THE ADAPTIVE IMMUNE SYSTEM

II. HUMORAL IMMUNITY

B. WAYS THAT ANTIBODIES HELP TO DEFEND THE BODY

2. Opsonization

Fundamental Statements for this Learning Object:

1. Opsonization, or enhanced attachment, refers to the antibody molecules IgG and IgE, the complement proteins C3b and C4b, and other opsonins attaching antigens to phagocytes.
2. The Fab portions of the antibody IgG react with epitopes of the antigen. The Fc portion of IgG can then bind to neutrophils and macrophages thus sticking the antigen to the phagocyte. The Fc portion of secretory IgA can also bind to macrophages and neutrophils for opsonization.
3. IgG and IgM can activate the classical complement pathway and C3b or C4b can stick the antigen to phagocytes.
4. IgE is
made against parasitic worms (helminths) and arthropods. The Fab portions of IgE bind to epitopes on the helminth or arthropod while the Fc portion binds to receptors on eosinophils enabling opsonization.

 

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 plasma of the blood and enter tissue and organs via the inflammatory response. 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.

The antibodies produced during humoral immunity ultimately defend the body through a variety of different means. These include:

1. Opsonization
2. MAC Cytolysis
3. Antibody-dependent Cellular Cytotoxicity (ADCC) by NK Cells
4. Neutralization of Exotoxins
5. Neutralization of Viruses
6. Preventing Bacterial Adherence to Host Cells
7. Agglutination of Microorganisms
8. Immobilization of Bacteria and Protozoans
9. Promoting an Inflammatory Response


In this section we will look at opsonization.


1. Opsonization (def)

Opsonization, or enhanced attachment, refers to the antibody molecules IgG and IgE, the complement proteins C3b and C4b, and other opsonins (def) attaching antigens to phagocytes. This results in a much more efficient phagocytosis.

A. Opsonization with IgG, IgA, C3b, and C4b

1. The process starts with antibodies of the isotype IgG, IgA, or IgM being made against a surface antigen of the organism or cell to be phagocytosed. The Fab portions (def) of the antibody react with epitopes of the antigen. The Fc portion (def) of IgG (but not IgM) can then bind to receptors on neutrophils and macrophages thus sticking the antigen to the phagocyte (see Fig. 1). The Fc portion of secretory IgA can also bind to macrophages and neutrophils for opsonization.

The Fc portion of secretory IgA can also bind to macrophages and neutrophils for opsonization.

2. Alternately, IgG, IgA, and IgM can activate the complement pathways (see Fig. 2) and C3b or C4b (def) can stick the antigen to phagocytes (see Fig. 1). Like IgG, C3b, and to a lesser extent C4b, can function as opsonins (def), that is, they can attach antigens to phagocytes. One portion of the C3b binds to proteins and polysaccharides on microbial surfaces; another portion attaches to CR1 receptors on phagocytes, B-lymphocytes, and dendritic cells for enhanced phagocytosis. (see Fig. 3). (Remember that C3b and C4b are also produced during the alternative complement pathway and the lectin pathway as was discussed in Unit 5.) Activation of the complement pathway also promotes inflammation to bring phagocytes and defense chemicals from the bloodstream to the infection site as discussed later under this topic.

Actually, C3b molecule can bind to pretty much any protein or polysaccharide. Human cells, however, produce Factor H that binds to C3b and allows Factor I to inactivate the C3b. On the other hand, substances such as LPS on bacterial cells facilitate the binding of Factor B to C3b and this protects the C3b from inactivation by Factor I. In this way, C3b does not interact with our own cells but is able to interact with microbial cells.

 

Attachment then promotes destruction of the antigen. Microorganisms are placed in phagosomes (see Fig. 4) where they are ultimately digested by lysosomes (see Fig. 5). If the antigen is a cell too large to be ingested - such as virus-infected host cells, transplant cells, and cancer cells - the phagocyte empties the contents of its lysosomes directly on the cell for extracellular killing (see Fig. 6 and Fig. 7).

Flash animation of opsonization and intracellular destruction.
Flash animation of opsonization and extracellular destruction.
html5 version of animation for iPad showing opsonization and intracellular destruction.
html5 version of animation for iPad showing opsonization and extracellular destruction.

Opsonization is especially important against microorganisms with antiphagocytic structures such as capsules since opsonizing antibodies made against the capsule are able to stick capsules to phagocytes (see Fig. 8). In vaccines against pneumococccal pneumonia (inf) and Haemophilus influenzae type b (inf), it is capsular polysaccharide that is given as the antigen (def) in order to stimulate the body to make opsonizing antibodies against the encapsulated bacterium.

 

Flash animation showing phagocytosis of an encapsulated bacterium through opsonization.
html5 version of animation for iPad showing phagocytosis of an encapsulated bacterium through opsonization.

 

B. Opsonization with IgE and the promotion of inflammation

The antibody isotype IgE is made against parasitic worms (helminths) and arthropods. The Fab portions of IgE bind to epitopes on the helminth or arthropod while the Fc portion binds to receptors on eosinophils enabling opsonization. In other words, IgE sticks phagocytic eosinophils to helminths and arthropods for the extracellular killing of that organism (see Fig. 9).

The Fc portion of IgE also binds to receptors on mast cells and basophils to trigger the release of inflammatory mediators (see Fig. 10) . The inflammatory response then enables phagocytes and defense chemicals to leave the bloodstream and go to the infected site as will be discussed later under this topic.

 

     

 

C. How Bacteria Resist Attachment to Phagocytes

As we learned in Unit 3, some bacteria by means of the activities described below are able to resist phagocytic attachment :

 


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