Lymphoid System and Cellular Immunology

Functional cells include B lymphocytes (humoral immunity), T lymphocytes (cellular immunity), macrophages (phagocytic and one of several types of antigen-presenting cells), and mast cells.

Immunity and T and B cells

There are two types of immunity:
  1. Innate immunity is the first-line of defense and comprises basic mechanisms of host defense including barriers (e.g., skin, zonula occludens/tight junctions) and phagocytic cells such as macrophages and neutrophils. Innate immunity is not specific for particular pathogens or individuals of the species.
  2. Adaptive immunity is a response to antigenic challenge and possesses four essential characteristics which are not part of innate immunity:
  • Specificity of response to antigen
  • Memory
  • Diversity
  • Recognition of self versus nonself

Lymphocytes display the four attributes listed above. There are two types of lymphocytes: B cells and T cells. B cells are involved in humoral immunity. On first exposure to an antigen it recognizes on its surface, a naïve B cell proliferates to produce a memory B cell and a plasma cell that is the effector, synthesizing antibodies for release. T cells are unable to recognize antigen on their own. T cells require antigen-presenting cells (macrophages, dendritic cells, and B cells) to process antigen and bind it to membrane proteins known as major histocompatibility molecules (MHC).
Lymphocytes display the four attributes listed above. There are two types of lymphocytes: B cells and T cells. B cells are involved in humoral immunity. On first exposure to an antigen it recognizes on its surface, a naïve B cell proliferates to produce a memory B cell and a plasma cell that is the effector, synthesizing antibodies for release. T cells are unable to recognize antigen on their own. T cells require antigen-presenting cells (macrophages, dendritic cells, and B cells) to process antigen and bind it to membrane proteins known as major histocompatibility molecules (MHC). 

Class I MHC is found on virtually all cells of the body, while Class II MHC is specific for antigen-presenting cells (APCs). On first encounter with a specific antigen-MHC II complex, the T cell proliferates resulting in a memory T cell and an effector T cell. There are several subtypes of T cells:
  • TH cells, which express the specific glycoprotein, CD4, are called CD4+
  • TC cells, which express the specific glycoprotein, CD8, are called CD8+
  • Treg cells, (suppressor T cells) are critical for maintenance of immunological tolerance.

The TH cell secretes cytokines (small protein or peptide intercellular communication molecules) that activate TC cells, B cells, and macrophages. Release of cytokines by TH cells induces TC cells to proliferate and differentiate into effector cells. In that case the effectors are cytotoxic T lymphocytes (CTLs) that recognize Class I MHC-antigen complex on the surface of altered self cells (e.g., cells of a foreign tissue graft or self cells infected with virus). CTLs recognize altered self-cells and form a conjugate with them; the target cell is killed by release of perforins (pore-forming proteins) and serine proteases (granzymes) leading to apoptosis of the target.

TH cells are regulated by APCs that internalize antigen and then process it through the secretory pathway to a membrane-bound MHC IIantigen complex. The TH cell is activated by a co-stimulatory signal from the APC. Cytokines from TH cells are required for B cells to proliferate and differentiate into a memory B cell and an antibody-producing plasma cell.

Two of the key cytokines involved in the interaction of those cells are IL-1 produced by activated macrophages and IL-2 that regulates T cell, but also B cell proliferation. Another critical cytokine is interferon-gamma (IFN-γ) that activates macrophages and is secreted by activated TH cells. There are two profiles of cytokines produced by TH cells:
  • TH1 response is primarily directed toward macrophages and T cells and the support of the inflammatory response.
  • TH2 response is primarily directed toward B cells and therefore antibody responses. Treg cells are CD4+, express CD25 and produce IL-10 and TGF-beta, lymphokines that are both strong immunosuppressants inhibiting TH1 and TH2 cells.

NK cells are not T cells, but kill cellular targets such as tumor cells in a nonspecific manner.

Organs

Lymphoid organs may be either primary (bone marrow and thymus) or secondary (lymph nodes and dispersed lymphatic nodules, spleen, and tonsils). The B lymphocytes are educated in the bone marrow [differentiation of antigen-binding receptors (antibodies)] and are seeded to specific B cell regions of the secondary lymphoid organs, while T lymphocytes are educated in the thymus [differentiation of T cell receptors (TcR)] and are seeded to T cell-dependent regions of the secondary lymphoid organs.

The thymus is recognized by lobulation, separate cortex and medulla in each lobule, the absence of germinal centers, and the presence of Hassall’s corpuscles. The lymph nodes, which filter lymph and blood, are characterized by a central medulla consisting of cords with many plasma cells and a cortex containing primary and secondary follicles. The spleen, which filters blood, is characterized by red and white pulp. The tonsils are characterized by crypts with an epithelial lining on one side. That lining is stratified squamous epithelium in palatine tonsils and pseudostratified epithelium on pharyngeal tonsils.

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