THE ADAPTIVE IMMUNE SYSTEM

II. HUMORAL IMMUNITY

A. ANTIBODIES (IMMUNOGLOBULINS)

3. The 5 Classes (Isotypes) of Human Antibodies

Fundamental Statements for this Learning Object:

1. IgG makes up approximately 80% of the serum antibodies, is a monomer with 2 Fab sites. The Fc portion can activate the classical complement pathway, bind to macrophages and neutrophils to enable opsonization, bind to NK cells to promote ADCC, and can cross the placenta.
2. IgM makes up approximately 13% of the serum antibodies, is the first antibody produced during an immune response, is found mainly in the blood, and is a pentamer with 10 Fab sites. The Fc portion can activate the classical complement pathway. Monomeric forms of IgM are found on the surface of B-lymphocytes as B-cell receptors.
3. IgA makes up approximately 6% of the serum antibodies, is a dimer with 4 epitope-binding sites and is found mainly in body secretions as secretory IgA (sIgA) where it protects internal body surfaces exposed to the environment by blocking the attachment of bacteria and viruses to mucous membranes.
4. The Fc portion of secretory IgA binds to components of mucous and contributes to the ability of mucous to trap microbes, and can bind to macrophages and neutrophils to enable opsonization, and can activate the lectin complement pathway and the alternative complement pathway.
5. IgD makes up approximately 0.2% of the serum antibodies, is a monomer with 2 Fab sites, is found on the surface of B-lymphocytes as a B-cell receptor, and may play a role in eliminating B-lymphocytes generating self-reactive autoantibodies.
6. IgE makes up about 0.002% of the serum antibodies, is a monomer with 2 Fab sites, and is made in response to parasitic worms (helminths) and arthropods. It is also often made in response to allergens. The Fc portion of IgE can bind to mast cells and basophils (see Fig. 8) where it mediates many allergic reactions, and the Fc portion of IgE made against parasitic worms can bind to eosinophils enabling opsonization. IgE may also protect external mucosal surfaces by promoting inflammation.

LEARNING OBJECTIVES FOR THIS SECTION

Humoral Immunity refers to the production of antibody molecules in response to an antigen (def). These antibody molecules circulate in the blood and enter the tissue via inflammation. Humoral immunity is most effective microbes or their toxins located in the extracellular spaces of the body.

Antibodies or immunoglobulins (def) are specific glycoprotein configurations produced by B-lymphocytes and plasma cells in response to a specific antigen and capable of reacting with that antigen.

In this section we will look at the 5 classes of human antibodies.

The 5 Classes or Isotypes of Human Antibodies (Immunoglobulins (def))

There are 5 classes or isotypes of human antibodies:

a. IgG (Immunoglobulin G; 4 subclasses, IgG1-4)

• IgG makes up approximately 80% of the serum antibodies.
  
• IgG has a half-life of 7-23 days depending on the subclass.
  
• IgG is a monomer and has 2 epitope-binding sites (see Fig. 1).
  
• The Fc portion of IgG can activate the classical complement (def) pathway (see Fig. 2).
  
• The Fc portion (def) of IgG can bind to macrophage and neutrophils for enhanced phagocytosis (opsonization) (see Fig. 3).
  
• The Fc portion of IgG can bind to NK cells (def) for antibody-dependent cytotoxicity or ADCC (see Fig. 4).
  
• The Fc portion of IgG enables it to cross the placenta. (IgG is the only class of antibody that can cross the placenta and enter the fetal circulation.)
• Feedback inhibition of B-lymphocyte activation. High levels of IgG feedback to B-lymphocytes to prevent their activation in order to turn off antibody production.

For More Information: Classical complement pathway from Unit 5

For More Information: Opsonization from Unit 6

For More Information: Antibody-dependent cellular cytotoxicity (ADCC) from Unit 6

 

b. IgM (Immunoglobulin M)

• IgM makes up approximately 13% of the serum antibodies and is the first antibody produced during an immune response.
• IgM is found mainly in the bloodstream rather than in the intracellular spaces of tissues where it can control infections in the blood.
  
• IgM has a half-life of about 5 days.
  
• IgM is a pentamer and has 10 epitope-binding sites (see Fig. 5).
  
• The Fc portions of IgM are able to activate the classical complement pathway. IgM is the most efficient class of antibody for activating the classical complement pathway.
  
• Monomeric forms of IgM are found on the surface of B-lymphocytes as B-cell receptors.

c. IgA (Immunoglobulin A; 2 subclasses, IgA1-2)

• IgA makes up approximately 6% of the serum antibodies where it has a half-life of approximately 6 days.
  
• IgA is found mainly in body secretions (saliva, mucous, tears, colostrum and milk) as secretory IgA (sIgA) where it protects internal body surfaces exposed to the environment by blocking the attachment of bacteria and viruses to mucous membranes. While only 6% of the antibodies in the serum are IgA, secretory IgA is the most immunoglobulin produced.
  
• IgA is made primarily in the mucosal-associated lymphoid tissues (MALT).
  
• IgA appears as a dimer of 2 "Y"-shaped molecules and has 4 epitope-binding sites and a secretory component to protect it from digestive enzymes in the secretions (see Fig. 6).
  
• The Fc portion of secretory IgA binds to components of mucous and contributes to the ability of mucous to trap microbes.
• The Fc portion of secretory IgA can bind to macrophages and neutrophils for enhanced attachment (opsonization).
  
• IgA can activate the lectin complement pathway and the alternative complement pathway (def).
  

d. IgD: (Immunoglobulin D)

• IgD makes up approximately 0.2% of the serum antibodies.
  
• IgD is a monomer and has 2 epitope-binding sites.
  
• IgD is found on the surface of B-lymphocytes (along with monomeric IgM) as a B-cell receptor where it may control of B-lymphocyte activation and suppression.
  
• IgD may play a role in eliminating B-lymphocytes generating self-reactive autoantibodies.

e. IgE (Immunoglobulin E)

• IgE makes up about 0.002% of the serum antibodies with a half-life of 2 days.
  
• Most IgE is tightly bound to basophils and mast cells via its Fc region .
  
• IgE is a monomer and has 2 epitope-binding sites.
  
• IgE is made in response to parasitic worms (helminths) and arthropods (def). It is also often made in response to allergens (def). (Allergens are antigens causing allergic reactions.)
  
• IgE may protect external mucosal surfaces by promoting inflammation, enabling IgG, complement proteins, and leukocytes to enter the tissues, as well as by triggering coughing, sneezing, and vomiting for mechanical removal of microbes and toxins. .
  
• The Fc portion of IgE can bind to mast cells and basophils (def) where it mediates many allergic reactions. Cross linking of cell-bound IgE by antigen triggers the release of vasodilators for an inflammatory response (see Fig 7).
  
• The Fc portion of IgE made against parasitic worms and arthropods can bind to eosinophils enabling opsonization (Fig. 8). This is a major defense against parasitic worms and arthropods.

For More Information: IgE-mediated hypersensitivity (Type-I) from Unit 6

Each day an average adult produces approximately three grams of antibodies, about two-thirds of this IgA.

 

Concept Map for Antibodies

• QUIZ YOURSELF ON THIS SECTION

Gary E. Kaiser, Ph.D.
Professor of Microbiology
The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html.