have Fc receptors for IgE, and IgE is thought to be one of the major mediators of the allergic or anaphylactoid reaction (see next section). It appears to be an important defense mechanism against parasites: one way IgE accomplishes this is to prime basophils and mast cells. Although its role in ocular surface disease has been well recognized, this has not been the case for intraocular inflammation.

IgD is found in minute quantities in the serum (0.5% of serum Ig). It is found simultaneously with IgM on B cells before specific stimulation. Little more is known about this antibody other than it is a major B-cell membrane receptor for antigen.

Antibodies directed toward specific antigens, particularly cell-surface antigens of the immune system, have provided the clinical and basic investigator with a powerful tool with which to identify various components of the immune system, as was described in the section on the T cell. The development of monoclonal antibodies using hybridoma technology has permitted the production of these immune probes in almost unlimited quantity. Immortalized myeloma cells can be fused with a B cell committed to the production of an antibody directed toward a relevant antigen. This is usually accomplished with the use of polyethylene glycol, which promotes cell membrane fusion. By careful screening, clones of these fused cells (i.e., hybrid cells or hybridomas) can be identified as producing the antibody needed. These can be isolated and grown, yielding essentially an unlimited source of the antibody derived from one clone of cells and directed against one specific determinant. Monoclonal antibodies have been raised against cell markers of virtually all cellular components of the immune system. Antibodies can now be ‘humanized’ so that only small parts of the variable end remains of mouse origin. The advantage to this is the reduced probability of an immune response to a foreign protein.

Other cells

Mast Cells

This large (15–20 µm) cell is intimately involved with type I hypersensitivity reactions (see next section). Its most characteristic feature is the presence of large granules in the cytoplasm. It is clear that there are subtypes of mast cells. In humans, mast cells are characterized by the presence or absence of the granule-associated protease chymase. It has been suggested that tryptase-positive, chymase-negative human mast cells are suggestive of mucosal mast cells found in the mouse. Mast cells contain a large number of biologically active agents, including histamine, serotonin, prosta­ glandins, leukotrienes, and chemotactic factors of anaphylaxis as well as cytokines and chemokines. Histamine is stored within the mast-cell granules. Once released into the environment, histamine can cause smooth muscle to contract and can increase small vessel permeability, giving the typical ‘wheal and flare’ response noted in skin tests. Serotonin, in humans, appears to have a major effect on vasoconstriction and blood pressure, whereas in rodents it may also affect vascular permeability. Prostaglandins, a family of lipids, are capable of stimulating a variety of biologic activities, including vasoconstriction and vasodilation. Leukotrienes are compounds produced de novo with antigen stimulation. Leukotriene B4 is a potent chemotactic factor for both

Elements of the immune system

neutrophils and eosinophils, whereas leukotrienes C4 and D4, for example, enhance vascular permeability. At least two chemotactic factors of anaphylaxis attract eosinophils to a site of mast-cell degranulation, whereas other factors attract and immobilize neutrophils.

Mast-cell involvement in several external ocular conditions has been established. However, it is not yet clear what role this cell may play in intraocular inflammatory disorders. Mast cells are present in abundance in the choroid, and appear to be related to the susceptibility of at least one experimental model for uveitis (see discussion on auto­ immunity). Human work supports the hypothesis that many cytokine-dependent processes are implicated in IgEassociated disorders. Many different cytokines and chemo­ kines have been seen in mast cells. These include IL-4, IL-6, IL-8, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and macrophage inflammatory protein (MIP)-1α.

All of these findings link the mast cell to a whole variety of immune processes. It can be speculated that when a mast cell degranulates in the choroid it also releases chemokines and lymphokines, which may be the initiating factor of what we describe as a T-cell-mediated disorder.

Eosinophils

These bilobed nucleated cells are about 10–15 µm in size and are thought to be terminally differentiated granulocytes. Their most morphologically unique characteristic is the approximately 200 granules that are highly acidophilic (taking up eosin in standard staining procedures) and which are found in the cytoplasm. They are almost entirely made up of major basic protein (molecular weight 9000 Da), but other toxic cationic granules include eosinophil-derived neurotoxia, eosinophil cationic protein, and eosinophil peroxidase. A minor percentage of these cells (5–25%) have IgG receptors, and about half may have complement receptors on their surface membranes, although it is not clear whether receptors for IgE are present. Eosinophils contain an abundant number of enzymes, which are quite similar in nature to those contained in neutrophils. Both cells contain a peroxidase and catalase, both of which can be antimicrobial, but eosinophils lack lysozymes and neutrophils lack the major basic protein. Eosinophils also contain several antiinflammatory enzymes such as kininase, arylsulfatase, and histaminase. In addition, eosinophils produce growth factors such as IL-3 and IL-5, chemokines such as RANTES and MIP-1, cytokines such as TGF-α and TGF-β, VEGF, TNF-α, IL-1α, IL-6, and IL-8.

The eosinophil arises in the bone marrow from a myeloid progenitor, perhaps from a separate stem cell than neutrophils. The time spent in the systemic circulation is probably quite short, and the number seen on a routine blood smear is usually very low (1% or less of nucleated cells). These cells can be attracted to an area in the body by the release of mast-cell products and, once localized to an inflammatory site, are capable of performing several functions. The eosinophil may play an immunomodulatory role in the presence of mast-cell and basophil activation.

As mentioned, the cell contains the anti-inflammatory agents histaminase and arylsulfatase, capable of neutralizing the effect of histamine release and slow-reacting substance, both products of mast cells. Further, basophil function may

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