A new synthesis for antibody-mediated immunity

Abstract

The view that immunoglobulins function largely by potentiating neutralization, cytotoxicity or phagocytosis is being replaced by a new synthesis whereby antibodies participate in all aspects of the immune response, from protecting the host at the earliest time of encounter with a microbe to later challenges. Perhaps the most transformative concept is that immunoglobulins manifest emergent properties, from their structure and function as individual molecules to their interactions with microbial targets and the host immune system. Given that emergent properties are neither reducible to first principles nor predictable, there is a need for new conceptual approaches for understanding antibody function and mechanisms of antibody immunity.

Figure 1

Effect of pro- and anti-inflammatory antibodies on three hosts that differ in their immune response to infection, as viewed in the context of the damage-response framework. (a) Positions of three infected hosts in the immune response: hosts 1 and 3 manifest disease at the two extremes of the immune response, whereas host 2 remains asymptomatic by mounting an immune response that is sufficiently strong to control infection while avoiding immune-mediated host damage. (b) The effect of a proinflammatory antibody on the three hosts in a. In this situation, the immune response of host 1 is shifted to a more optimal position and the antibody is protective, whereas for hosts 2 and 3 it has the potential to promote disease by enhancing inflammation. (c) The effect of an anti-inflammatory antibody on the three hosts in a. In this situation, host 3 benefits, whereas the same antibody can be detrimental to host 1 and ‘indifferent’ to host 2.