FIGURE 22.3 Building the T cell repertoire.

properties in humans are only partially known. Th17 cells, some of which produce both interleukin (IL)-17 and interferon gamma (IFNy) have the ability to help B cells, have low cytotoxicity and poor susceptibility to regulation by autologous regulatory T cells.

Regulatory T cells (Tregs) is a cell population of the T cell repertoire that is recognized by specific cell surface markers, most importantly FOXP3, and is reported to have regulatory activity. They are found both in the CD4+ and CD8+ T cell population. Tregs specifically suppress the action of other cells in the immune system and maintain homeostasis of immune system and tolerance to self. Thereby, they prevent the establishment of an immune response. The interest in regulatory T cells has increased due to the evidence gathered from experimental mouse models demonstrating that the immunosuppressive potential of these cells can be used therapeutically to treat autoimmune diseases and facilitate transplantation tolerance or the regulatory T cells can be specifically eliminated to potentiate cancer immunotherapy.

22.2.2 Antibodies

Antibodies are glycoproteins that are built of subunits containing two identical light chains (L chains), and two identical heavy chains (H chains), which are at least twice as long as light chains. The first ~100 amino acids at the N-terminal of both H and L chains vary greatly from antibody to antibody. These are the variable (V) regions. The amino acid sequence variability in the V regions is especially pronounced in three hypervariable regions. The structure of antibodies brings the three hypervariable regions of both the L and the H chains together. Together they construct the antigen binding site against which the epitope fits. For this reason, the hypervariable regions are also called complementarity determining regions (CDRs) (Figure 22.4).

Antibody molecules have two functions, to recognize and bind to an epitope on an antigen and trigger a useful response to the antigen. The V regions are responsible for epitope recognition and the C regions are responsible for triggering recruitment of other cells and molecules to destroy and dispose of pathogens to which the antibody is bound. The Fc part of the C region recognizes Fc receptors that are specialized receptors present on immune effector cells. The Fc part also facilitates active transport of the antibodies and initiation of the complement cascade.

22.2.3 Natural Killer Cells

Natural killer cells (NK cells) are large granular, non-T- and non-B-lymphocytes that are able to kill diseased cells. They are part of the innate immune system and help to fight viruses and other f

108 Light chain 214

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