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Physiologic role of the complement system in host defense, disease, and malnutrition
M Sakamoto1, Y Fujisawa, K Nishioka
1Wayo Womens University, Chiba, Japan.
Insights
The complement system protein C3 is crucial for immunity. Malnutrition lowers C3 levels, weakening host defense, but nutritional rehabilitation restores C3 and improves resistance to infection.
Area of Science:
- Immunology
- Nutritional Science
Background:
- The complement system bridges innate and acquired immunity.
- C3 protein is central to complement activation via multiple pathways.
- Complement activation drives essential immune responses like phagocytosis and pathogen killing.
Purpose of the Study:
- To review complement system pathology, focusing on hypocomplementemia in malnutrition.
- To investigate the link between C3 levels and host defense against infection.
- To explore nutritional rehabilitation's impact on complement levels and immunity.
Main Methods:
- Literature review of complement system roles and diseases.
- Analysis of studies on hypocomplementemia in malnourished humans and animals.
- Examination of experiments involving C3 level manipulation in rats.
Main Results:
- Reduced C3 levels correlate with impaired host defense in malnutrition.
- Nutritional rehabilitation improved hypocomplementemia, clinical status, and host resistance.
- Elevated C3 levels enhanced resistance to bacterial infections in rats.
Conclusions:
- Hypocomplementemia due to malnutrition compromises host defense.
- Nutritional interventions can restore C3 levels and bolster immunity.
- Findings offer insights for managing compromised immunity in malnourished states.
Abstract:
The role of the complement system as a system merging early-phase innate immunity with later-phase acquired immunity has been established. C3 is a key protein of the complement system. It is activated in four pathways: (1) the alternative pathway, (2) the mannan binding protein pathway, (3) the C-reactive protein pathway, and (4) the natural IgM pathway in innate immunity. It is also activated in (1) a classic pathway, i.e., through an antigen-antibody complex, and (2) by injured host cells in acquired immunity. Activation of C3 results in a variety of immunologic reactions such as immune adherence, phagocytosis, antibody response, cytolysis, inflammation, and killing of pathogenic microorganisms. Pathologic pictures of the complement system in various diseases were reviewed. Attention was focused on hypocomplementemia in the malnourished state. In humans and in experimental animals, reduced complement levels, especially of C3, were observed in relation to lowered host defense against infection. Hypocomplementemia improved after nutritional rehabilitation with a concomitant improvement of the clinical picture and recovery of host resistance. Enhancement of C3 levels in malnourished or well-nourished rats resulted in heightened resistance against bacterial infections. On the basis of these experimental and clinical observations, we obtained clues to prevent or treat a compromised host defense system in malnourished states.