The adaptive immune response, also known as acquired or specific immunity, is the body’s defense system tailored to target a specific pathogen. It has two branches: cellular or cell-mediated immunity, and humoral, or antibody-mediated immunity. The major players of cellular immunity are T-lymphocytes.
They develop in the thymus, for which they are named. During the process of maturation, billions of variations of T-cells are formed, each carrying a unique surface protein, called T-cell receptor, TCR. In addition, a population of T-cells, called helper T-cells, also has a receptor named CD4; while a second population, of cytotoxic T-cells, carries CD8 receptor.
In the process of development, T-cells also learn to not react to the body’s own antigens; those that react to self-molecules are eliminated. Mature T-cells then migrate to lymph nodes and other lymphoid tissues, where they await exposure to pathogens. Basically, specific immunity relies on the invading pathogen finding a match among these billions of T-cell variations.
Only the ones that can bind to the pathogen, are selectively activated. T-cells, however, cannot bind free-floating pathogens. They can only bind to pieces of the pathogen bound to a certain host molecule called major histocompatibility complex, or MHC, on the surface of so-called “antigen-presenting cells”.
There are two classes of MHC: - MHC class I molecules are expressed by all nucleated cells of the body. These molecules are constantly produced in the cytoplasm and, on their way to the cell membrane, pick up pieces of peptides and display them on the cell surface. If a cell is infected by a virus or is cancerous, a foreign or an abnormal antigen is displayed; and the cell can bind and activate a matching T-cell.
MHC-I only binds CD8 receptor, thus activating only cytotoxic T-cells. - MHC class II molecules occur exclusively on professional antigen-presenting cells, of which dendritic cells are most effective. Resident dendritic cells on the site of infection swallow up pathogens, cut them into pieces, and display them on MHC-II molecules on their surface.
These dendritic cells then migrate to the nearest lymph node, where they present the antigens to a matching T-helper cell, whose CD4 receptor binds to MHC-II. Activation of T-cells, however, requires a second binding between the two cells. This is the verification step, a safeguard mechanism serves to prevent the immune system from overreacting.
Once activated, T-cells undergo repeated cycles of mitosis in a process called clonal expansion. This process produces clones of identical cytotoxic and helper T-cells, both of which are specific to the pathogen. Some of these cells differentiate into effector cells, while other become memory cells.
Most effector T-cells leave the lymph node for the bloodstream and are delivered to the site of infection, where they carry out immune attack against the pathogen. Helper T-cells produce interleukins which help with the activation of cytotoxic T-cells, B cells, and other immune cells. With such diverse functions, helper T-cells are central to adaptive immunity.
Cytotoxic T-cells, on the other hand, are the main actors of cellular immunity. They release toxins and directly kill infected or cancerous host cells. While effector cells die during or shortly after the infection, memory cells live for much longer periods of time.
Some of them remain in lymph nodes, while other circulate the blood or migrate to peripheral tissues. Memory T-cells are also more numerous than the original naïve T-cells. Upon reexposure to the same pathogen, they can mount a much faster immune response, destroying the pathogen so quickly that no signs of illness are noticeable.
It is important to note the role of a third T-cell population, known as regulatory, or suppressor T-cells, in dampening the immune response when it’s no longer needed. Once the pathogen is cleared, regulatory T-cells downregulate the proliferation of effector T-cells, keeping the immune reaction from running out of control. They also help differentiate between self and non-self antigens, and thus preventing autoimmune diseases.
