I. BACTERIAL PATHOGENESIS
B. VIRULENCE FACTORS THAT PROMOTE BACTERIAL COLONIZATION OF THE HOST
6. The ability to evade adaptive immune defenses
Fundamental Statements for this Learning Object:
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.
LEARNING OBJECTIVES FOR THIS SECTION
In this section on Bacterial Pathogenesis we will be looking at virulence factors that promote bacterial colonization of the host. The following are virulence factors that promote bacterial colonization of the host .
1. The ability to use motility and other means to contact host cells and disseminate within a host.
2. The ability to adhere to host cells and resist physical removal.
3. The ability to invade host cells.
4. The ability to compete for iron and other nutrients.
5. The ability to resist innate immune defenses such as phagocytosis and complement.
6. The ability to evade adaptive immune defenses.
We will now look at the ability of bacteria to evade adaptive immune defenses.
6. The Ability to Evade Adaptive Immune Defenses
One of the major defenses against bacteria is the immune defenses' production of antibody molecules (def) against the organism. The "tips" of the antibody, called the Fab portion (see Fig. 1 and Fig. 5A) have shapes that are complementary to portions of bacterial proteins and polysaccharides called epitopes (def). The "bottom" of the antibody, called the Fc portion (see Fig. 1) binds to receptors on phagocytes and NK cells (def)) and can activate the classical complement pathway (def).
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 (def) and stick bacteria to phagocytes (see Fig. 2).
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 (def) providing all of its associated benefits.
d. IgA and IgM can clump bacteria together enabling them to be more readily removed by phagocytes (see Fig. 3).
These mechanisms will be discussed in greater detail in Unit 6.
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 (def) as mentioned above with Escherichia coli (inf) and Neisseria gonorrhoeae (inf) (see Fig. 4). Bacteria can also vary other surface proteins so that antibodies previously made against those proteins will no longer "fit." See Fig. 5A and Fig. 5B. 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.
b. Strains of Neisseria meningitidis (inf) have a capsule (def) composed of sialic acid while strains of Streptococcus pyogenes (group A beta streptococci) (inf) 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 (inf) produces protein A while Streptococcus pyogenes (inf) 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 (see Fig. 1). The bacteria become coated with antibodies in a way that does not result in opsonization (see Fig. 6).
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. See Fig. 5A and Fig. 5B.
e. Bacteria such as Haemophilus influenzae (inf), Streptococcus pneumoniae (inf), Helicobacter pylori (inf), Shigella flexneri (inf), Neisseria meningitidis (inf), Neisseria gonorrhoeae (inf) and enteropathogenic E. coli (inf) 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:
1. better able to resist attack by antibiotics, and
2. are better able to resist the host immune system.
Medscape article on infections associated with organisms mentioned in this Learning Object. Registration to access this website is free.
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