Arachidonic acid – The substance that is a pre- cursor of inflammatory mediators such as prostaglandins and leukotrienes

Chemokines – An agent of the inflammatory process that attracts or recruits cells to the site

Cyclooxygenase pathway – One arm of the arachidonic acid cascade that leads to pro- duction of prostaglandins and thromboxanes

Cytokines – Proteins produced by a cell to modulate the actions of other cells; also known as messenger proteins

Growth factors – The molecules that stimulate cell growth or activation

Lipoxygenase pathway –  One arm of the arachidonic acid cascade that leads to pro- duction of leukotrienes and lipoxins

 Major histocompatibility complex (MHC) – A cluster of genes important in immune rec- ognition and signaling between cells of the immune system; also called human leukocyte antigen

Matrix metalloproteinases (MMP) – Agents of the inflammatory process that degrade the extracellular matrix

Phagocytosis – The process by which white blood cells ingest debris or micro- organisms

The immune response to an antigen can be classified as humoral (antibody based) or cell mediated. Both processes require lympho- cytes and antigen-presenting cells (APCs), which may be lymphocytes, macrophages, or dendritic cells. Lymphocytes are de- scribed as B cells or T cells, a naming con- vention based on the site of their original differentiation—bone marrow (B cells) or thymus (T cells).5

Humoral immunity occurs through B cells, which produce soluble, membrane- bound immunoglobulin (antibody) for a spe- cific antigen. Cell-mediated immunity occurs through T cells that recognize an antigen when it is bound to a major histocompatibility complex (MHC) molecule, also termed a human leukocyte antigen (HLA). Thus, B cells are frequently the APCs to the T-cell receptors. Binding of the APCs with the T-cell receptors stimulates division of T cells into one of two types of helper cells (Th1 or Th2) and secretion of numerous cytokines that in- duce an inflammatory response (Fig. 3).

Stimulation of the immune response involves internalization of an anti- gen by macrophages. The antigen is then bound to a receptor (MHC II) and expressed on the cell surface.The CD4-expressing helperT cells are activated by receptor interaction with the antigen (2) if it is recognized as foreign. The activated CD4 cell (3) elaborates factors that stimulate B cells to express antibody and also inflammatory cytokines. B cells can differentiate into antibody- producing plasma cells or remain as memory cells. Similarly, the sensitized T cells can expand by proliferation and mediate cytotoxicity or be retained as memory cells.

There are two classes of MHC molecules (class I and II), both of which contain a large number of alleles (variable regions). Although MHC molecules bind antigens, they differ from B-cell receptors in that MHC molecules are expressed by a number of cell types. They also lack the specificity of the antibodies produced by B cells. Several chronic inflammatory diseases, such as RA, are associated with distinct alleles that may confer genetic predisposition to the disease. That the inflammation persists or recurs in these chronic diseases indicates that at- tempts to achieve homeostasis are impeded, possibly by a recurrent trigger.