Introductory Course in Swine Immunology. 2nd ed.
Chapter 4. Porcine immunoglobulins.
 
What role do the immunoglobulins play in the immune response?
The main purpose of the immunoglobulins is to react against antigens to bring about their removal.

Immunoglobulins react against antigens in two ways: 

  1. Bound to B lymphocytes forming the BcR receptor. This enables them to react with the antigen in its native form, and permits the B lymphocytes to act as an effective presenting cell.
     

  2. Free in the fluids. Enables the immunoglobulins to act as antibodies in different biological functions. 

Diagram of BcR complex.

 1. Bound to the membrane of the B lymphocytes. As we saw in chapter 2, the membrane of the B lymphocytes is formed by the BcR complex (B Cell Receptor). BcR is made up of several chains; some are variable, formed by immunoglobulins, in which each B lymphocyte presents variations according to the immunoglobulin isotype (IgM and IgG, IgA and IgE) or according to the type of antigen inductor. The other two chains are invariable (formed by two a and b chains), and common to all B lymphocytes. The job of the variable chains, which are immunoglobulins, is to react with the specific antigen, whilst the invariable chains serve to transmit the signal to the interior of the cell to start antibody production. This system allows the B lymphocytes to act as effective antigen-presenting cells in their native form.(chapter 3)

 

2. Free immunoglobulins in the fluids. We have seen that the specificity of an immunoglobulin depends on the variable region of both chains, with the reaction with the specific antigen being one of its main roles. Immunoglobulins also have other functions which depend on the constant regions (effector functions). In other words, it could be the case that immunoglobulins with the same specificity against an antigen, but of a different isotype, carry out different effector functions. In short, an antigen can be attacked in different ways according to the immunoglobulin isotype.

The main biological functions of immunoglobulins are: 

Complement activation
Agglutination
Antibody dependent cell-mediated cytotoxicity. 
Neutralization
Opsonization
Protection of mucosae

Complement activation The complement is a non-specific immune system defence mechanism (innate immunity) which takes part in many inflammatory and cytotoxic reactions and in macrophage activation. It is activated by several mechanisms (classic pathway, alternative activation). Some immunoglobulins can activate the complement by the route known as the classic pathway. Complement activation by the classic pathway is mainly carried out by IgM followed by IgG by means of their Fc fragments. This complement activation by antibodies bound to the membrane of an infected cell or bacteria unleashes a highly effective cytotoxic action capable of destroying the cell membrane. IgG and IgA can activate the complement by an alternative pathway (chapter 7). 

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Agglutination. The agglutination of particles, bacteria and/or viruses is another of the biological activities of the immunoglobulins, above all IgM.

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Antibody dependent cell-mediated cytotoxicity.

Antibody dependent cell-mediated cytotoxicity (ADCC). Cytotoxic phenomena are not only induced by CD 8+ T lymphocytes, as other cells of the immune system such as macrophages or NK cells can also destroy cells through collaboration with antibodies. This process occurs when an antibody, generally type IgG and to a lesser extent IgE, recognises an antigen in the cell membrane and reacts with it, surrounding it (a similar phenomenon to opsonization) and leaving the Fc fraction free. Cells with cytotoxic capacity and Fc receptors, such as NK cells and macrophages, bind to the Fc fragment of the immunoglobulin and induce cytotoxicity in the cell. In this case cytotoxicity is induced by the cells but the specificity of the reaction is provided by the antibody. In this phenomenon the Fab (binding to the antigen membrane) and Fc (binding to the effector cell: NK, macrophage) fragments are involved.

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Neutralization. This is the phenomenon by which some immunoglobulin isotypes such as IgG, IgM and IgA are able to bind to a toxin, bacteria or virus and neutralize its activity (chapter 5). In the case of viruses, the neutralization phenomenon enables the antibodies to prevent a virus from infecting a cell by covering the part of the virus necessary for anchorage onto the cell. In this case only Fab fragments are involved.

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Opsonization

Opsonization. This is the phenomenon by which antibodies engulfing an antigen (bacteria, virus, etc) activate phagocytosis by means of the Fc receptors of macrophages, neutrophils or polymorphonuclears. 

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DIAGRAM OF IgA ACTIVITY. IgA can act at intestinal lumen level, preventing attachment of viruses and/or bacteria to the epithelium (1), neutralizing a virus within the enterocytes (2) and finally, in the cell fluid (3). 

Protection of mucosae. IgA coats the mucosae, protecting them from the entry of infectious agents. Their dimeric or tetrameric structure means that they have between 4 and 8 antigen binding sites available to them. This makes them tremendously effective against certain bacterial antigens through ADCC type reactions, as IgA is not bactericidal, and through their capacity to neutralize certain viruses. 

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© 2006. José Manuel Sánchez-Vizcaíno.
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