Complexes not Involving Covalent Linkage Between Hapten and Carrier

A different classification problem is raised by immunogens produced by metal salts. In these cases, autologous carriers are thought to become modified by metal ion interaction, and NAD which contain the metal and others which may not contain it can be envisaged. The question here is rather whether the coordinate bonds which are inferred for the transition metals should not be simply considered as covalent. 

Various immunogenic substances requiring association with carriers are listed in Table 2. Picric acid, discussed as an exceptional low molecular weight sensitizer in Sect. C.II.l, may be cited with some confidence as a compound which associates with autologous carriers, giving rise to an immunogenic complex. This may be inferred from the cross-reactivity data already mentioned, namely that reactions in contact-sensitized animals may only be evoked by contact application of picryl chloride, not by intradermal application or by means of picrylated protein. 

The lipids are classical substances to be complexed for immunization with heterologous proteins, formerly called Schlepper proteins. On the other hand, nucleic acids and nucleotides have only recently been jfound to be immunogenic, provided these polyacidic derivatives are combined with polybasic carriers like methylated serum albumin. 

A number of metal salts have been found to induce delayed hypersensitivity, mainly of the contact type, in humans or in laboratory animals. Sensitivity to ions of chromium, mercury, platinum, nickel, beryllium, and others seem well established and Table 2 shows some recent findings. The best studied metal sensitizers are the chromium salts, since chromium eczema due to cement is the most important occupational dermatosis (Polak et al. 1973). Hexavalent chromium, in the form of potassium dichromate, is a better sensitizer than trivalent chromium. This seems related to the much better skin penetrating capacity of the dichromate, since numerous studies have shown that trivalent chromium compounds as opposed to hexavalent salt are the actual sensitizers (Polak et al. 1973). The same authors conclude that chromium is probably a component of the determinants formed with autologous carriers and does not produce autoantigens without further participation of the metal ion. In particular, oxidation reactions as generators of determinants seem inoperative in chromium hypersensitivity, since other strong oxidizers like 

Immunogen Carrier Adjuvant Response Species Reference 

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