The ability of a particular antibody to combine with a particular antigen is referred to as its specificity. This property resides in the portion of the Fab molecule called the combining site, a cleft formed largely by the hypervariable regions of heavy and light chains. Evidence indicates that an antigen may bind to larger, or even separate, parts of the variable region. The closer the fit between this site and the antigen determinant, the stronger are the noncovalent forces (e.g., hydrophobic or electrostatic bonds) between them, and the higher is the affinity between the antigen and antibody. Binding depends on a close three-dimensional fit, allowing weak intermolecular forces to overcome the normal repulsion between molecules. When more than one combining site interacts with the same antigen, the bond has greatly increased strength.

Antigen-antibody reactions can show a high level of specificity. Specificity exists when the binding sites of antibodies directed against determinants of one antigen are not complementary to determinants of another dissimilar anti gen. When some of the determinants of an antigen are shared by similar antigenic determinants on the surface of apparently unrelated molecules, a proportion of the antibodies directed against one type of antigen will also react with the other type of antigen; this is called cross-reactivity. Anti bodies directed against a protein in one species may also react in a detectable manner with the homologous protein in another species.

Cross-reactivity occurs between bacteria that possess the same cell wall polysaccharides as mammalian erythrocytes. Intestinal bacteria, as well as other substances found in the environment, possess A-like or B-like antigens similar to the A and B erythrocyte antigens. If A or B antigens are foreign to an individual, production of anti-A or anti-B occurs, despite lack of previous exposure to these erythrocyte antigens. Cross- reacting antibodies of this type are termed heterophile antibodies .

Antibody Affinity

 Affinity is the initial force of attraction that exists between a single Fab site on an antibody molecule and a single epitope or determinant site on the corresponding antigen. The antigen is univalent and is usually a hapten. Several types of noncovalent bonds hold an epitope and binding site close together (see later, “Type of Bonding”).

Antibody Avidity

 Each four-polypeptide–chain antibody unit has two antigen binding sites, which allows them to be potentially multivalent in their reaction with an antigen. The functional combining strength of an antibody with its antigen is called avidity, in contrast to affinity, the binding strength between an antigenic determinant (epitope) and an antibody-combining site (Fig. 1). When a multivalent antigen combines with more than one of an antibody’s combining sites, the strength of the bonding is significantly increased. For the antigen and antibody to dissociate, all the antigen-antibody bonds must be bro ken simultaneously.

Fig1. Affinity versus avidity. (From Zane HD: Immunology: theoretical and practical concepts in laboratory medicine, Philadelphia, 2001, Saunders.)

Decreased avidity can result when an antigen (e.g., hapten) has only one antigenic determinant (monovalent).

 Immune Complexes

 The noncovalent combination of antigen with its respective specific antibody is called an immune complex. An immune complex may be of the small (soluble) or large (precipitating) type, depending on the nature and proportion of antigen and antibody. Under conditions of antigen or antibody excess, soluble complexes tend to predominate. If equivalent amounts of antigen and antibody are present, a precipitate may form. However, all antigen-antibody complexes will not precipitate, even at equivalence.

Antibody can react with antigen that is fixed or localized in tissues or that is released or present in the circulation. Once formed in the circulation, the immune complex is usually removed by phagocytic cells through the interaction of the Fc portion of the antibody with complement and cell surface receptors.

Under normal circumstances, this process does not lead to pathologic consequences and it may be viewed as a major host defense against the invasion of foreign antigens. It is only in unusual circumstances that the immune complex persists as a soluble complex in the circulation, escapes phagocytosis, and is deposited in endothelial or vascular structures—where it causes inflammatory damage, the principal characteristic of immune complex disease—or in organs (e.g., kidney), or inhibits useful immunity (e.g., tumors, parasites). The level of circulating immune complex is determined by the rate of formation, rate of clearance and, most importantly, nature of the complex formed. Detection of immune complexes and identification of the associated antigens are important to the clinical diagnosis of immune complex disorders.

مواضيع ذات صلة

ANTIBODY SYNTHESIS

Tolerance to Commensal Microbes and Fetal Antigens

B Lymphocyte Tolerance

Peripheral T Lymphocyte Tolerance

Immune Memory

B Cells

T Cells

إزالَةُ التَحسس نحو البنسلين Penicillin Desensitization

الحساسية نحو البنسلين

الفرق بين فَرْطُ التحسس والحساسية الدوائية

Immunologic Tolerance: General Principles and Significance

Functions of Antibodies at Special Anatomic Sites