The Complement System And Its Biological Consequences.
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Anushi jain Roll NO : 12 Paper 2 msC I The Complement System
INTRODUCTION The complement system is a group of serum proteins, which participate in innate as well as adaptive immune response. The complement system is characteristically activated by the antigen-antibody interaction. It helps antibacterial cells and molecules of the immune system .
PATHWAYS The complement system can be activated by three ways : CLASSICAL PATHWAY ALTERNATIVE PATHWAY LECTIN PATHWAY
COMPONENTS
BIOLOGICAL CONSEQUENCES Complement system serves as an important mediator of the humoral response , It plays a major role in host defense through destruction of invading micro0organisms. The Membrane-Attack Complex (MAC) mediates cell lysis. The split products or the active forms of the components of the complement participate in Inflammatory response , Opsonization of antigen , viral neutralization and clearance of the immune complexes.
CELL LYSIS The membrane-attack complex (MAC) formed by complement activation can lyse gram-negative bacteria , parasites , viruses , erythrocytes , and nucleated cells . Gram-positive bacteria are generally resistant to the complement mediated lysis because of thick peptidoglycan layer in their cell wall which prevents the insertion MAC into their inner membrane. The complement system lyses these target cells through the alternative pathway and lectin (MBL) pathway in absence of antibodies and through the classical pathway in the presence of antibodies.
MAC formed forms a pore in the cells and disturbs the osmotic balance of the cell and ultimately destroys it. Lysis of nucleated cells require multiple MACs , whereas lysis of RBC requires single MAC. If MAC is removed in time ,the cells are capable of repairing the damage and restoring its osmotic stability.
2. INFLAMMATION Inflammation is the most important consequence of the complement activation. C3a , C4a and C5a act as anaphylatoxins , i.e. , they cause smooth muscles to contract. C5a and C3a act as chemoattractants , i.e. , they effect the motility of the cells.
3.OPSONIZATION It’s a process in which bacteria and other cells are altered in such a manner that they are more readily engulfed by the phagocytes. C3b is a major opsonin and the receptors for C3b are CR1 , CR3 and CR4.
4. VIRAL NEUTRALIZATION Viral neutralization means neutralization of viral infectivity. There are various ways by which viruses can be neutralized : Formation of larger viral aggregates Reduces the net number of infectious viral particles. Coating of a antibody and/or complement (Cb3) to the surface of the viral particle Blocking attachment to host cells Binding of binding particle to cells possessing CR1 receptor or Fc. Lysing most enveloped viruses.
5. CLEARANCE OF IMMUNE COMPLEXES Erythrocytes plays an important role in clearance of the immune complexes. The coating of the soluble immune complexes with C3b facilitates their binding to the CR1. This interaction between CR1 and C3b results in adherence of immune complexes to the erythrocytes. Erythrocytes carry these immune complexes to the spleen and liver ; wherein these immune complexes are removed from erythrocytes and phagocytosed. The importance of clearing immune complexes can be seen in patients with autoimmune disease Systemic Lupus Erythematosus .