Question

How does the complement cascade link innate and adaptive immunity?

Answer 1

Complement system

The liver is the major site of synthesis of complements followed by macrophages and fibroblast. Furthermore, they are synthesized during 2^nd month of pregnancy. Complement serves as an important mediator of the humoral response by amplifying the response and converting it into an effective defense mechanism to destroy invading microorganisms in the form of membrane attack complex (MAC) mediated cell lysis, and the other complement components participate in the inflammatory response, opsonization of antigen, viral neutralization, and clearance of immune complexes. It is a component of specific immunity. The classical pathway requires for an initial antigen-antibody reaction. The lgG and lgM activate the complement when it interacts with its specific antigen. IgM has highest compliment activity followed by lgG. The component that binds to the domain of C1 and it has three molecules namely (qrs) which are held together by ca2+ ions and q is like a collagen and it is made of 18 polypeptide chains. C1q binds to the domain which intern activates r, r intern activates s then followed by C4b and C2a and C3 convertase and C5 convertase then C5b followed by formation of membrane attack complex that inserted to the target cell forms to pore channel and causes leakage of cell content.

The other one is alternative pathway which belongs to innate immunity and the components of the alternative pathway are c3, c5-c9, factor-B, factor-D, and properdin. It will be activated by the teichoic acid of gram-positive bacteria, LPS of gram-negative bacteria, the cell wall of fungus, membrane of protozoa. In the presence of factors C3 is slowly hydrolyzed by breaking the internal thiol ester bond and forms a smaller fragment and larger fragment which intern in the formation of c3 convertase, and in the presence of properdin it activates the C3 convertase and further C5 convertase then C5b and followed by MAC leads to killing of bacterial cells.

Role of Complement

• The importance of cell-mediated immunity (adaptive immunity) in host defense against viral infections and antibody and complement do play a role in host defense against viruses and crucial in acute infection and in protecting against reinfection in enveloped viruses are susceptible to lysis by complement-mediated lysis (herpesviruses, orthomyxoviruses, paramyxoviruses, and retroviruses)

• The smaller fragments resulting from complement cleavage, C3a, C4a, and C5a, called anaphylatoxins, bind to receptors on mast cells and blood basophils and induce degranulation, with the release of histamine and other pharmacologically active mediators and these molecules induces smooth-muscle contraction and increased vascular permeability leads to influxes of fluid that carries antibody and phagocytic cells to the site of antigen entry.

• Recent studies indicate that complement fragment C3b acts as an adjuvant when coupled with protein antigens. C3b targets the antigen directly to the phagocyte, enhancing the initiation of antigen processing and accelerating specific antibody production.

• Patients with C3 deficiencies have the most severe clinical bacterial infections and having agammaglobulinemia. This case highlights the critical function of the complement system in converting a humoral antibody response into an effective defense mechanism.