TLR-2 is the name of a biomolecule that plays a role in the human immune system. It is a membrane protein, referred to as a receptor, that sits on the surface of certain cells and is able to recognize foreign or host molecules and transmit corresponding signals to the cell or to the nervous system.
The TLR-2 under discussion is a member of a large family of homologous toll-like receptors (TLRs) and is described here as an example.
The immune system recognizes foreign pathogens and eliminates them. This occurs in several phases. In the early inflammation phase, the pathogens are recognized by antibodies that are already present (innate or acquired through prior infection; see also cross-reactivity). These are then disabled by immune-system components (e.g. complement) bound to the antibodies and deposited in the vicinity and are phagocytized by scavenger cells (e.g. macrophages). Dendritic cells can phagocytize, too, but do not perform this for the purpose of direct pathogen elimination. Rather, they infiltrate the spleen and lymph nodes and present components of an antigen there, as the result of which specific antibodies are formed that recognize exactly that antigen.
These antibodies would arrive too late in an acute infection, however, so what we think of as "immunology" constitutes only the second half of what happens. Because this later phase would always start too late to play an essential role in the defense process, a more effective approach is applied ahead of it, one that occurs only in forms of life that are phylogenetically more highly developed.
What are called pattern-recognition receptors come into play here. This refers to receptors that recognize the gross, primarily structural features of molecules that do not occur in the host organism. These include, for example, lipids with a totally different basic chemical structure. Such receptors are bound directly to cells of the immune system and cause immediate activation of the individual nonspecific immune cell.
The first example of such a foreign ligand is the bacterial endotoxin, whose effects have been known for generations. When it enters the bloodstream it causes systematic activation of the early-phase response, with all the side effects of septic shock. This is known in the laboratory as the Shwartzman reaction. The intended effect is to mobilize the organism for "war", so to speak, and eliminate most of the pathogens.
TLR-2 is expressed on microglia, Schwann cells, monocytes, macrophages, dendritic cells, polymorphonuclear leukocytes (PMNs or PMLs), B cells (B1a, MZ B, B2), and T cells, including Tregs (CD4+CD25+ regulatory T cells). In some cases it occurs in a heterodimer (combination molecule), e.g .combined with TLR-1 or TLR-6. TLR-2 is also found in the epithelia of the air passages, the pulmonary alveoli, the renal tubules, and the Bowman's capsules of renal corpuscles. In the skin it is found on keratinocytes and sebaceous glands; spc1 in induced here, allowing a bactericidal sebum to be formed.
As a membrane surface receptor, TLR-2 recognizes many bacterial, fungal, viral, and certain endogenous molecules. In general, this results in the uptake (internalization, phagocytosis) of bound materials by endosomes/phagosomes and in cellular activation; thus such elements of innate immunity as macrophages, PMNs and dendritic cells assume functions of non-specific immune defense, B1a and MZ B cells form the first antibodies, and specific antibody formation eventually gets started. Cytokines participating in this include tumor necrosis factor alpha (TNF-α) and various interleukins (IL-1α, IL-1β, IL-6, IL-8, IL-12). Before the TLRs were known, several of the substances mentioned were classified as "modulins". Due to the cytokine pattern, which corresponds more closely to Th1, an immune deviation is seen in this direction in most experimental models, away from Th2 characteristics. Conjugates are being developed as vaccines or are already being used without advance information.
A peculiarity first recognized in 2006 is the expression of TLR-2 on Tregs (a type of T cell), which are similarly brought to TCR-controlled proliferation and functional inactivity. This leads to disinhibition of the early inflammation phase andof specific antibody formation. Following a reduction in pathogen count, many pathogen-specific Tregs are present that, now without a TLR-2 signal, become active and inhibit both the specific and the inflammatory immune reactions (see also TGF-β, IL-10). Older literature that ascribes a direct immunity-stimulating effect via TLR-2 to a given molecule must be interpreted in light of the fact that the TLR-2 knockouts that were used generally have very few Tregs.
Functionally relevant polymorphisms are described that cause functional impairment and thus generally reduced survival rates, particularly in infections/sepsis with Gram-positive bacteria.
Signal transduction is shown in the article on the Toll-like receptor.