THE ADAPTIVE IMMUNE SYSTEM

II. HUMORAL IMMUNITY

B. WAYS THAT ANTIBODIES HELP TO DEFEND THE BODY

4. Antibody-Dependent Cellular Cytotoxicity (ADCC) by NK Cells

The overall purpose of this Learning Object is to understand the mechanisms by which antibodies work with NK cells to remove or neutralize antigens through a process called antibody-dependent cellular cytotoxicity (ADCC).

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 antibody-dependent cellular cytotoxicity (ADCC) by NK cells.


Antibody-Dependent Cellular Cytotoxicity (ADCC) by NK cells

NK cells are capable of antibody-dependent cellular cytotoxicity or ADCC. NK cells (def) have receptors on their surface for the Fc portion of certain subclasses of IgG. When the antibody (def) IgG is made against epitopes (def) on "foreign" membrane-bound cells, e.g., virus-infected cells and cancer cells, the Fab portions (def) of the antibodies react with the "foreign" cell. The NK cells then bind to the Fc portion (def) of the antibody (see Fig. 1).

The NK cell then releases pore-forming proteins called perforins, proteolytic enzymes called granzymes, and chemokines. Granzymes pass through the pores and activate the enzymes that lead to apoptosis (def) of the infected cell by means of destruction of its structural cytoskeleton proteins and by chromosomal degradation (see Fig. 1A and Fig. 2). As a result, the cell breaks into fragments that are subsequently removed by phagocytes. Perforins can also sometimes result in cell lysis. (When NK cells are carrying out ADCC, they are sometimes also referred to as killer cells.)


The NK cell then releases pore-forming proteins called perforins and proteolytic enzymes called granzymes. Granzymes pass through the pores and activate the enzymes that lead to apoptosis of the infected cell by means of destruction of its structural cytoskeleton proteins and by chromosomal degradation (see Fig. 1A and Fig. 2). As a result, the cell breaks into fragments that are subsequently removed by phagocytes. Perforins can also sometimes result in cell lysis. (When NK cells are carrying out ADCC, they are sometimes also referred to as killer cells.)

Flash animation of ADCC contact by NK cells.

Flash animation of apoptosis by NK cells.

 

 

 

 


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