The immune system is very efficient, but before immune cells can start working, they need to identify the pathogen they are facing. To do this, there is a special antigen presentation system, which will be discussed in this topic.
What is antigen presentation and why is it needed?
Antigen presentation is the presentation of a pathogen's antigen to T-lymphocytes. The antigen-presenting cell (APC) is the first to encounter the antigen (pic 1). The APC takes up the antigen, and then inside its cytosol, it splits it into separate pieces - peptides. These peptides bind to APC receptors and are shuttled to the cell's surface. In simple terms, the APC cuts the antigen into short, recognizable sections, and by placing them directly on its surface, shows them to T-lymphocytes. There is also a presentation process for B-lymphocytes, which we will consider later.
Why is such a system needed? In fact, the answer is quite simple: T-lymphocytes themselves are not able to independently recognize the pathogen as a pathogen and so need to be activated. This is different from B-lymphocytes, which are able to recognize the antigen as it is. T-cells only recognize a special complex of proteins on the cell surface called the major histocompatibility complex (MHC). This is what antigen-presenting cells use to present the peptides they cleaved from the antigen. Antigen presentation provides for the initiation of adaptive immune responses to invading pathogens.
There are two types of MHC. The first (MHC-1) works like a screen on which cells can show their status ("sick" or "healthy"). Infection of a cell with a virus or mutation changes the structure of MHC-1. This is a signal for the activation of T-killers — the cell becomes "foreign" for them. The second (MHC-2) is necessary for antigen-presenting cells.
Pathogens often disrupt the presentation process by disabling the function of a number of signaling molecules or enzymes. Tumor cells sometimes behave in the same way. In the absence of functional antigen presentation, T-lymphocytes can no longer detect an antigen derived from the pathogen, letting it "escape" the immune system's notice.
Presentation participants
There are a lot of cells function as APCs. Among them are dendritic cells (they are most often found in the skin and mucous membranes), macrophages, B-lymphocytes, and in rare situations some other non-specific cells. Dendritic cells, macrophages, and B cells are the principal antigen-presenting cells for T-lymphocytes, whereas special types of dendritic cells — follicular dendritic cells — are the main antigen-presenting cells for B-lymphocytes. APCs can interact with two classes of lymphocytes, but mainly "work" with T-lymphocytes.
Antigen capture occurs either by pinocytosis or phagocytosis (this is more typical for macrophages). Then APCs process the antigen into a form that can be recognized by T-lymphocytes. Non-infectious antigenic material (for example, inactivated viral particles) is taken up by APC by endocytosis and travels through the endocytic pathway into lysosomes, special vesicle-like compartments containing digestive enzymes.
In addition to cells, many biomolecules are involved in the regulation of the presentation process, among the most important are cytokines — small proteins that work as cellular messengers and direct the body's immune response.
Presentation process
The process of antigen presentation is quite simple and well understood.
- The antigen enters the antigen-presenting cell, where it is cleaved into its constituent peptides. The resulting peptides bind to receptor MHC-1, and the complex is transported and presented on the plasma membrane
- The activated MHC-1 complex binds to receptors of immature T-lymphocytes.
- The lymphocyte, having received the "all points bulletin" of the pathogen from the APC, is reconfigured to fight that pathogen specifically.
- The lymphocyte completes its maturation process and proliferates, forming a colony of T-lymphocytes that quickly attack everything containing the presented antigen.
Antigen-independent presentation
Activation of lymphocytes without presenting them with an antigen is called antigen-independent. This is the "standard" maturation of lymphocytes (for example, T-lymphocyte in the thymus) and its subsequent selection. Differentiation of B-lymphocytes is conditionally divided into two stages – antigen-independent (in which immunoglobulin genes are rearranged and expressed – read topic Lymphocytes for more information) and antigen-dependent (in which activation, proliferation and differentiation into mature plasma cells occur).
Conclusion
Antigen presentation is the process by which a special helper cell, the antigen presenting cell, catches an antigen, breaks it down into small peptides, and then incorporates it into its MHC. Only then can T-lymphocytes recognize the pathogen and begin to fight them. B-lymphocytes also have antigen-independent activation, when the maturation of the lymphocyte does not require an encounter with a pathogen.