Chemistry and Biology of Proteins - F. Haurowitz 1953

The Role of Proteins in Immune Reactions
Other Immunological Phenomena

While it is not yet possible to provide a fully satisfactory explanation for all phenomena accompanying immunization, it may nevertheless be assumed that these phenomena are fundamentally based on the Antigen-Antibody Reaction. In some cases, this reaction is followed by a second one, namely, the combination of the antigen-antibody complex with Complement. It can now be considered established that precipitation, agglutination, lysis, and other immunological phenomena represent various manifestations of The activity of one and the same antibody. For example, Antibodies against pneumococcal Polysaccharides possess The ability to precipitate these polysaccharides, agglutinate and lyse these bacterial Cells, and enhance their phagocytosis [132]. These exact same antibodies are capable of protecting humans and animals against infection by virulent pneumococci [133, 134].

It has already been mentioned above that the structural Proteins of certain cells contain insoluble antibodies. These antibodies are responsible for the so-called anaphylactic reaction observed following the re-injection of an antigen into a sensitized Organism. This example demonstrates that certain immunological reactions (such as anaphylaxis) can be detrimental to the organism and may even lead to death. Nevertheless, they are based on the very same phenomenon as protective reactions, namely, the presence of antibodies in an organism that has been parenterally administered an antigen. Sometimes the term allergy is used to designate this altered reactivity of the organism caused by the presence of antibodies.

It is a well-known fact that many animal species are resistant to certain Bacteria, whereas other species are easily infected by them. Natural Immunity in higher animals is due either to the presence in their bodies of antibodies that interact with the invading bacteria, or to the absence of reactive groups with which these bacteria or the products they secrete can react. The existence of such reactive groups is, in all probability, one of the prerequisite conditions for infection in higher organisms [135].

One of the unresolved and yet-to-be-explained mysteries of immunology is related to the fact that an animal, following immunization, is sometimes able to maintain resistance for many years or even throughout its entire life. The presence of antibodies can be detected in such animals throughout the entire period of resistance [136]. It is very difficult to resolve the question of whether small amounts of antigen, which actively promote antibody formation, persist in the bodies of these animals. This apparently occurs in certain viral diseases accompanied by long-lasting immunity [2]. Small amounts of an attenuated virus may persist in the organism and induce antibody formation. An even more striking example is the fact that antigenic pneumococcal polysaccharides administered to mice at a dose of 0.5 mg can still be detected in the Organs of the experimental animal several months after injection [137]. These data support the view that, even in cases where immunity persists for a long period, antibody formation occurs in the same manner as described above, i.e., through the alteration of Protein Synthesis under METABOLISM/18.html">The Influence of antigen molecules. The prolonged retention of antibodies in body Tissues may also explain the so-called anamnestic reaction, i.e., the appearance of significant amounts of antibodies in the organism when an animal is re-injected with a small dose of antigen long after the initial injection. The sudden increase in antiserum titer observed in this case is apparently due to the transition of antibodies from the tissues into the bloodstream. True de novo antibody formation in these cases has not yet been convincingly demonstrated by anyone [139].

To explain the longevity of immunity as well as the anamnestic reaction, Burnet [138] put forward the hypothesis that antibody formation can occur even in the absence of the antigen. Burnet believes that antibody formation is associated with the action of specific Enzymes that are modified by the antigen [138]. This hypothesis is hardly reconcilable with the fact that the organism is capable of producing antibodies against arsanilic acid, sulfanilic acid, and A number of other synthetic products. It is difficult to believe that the organism possesses enzymes capable of catalyzing The formation of specific proteins whose conformation matches the configuration of the molecules of these synthetic products. It is considerably simpler to conceive that these synthetic Antigens act directly as templates in the formation of a modified protein molecule whose reactive group configuration geometrically complements the configuration of the determinant group of the antigen (see Chapter XVII).