T helper cell
Helper T cells are a subset of T - lymphocytes in the blood, which have a helper function. They are classified on the basis of of them distributed cytokines into two major subgroups ( subpopulations ), which have different functions. A sub-group ( known as type-1 helper T cells ) involved in the cellular immune response, while the other sub-group ( type 2 helper T cells) involved in the humoral immune response. Another T-helper cell type was discovered in 2005. This type forms, inter alia, IL-17 and, therefore, plays a role in the regulation of inflammatory processes.
General characterization of the T-helper cells
Functionally opposing division ( dichotomy ) in type 1 and type 2 T cells have been described by way of example for CD4-positive lymphocytes, however, also applies to CD8-positive T cells, and for cells with a γδ T- cell antigen receptor. As a type-1 T cells CD4 -positive and CD8 - positive lymphocytes are determined that distribute typically γ interferon (IFN- γ ), IL -2 and TNF- α. Accordingly, CD4-positive or CD8-positive lymphocytes, which have as a typical property that cell release of cytokines IL- 4, IL- 5, IL -6, IL -10 and IL -13, referred to as type-2 T cells.
This classification is a simplified view due to extreme response options of cytokine -secreting T cells. Both in the tissue as well as in peripheral blood T cells can be found with a cytokine, which is typical for both type 1 and type 2 for T cells. These cells are sometimes referred to as type 0 T- cells.
The differences between type 1 and type 2 T cells T cells were first described in 1986 by Tim Mosmann and Robert L. Coffman.
Type 1 T Helper cells ( Th1 lymphocytes )
The cell- mediated defense of the adaptive immune system primarily by activated T lymphocytes and macrophages. Certain antigens cause activation accelerated proliferation and differentiation of T- cells having specificity for these antigens. For activated type 1 T cells, the release of cytokines such as IFN- γ, IL -2 and TNF- α is characteristic by which the activation and differentiation of macrophages.
The macrophages in turn promote through their cytokine (IL -12), the type-1 polarization of reactive T cells. At the same time macrophages intensify their action as antigen presenting cells (APC ) and improve their antimicrobial abilities to act against extracellular and intracellular antigens. There is the upregulation of costimulatory surface molecules CD40, CD80 and CD86 and MHC II molecules. In consequence of the MHC - production and Peptidprozessierung (a total of peptide presentation) increases.
The T cell -mediated inflammatory reaction increases blood flow through the expansion of local vessels ( vasodilation ). The upregulation of adhesion molecules on endothelial cells results in the increased migration of additional cells from the peripheral blood into the tissue. As a local anti-inflammatory factor, fibrin is formed finally. In the inhibition of the spread of disease triggers ( pathogens ) and CD8 -positive T - cells are involved. Through their secretion of IFN- γ and direct cytotoxicity, they contribute to tissue damage.
B- lymphocytes are also encouraged (but not as much as by Type2 ), by class switching to the production of opsonic antibodies ( mainly IgG), ie such antibodies, the objects can be eaten by macrophages. At the same time a type 2 response is inhibited by the distributed cytokines. Is triggered such a response by IFN- γ and IL- 12, which by natural killer cells ( NK) cells and dendritic cells are formed. This path is used in particular combating some intracellular bacteria and viral infections. The production of IFN- γ simultaneously blocks the differentiation into type-2 cells.
In addition, type 1 cells are able to combat infections caused by bacteria which multiply in the vesicles of macrophages. Examples of this are the causative agent of tuberculosis ( Mycobacterium tuberculosis ) and leprosy pathogen ( Mycobacterium leprae ). The type-1 cells activate the infected macrophages and triggering of the fusion of infected vesicles with lysosomes, which the pathogens are digested.
Type 2 helper T cells (TH2 lymphocytes)
The main function of the type 2 -polarized CD4 T cells interact with B-lymphocytes, which takes place via cytokines and cell-bound molecules, and this leads to production and secretion of antibodies. This is for the humoral immune response and significantly effected by the typical type 2 cytokine profile of CD4-positive T cells (IL-4, IL-5, IL-6, IL-10, IL -13 and lymphotoxin - α ).
Distributed by type 2 T cell cytokines inhibit the mechanisms that lead to a type 1 response. Through this cross -locking, a once chosen direction for the immune response is maintained. Particularly IL-10 inhibits macrophage activation. The granted in the immune response of type 2 T- cell antigen - specific help for B cells leads not only to their activation, proliferation and differentiation, but also stimulates mast cells and basophils and eosinophils. Within the series of cytokines that stimulate the secretion of immunoglobulins, IL-4 has a special function. It is within the responsibility of the activation and differentiation of B cells, especially for the formation of neutralizing antibody classes, that is, for a class change (English isotype switch) to IgA, IgG, IgE. Type 2 T cells can stimulate B cells thereby greatly. Thus, the humoral immune response is triggered primarily by the cytokine IL- 4, IL- 6 reinforced this tendency. IL-4 inhibits the activation of macrophages. IL-10 reduces the production of IFN- γ in T cells and macrophages.
Typ17 T- helper cells ( TH17 - lymphocytes)
The recently discovered TH17 lymphocytes appear to play an important role in the regulation of inflammatory processes. In this case, interleukin-6 is a necessary signal which coordinates the conversion of naive CD4 T - cell in a TH17 cell. The role of TH17 lymphocytes is not yet fully understood and the subject of current research.
Antigen recognition of CD4 T - cells
In their function as antigen presenting cells B cells can recognize and absorb antigens based on specific epitopes. Inside the cell, the antigen is processed and presented in the form of small peptides in conjunction with MHC class II molecules, CD4 -positive T - cells.