Immune Complex Disease

Abstract

Immune complexes derive from complex interactions between antibody, antigens, complement and various receptors as a part of adaptive immunity. Antigens bound to antibodies in immune complexes are normally cleared by various cellular mechanisms physiologically capable of eliminating even small quantities of ‘foreign’ antigens from circulation. Immune complexes can form when humans are exposed to foreign substances like proteins (infections, vaccines, drugs, etc.) or nonprotein materials (haptens) which need a protein carrier to activate the cascade. Autoimmune disorders develop when immune complexes deposit pathologically in different organs, initiating inflammatory cascades which lead to organ damage/disease. Immune complex disease can manifest in a myriad of ways when dysregulation in one or more of these components occur. Even some recombinant protein therapeutic agents used to treat autoimmunity may paradoxically form immune complexes, neutralizing therapeutic efficacy and/or manifesting as immune complex disease. Key Concepts Immunological defence mechanisms evolved from primitive, unspecialized ‘innate’ mechanisms of lower animals to more sophisticated, highly specialized ‘adaptive’ mechanisms as seen in higher animals and man. Adaptive immunity uniquely involves specialized cells called lymphocytes capable of producing antibodies against a wide range of microbial and nonmicrobial antigens. Antibodies are capable of complexing with soluble and/or immobilized antigens, forming a tightly bound structure called an immune complex. Soluble antigens bound to antibodies in immune complexes are normally cleared by various cellular mechanisms physiologically capable of eliminating even small quantities of ‘foreign’ antigens from circulation. If sufficiently large quantities of soluble antigens and their antibodies develop, large latticed immune complexes may form for a variety of different reasons. Latticed immune complexes are pathologically capable of depositing systemically in any of a variety of tissue sites, creating downstream cellular damage with many different clinical presentations, all of which fall into the category of ‘immune complex disease’ (the prototype originally being referred to as ‘serum sickness’). Several experimental animal models of immune complex disease have emerged yielding useful information on the cellular and soluble elements involved in its pathogenesis. Immune complex disease in humans is seen primarily in the setting of infection and/or in response to various therapeutic agents of protein or nonprotein nature. Adaptive immunity has also evolved to readily discriminate between self‐ and foreign antigens. Loss of ability to recognize self‐antigens results in ‘Autoimmunity’ in which both cellular and soluble immune responses against self‐antigens pathologically occur. Many different autoimmune disorders in humans feature immune complex disease manifestations and generally derive from unknown self‐antigens complexed to self‐antibodies. Even some recombinant protein therapeutic agents used to treat autoimmunity may induce formation of immune complexes, neutralizing therapeutic efficacy and/or manifesting as immune complex disease.

Characterization of multivalent complexes formed in the presence of more than one conventional antibody to terminal complement component C5

“…Immune complexes are taken up by cells of the reticuloendothelial system (RES) both through interaction of antibody Fc domains with fragment crystallizable gamma (Fcɤ) receptors and interaction of complement-dependent opsonins such as deposited C3 fragments with complement receptors and impairment of these processes can lead to tissue deposition and immune complex disease as reviewed elsewhere [ 28 ]. It is important therefore to understand whether large multivalent complexes such as those described presently might have an increased potential for tissue deposition because they comprise antibodies that have been Fc-engineered to eliminate or reduce their capacity to activate complement or bind to Fcɤ receptors [ 1 , 11 , 12 ].…”

Serum proteins and lipids in mild form of calf bronchopneumonia: candidates for reliable biomarkers

“…An elevated level of CIC was detected in many infectious/infl ammatory diseases in humans [27]. It is believed that CIC are formed at the site of infl ammation and represent an overfl ow from the infl amed/injured tissue.…”