release cytokines that activate macrophages and B-cells respectively. A loss of T-helper cells produces immuno-suppression.
In cell-mediated (humoral) immunity, TH1 suppressor/inducer cells bind to epitopes in the Class II MHC molecule on the surface of antigen-presenting cells (APCs) such as macrophages and dendritic cells. TH1 cells then release lymphokines that attract other cells (such as natural killer cells, cytotoxic T-cells, more macrophages) to the area. The result is inflammation: the accumulation of cells and molecules that attempt to wall off and destroy the antigenic material.
In antibody-mediated immunity, TH2 cells bind to antigen epitopes presented in the class II MHC molecule on the surface of B-cells. The result is the development of plasma cells, secreting antibodies against the antigenic material. While Class I and Class II Major Histocompatibility molecules appear somewhat structurally similar and both present antigen to T-cells, their functions are really quite distinct. First, Class I molecules are found on virtually every cell in the human body. Class II molecules, in contrast, are only found on B-cells, macrophages and other "antigen-presenting cells" (APCs). Second, Class I molecules present antigen to cytotoxic T-cells (TC-cells) while Class II molecules present antigen to helper T-cells (TH-cells). This specificity reflects the third difference, the type of antigen presented. Class I molecules present "endogenous" antigen while Class II molecules present "exogenous" antigens. An endogenous antigen might be fragments of viral proteins or tumor proteins. Presentation of such antigens would indicate internal cellular alterations that if not contained could spread throughout the body. Hence, destruction of these cells by TC-cells is advantageous to the body as a whole. Exogenous antigens, in contrast, might be fragments of bacterial cells or viruses that are engulfed and processed by e.g. a macrophage and then presented to helper T-cells. The TH-cells, in turn, could activate B-cells to produce antibody that would lead to the destruction of the pathogen (1).
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1. http://www.cehs.siu.edu/fix/medmicro/mhc.htm
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Progenitors: 1 : an ancestor of an individual in a direct line of descent along which some or all of the ancestral genes could theoretically have passed
2 : a biologically ancestral form. (M+)
Thymus: The lymphoid organ in which T lymphocytes are educated, mature and multiply. It is composed of stroma (thymic epithelium) and lymphocytes, almost entirely of the T-cell lineage. In mammals the thymus is just anterior to the heart within the rib cage. The thymus tends to atrophy as the animal matures. OMD
Cluster Differentiation (CD) Antigens: The cluster of differentiation (CD) antigens are cellular molecules, displayed on the surface of T-cells, that are each recognized by monoclonal antibodies (MAbs) that allow for the identification each molecule's biochemical properties and cellular distribution. The CD number for each molecule is defined at international workshops that exchange such Mabs and compare their ability to react with human cells and/or human cell molecules
Phenotype: The total observable properties or characteristics displayed by an organism under a particular set of environmental factors.
The phenotype of an organism is produced by the interaction of genotype and the environment, regardless of the actual genotype of the organism.
Antigen: A (usually) protein or carbohydrate substance (as a toxin or enzyme) capable of stimulating an immune response. (M+)
Cytokine: Substance produced by a leucocyte that acts upon another cell. Small proteins or biological factors (in the range of 5-20 kD) that are released by cells and have specific effects on cell-cell interaction, communication and behaviour of other cells. Not really different from hormones, but the term tends to be used as a convenient generic shorthand for interleukins, lymphokines and several related signaling molecules such as TNF (tumour necrosis factor alpha) and interferons. Generally growth factors would not be classified as cytokines, though TGF is an exception. Rather an imprecise term. Chemokines are a subset of cytokines. (OMD)
Adhesion Molecules: Molecules that are involved in T helper-accessory cell, T helper-B-cell, and T cytotoxic-target cell interactions. (OMD)
During an inflammatory response adhesion molecules serve to enhance pairing between many less avid receptors and their ligands and transmit signals that direct specific effector functions. At least four superfamilies of adhesion molecules participate in these events: the selectins, the integrins, certain members of the immunoglobulin superfamily and cadherins
Glycoprotein: A conjugated protein in which the nonprotein group is a carbohydrate -- called also glucoprotein. (M+)
Proteins with covalently attached sugar units, either bonded via the OH group of serine (C3H7NO3) or threonine (C4H9NO3 - O glycosylated) or through the amide NH2 of asparagine (C4H8N2O3 - N glycosylated).
Includes most secreted proteins (serum albumin is the major exception) and proteins exposed at the outer surface of the plasma membrane. Sugar residues found include: mannose, N acetyl glucosamine, N acetyl galactosamine, galactose, fucose and sialic acid. (OMD)
T-lymphocytes, helper-inducer: (TH2) - Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions. (OMD)
Cytotoxic/Suppressor: Explanation will come soon.
Medulla: The inner portion of an organ
Peptide: A compound of two or more amino acids (amide) where the alpha carboxyl group of one is bound to the alpha amino group of another. (OMD)
Usually obtained by partial hydrolysis of proteins
Major Histocompatibility Complex: (MHC) - The set of gene loci molecules in mammals specifying major histocompatibility antigens displayed on cell surfaces that are responsible for lymphocyte recognition and antigen presentation.
For example HLA (the alleles occurring at four loci on the short arm of chromosome 6) in man, H2 in mice, RLA in rabbits, RT1 in rats, DLA in dogs, SLA in pigs, etc.
The MHC molecules control the immune response through recognition of 'self' and 'non-self' and, consequently, serve as targets in transplantation rejection.
The Class I and Class II MHC molecules belong to a group of molecules known as the Immunoglobulin Supergene Family, which includes immunoglobulins, T-cell receptors, CD4, CD8, and others
Apoptosis: The genetically determined process of cell self-destruction that is marked by the fragmentation of nuclear DNA, is activated either by the presence of a stimulus or by the removal of a stimulus or suppressing agent, is a normal physiological process eliminating DNA-damaged, superfluous, or unwanted cells (as immune cells targeted against the self in the development of self-tolerance or larval cells in amphibians undergoing metamorphosis), and when halted (as by genetic mutation) may result in uncontrolled cell growth and tumor formation -- called also programmed cell death. (M+)
Programmed cell death as signalled by the nuclei in normally functioning human and animal cells when age or state of cell health and condition dictates.
An active process requiring metabolic activity by the dying cell, often characterised by cleavage of the DNA into fragments that give a so called laddering pattern on gels.
Cells that die by apoptosis do not usually elicit the inflammatory responses that are associated with necrosis, though the reasons are not clear.
Cancerous cells, however, are unable to experience the normal cell transduction or apoptosis-driven natural cell death process. (OMD)
Autoimmune Diseases: are illnesses which occur when the body tissues are attacked by its own immune system. The immune system is a complex organisation within the body that is designed normally to seek and destroy invaders of the body, particularly infections. Patients with these diseases have unusual antibodies in their blood that target their own body tissues. (OMD)
Epitopes: A molecular region on the surface of an antigen molecule capable of eliciting an immune response and of combining with the specific antibody produced by such a response. (M+)
An antigen has many different epitopes and reacts with antibodies of many different specificities. (OMD)
Somatic: 1. Pertaining to or characteristic of the soma or body. (OMD)
Of, relating to, or affecting the body especially as distinguished from the germ plasm or psych. (M+)
2. Pertaining to the wall of a body in contrast to the viscera. (OMD)
Cytotoxic: (cell poison) Chemicals that are directly toxic to cells, preventing their reproduction or growth. Cytotoxic agents can, as a side effect, damage healthy, non-cancerous tissues or organs which have a high proportion of actively dividing cells, for example, bone marrow, hair follicles. These side effects limit the amount and frequency of drug administration. (OMD)
Lymph: The almost colourless fluid that bathes body tissues and is found in the lymphatic vessels that drain the tissues of the fluid that filters across the blood vessel walls from blood. Lymph carries lymphocytes that have entered the lymph nodes from the blood. OMD
Proteins: Nitrogenous organic compounds, containing more than about 100 amino acid residues, molecular weight 8,000-200,000, in vegetable and animal matter. Proteins yield amino acids on hydrolysis and are foods assimilated as amino acids and reconstructed in the protoplasm.
Cytokines: Substance produced by a leucocyte that acts upon another cell. Small proteins or biological factors (in the range of 5-20 kD) that are released by cells and have specific effects on cell-cell interaction, communication and behaviour of other cells. Not really different from hormones, but the term tends to be used as a convenient generic shorthand for interleukins, lymphokines and several related signaling molecules such as TNF (tumour necrosis factor alpha) and interferons. Generally growth factors would not be classified as cytokines, though TGF is an exception. Rather an imprecise term. Chemokines are a subset of cytokines. (OMD)
Cell-Mediated Immunity: Immune response that involves effector T-lymphocytes and not the production of humoral antibody.
Responsible for allograft rejection, delayed hypersensitivity and in defence against viral infection and intracellular protozoan parasites. (OMD)
Epitopes: A molecular region on the surface of an antigen molecule capable of eliciting an immune response and of combining with the specific antibody produced by such a response. (M+)
An antigen has many different epitopes and reacts with antibodies of many different specificities. (OMD)
Dendritic: Any of the usually branching protoplasmic processes that conduct impulses toward the body of a nerve cell. (M+
Lymphokines: Any of various soluble protein factors (such as an interleukin) of low molecular weight that are not antibodies, are secreted by activated T-cells in response to stimulation by antigens, and have a primary role (such as the activation of macrophages or the enhancement or inhibition of antibody production) in cell-mediated immunity.
Antibody-Mediated Immunity: Usually long-lasting immunity that is acquired through production of antibodies within the organism in response to the presence of antigens. (OMD)
Plasma Cells: Specialised B-lymphocytes that produce antibodies.
Antigenic: A (usually) protein or carbohydrate substance (as a toxin or enzyme) capable of stimulating an immune response. (M+)
Major Histocompatibility Complex: (MHC) - The set of gene loci molecules in mammals specifying major histocompatibility antigens displayed on cell surfaces that are responsible for lymphocyte recognition and antigen presentation.
For example HLA (the alleles occurring at four loci on the short arm of chromosome 6) in man, H2 in mice, RLA in rabbits, RT1 in rats, DLA in dogs, SLA in pigs, etc.
The MHC molecules control the immune response through recognition of 'self' and 'non-self' and, consequently, serve as targets in transplantation rejection.
The Class I and Class II MHC molecules belong to a group of molecules known as the Immunoglobulin Supergene Family, which includes immunoglobulins, T-cell receptors, CD4, CD8, and others.