Antibody isotypes

Although human anaphylaxis is a systemic reaction, the mouse model of passive cutaneous anaphylaxis (PGA) has been used extensively to enhance our understanding of mechanisms which also may contribute to systemic anaphylaxis. Unlike systemic anaphylaxis in the mouse, PGA appears to be entirely dependent on mast cells [4,6]. While IgE appears to be the primary antibody isotype that mediates PCA reactions in actively immunized mice, activation of FcyRIII by a fraction of IgGl antibodies (called anaphylactic IgGl) can also mediate PCA reactions in mice [4]. 

Maizels, R.M., Sartono, E., Kurniawan, A, Partono, F., Selkirk, M.E. and Yazdanbash, M. (1995) T-cell activation and the balance of antibody isotypes in human lymphatic filariasis. Parasitology Today 11, 50-56. 

Measles virus hemagglutinin (H) protein Carrot leaf and root H-specific antibody isotypes and subclasses in mouse sera mouse sera neutralized wt virus. Immunogenic in mice when administered parenterally. 104... 

Chauhan, N. B. and Siegel, G. J., Efficacy of anti-A(3 antibody isotypes used for intracerebroventricular immunization in TgCRND8. Neurosci. Lett. 575 143-147, 2005. 

Dearman, R.J., Caddick, H., Basketter, D.A. and Kimber, I., Divergent antibody isotype responses induced in mice by systemic exposure to proteins A comparison of ovalbumin with bovine serum albumin. Food Chem. Toxic., 38, 351, 2000. 

Antibody isotypes Differences in the amino acid sequence and disulfide bonding patterns of the heavy chain in antibody classes give rise to antibody subclasses (also referred to as isotypes). For instance, mouse IgG antibodies are divided into four isotypes IgGl, IgG2, IgG2a, and IgG3. 

Yazdanbakhsh M, Paxton WA, Kruize YCM, et at T-cell responsiveness correlates differentially with antibody isotype levels in clinical and asymptomatic filariasis. J Infect Dis 1993 167 925-931. 

Peripheral T-Cell Tolerance to Allergens Is Associated with Regulation of Antibody Isotypes and Suppression of Effector Cells... 

As is documented in Table 2, the induction of anti-carbohydrate immune responses has been successfully demonstrated for many peptides. However, certain challenges remain. Often, the induced antibody titer (concentration) directed against the carbohydrate is rather weak, especially in comparison to the anti-peptide response the majority of antibodies recognize the peptide presumably in a nonmimetic conformation. Several recent studies have investigated these immime responses in more detail, with an extensive analysis of antibody isotypes and adjuvant effects [70,75], the effect of different protein carriers [194], the use of DNA vaccines [48,195], and the demonstration of protection by passive immunization [72,75,194]. In several cases, the anti-carbohydrate immune response has also been shown to be protective against infection in mice [30,72,75,78], and these cases are probably the most promising for the development of vaccines. 

Antibody isotypes can change upon B-cell activation. Upon maturity, both IgM and IgD become expressed as membrane-bound forms on the B cell surface. Activation results in the production of antibody in secreted forms. Isotype switching takes place with some daughter cells to pro-... 

FIGURE 7.1(c) Antibody isotypes. Description of various antibody isotype structures and functions. 

The major antibody isotype in external secretions is sIgA, and the total amount of IgA synthesized is twice the amount of IgG produced daily in humans. IgA cells represent up to 80% of the entire mucosal lymphoid cell population. sIgA in mucosal secretions results from polymeric IgA transported across mucosal epithelium via binding to the pIgRreceptor (also known as the secretory component). The receptor is eventually cleaved and results in an IgAipIgR complex, referred to as sIgA (Figure 7.2) (Rojas and Apodaca, 2002). 

Feltquate, D.M., Heaney, S., Webster, R.G. and Robinson, H.L. (1997) Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization. J. Immunol., 158, 2278-2284. 

In summary, structural analyses of anti-DNA antibodies support the hypothesis that autoimmunity to DNA is both initiated and sustained as a clonally selected, antigen-specific immune response to DNA. The initial autoimmune response to DNA is dominated by lower affinity IgM antibody primarily specific for single-stranded, denatured mammalian DNA. As the autoimmune response progresses, the antibody isotype switches to IgG, and the antibody acquires increasing affinity for native, double-stranded DNA. 

Quality criteria that need to be addressed comprise issues such as antibody isotype specificity, no unspecific antibody binding to the solid phase, level of background signals, and known level of interference of IgG antibodies with the IgE-based assay. Needless to say, that the quality of the allergen preparation plays a crucial role for the reliability of the test. 

Granulomatous hypersensitivity Intestinal mastocytosis Macrophage activation Serological Antibody isotype Antibody specificity Complement components Hypergammaglobulinaemia Rate of antibody production Functional... 

Moss RB, Hsu YP, Van Eede PH, Van Leeuwen AM, Lewiston NJ, De Lange G, Altered antibody isotype in cystic fibrtosis impaired natural antibody response to polysaccharide antigens, Pediatr. Res., 22 708-713, 1987. 

May be different for monoclonal antibody isotype (with associated activity)... 

In humans, there are five isotypes of antibodies, IgG, IgA, IgD, IgE, and IgM, which are defined by the structures of their heavy chains and their abilities to form multimers (Figure 10.1) [8], IgG is the most abundant isotype present in serum with average serum concentrations ranging from 0.5 to 9mg/ml depending on the IgG subtype. This is followed by IgA (3mg/ml), IgM (1.5mg/ml), IgE (0.05 mg/ml), and IgD (trace). Each antibody isotype has unique functions. Critical functions of IgG include opsonization, complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), passive immunity, and regulation of B cells. Both IgM and IgD act as antigen receptors on naive B cells, and soluble, multimeric forms of IgM are involved in complement activation. IgA is involved in mucosal and passive neonatal immunity, while IgE is involved in immediate hypersensitivity [8],... 

Tissue cross-reactivity studies, although burdensome, provide a rational in vitro assay to determine the range and intensity of distribution of potential epitopes reactive with a monoclonal antibody test article prior to its administration to humans. In addition, cross-reactivity studies provide a useful tool to identify animal species for safety assessment. The cross-reactivity profiles of different species can be compared to the profiles obtained in human tissues. The predictive value of the assay lies in incorporating the characteristics of the monoclonal antibody (isotype, subtype, and other molecular modifications) with the biological activity of the molecule itself, and the potential in vivo distribution of it. 

Wing MG, Waldmann H, Isaacs J, Compston DAS, Hale G. Ex-vivo whole blood cultures for predicting cytokine-release syndrome dependence on target antigen and antibody isotype. Ther Immunol 1995 2 183-90. 

Generic Name Trade Name Sponsor Company Mechanism Antibody Isotype Indication Approval Date... 

Linkage of enzyme and antibody by auxiliary molecules provides a potentially universal and variable number of systems for use in bioassays. The most common linkage system involves the recognition of biotin by avidin, or more commonly streptavidin (due to its higher affinity for biotin), although the use of staphylococcal protein A can be used for some antibody isotypes (11). An alternative system, but one that is not often used, involves liposomes loaded with enzyme that has antibody molecules on its surface (49). 

Despite this initial clinical setback, Ap-directed active vaccination continues to v arrant further assessment via careful step-vdse refinement and testing of novel immunotherapeutic approaches. It is clearly important to evaluate the antibody isotypes that are induced by candidate vaccine conshvcts, as well as determining the types of CD4 and CDS T cell immunity that are elicited. This information vdll undoubtedly facilitate the design of safer active vaccination strategies to direct the resultant immune response tov ards more desired effector functions. 

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