Human Immunology

The immune system is an intricate network of cells and tissues that resists invasion from infectious agents (pathogens) and combats environmental stresses that induce allergic reactions, viral infections, infectious diseases, autoimmune syndromes, and cancer. The body eradicates foreign substances using innate (natural or nonspecific) and adaptive (acquired or specific) immune responses. Innate immunity refers to the body's initial nonspecific response to the invading substance using natural defensive barriers (skin, mucous membranes, temperature, and chemical mediators) and cells (macrophages, neutrophils, and natural killer [NK] cells) to limit or clear the foreign substance.

During an adaptive immune response, the body engages immune cells (T and B lymphocytes) that specifically recognize and selectively eliminate foreign substances. Adaptive immunity has four major characteristics: 1) antigen specificity, 2) diversity, 3) immunologic memory, and 4) ability to differentiate self from nonself. Antigen specificity is mediated by receptors on immune cells that recognize defined peptides called antigens. Receptor development is a spontaneous and random process that begins during fetal development so that the repertoire of receptors is present on lymphocyte membranes at birth. This large array of receptors, each having its own specificity for a particular antigen, is the basis for the diversity of the adaptive immune response. When a lymphocyte binds a peptide specific for its receptor, it becomes activated. Activation is multifaceted and induces proliferation and subsequent expansion of cells with that particular receptor. This clonal expansion of antigen-specific lymphocytes is the basis for immunologic memory. Immunologic memory enables immune cells to "remember" a previous encounter with a pathogen so that a more rapid response of higher magnitude can be produced after re-exposure to that same peptide. An absolutely critical feature of adaptive immunity is that immune cells must distinguish self from nonself. This recognition phase not only ensures that a specific immune response against only the invading pathogen is produced, but also prevents nonspecific responses against cells of the body that would result in autoimmunity.

Adaptive immunity consists of humoral and cell-mediated immune responses. The primary cells in adaptive immunity are B and T lymphocytes. B lymphocytes, which are principal mediators of humoral responses, originate in bone marrow and mature in the liver during fetal development, and subsequently in gut-associated mucosal lymphoid tissue. The antigen receptor on the B cell membrane is the immunoglobulin (Ig) molecule, which confers both specificity and diversity to humoral responses. During a humoral immune response, B cells differentiate into plasma cells, which secrete antibodies specific for the invading pathogen. T lymphocytes are responsible for the cell-mediated response. T cells originate in bone marrow and mature in the thymus. Upon exiting from the thymus, T cells will have differentiated into two subpopulations: helper (CD4+) T cells and cytotoxic (CD8+) T cells. These two populations facilitate cell-mediated immunity in two ways: CD4+ T cells produce cytokines (they are soluble factors that are released from cells after contact with specific antigens), enhance innate immunity, and induce antibody responses, while CD8+ T cells directly kill tumors or virus-infected cells.

Despite the presence of B and T cells at birth, neonates cannot produce a maximal adaptive immune response because their immune system has not yet fully matured. Maturational changes in the immune system continue after birth and are fairly complete by two years of age. However, subtle changes do occur until about puberty, at which point the immune response is fully developed.