5.6: The Ability to Evade Adaptive Immune Defenses

Learning Objectives

1. State four ways the antibody molecules made during adaptive immunity protect us against bacteria.
2. Briefly describe at least three ways a bacterium might evade our adaptive immune defenses and name a bacterium that does each.

Overview of Adaptive Immune Defenses

One of the major defenses against bacteria is the immune defenses' production of antibody molecules against the organism. The "tips" of the antibody, called the Fab portion (Figure \(\PageIndex{1}\)) have shapes that are complementary to portions of bacterial proteins and polysaccharides called epitopes. The "bottom" of the antibody, called the Fc portion (Figure \(\PageIndex{1}\)) binds to receptors on phagocytes and NK cells) and can activate the classical complement pathway.

Figure \(\PageIndex{1}\): Normal Antibody-Antigen Reaction. The Fab portion of the antibody has specificity for binding an epitope of an antigen. An epitope is the portion of an antigen - such as a few amino acids sticking out of a protein - to which the Fab portion of an antibody molecule fits. The Fc portion directs the biological activity of the antibody. In the case of IgG, the Fc portion can bind to phagocytes for enhanced attachment (opsonization) as well as activate the classical complement pathway. Antibodies are composed of 4 protein chains: 2 identical heavy chains and 2 identical light chains. Disulfide (S-S) bonds join the protein chains together.

There are various ways that the antibodies the body makes during adaptive immunity protect the body against bacteria:

a. As mentioned above under phagocytosis, some antibodies such as IgG and IgE function as opsonins and stick bacteria to phagocytes (Figure \(\PageIndex{2}\)).

Figure \(\PageIndex{2}\): An epitope is the portion of an antigen - such as a few amino acids sticking out of a protein - to which the Fab portion of an antibody molecule fits. One of the functions of certain antibody molecules known as IgG is to stick antigens such as bacterial proteins and polysaccharides to phagocytes. The tips of the antibody, the Fab portion, have a shape that fits epitopes, portions of an antigen with a complementary shape. The stalk of the antibody is called the Fc portion and is able to bind to Fc receptors on phagocytes. Also, when body defense pathways known as the complement pathways are activated, one of the beneficial defense proteins made is called C3b. C3b binds by one end to bacterial surface proteins and by the other end to C3b receptors on phagocytes. The IgG and C3b are also known as opsonins and the process of enhanced attachment is also called opsonization.

b. Antibodies, such as IgG, IgA, and IgM, can bind to bacterial adhesins, pili, and capsules and in this way block their attachment to host cells.

c. IgG and IgM can also activate the classical complement pathway providing all of its associated benefits.

d. IgA and IgM can clump bacteria together enabling them to be more readily removed by phagocytes (Figure \(\PageIndex{3}\)).

Figure \(\PageIndex{3}\): Agglutination of Microorganisms. The multiple Fab portions of IgM link microorganism together so out of the lymph and blood and phagocytosed more effectively.

These mechanisms will be discussed in greater detail in Unit 6.

Exercise: Think-Pair-Share Questions

1. Staphylococcus aureus produces protein A, a protein that binds to the Fc portion of antibodies.

How might this enable S. aureus to resist adaptive immunity?

2. Many bacteria that colonize the mucous membranes produce immunoglobulin protease, an enzyme that hydrolizes antibodies of the IgA class.

How might this enable these bacteria to resist adaptive immunity?

Resisting Adaptive Immune Defenses

Bacteria utilize a variety of mechanisms to resist antibodies made during adaptive immunity. These include the following:

a. Certain bacteria can evade antibodies is by changing the adhesive tips of their pili as mentioned above with Escherichia coli and Neisseria gonorrhoeae (Figure \(\PageIndex{4}\)).

Figure \(\PageIndex{4}\): Bacteria Altering the Adhesive Tips of Their Pili. By genetically altering the adhesive tips of their pili, certain bacteria are able to: 1) adhere to and colonize different cell types with different receptors, and 2) evade antibodies made against the previous pili.

Bacteria can also vary other surface proteins so that antibodies previously made against those proteins will no longer "fit." (Figure \(\PageIndex{5}\)). For example, N. gonorrhoeae produces Rmp protein (protein III) that protects against antibody attack by antibodies made against other surface proteins (such as adhesins) and the lipooligosaccharide (LOS) of the bacterium.

Figure \(\PageIndex{5}\): (A) Normal Antibody-Antigen Reaction. The Fab portion of the antibody has specificity for binding an epitope of an antigen. An epitope is the portion of an antigen - such as a few amino acids sticking out of a protein - to which the Fab portion of an antibody molecule fits. The Fc portion of an antibody directs the biological activity of the antibody. In the case of IgG, the Fc portion can bind to phagocytes for enhanced attachment (opsonization) as well as activate the classical complement pathway. (B) Altering Epitopes of an Antigen in order to Resist Antibody Molecules. The Fab portion of the antibody has specificity for binding an epitope of an antigen. By altering the molecular shape of an epitope of an antigen through mutation or genetic recombination, previous antibody molecules agains the original shaped epitope no longer fit or bind to the antigen.

b. Strains of Neisseria meningitidis have a capsule composed of sialic acid while strains of Streptococcus pyogenes (group A beta streptococci) have a capsule made of hyaluronic acid. Both of these polysaccharides closely resemble carbohydrates found in human tissue and because they are not recognized as foreign by the lymphocytes that carry out the adaptive immune responses, antibodies are not made against those capsules. Likewise, some bacteria are able to coat themselves with host proteins such as fibronectin, lactoferrin, or transferrin and in this way avoid having antibodies being made against them because they are unable to be recognized as foreign by lymphocytes.

c. Staphylococcus aureus produces protein A while Streptococcus pyogenes produces protein G. Both of these proteins bind to the Fc portion of the antibody IgG, the portion that is supposed to bind the bacterium to phagocytes during enhanced attachment (Figure \(\PageIndex{1}\)). The bacteria become coated with antibodies in a way that does not result in opsonization (Figure \(\PageIndex{6}\)).

Figure \(\PageIndex{6}\): Staphylococcus aureus Resisting Opsonization via Protein A. The Fc portion of the antibody IgG, the portion that would normally binds to Fc receptors on phagocytes, instead binds to protein A on Staphylococcus aureus. In this way the bacterium becomes coated with a protective coat of antibodies that do not allow for opsonization.

d. Salmonella species can undergo phase variation of their capsular (K) and flagellar (H) antigens, that is, they can change the molecular shape of their capsular and flagellar antigens so that antibodies made against the previous form no longer fit the new form (Figure \(\PageIndex{5}\)).

e. Bacteria such as Haemophilus influenzae, Streptococcus pneumoniae, Helicobacter pylori, Shigella flexneri, Neisseria meningitidis, Neisseria gonorrhoeae and enteropathogenic E. coli produce immunoglobulin proteases. Immunoglobulin proteases degrade the body's protective antibodies (immunoglobulins) that are found in body secretions, a class of antibodies known as IgA.

f. Many pathogenic bacteria, as well as normal flora, form complex bacterial communities as biofilms. Bacteria in biofilms are often able to communicate with one another by a process called quorum sensing (discussed later in this unit) and are able to interact with and adapt to their environment as a population of bacteria rather than as individual bacteria. By living as a community of bacteria as a biofilm, these bacteria are better able to resist attack by antibiotics and are better able to resist the host immune system.

Summary

1. There are various ways that the antibodies the body makes during adaptive immunity protect the body against bacteria.
2. Some antibodies such as IgG and IgE function as opsonins and stick bacteria to phagocytes (opsonization or enhanced attachment).
3. Antibodies, such as IgG, IgA, and IgM, can bind to bacterial adhesins, pili, and capsules and in this way block their attachment to host cells.
4. IgG and IgM can activate the classical complement pathway providing all of its associated benefits.
5. IgA and IgM can clump bacteria together enabling them to be more readily removed by phagocytes.
6. Antitoxin antibodies, mainly IgG, are made against bacterial exotoxins. They combine with the exotoxin molecules before they can interact with host target cells and thus neutralize the toxin.
7. Bacteria utilize a variety of mechanisms to resist antibodies made during adaptive immunity.
8. Some bacteria can vary their surface proteins or polysaccharides so that antibodies previously made against those proteins will no longer "fit."
9. Some bacteria are able to coat themselves with host proteins and in this way avoid having antibodies being made against them because they are unable to be recognized as foreign
10. Some bacteria produce immunoglobulin proteases that degrade the body's protective antibodies (immunoglobulins) that are found in body secretions.