Antigen-presenting cells (APCs)
Antigen-presenting cells are a class of immune cells that capture antigens, process the antigens and display fragments of the antigen for recognition by T-lymphocytes.
Classical antigen-presenting cells are dendritic cells, macrophages, and B-cells. Aside from the classical antigen-presenting cells listed above, a good number of cells of the immune system (e.g. monocytes) can present foreign antigens to initiate an immune response. However, just a few of these immune cells are specifically equipped to capture, digest, and display foreign antigens and concomitantly stimulate resting/naïve helper T-cells. Classical antigen-presenting cells possess special co-stimulatory receptors that enable them to promote and enhance the action of T-cells.
Antigen presentation, a necessity for T-cell activation
B-cells can recognize and bind directly to intact foreign antigens in blood (and lymph) and become activated without the need of antigen-presenting cells. However, for a helper T-cells to recognize and bind a foreign antigen, antigen-presenting cells must process the antigen into forms that T-cells are able to recognize.
Unlike B-cell, receptors (surface immunoglobulins), T-cell receptors cannot bind free antigens, and they bind antigens if and only if the antigens form complexes with MHC-II molecules, which antigen-presenting cells possess.
Role of antigen-presenting cells
The primary responsibility of antigen-presenting cells is to deliver foreign antigens, which invade the body, to helper T-cells.
The ability of our immune cells to distinguish host cells from potential harmful pathogenic invaders underpins any specific immune response.
For the immune system to detect harmful foreign invaders on spot there must be well-defined mechanisms that enable helper T-cells to recognize pathogen-derived antigens.
Antigen-presenting cells activate different subtypes of helper T-cells (Th1 or Th2). The nature of the pathogen (whether intracellular or extracellular) determines which helper T-cell subtype becomes activated. Th1 subtype activates cytotoxic T-cells whereas Th2 subtype activates plasma cells to flood the system with antibodies. Moreover, the type of helper T-cell activated determines whether cellular or humoral immune response will occur since different T-cell subtypes are equipped to fight different classes of pathogens.
In addition to presenting pathogen-derived antigens to helper T-cells, antigen-presenting cells concomitantly stimulate the T-cells, which is very important in immune responses.
Generation of endogenous antigens
Endogenous antigens (aberrant proteins) form within host cells whenever intracellular pathogens infect host cells or when host cells become cancerous. These proteins are unfamiliar to host and serve to inform the immune system that something is wrong.
However, normal healthy host cells do not generate foreign antigens; host cells generate foreign antigens and other aberrant proteins only when intracellular antigens alter genetic code of a host cell making genes of host cells to direct the synthesis of aberrant proteins (which could be viral proteins or cancerous proteins).
All viruses are intracellular pathogens; moreover, a handful of bacteria are intracellular pathogens also.
Presentation of endogenous antigens
- Once inside the cell, intracellular pathogens use host cells machinery to produce more pathogenic proteins, within host cells.
- The redeeming feature is that all human cells possess a special enzyme complex, being the proteosome, which digest antigens generated in host cells into much smaller peptides within the cytoplasm.
- A special carrier protein complexes the small peptides to a MHC-I molecule and moves the complex to the cell surface. (All nucleated human cells express class-I MHC molecules).
- Cytotoxic T-cells bind any host cell that displays antigen fragments on MHC-I proteins and kill the target host cell.
Any host that displays antigen fragments nestled to MHC-I proteins is infected by an intracellular pathogen.
Presentation of exogenous antigens
- Once exogenous pathogens breach the anatomical barriers of the body and invade the body, antigen presenting cells capture (engulf) foreign harmful material by endocytosis and form a membrane-bound vesicle (endosome) within their cytoplasm. Endosome contains the engulfed material.
- Lysosomes fuse to endosomes, still within the APC; lysosomal enzymes digest engulfed material and degrade the pathogen-derived antigen into smaller fragments.
- Simultaneously, the APC begin to migrate to nearby lymph nodes.
- By the time they arrive in the lymph node, the dendritic cells are displaying small fragments of antigens derived from the degraded pathogen on its cell surface using MHC-II proteins.
- In lymph nodes, T-lymphocytes, specifically those that bear receptors for the displayed antigen fragments, recognize the antigens once they encounter the foreign antigen. (Recall that lymphocytes continually circulate in lymph passing from one lymph node to another).
Dendritic cells are the best-known antigen-presenting cells. A great many of dendritic cells lurk around in the skin and other body sites that are interfaces between the external environment and internal environment. Other antigen presenting cells are macrophages and B-lymphocytes.
Our immune system processes and presents endogenous and exogenous antigens to helper T-cells in two distinct ways. Infected host cells display endogenous antigens on class-I MHC whereas antigen-presenting cells display exogenous antigens on class-II MHC proteins.
Cytotoxic T-cells (CD8+ T-cells), bearing receptors for the displayed antigen responds to endogenous antigens whereas helper T-cells (CD4+ T-cells) responds exogenous antigens.
Helper T-cells are helpers, mediators, and facilitators of specific immune responses.
B-lymphocytes and antigen presentation
Actually, the case of B-lymphocytes (B-cells) is special because they both present and receive antigens. B-cells encounter foreign antigens in two basic ways
- intact antigens in lymph
- processed antigens presented by APC
Antigen presentation by B-cell results in B-cell co-activation by helper T-cells
- B-cells bind intact antigens using their BCRs.
B-cell receptors are surface immunoglobulins expressed on the membranes of B-cells.
- B-cells internalize the bound antigen; digest the antigen and presents fragments to helper T-cells, using class-II MHC proteins.
- A helper T-cell, which bears receptors for the displayed antigen, encounters the antigen and becomes active.
- Activated helper-T-cell releases a cell factor (lymphocytes), which co-activates the B-cell.
- Co-activated B-cell differentiates and proliferates into a massive clone of antibody-secreting cells (plasma cells).
Plasma cells flood the surroundings with antibodies with specific attachment sites for the inducing antigens.