T helper cell
From Freepedia
A T helper cell (or TH cell), is a T cell (a type of white blood cell or leukocyte) that only plays a role in the adaptive immune system. These cells are unique within the immune system because they have no cytotoxic or phagocytic activity. This means they cannot kill infected cells or invading pathogens, and without other immune cells they are ineffective during an infection.
Helper T cells are essential in establishing an acquired immune response against antigens. TH cells are involved in activating and directing other immune cells. They are believed to be necessary in determining B cell antibody class switching, in the activation and growth of killer T cells, and in maximising bactericidal activity in phagocytes such as macrophages. It is this diversity in function and its role in influencing other cells that give Helper T cells their namesake.
Mature TH cells are believed to always express the surface protein CD4. T cells expressing CD4 are also known as called CD4+ T cells. The importance of these cells can be seen via HIV infection, where the virus infects cells that are CD4+ (including 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 genetic disorders that result in dysfunctional CD4+ T cells, all of which result in similar symptoms, many of which are fatal.
Activation of naïve helper T cells
Following T cell development, matured naïve (meaning they have never been exposed to the antigen they target) T cells leave the thymus and begin to spread throughout the body, including in the lymph nodes. Like all T cells, they express T antigen receptors (also known as the TcR) that have an affinity with Class II MHC molecules. Class II MHC proteins are found specifically on the surface of professional antigen-presenting cells (APCs). The antigens that bind to MHC proteins are almost always peptides.
Following an infection, antigen-presenting cells with processed antigen travel from the site of infection to the lymph nodes and begin to present various antigenic peptides, which bind to either MHC Class I and Class II. Depending on the APC, some also express unprocessed antigen (e.g. for use in antibody class switching), such as follicular dendritic cells. T cells are then exposed to these APCs and those T cells with T cell receptors (also known as TcR) that are capable of binding with antigen-bound MHC begin to activate. It should be noted that memory T cells are also activated this way if the body is re-infected with the same antigen.
CD4 is believed to be important for TH cell stabilisation during activation, possibly by binding to specific portions of the Class II MHC molecule. This stabilises the binding between the two cells, allowing for activation. CD4 is believed to determine which MHC class the T cell will interact with (in this case MHC Class II), and it appears that CD4+ T cells almost always have a pre-defined role in the immune system.
Once the naïve T cell has been exposed to antigen (a high affinity interaction between the TcR and the antigen-bound Class II MHC has occurred), the cell produces a potent T cell growth factor called interleukin-2 (IL-2). The IL-2 that is produced binds to the same (or other) activated T cells (only activated T cells produce all the subunits of the IL-2 receptor), resulting in auto-regulation and self proliferation. After many cell generations, these progenitors differentiate into either activated TH cells and memory TH cells.
- Activated TH cells secrete cytokines, proteins or peptides that stimulate or interact with other leukocytes, including TH cells.
- Memory TH cells retain the TcR affinity of the originally activated T cell, and can be called upon during the secondary immune response.
TH1/TH2 Model for Helper T cells
Activated, proliferating TH cells can differentiate into two major subtypes of cells, TH1 and TH2 cells. These subtypes are defined on the basis of specific cytokines produced. TH1 cells produce interferon-gamma (or IFN-gamma) and lymphotoxin (also known as tumor necrosis factor-beta or TNF-beta), while TH2 cells produce interleukin-4 (IL-4), interleukin-5 and interleukin-13, among other cytokines. The TH1/TH2 model also states that interleukin-12 plays an essential role during TH1 development, but IL-12 is not produced by helper T cells, but rather by certain professional APCs, such as activated macrophages and dendritic cells. IL-2 is associated with TH1 cells as it is necessary for CD8+ T cells to proliferate, but since it is produced by all activated T cells (at least initially) this could be misleading.
TH1 cells mainly interact with macrophages, activating those displaying antigen fragments through MHC Class II molecules. TH2 cells mainly act to stimulate B-cells into antibody producing plasma cells; this interaction also occurs through MHC Class II molecules.
Movement of activated helper T cells
Activated TH cells then leave the lymph node and transport through the lymphatic system and into the bloodstream. These cells then spread throughout the body, moving to inflammed tissues or other lymph nodes via a process known as chemotaxis. Diapedesis is the mechanism by which immune cells cross the endothelium (lining of the blood vessels).
Once in the site of infection/lymph nodes, CD4+ T cells may bind to APCs expressing MHC Class II, and if the antigen it recognises is bound to the MHC molecule, it reactivates. Once reactivated, the T cell releases various products, including cytokines listed above, although it is likely that the cytokines it produces depends on its location, the cells it is interacting with, the presence of other cytokes, as well as other things that are not yet known. Considering most infections involve most, or even all of the cell types CD4+ T cells interact with, its role during infection is complex and yet to be fully elucidated.
