T helper cells (also known as effector T cells or T_h cells) are a sub-group of lymphocytes (a type of white blood cell or leukocyte) that play an important role in establishing and maximising the capabilities of the immune system. These cells are unusual in that they have no cytotoxic or phagocytic activity; they cannot kill infected host (also known as somatic) cells or pathogens, and without other immune cells they would usually be considered useless against an infection. T_h cells are involved in activating and directing other immune cells, and are particularly important in the acquired immune system. They are essential in determining B cell antibody class switching, in the activation and growth of cytotoxic T cells, and in maximising bactericidal activity of phagocytes such as macrophages. It is this diversity in function and its role in influencing other cells that give helper T cells their namesake. A lymphocyte is a type of white blood cell involved in the human bodys immune system. ... White blood cells (a. ... White Blood Cells is also the name of a White Stripes album. ... The Immune System (also known as the Immunlological System) is made up of all the mechanisms through which a multicellular organism defends itself from internal invaders such as bacteria, virus or parasites. ... Cytotoxicity is the quality of being poisonous to cells. ... Phagocytosis (literally cell-eating) is a form of endocytosis wherein large particles are enveloped by the cell membrane of a (usually larger) cell and internalized to form a phagosome, or food vacuole. ... The term somatic refers to the body. ... A pathogen (literally birth of pain from the Greek παθογένεια) is a biological agent that can cause disease to its host. ... The immune system is the system of specialised cells and organs that protect an organism from outside biological influences. ... B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response). ... A cytotoxic (or TC) T cell is a T cell (a type of white blood cell) which has on its surface antigen receptors that can bind to fragments of antigens displayed by the Class I MHC molecules of virus (or other intracellular pathogen) infected somatic cells and tumor cells. ... A bacteriocide or bactericide is a substance that kills bacteria and, preferably, nothing else. ... A phagocyte is a cell that ingests (and destroys) foreign matter, such as microorganisms or debris via a process known as phagocytosis, in which these cells ingest and kill offending cells by cellular digestion. ... Macrophages (Greek: big eaters) are cells found in tissues that are responsible for phagocytosis of pathogens, dead cells and cellular debris. ...

Mature T_h cells are believed to always express the surface protein CD4. T cells expressing CD4 are also known as called CD4⁺ T cells. CD4⁺ T cells are generally treated as having a pre-defined role as helper T cells within the immune system, although there are known rare exceptions. For example, there are sub-groups of suppressor T cells, natural killer T cells, and cytotoxic T cells that are known to express CD4 (although cytotoxic examples have been observed in extremely low numbers in specific disease states, they are usually considered non-existent). All of the latter CD4⁺ T cell groups are not considered T helper cells, and are beyond the scope of this article. CD4 (cluster of differentiation 4) is a molecule that is expressed on the surface of T helper cells (as well as regulatory T cells and dendritic cells). ... The Immune System (also known as the Immunlological System) is made up of all the mechanisms through which a multicellular organism defends itself from internal invaders such as bacteria, virus or parasites. ... This article or section should be merged with regulatory T cell There were debates over the existence of suppressor cells, but recent years studies have confirmed a central role of suppressor cell populations in regulating immunity. ... Natural killer T cells (NK T cells) are a type of lymphocyte, or white blood cell. ... A cytotoxic (or TC) T cell is a T cell (a type of white blood cell) which has on its surface antigen receptors that can bind to fragments of antigens displayed by the Class I MHC molecules of virus (or other intracellular pathogen) infected somatic cells and tumor cells. ...

The importance of helper T cells can be seen via HIV infection, a virus that infects cells that are CD4⁺ (including helper T cells). Towards the end of a HIV infection there is decrease in functional CD4⁺ T cells, resulting in symptoms known as AIDS. There are rare disorders, probably genetic in etiology, that result in dysfunctional CD4⁺ T cells producing similar symptoms; many of which are fatal (see CD4⁺ lymphocytopenia). Human immunodeficiency virus (commonly known as HIV, and formerly known as HTLV-III and lymphadenopathy-associated virus) is a retrovirus that is the cause of the disease known as AIDS, or Acquired Immunodeficiency Syndrome, a syndrome where the immune system begins to fail, leading to many life-threatening opportunistic infections. ... Acquired Immunodeficiency Syndrome or Acquired Immune Deficiency Syndrome (AIDS or Aids) is a collection of symptoms and infections in humans resulting from the specific damage to the immune system caused by the human immunodeficiency virus (HIV). ...

Activation of naïve helper T cells

Following T cell development, matured naïve (meaning they have never been exposed to the antigen they can respond to) T cells leave the thymus and begin to spread throughout the body, including the lymph nodes. Like all T cells, they express the T cell receptor/CD3 complex. The T cell receptor (TcR) consists of both constant and variable regions, the latter of which determines what antigen the T cell can respond to. CD4⁺ T cells have TcR's with an affinity towards Class II MHC, and it is believed that CD4 is involved in determining this affinity during maturation in the thymus. Class II MHC proteins are generally only found on the surface of professional antigen-presenting cells (APCs). Professional antigen presenting cells are primarily dendritic cells, macrophages and B cells, although dendritic cells are the only cell group that expresses MHC Class II endogenously (that is, at all times). Some APCs also express native (or unprocessed) antigen, such as follicular dendritic cells, but unprocessed antigens do not interact with T cells and are not involved in their activation. The antigens that bind to MHC proteins are always peptides. T cells are a subset of lymphocytes that play a large role in the immune response. ... An antigen is a substance that stimulates an immune response, especially the production of antibodies. ... In human anatomy, the thymus is a ductless gland located in the upper anterior portion of the chest cavity. ... Lymph nodes are components of the lymphatic system. ... The T cell receptor or TCR is responsible for recognizing antigen bound to Major histocompatibility complex (MHC). ... In human anatomy, the thymus is a ductless gland located in the upper anterior portion of the chest cavity. ... An antigen presenting cell (APC) is a cell that displays foreign antigen complexed with MHC on its surface. ... Dendritic cells (DC) are immune cells and form part of the mammal immune system. ... Macrophages (Greek: big eaters) are cells found in tissues that are responsible for phagocytosis of pathogens, dead cells and cellular debris. ... B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response). ... Dendritic cells (DC) are immune cells and form part of the mammal immune system. ... Peptides are the family of molecules formed from the linking, in a defined order, of various amino acids. ...

Initial antigen exposure (Signal 1)

During an immune response, professional APCs absorb foreign material (typically bacteria or viruses), and undergo antigen processing, travelling from the site of infection to the lymph nodes. Once at the lymph nodes, the APC begins to present antigen peptides that are bound to Class II MHC, allowing CD4⁺ T cells that express high-affinity TcR's to activate. Subgroups Actinobacteria Aquificae Bacteroidetes/Chlorobi Chlamydiae/Verrucomicrobia Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Nitrospirae Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Bacteria (singular: bacterium) are a major group of living organisms. ... Groups I: dsDNA viruses II: ssDNA viruses III: dsRNA viruses IV: (+)ssRNA viruses V: (-)ssRNA viruses VI: ssRNA-RT viruses VII: dsDNA-RT viruses A virus (Latin, poison) is a microscopic particle that can infect the cells of a biological organism. ... Two methods exist for an antigen to be processed and presented on the cell surface. ...

Since CD4 has structural affinity towards the MHC Class II molecule, the MHC molecule attracts the CD4 protein towards the TcR-CD3 complex, making various intracellular kinases within these proteins accessible to each other. These kinases then interact and activate each other within the T cell. With the assistance of a kinase present in the intracellular section of CD45 (common leukocyte antigen), these kinases stimulate the major biochemical pathways of the T_h cell. These pathways are known as Signal 1. Memory T cells are also re-activated via these TcR pathways if the body is again exposed to the same antigen. CD4 (cluster of differentiation 4) is a molecule that is expressed on the surface of T helper cells (as well as regulatory T cells and dendritic cells). ... The T cell receptor or TCR is responsible for recognizing antigen bound to Major histocompatibility complex (MHC). ... CD3 or CD-3 is an abbreviation with multiple meanings, including: Ford CD3 platform MediaMax CD-3, a copy protection scheme a 3-inch CD or MiniCD This is a disambiguation page — a navigational aid which lists pages that might otherwise share the same title. ... In cell biology, molecular biology and related fields, the word intracellular means inside the cell. It is used in contrast to extracellular (outside the cell). ... In biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific target molecules (substrates); the process is termed phosphorylation. An enzyme that removes phosphate groups from targets is known as a phosphatase. ...

These proteins may also have other functions during T cell activation. As CD4 is drawn towards the antigen-MHC/TcR-CD3 interaction, it may also play a role in increasing the adhesion between the cells. There are also dedicated adhesion molecules expressed on each cell's surface, such as LFA-1 on the T cell binding to the ICAM receptor on the APC, making the cells sticky and giving the cells time to interact and activate. Intercellular adhesion molecules (ICAMs) are molecules that promote adhesion between cells. ...

The huge extracellular region of CD45 may also play some role during cell interactions, as it has various isoforms that change depending on the T_h cell's activation and maturation status. For example, CD45 shortens in length following T_h activation (CD45RA⁺ to CD45RO⁺), but whether this change in protein length influences activation is unknown. It has been proposed that initially longer CD45 may affect the accessibility of the T cell receptor against the antigen-MHC molecule, thereby forcing an increase in the affinity (and specificity) of the T cell involved. Once the activation has occurred however, CD45 shortens, allowing for easier interaction and activation as an effector T helper cell.

Verification (Signal 2)

Once the naïve T cell has received the first TcR/CD3 based signal, it also needs the activation of a second independent biochemical pathway, known as Signal 2. This verification step reinforces that the antigen detected is foreign, reducing the risk of autoimmunity. If this second signal is not present during initial antigen exposure, the T cell believes it does not target a foreign protein, and becomes anergic. Anergic cells will not respond to any antigen in the future, even if both signals are present later on. Anergy is a theory in immunobiology in which there is a lack of reaction by the bodys defence mechanisms when foreign substances come into contact with the body. ...

The second signal involves an interaction between CD28 on the CD4⁺ T cell and the proteins CD80 (B7.1) or CD86 (B7.2) on the professional APC's. Both CD80 and CD86 activate CD28. These proteins are known as co-stimulatory molecules, and it has been proposed that they act as a quality control system within the T cell, ensuring that the antigen is foreign. It is considered to be another mechanism to protect the host against T cell auto-immunity (as an adjunct to the negative selection stage of self/non-self recognition "learned" by the T cell during development). Structure of human CD28. ... During the activation of T cells, co-stimulation of molecules is often crucial to the development of an effective immune response. ... T cells are a subset of lymphocytes that play a large role in the immune response. ...

Although this stage is necessary and important for the activation of naïve helper T cells, its importance is best demonstrated during the similar activation of CD8⁺ cytotoxic T cells. The primary signal in CD8⁺ T cells does not have any specific affinity towards professional APCs (as almost all cells express MHC Class I), and therefore without other interactions the cytotoxic T cells cannot determine they are actually auto-reactive (they respond to a host protein, and its activation would kill healthy host cells). Since CD80 and CD86 are only present on professional APC's, their interaction with CD28 confirms that the T cell is interacting with a foreign antigen (as it is coming from a professional APC). A cytotoxic (or TC) T cell is a T cell (a type of white blood cell) which has on its surface antigen receptors called T-cell receptors (TCRs) that can bind to fragments of antigens displayed by the Class I MHC molecules of virus (or other intracellular pathogen) infected somatic... Autoimmunity is the failure of an organism to recognise its own constituent parts (down to the sub-molecular levels) as Self, which results in an immune response against its own cells and tissues. ...

Once the naïve T cell has both pathways activated, the second signal induces permanent changes to the T cell. The second signal is then obsolete; the first signal from the TcR pathways suffices in later interactions. This remains true for memory T cells, since they have already undergone this initial activation mechanism and therefore know that they are not auto-reactive.

Proliferation

If both stimulatory signals are active within the helper T cell, the cell then makes itself proliferate. It does this by producing a potent T cell growth factor called interleukin-2 (IL-2). The activated T cell will also begin to produce all of the sub-units of the IL-2 receptor (CD25 or IL-2R). The IL-2 that is produced is released from the cell, and then binds to IL-2 receptors on the same (or other) activated T cell, resulting in auto-regulation (also known as autocrine stimulation). After many cell generations, the progenitors differentiate into effector T_h cells, memory T_h cells, and suppressor T_h cells. The term cell growth is used in two different ways in biology. ... Interleukin-2 (IL2) is an interleukin, a type of biological response modifier that can improve the bodys natural response to disease. ... Autocrine signaling is a form of signalling in which a cell secretes a chemical messenger (called the autocrine agent) that signals the same cell. ...

• Effector T_h cells secrete cytokines, proteins or peptides that stimulate or interact with other leukocytes, including T_h cells themselves.

• Memory T_h cells retain the antigen affinity of the originally activated T cell, and are used to act as later effector cells during a second immune response (e.g. if there is re-infection of the host at a later stage).

• Suppressor T cells do not promote immune function, but act to decrease it instead. Despite their low numbers during an infection, these cells are believed to play an important role in the self-limitation of the immune system; they prevent the development of various auto-immune diseases.

The production of IL-2 by helper T cells is also necessary for the proliferation of activated CD8⁺ T cells. Without helper T cell interactions, CD8⁺ T cells do not proliferate and eventually become anergic. This cross-reliance on helper T cells is another way the immune system tries to prevent T cell-mediated auto-immune disease. Cytokines is a group of proteinaceous signalling compounds that like hormones and neurotransmitters are used extensively for inter-cell communication. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Peptides (from the Greek πεπτος, digestible), are the family of short molecules formed from the linking, in a defined order, of various α-amino acids. ... White Blood Cells is also the name of a White Stripes album. ... This article or section should be merged with regulatory T cell There were debates over the existence of suppressor cells, but recent years studies have confirmed a central role of suppressor cell populations in regulating immunity. ... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... A cytotoxic (or TC) T cell is a T cell (a type of white blood cell) which has on its surface antigen receptors called T-cell receptors (TCRs) that can bind to fragments of antigens displayed by the Class I MHC molecules of virus (or other intracellular pathogen) infected somatic... CD8 (cluster of differentiation 8) is a molecule that is expressed on the surface of cytotoxic T cells. ... Anergy is a theory in immunobiology in which there is a lack of reaction by the bodys defence mechanisms when foreign substances come into contact with the body. ... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ...

Determination of the effector T cell response

Helper T cells are capable of influencing a variety of immune cells, and the T cell response generated (including the extracellular signals such as cytokines) can be essential for a successful outcome from infection. In order to be effective helper T cells must determine which cytokines will allow the immune system to be most useful or beneficial for the host. It must do so based on the type of challenge the immune system has. Understanding exactly how helper T cells respond to immune challenges is currently of major interest in immunology, because such knowledge may be very useful in the treatment of disease and in increasing the effectiveness of vaccination. In cell biology, molecular biology and related fields, the word extracellular means outside the cell. It is used in contrast to intracellular (inside the cell). ... Cytokines is a group of proteinaceous signalling compounds that like hormones and neurotransmitters are used extensively for inter-cell communication. ... Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. ... A disease is an abnormal condition of the body or mind that causes discomfort, dysfunction, or distress to the person afflicted or those in contact with the person. ... Vaccination is the process of administering live, albeit weakened, microbes to patients, with the intent of conferring immunity against a targeted form of a related disease agent. ...

T_h1/T_h2 Model for helper T cells

Proliferating helper T cells that develop into effector T cells differentiate into two major subtypes of cells known as T_h1 and T_h2 cells (also known as Type 1 and Type 2 helper T cells respectively). These subtypes are defined on the basis of the specific cytokines they produce. T_h1 cells produce interferon-gamma (IFN-gamma) and tumor necrosis factor-beta (TNF-beta, also known as lymphotoxin), while T_h2 cells produce interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-13 (IL-13), among numerous other cytokines. The T_h1/T_h2 model also states that interleukin-12 (IL-12) plays an essential role during T_h1 development, however IL-12 is not produced by helper T cells themselves, but by certain professional antigen presenting cells, such as activated macrophages and dendritic cells. Interleukin-2 was classically associated with T_h1 cells, but this association may be misleading; IL-2 is produced by all helper T cells early in their activation. Interferon-gamma or IFN-g is a dimerized soluble cytokine which is a Type II Interferon. ... Interleukin-4, abreviated IL-4, is a lymphokine that stimulates the proliferation of activated B-cells and T-cells, among other effects. ... IL-5 is an interleukin produced by T helper-2 cells and mast cells. ... Interleukin 13 (IL-13) is a cytokine secreted by many cell types, but especially T helper type 2 (Th2) cells, that is an important mediator of allergic inflammation and disease. ... Interleukin 12 (IL-12) is an interleukin that are naturally produced by macrophages and human B-lymphoblastoid cells (NC-37)in response to antigenic stimulation. ... An antigen presenting cell (APC) is a cell that displays foreign antigen complexed with MHC on its surface. ... Macrophages (Greek: big eaters) are cells found in tissues that are responsible for phagocytosis of pathogens, dead cells and cellular debris. ... Dendritic cells (DC) are immune cells and form part of the mammal immune system. ... Interleukin-2 (IL2) is an interleukin, a type of biological response modifier that can improve the bodys natural response to disease. ...

Both of these cytokine profiles appear to be biased in the type of immune stimulation they promote. For example, cytokines in the T_h1 response maximises the killing efficacy of the macrophages and in the proliferation of cytotoxic CD8⁺ T cells, and it has been suggested that their primary role during an immune response is to activate and/or proliferate the cellular immune system. T_h2 cells express a variety of cytokines, many of which stimulate B-cells into proliferation, to induce B-cell antibody class switching, and to increase antibody production. T_h2 cells are therefore considered necessary for the full maturation of the humoral immune system. Macrophages (Greek: big eaters) are cells found in tissues that are responsible for phagocytosis of pathogens, dead cells and cellular debris. ... CD8 (cluster of differentiation 8) is a molecule that is expressed on the surface of cytotoxic T cells. ... B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response). ... Schematic of antibody binding to an antigen An antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Humoral immunity is mediated by secreted antibodies, produced in cells of the B lymphocyte lineage (B cell). ...

The stimulation of the above systems is only one way helper T cells manipulate the immune system. Many of the cytokines also act on helper T cells themselves, or on other immune cells, such as the actions of interleukin-5 on eosinophils. There are cytokines in both T_h responses that play an important role in preserving the response itself, or in suppressing other functions of the immune system. IL-5 is an interleukin produced by T helper-2 cells and mast cells. ... Eosinophils are white blood cells that are responsible for combating infection by parasites in the body. ...

The Type 2 response promotes its own profile using two different cytokines. Interleukin-4 acts on helper T cells to promote the production of T_h2 cytokines (including itself), while interleukin-10 (IL-10) inhibits a variety of cytokines including interleukin-2 and interferon-gamma in helper T cells and IL-12 in dendritic cells and macrophages. The combined action of these two cytokines suggests that once the T cell has decided to produce these cytokines, that decision is preserved (and also encourages other T cells to do the same). Interleukin-4, abreviated IL-4, is a lymphokine that stimulates the proliferation of activated B-cells and T-cells, among other effects. ... Interleukin-10 (IL-10 or IL10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine, capable of inhibiting synthesis of pro-inflammatory cytokines like IFN-gamma, IL-2, IL-3, TNFα and GM-CSF by cells such as macrophages and Th1 cells. ... Interleukin-2 (IL2) is an interleukin, a type of biological response modifier that can improve the bodys natural response to disease. ... Interferon-gamma or IFN-g is a dimerized soluble cytokine which is a Type II Interferon. ...

A similar phenomenon occurs with the Type 1 response. The Type 1 cytokine interferon-gamma increases the production of interleukin-12 by dendritic cells and macrophages, and via positive feedback, IL-12 stimulates the production of IFN-gamma in helper T cells, thereby promoting the T_h1 profile. IFN-gamma also inhibits the production of cytokines such as interleukin-4, an important cytokine associated the Type 2 response, and thus it also acts to preserve its own response. Interferon-gamma or IFN-g is a dimerized soluble cytokine which is a Type II Interferon. ... Interleukin 12 (IL-12) is an interleukin that are naturally produced by macrophages and human B-lymphoblastoid cells (NC-37)in response to antigenic stimulation. ... Interleukin-4, abreviated IL-4, is a lymphokine that stimulates the proliferation of activated B-cells and T-cells, among other effects. ...

While we know about the types of cytokine patterns helper T cells tend to produce, we understand less about how the patterns themselves are decided. Various evidence suggests that the type of APC presenting the antigen to the T cell has a major influence on its profile. Other evidence suggests that the concentration of antigen presented to the T cell during primary activation influences its choice. The presence of some cytokines (such as the ones mentioned above) will also influence the response that will eventually be generated, but our understanding is nowhere near complete.

Complexities surpassing the T_h model

The interactions between cytokines from the T_h1/T_h2 model can be more complicated in some animals. For example, the T_h2 cytokine IL-10 inhibits cytokine production of both T_h subsets in humans. Human IL-10 (coded hIL-10) suppresses the proliferation and cytokine production of all T cells and the activity of macrophages, but continues to stimulate plasma cells, ensuring that antibody production still occurs. As such, hIL-10 is not believed to truly promote the T_h2 response in humans, but acts to prevent over-stimulation of helper T cells while still maximising the production of antibodies. Interleukin-10 (IL-10 or IL10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine, capable of inhibiting synthesis of pro-inflammatory cytokines like IFN-gamma, IL-2, IL-3, TNFα and GM-CSF by cells such as macrophages and Th1 cells. ... Plasma cells are B lymphocytes that secrete immunoglobulins (antibodies). ... Schematic of antibody binding to an antigen An antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ...

There are also other types of T cells that can also influence the expression and activation of helper T cells, such as natural suppressor T cells, along with less common cytokine profiles such as the T_h3 subset of helper T cells. Terms such as "regulatory" and "suppression" have become ambiguous after the discovery that helper CD4⁺ T cells are also capable of regulating (and suppressing) their own responses outside of dedicated supressor T cells. Regulatory T cells (also known as suppressor T cells) are a specialized subpopulation of T cells that act to suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self. ...

One major difference with "suppressor" (or "natural regulatory") T cells is that they always suppress the immune system, while effector T cell groups usually begin with immune-promoting cytokines and then switch to inhibitory cytokines later in its repertoire. The latter is a feature of T_h3 cells, which transform into a suppressor subset after its initial activation and cytokine production. Immunosuppression is the medical suppression of the immune system. ...

Both suppressor T cells and T_h3 cells produce the cytokine transforming growth factor-beta (TGF-beta) and IL-10. Both cytokines are inhibitory to helper T cells; TGF-beta suppresses the activity of most of the immune system. Regulatory T cells (also known as suppressor T cells) are a specialized subpopulation of T cells that act to suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self. ... Rich in anti-oxidents, TGF beta is a welcome addition to the female diet. ...

Many of the cytokines in this article are also expressed by other immune cells (see individual cytokines for details), and it is becoming clear that while the original T_h1/T_h2 model is enlightening and gives insight into the functions of helper T cells, it is far too simple to define its entire role or actions. Some immunologists question the model completely, as some in vivo studies suggest that individual helper T cells usually do not match the specific cytokine profiles of the T_h model, and many cells express cytokines from both profiles. That said, the T_h model has still played an important part in developing our understanding of the roles and behaviour of helper T cells and the cytokines they produce during an immune response. In vivo (Latin for (with)in the living). ...

Role of helper T cells in disease

Considering the diverse and important role helper T cells play in the immune system, it is not surprising that these cells often influence the immune response against disease. They also appear to make occasional mistakes, or generate responses that would be politely considered non-beneficial. In the worst case scenario, the helper T cell response could lead to a disaster and the fatality of the host. Fortunately this is a very rare occurrence.

Helper T cells and Hypersensitivity

The immune system must achieve a balance of sensitivity in order to respond to foreign antigens without responding to the antigens of the host itself. When the immune system responds to very low levels of antigen that it usually shouldn't respond to, a hypersensitivity response occurs. Hypersensitivity is believed to be the cause of allergy and some auto-immune disease. Hypersensitivity is an immune response that damages the bodys own tissues. ... An allergy can refer to several kinds of immune reactions including Type I hypersensitivity in which a persons body is hypersensitised and develops IgE type antibodies to typical proteins. ... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ...

Hypersensitivity reactions can be divided into four types:

Type 1 hypersensitivity includes common immune disorders such as asthma, allergic rhinitis (hay fever), eczema (hives), and anaphylaxis. These reactions all involve IgE antibodies, which require a T_h2 response during helper T cell development. Preventative treatments, such as corticosteroids and montelukast, focus on suppressing mast cells or other allergic cells; T cells do not play a primary role during the actual inflammatory response. It's important to note that the numeral allocation of hypersensitivity "types" does not correlate (and is completely unrelated) to the "response" in the T_h model. For the play, see Hay Fever. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... In medicine, anaphylaxis is a severe and rapid systemic allergic reaction. ... IGE (Internet Gaming Entertainment) is a MMORPG services company. ... Schematic of antibody binding to an antigen An antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. ... Montelukast is an oral leukotriene receptor antagonist (LTRA) for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies. ...

Type 2 and Type 3 hypersensitivity both involve complications from auto-immune or low affinity antibodies. In both of these reactions, T cells may play an accomplice role in generating these auto-specific antibodies, although some of these reactions under Type 2 hypersensitivity would be considered normal in a healthy immune system (for example, Rhesus factor reactions during child-birth is a normal immune response against child antigens). The understanding of the role of helper T cells in these responses is limited but it is generally thought that T_h2 cytokines would promote such disorders. For example, studies have suggested that lupus (SLE) and other auto-immune diseases of similar nature can be linked to the production of T_h2 cytokines. A blood type is a description an individuals characteristics of red blood cells due to substances (carbohydrates and proteins) on the cell membrane. ... Systemic lupus erythematosus (SLE or lupus) is a chronic, potentially debilitating or fatal autoimmune disease in which the immune system attacks the body’s cells and tissue, resulting in inflammation and tissue damage. ...

Type 4 hypersensitivity, also known as delayed type hypersensitivity, are caused via the over-stimulation of immune cells, commonly lymphocytes and macrophages, resulting in chronic inflammation and cytokine release. Antibodies do not play a direct role in this allergy type. T cells play an important role in this hypersensitivity, as they activate against the stimulus itself and promote the activation of other cells; particularly macrophages via T_h1 cytokines. Hypersensitivity is an immune response that damages the bodys own tissues. ... A lymphocyte is a type of white blood cell involved in the human bodys immune system. ... Macrophages (Greek: big eaters) are cells found in tissues that are responsible for phagocytosis of pathogens, dead cells and cellular debris. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ...

Other cellular hypersensitivities include cytotoxic T cell mediated auto-immune disease, and a similar phenomenon; the rejection of transplant organs. Helper T cells are required to fuel the development of these diseases. In order to create sufficient auto-reactive killer T cells, interleukin-2 must be produced, and this is supplied by CD4⁺ T cells. CD4⁺ T cells can also stimulate cells such as natural killer cells and macrophages via cytokines such as interferon-gamma, thereby encouraging these cytotoxic cells to kill host cells in certain circumstances. A cytotoxic (or TC) T cell is a T cell (a type of white blood cell) which has on its surface antigen receptors called T-cell receptors (TCRs) that can bind to fragments of antigens displayed by the Class I MHC molecules of virus (or other intracellular pathogen) infected somatic... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... An organ transplant is the transplantation of an organ (or part of one) from one body to another, for the purpose of replacing the recipients damaged or failing organ with a working one from the donor. ... Autoimmunity is the failure of an organism to recognise its own constituent parts (down to the sub-molecular levels) as Self, which results in an immune response against its own cells and tissues. ... Interleukin-2 (IL2) is an interleukin, a type of biological response modifier that can improve the bodys natural response to disease. ... Natural NK cells are cytotoxic; small granules in their cytoplasm contain special proteins such as perforin and proteases known as granzymes. ... Interferon-gamma or IFN-g is a dimerized soluble cytokine which is a Type II Interferon. ...

The mechanism that killer T cells use during auto-immunity is almost identical to their response against viruses, and some viruses have been accused of causing auto-immune disease, such as Type 1 Diabetes mellitus. Cellular auto-immune disease occurs because the host antigen recognition systems fail, and the immune system believes, by mistake, that the host cell is virus infected. The CD8⁺ T cells then remember the host antigen as being foreign, and then go on to destroy all of the host cells (or the transplant organ) that express that antigen. A common alternate meaning of virus is computer virus. ... For the disease characterized by excretion of large amounts of severely diluted urine, see diabetes insipidus. ... The Immune System (also known as the Immunlological System) is made up of all the mechanisms through which a multicellular organism defends itself from internal invaders such as bacteria, virus or parasites. ...

It should be noted that some of this section is a simplification, and that many auto-immune diseases are more complex; a well known example is rheumatoid arthritis, where both antibodies and immune cells are known to play a role in the pathology. Generally the immunology of most auto-immune diseases is not well understood. Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. ...

HIV infection

Perhaps the best example of the importance of CD4⁺ T cells is demonstrated with human immunodeficiency virus (HIV) infection. HIV targets cells that express CD4, and can infect macrophages, dendritic cells (both groups express CD4 at low levels) and CD4⁺ T cells. CD4 (cluster of differentiation 4) is a molecule that is expressed on the surface of T helper cells (as well as regulatory T cells and dendritic cells). ... Human immunodeficiency virus (commonly known as HIV, and formerly known as HTLV-III and lymphadenopathy-associated virus) is a retrovirus that is the cause of the disease known as AIDS, or Acquired Immunodeficiency Syndrome, a syndrome where the immune system begins to fail, leading to many life-threatening opportunistic infections. ... Macrophages (Greek: big eaters) are cells found in tissues that are responsible for phagocytosis of pathogens, dead cells and cellular debris. ... Dendritic cells (DC) are immune cells and form part of the mammal immune system. ...

It has been proposed that during the non-symptomatic phase of HIV infection, the virus has a relatively low affinity towards T cells (and has a higher affinity for macrophages), resulting in a slow kill rate of CD4⁺ T cells by the immune system. This can then be compensated for via the production of new helper T cells from the thymus (originally from the bone marrow). Once the virus becomes lymphotropic (or T-tropic) however, it begins to infect CD4⁺ T cells far more efficiently (likely due to a change in the co-receptors it binds to during infection), and the immune system is overwhelmed. In human anatomy, the thymus is a ductless gland located in the upper anterior portion of the chest cavity. ... Grays Anatomy illustration of cells in bone marrow. ... Human immunodeficiency virus (commonly known as HIV, and formerly known as HTLV-III and lymphadenopathy-associated virus) is a retrovirus that is the cause of the disease known as AIDS, or Acquired Immunodeficiency Syndrome, a syndrome where the immune system begins to fail, leading to many life-threatening opportunistic infections. ... This page is a candidate to be copied to Wiktionary. ...

At this point, functional CD4⁺ T cell levels begin to decrease, eventually to a point where the CD4⁺ T cell population is too small to recognise the full range of antigens that could potentially be detected. The lack of full antigen cover results in the core symptoms of acquired immune deficiency syndrome (AIDS). AIDS allows various antigens (and later entire pathogens) to break through T cell recognition, resulting in no helper T cell response. This allows for various opportunistic infections that require a helper T cell response to bypass the immune system. Two components of the immune system are particularly affected in AIDS, due to its CD4⁺ T cell dependency: An antigen is a substance that stimulates an immune response, especially the production of antibodies. ... Acquired Immunodeficiency Syndrome or Acquired Immune Deficiency Syndrome (AIDS or Aids) is a collection of symptoms and infections in humans resulting from the specific damage to the immune system caused by the human immunodeficiency virus (HIV). ... A pathogen (literally birth of pain from the Greek παθογένεια) is a biological agent that can cause disease to its host. ... Opportunistic infections are infections in immunodeficient patients caused by pathogens which are incapable of causing infection in immunocompetent individuals. ...

1. CD8⁺ T cells are not stimulated as effectively during the AIDS period of HIV infection, making AIDS patients very susceptible to most viruses, including HIV itself. This decline in killing of CD4⁺ T cells results in the virus being produced for a longer period (the infected CD4+ T cells are not killed as quickly), increasing the proliferation of the virus, and accelerating the development of the disease.
2. Antibody class switching declines significantly once helper T cell function fails. The immune system loses the ability to improve the specificity of their antibodies, and the production of important antibody groups such as IgG and IgA decreases significantly due to a lack of cytokines such as IL-4. The production of all antibodies also declines because the T_h2 cytokines that promote antibody production are no longer present in sufficient amounts. All of this results in an increased susceptibility to aggressive bacterial infections, especially in areas of the body not accessible by IgM antibodies.

If the patient does not respond to HIV treatment they will succumb usually to either cancers or infections, because the immune system finally reaches a point where it is no longer coordinated or stimulated enough to deal with the disease. CD8 (cluster of differentiation 8) is a molecule that is expressed on the surface of cytotoxic T cells. ... In binary testing, e. ... Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... IGA may stand for: Koji Igarashi, a video game producer Interactive genetic algorithm International Geothermal Association Independent Glass Association International Gothic Association International Gamers Award International Goat Association Irish Games Association Irish Geological Association ImmunoGlobulin A - see IgA nephritis which is a renal disease IGA (supermarkets) Independent Grocers Association or... Interleukin-4, abreviated IL-4, is a lymphokine that stimulates the proliferation of activated B-cells and T-cells, among other effects. ... Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Human immunodeficiency virus (commonly known as HIV, and formerly known as HTLV-III and lymphadenopathy-associated virus) is a retrovirus that is the cause of the disease known as AIDS, or Acquired Immunodeficiency Syndrome, a syndrome where the immune system begins to fail, leading to many life-threatening opportunistic infections. ...