Types And Functions Of Lymphoid Cells

Lymphoid cells provide efficient, specific and long-lasting immunity against microbes and are responsible for acquired immunity. Lymphocytes differentiate into three separate lines: thymic-dependent cells or T lymphocytes that operate in cellular and humoral immunity, B lymphocytes that differentiate into plasma cells to secrete antibodies, and natural killer (NK) cells. T and B lymphocytes are the only lymphoid cells that produce and express specific receptors for antigens.

There are three major types of lymphocytes (T, B, and NK) that have distinctive surface markers and functions. Furthermore, the T and B cells in the lymph nodes are confined to discrete zones.

T Lymphocytes: These cells are involved in the regulation of the immune response and in cell mediated immunity and help B cells to produce antibody (humoral immunity). Mature T cells express antigen-specific T cell receptors (TcR) that are clonally segregated (i.e., one cell lineage-one receptor specificity). Every mature T cell also expresses the CD3 molecule, which is associated with the TcR. In addition mature T cells display one of two accessory molecules, CD4 or CD8. The TcR/CD3 complex recognizes antigens associated with the major histocompatibility complex (MHC) molecules on target cells (e.g. virus-infected cell). The TcR is a transmembrane heterodimer composed of two polypeptide chains (usually, α and β chains). Each chain consists of a constant (C) and a variable (V) region, and are formed by a gene-sorting mechanism similar to that found in antibody formation. The repertoire is generated by combinatorial joining of variable (V), joining (J), and diversity (D) genes, and by N region (nucleotides inserted by the enzyme deoxynucleotidyl-transferase) diversification. Unlike immunoglobulin genes, genes encoding TcR do not undergo somatic mutation. Thus there is no change in the affinity of the TcR during activation, differentiation, and expansion.

T Helper Cells: These cells are the primary regulators of T cell- and B cell-mediated responses. They 1) aid antigen-stimulated subsets of B lymphocytes to proliferate and differentiate toward antibody-producing cells; 2) express the CD4 molecule; 3) recognize foreign antigen complexed with MHC class II molecules on B cells, macrophages or other antigen-presenting cells; and 4) aid effector T lymphocytes in cell-mediated immunity. Currently, it is believed that there are two functional subsets of T helper (Th) cells. Th1 cells aid in the regulation of cellular immunity, and Th2 cells aid B cells to produce certain classes of antibodies (e.g., IgA and IgE). The functions of these subsets of Th cells depend upon the specific types of cytokines that are generated, for example interleukin-2 (IL-2) and interferon-γ (IFN-γ) by Th1 cells and IL-4 and IL-10 by Th2 cells.

Cell-mediated immunity (delayed hypersensitivity) plays an important role in defense against many intracellular infections such as Mycobacterium tuberculosis. This inflammatory reaction is initiated by the recognition of specific antigens by Th1 cells. Consequently, lymphokines are generated which recruit activated macrophages to eliminate foreign antigens or altered host cells.

T Cytotoxic Cells: These cells are cytotoxic against tumor cells and host cells infected with intracellular pathogens. These cells 1) usually express CD8, 2) destroy infected cells in an antigen-specific manner that is dependent upon the expression of MHC class I molecules.

T Suppressor Cells: These cells suppress the T and B cell responses and express CD8 molecules.

Natural Killer Cells: NK cells are large granular lymphocytes that nonspecifically kill certain types of tumor cells and virus-infected cells. Killing by NK cells is enhanced by cytokines such as IL-2 and IFN-γ. NK cells are also activated by microorganisms to produce a number of cytokines [(IL-2, IFN-γ, IFN-α, and tumor necrosis factor-α (TNF-α)]. These circulating large granular lymphocytes do not express CD3, TcR or immunoglobulin, but display surface receptors (CD16) for the Fc fragment of IgG antibodies. In contrast to cytotoxic T cells, the NK cell-mediated cytotoxicity neither requires previous sensitization nor is MHC-restricted.


Interactions of human NK cells with dendrytic cells.
Credit: PubMed Central - PubMed

B Lymphocytes: These cells differentiate into plasma cells to secrete antibodies and are involved in processing proteins and presenting the resultant peptide antigen fragments in the context of MHC molecule to T cells. The genesis of μ and δ chain-positive, mature B cells from pre-B cells is antigen-independent. Pre-B cells in the bone marrow undergo gene rearrangement for IgM heavy (H) chains and consequently express those proteins in the cytoplasm (the μ chain), but no immunoglobulin light (L) chains. B cell development is characterized by recombinations of immunoglobulin H and L chain genes and expression of specific surface monomeric IgM molecules. At this stage of development, B cells are highly susceptible to the induction of tolerance. Once these cells acquire IgD molecules on their surface, they become mature B cells that are able to differentiate after exposure to antigen into antibody-producing plasma cells.

References

  • Medical Microbiology. 4th edition. Armond S. Goldman and Bellur S. Prabhakar