Cellular communication is essential to the development, tissue organization, and function of all multicellular organisms. Cells communicate with each other and their environment through soluble mediators and during direct contact (e.g., phagocytosis). An immunologic response is a result of the interactions of various leukocytes with each other and other cells in the body. These interactions occur through cell surface receptors that mediate cell-cell binding, or adhesion, of leukocytes.

The discovery of several cell surface receptors involved in cellular communication has been a key factor in understanding the mechanisms underlying inflammatory and immune phenomena. Three protein families—the immunoglobulin (Ig) family, integrin family, and the rather recently designated selectin family—form a network of cellular interactions in the immune system. Neutrophil tether to and roll on P- and E-selectin expressed on activated endothelial cells. Rolling neutrophils encounter immobilized chemokines. Chemokines activate integrins to their high-affinity states that enable interactions with intercellular adhesion molecule-1 (ICAM1), which promote arrest, adhesion strengthening, intraluminal crawling, and transendothelial migration. E-selectin directly triggers signals in rolling PMN that cooperate with chemokine signals to minimize neutrophil recruitment during inflammation.

Members of the Ig superfamily include antigen-specific receptors (e.g., T cell receptor [TCR] and surface immunoglobulin [sIg]), as well as antigen-independent receptors and their counterreceptors, such as CD2 and lymphocyte function associated antigen-3. Ig superfamily members function in cell activation, differentiation, and cell-cell interaction. In some cases, both an adhesion receptor and the counterreceptor to which it binds are members of the Ig superfamily.

Three selectin family molecules—endothelial cell adhesion molecule-1, leukocyte adhesion molecule (LAM-1, Mel-14), and CD62, also known as platelet activation–dependent granule–external membrane protein and granule membrane protein of 140 kDa (GMP-140)—have been implicated in a number of leukocyte adhesion phenomena, including leukocyte homing to lymphoid tissue. Selectins are expressed on leukocytes and endothelial cells. Mel-14 functions early in neutrophil-endothelium adhesion.

The integrin family consists of at least 14 alpha-beta heterodimers divided into subfamilies with distinct structural and functional characteristics. The subfamily of leukocyte integrins contains three members—LFA-1, Mac-1, and p150,95. These molecules are glycoproteins composed of noncovalently associated alpha and beta subunits. LFA-1 is expressed on all leukocytes, whereas Mac-1 and p150,95 are found primarily on granulocytes and monocytes.

The integrin family is phylogenetically ancient. Integrin family members engage in interactions with cell surface ligands and extracellular matrix (ECM) components. ECM components, including fibronectin, collagen, and laminin, have been shown to be ligands for members of the beta-1 and beta-3 subfamilies. Members of these subfamilies are of great significance in embryogenesis, growth and repair, and hemostasis. The leukocyte integrins, or beta-2 subfamily, have been shown to be involved in a diverse number of leukocyte adhesion–dependent phenomena, giving them a critical role in inflammatory and immune responses. The term integrin was initially used to emphasize that these receptors integrate signals from the extracellular environment with the intracellular cytoskeleton. A signal is transduced from outside to inside the cell.

In addition to the involvement of these receptors in a variety of immune functions, integrin molecules play a role in the spread of malignant cells. The major cause of death in malignant disease is not the primary tumor but rather the metastasis of tumor cells to distant sites within the body. Metastasis is a complex multistep process that begins with the detachment of a few tumor cells from the primary tumor. The tumor cells then move into the circulatory system, where they can be transported to other organs. While in the circulatory system, tumor cells must survive the natural defense system of the body before attaching to and invading the tissues of another organ. A better understanding of the metastatic process could provide the basis for diagnostic and therapeutic strategies.

مواضيع ذات صلة

Congenital Immunodeficiencies: Defects in Lymphocyte Maturation

Congenital Immunodeficiencies: Defects in Innate Immunity

Congenital (Primary) Immunodeficiencies

Neuroimmunology: Interactions Between the Immune and Nervous Systems

Disorders of Neutrophils

Sepsis

Acute Inflammation

Diseases Caused by T Lymphocytes

Etiology, Examples, and Therapy of Immune Complex–Mediated Diseases

Examples and Treatment of Diseases Caused by Cell- or Tissue-Specific Antibodies

Mechanisms of Antibody-Mediated Tissue Injury and Disease

Hypersensitivity Disorders Caused by Immune Responses : Clinical Syndromes and Therapy