THE ADAPTIVE IMMUNE SYSTEM
II. HUMORAL IMMUNITY
B. WAYS THAT ANTIBODIES HELP TO DEFEND THE BODY
3. MAC Cytolysis
The overall purpose of this Learning Object is to understand the mechanisms by which antibodies work with the classical complement pathway to remove or neutralize antigens through a process called membrane attack complex (MAC) cytolysis.
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
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 MAC cytolysis.
3. MAC Cytolysis (def)
The process starts with IgG or IgM being made against epitopes on membranes. The Fab portion (def) of IgG or IgM reacts with the epitopes on the membrane and the Fc portion (def) of the antibody then activates the classical complement pathway. C5b6789n (the membrane attack complex or MAC) (def) then puts holes in the membrane. (Remember that MAC is also produced during the alternative complement pathway and the lectin pathway as was discussed in Unit 4.)
a. In the case of bacteria, MAC can put holes in the outer membrane and possibly the cytoplasmic membrane of the gram-negative cell wall (see Fig. 1) causing lysis (see Fig. 2).
b. With enveloped viruses, the MAC can damage the viral envelope (see Fig. 3 and Fig. 4).
c. In the case of "foreign" human cells - virus-infected cells, transplanted cells, transfused cells, cancer cells - the MAC causes direct cell lysis (see Fig. 5 and Fig. 6).
However, as learned in Unit 2, some bacteria by means of the activities described below are more resistant to MAC lysis.
- The LPS of the cell wall is the principle target for complement in gram-negative bacteria by activating the alternative complement pathway (def) and serving as a binding site for C3b as well as the site for formation of MAC. Some gram-negative bacteria attach sialic acid to the LPS O antigen (see Fig. 7) and this prevents the formation of the complement enzyme C3 convertase that is needed for the eventual formation of all the beneficial complement proteins such as C3b, C5a, and MAC. Blood-invasive strains of Neisseria gonorrhoeae (inf), as well as Bordetella pertussis (inf) and Hemophilus influenzae (inf) are examples of Gram-negative bacteria that are able to alter their LPS in this maner.
- Some gram-negative bacteria, such as Salmonella (inf), lengthen the LPS O antigen side chain (see Fig. 7) and this prevents the formation of MAC. Neisseria meningitidis (inf) and Group B Streptococcus (inf), on the other hand, produces capsular polysaccharides composed of sialic acid and as mentioned above, sialic acid prevents MAC lysis.
- An outer membrane molecule of Neisseria gonorrhoeae (inf) called Protein II binds factor H of the complement pathway and this leads to the degradation of the opsonin C3b by factor I and the formation of C3 convertase. Without C3 convertase, no MAC is produced.
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Updated: July, 2012
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