Immunological Disorders and Immunotherapy
Open Access

The Relationship Between Immunoglobulins and the Complement System in Immunity

Imenz Sony^{* *}Correspondence: Imenz Sony, Department of Immunology, Harvard University, Cambridge, United States of America, Email:

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About the Study

Immunoglobulins (Ig) and the complement system are important components of the immune system, working in concert to protect the body from infections and maintain homeostasis. Understanding the interplay between immunoglobulins and the complement system is necessary for elucidating the mechanisms of immune defense and discussing various immunological disorders.

Classifications of Ig

Ig, commonly known as antibodies, are glycoproteins produced by plasma cells in response to antigens. They play a central role in the adaptive immune response by recognizing and binding to specific antigens, which include pathogens such as bacteria, viruses and toxins. There are five main classes of Ig, each with distinct functions:

IgG: The most abundant antibody in blood and extracellular fluid, IgG is important for long-term immunity and can cross the placenta to provide passive immunity to the fetus.

IgA: Found primarily in mucosal areas, such as the gut, respiratory tract and urogenital tract, IgA protects mucosal surfaces from pathogens.

IgM: The first antibody produced in response to an infection, IgM is effective in forming antigen-antibody complexes and activating the complement system.

IgE: Involved in allergic reactions and defense against parasitic infections, IgE binds to allergens and triggers histamine release from mast cells and basophils.

IgD: Present in small amounts in the blood and on the surface of B cells, IgD’s precise function is less well understood but is thought to play a role in initiating immune responses.

Mechanisms of complement system

The complement system is a complex network of proteins found in blood plasma and tissues that work together to improve the immune response. It is divided into three main pathways: the classical pathway, the alternative pathway and the lectin pathway. All three pathways converge on a common terminal pathway that leads to the formation of the Membrane Attack Complex (MAC) and subsequent pathogen destruction. Classical pathway activated by antigen-antibody complexes, specifically by the binding of IgG or IgM to an antigen. This pathway is initiated when the C1 complex binds to the Fc region of IgG or IgM. Alternative pathway activated independently of antibodies, this pathway is triggered by the spontaneous hydrolysis of C3 and the binding of C3b to pathogen surfaces. Lectin pathway activated by the binding of lectins, such as Mannose-Binding Lectin (MBL), to carbohydrate structures on pathogen surfaces. The complement system enhances immune responses through several mechanisms:

Opsonization:

Complement proteins, such as C3b, bind to pathogens, marking them for phagocytosis by immune cells.

Inflammation: Complement activation produces peptides, such as C5a, that recruit and activate inflammatory cells, contributing to the inflammatory response.

Cell lysis: The formation of the MAC (C5b-9) creates pores in pathogen membranes, leading to cell lysis and death.

Interaction between Ig and the complement system

The relationship between Ig and the complement system is integral to the efficiency of the immune response. Immunoglobulins can activate the complement system through the classical pathway, leading to enhanced pathogen clearance. Activation of the classical pathway when IgG or IgM binds to an antigen, the Fc region of the antibody exposes binding sites for the C1 complex of the complement system. This interaction triggers the classical pathway of complement activation. Formation of C3 Convertase the activation of C1 leads to the cleavage of C4 and C2, forming the C3 convertase enzyme (C4b2a) which then cleaves C3 into C3a and C3b. C3b binds to the surface of pathogens, tagging them for phagocytosis by immune cells. The complement system thus enhances the ability of antibodies to clear pathogens. The complement system enhances the phagocytic activity of macrophages and neutrophils by coating pathogens with complement components, which are recognized by complement receptors on these cells. The relationship between immunoglobulins and the complement system is necessary for effective immune responses. Immunoglobulins activate the complement system through the classical pathway, leading to enhanced pathogen clearance, opsonization and inflammation. Understanding this interplay provides insights into immune function and informs the development of therapies for immunological disorders.