Question

one effect of antibodies produced during humoral immunity is to trigger activation of the complement system. Despite this, the complement system is considered part of the innate immune system. explain why

Answer 1

Complement system represents a major part of the innate immunity. It is a cascade of soluble proteins and membrane expressed receptors and regulators , which operates in plasma, in tissues, on cell surface, and even within the cell. It is composed of more than 40 proteins, the soluble ones being produced mainly by the liver. Complement was discovered at the end of the nineteenth century and described as a “factor” or “principle” capable to induce bacterial lysis. After that, for a long time, complement system has been considered as a supportive part of the innate immunity and received relatively little attention from the immunologists. Over the years, it became clear that complement has versatile functions and that its action extends far beyond the simple bactericidal activity. In a healthy individual, it orchestrates the immunologically silent clearance of host cells after their programed cell death. Complement cascade is activated immediately after encountering the pathogen. Hence, complement participates in pathogen opsonization, tagging it for engulfment by antigen presenting cells (APC); it plays a central role in the inflammatory process and modulates the activity of T- and B-cells. After generation of pathogen-specific antibodies, complement contributes in the clearance of immune complexes and pathogen elimination. Studies over the years demonstrated that complement takes part in nearly every step of the immune reaction and that it deserves a central position in the immunological research. Unfortunately, the lack of coherence in complement proteins nomenclature and the complexity of the enzymatic cascade render complement one of the “most complicated and incomprehensible” parts of immunology and is frequently avoided by students and scientists. With this review, we aim to underline the crucial importance of complement in physiology and pathology.

The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis) of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing opsonization and a direct killing by C5b–9 membrane attack complex and by triggering inflammatory responses with the anaphylatoxins C3a and C5a. Opsonization plays also a major role in the mounting of an adaptive immune response, involving antigen presenting cells, T-, and B-lymphocytes. Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies.

So, complement system is considered part of the innate immune system.