B lymphocytes B cells recognise antigens through surface immunoglobulin (sIg). Terminally differentiated B cells, called plasma cells, produce and secrete antibodies, the specificity of which is identical to the sIg expressed by their B cell precursors. Following maturation in the bone marrow, most B cells that survive the selection process circulate through secondary lymphoid tissues. These are conventional or B-2 B cells.
B-1 B cells are a smaller subset of B cells, which produce a limited repertoire of low affinity and polyspecific antibodies reactive with common bacterial antigens. B-1 B cells may represent a primitive population whose function is intermediate between innate and specific immune responses.
T lymphocytes T lymphocytes express T cell receptors (TCRs) and CD3. Most T lymphocytes express a TCR comprising a and β chains (αβ T cells) and also either CD4 or CD8, which direct
LYMPHOCYTE MATURATION the pattern of antigen interaction. Antigens recognised by αβ T cells are processed peptides, presented by host-derived MHC molecules. Factors influencing the pattern of T cell response include the pattern of innate immune activation, characteristics of the stimulating antigen, and type of antigen presentation.
αβ T cells
Two broad categories of αβ T cells are described as follows:
♦Cytotoxic T cells (CTLs or Tcs) – usually express CD8 and recognise endogenous antigens (viruses, tumours).
♦Helper T cells (THs) usually express CD4. They respond to extracellular antigens including bacteria that are taken up into vesicles in the cells. Activation of helper T cells requires processing and presentation of antigen in association with MHC Class II molecules by professional APCs. These cells typically ‘help’ other cells of the immune system rather than having a direct effector function.
Helper T cells are in turn further sub-divided based on patterns of cytokine expression. The two extremes are:
- TH1 – produce IFN-y and tumour necrosis factor that enhance macrophage function, cellular immunity, production of some antibody types and granulomatous
- TH2 – enhance IgE-mediated responses through the action of IL-4 and IL-5.
TH1 and TH2 responses are for the most part mutually exclusive and suppressive of the other. Further T cell subpopulations are increasingly recognised, such as regulatory T cells – TR – and TH3 that impose control on cell-mediated immune responses through the action of cytokines including IL-10 and TGF-β.
γδ T cells γδ T cells express a TCR composed of y- and δ-chains and are preferentially expressed in skin and at mucosal surfaces. Their antigen interactions are not as specific as those of αβ T cells. Diverse effector functions mirroring those of αβ T cells have been identified. These cells may represent a T cell equivalent of B-l B cells.
Unconventional T cells CD3+ T cells expressing unusual patterns of surface molecules common to conventional T cells and NK cells are called NK-T cells. Antigen recognition by NK-T cells extends beyond peptide fragments expressed by MHC molecules. The functional significance of this population is not fully understood.
NK cells These can kill certain tumour targets and virus-infected cells. Early production of IL-12 by NK cells encountering viruses and intracellular bacteria skews the later specific immune responses towards a THl-type response.
NK cells express activating receptors and inhibitory receptors, which interact with MHC Class I molecules, preventing uncontrolled activation of NK cells. If MHC expression is disturbed, as occurs in virus-infected or tumour-laden cells, inhibition is lost resulting in NK cell cytotoxicity.