Introduction Course to Porcine Immunology

WHAT IS THE ROLE OF IMMUNOGLOBULINS IN THE IMMUNE RESPONSE?

 

The main function of immunoglobulins is to react against antigens in order to mediate their elimination.

Immunoglobulins react with antigens in two different ways: 

  1. Bound to B lymphocytes forming the BcR receptor, which allows their reaction with antigens in their native form. B lymphocytes can thus act as an effective presenting cell.  
     

  2. As free molecules in fluids. This allows immunoglobulins to act as antibodies in different biological reactions.

  1. Bound  to B lymphocytes membrane. Just as we said in chapter 2, the membrane of B lymphocytes has the BcR complex (B Cell Receptor). The BcR consist of several chains. Some of them are variable and formed by immunoglobulins, with different variants in the lymphocytes depending on the immunoglobulin isotype (IgM and IgG; IgA and IgE) or on the kind of inducting agent. The other two chains  are non-variable. They consist of two chains (a and b) and are common to all B lymphocytes. The function of the variable chains (which are immunoglobulins) is to react against specific antigens, while the non variable chains deliver signals to the cell interior. This is to initiate antibody production. This system allows B lymphocytes to act as effective antigen presenting cells (chapter 3). 

BcR complex diagram

  1. Immunoglobulins as free molecules in the body fluids.  We already know that immunoglobulin specifity depends on the variable region of both chains, and that one of their most important functions is reacting with antigens. Moreover, immunoglobulins have other functions which depend on the constant regions (effector regions). Thus, it is possible that immunoglobulins with the same specifity against a given antigen, but with different isotypes, perform different effector functions. So, one given antigen can be attacked in different ways depending on the immunoglobulin isotype.   

The main biological functions of immunoglobulins are:

Complement activation
Agglutination
Cellular cytotoxicity antibody dependent. 
Neutralization 
Opsonization 
Mucosa protection

Complement activation. The complement system is an unspecific defence mechanism of the immune system (innate immunity). It has a role in a large number of inflammatory and cytotoxic reactions and macrophage activation. It is activated by several mechanisms (classical pathway, alternative pathway, chapter 7). Some immunoglobulins can activate the complement by the classical pathway. This type of activation is performed mainly by IgM, followed by IgG by means of their Fc fragments. Antibodies bound to the infected cell membrane or to bacteria trigger a cytotoxic reaction, which is very effective and able to destroy the cell membrane. The alternative pathway (chapter 7) is activated by IgG and IgA. 

Back to table

 

Agglutination. Agglutination of bacteria and viruses is another biological activity of the immunoglobulins, above all of the IgM.

Back to table

Antibody  dependent cellular cytotoxiciy  (ADCC). Cytotoxic phenomena are not only induced by T CD 8+ lymphocytes; other immune cells, such as macrophages or NK cells, can also destroy cells with the cooperation of antibodies. This process happens when an antibody, usually IgG and sometimes also IgE, recognizes an antigen in the membrane of a cell, and then reacts with it, engulfing it (a process similar to opsonization);. The Fc fragment remains free. Those cells with cytotoxic activity and Fc receptors, such as NK cells and macrophages, bind the Fc fragment of the immunoglobulin and then trigger the citotoxicity activity. In this case, cytotoxicity is cell induced, but the reaction specifity will depend on the antibody. Both the Fab fragment (for antigen binding the membrane) and Fc fragment (for effector cell binding: NK or macrophage) act in this process.  

Back to table

Antibody depending cytotoxicity processes

Neutralization. Some immunoglobulin isotypes, such as IgG, IgM and IgA, are able to bind toxins, bacteria or viruses and neutralize their activity. In the case of viruses, the neutralization process allows antibodies to prevent viruses from infecting cells, due to the fact that antibodies coat the virus fragment needed for it to bind to the cell. In this case, only the Fab fragment acts

Back to table  

Opsonization

Opsonization. This is the phenomenom by which the antibodies enwrap an antigen (viruses, bacteria, etc), and activate phagocytosis by means of Fc fragments of macrophages, neutrophils or polymorphonuclear leukocytes. 

Back to table

Mucosa protection. IgA protects the epithelial surfaces from infectious agents. Its dimer or tetramer conformation allows having four to eight antigen binding sites. This make IgA tremendously effective against different bacterial antigens, by means of ADCC reactions (IgA is not bactericidal). IgA has a great capability to neutralize some viruses. 

Back to table


IgA ACTIVITY DIAGRAM


IgA ACTIVITY DIAGRAM:
at the gut level, IgA prevents the attachment of bacteria or viruses to the intestinal epithelium (1); inside enterocytes (2) they can even neutralize some viruses; in the tissue fluid (3). It can act at the intersticial lumen level avoiding virus or bacteria to adhere to the epithelium (1), inside enterocytes neutralizing the virus (2), and finally in the histic liquid  (3).

CHAPTER 4 Previous theme Bibliography Course program