I. BACTERIAL PATHOGENESIS
C. VIRULENCE FACTORS THAT DAMAGE THE HOST
1. Producing Cell Wall Components (Pathogen-Associated Molecular Patterns or PAMPs) that Bind to Host Cells Causing them to Synthesize and Secrete Inflammatory Cytokines and Chemokines
d. Acid-fast cell wall components: mycolic acid and peptidoglycan fragments (muramyl dipeptides)
The overall purpose of this Learning Object is:
1) to learn how various cells involved in body defenses are able to recognize conserved molecules from the acid-fast cell wall and subsequently produce cytokines that initiate innate immune defenses such as the inflammatory response, the complement pathways, and the coagulation pathway;
2) to learn how innate immune defenses such as the inflammatory response, the complement pathways, and the coagulation pathway work to remove remove acid-fast bacteria and protect the body; and
3) to learn how innate immune defenses such as the inflammatory response, the complement pathways, and the coagulation pathway can be harmful to the body if there is an excessive production of cytokines.
In this section on Bacterial Pathogenesis we are looking at virulence factors that damage the host. Virulence factors that damage the host include:
1. The ability to produce cell wall components (Pathogen-Associated Molecular Patterns or PAMPs) that bind to host cells causing them to synthesize and secrete inflammatory cytokines;
2. The ability to produce harmful exotoxins.
3. The ability to induce autoimmune responses.
We will now look at the ability of bacteria to produce cell wall components that bind to host cells and cause them to synthesize and secrete inflammatory cytokines.
The Ability to Produce Cell Wall Components (Pathogen-Associated Molecular Patterns or PAMPs) that Bind to Host Cells causing them to Synthesize and Secrete Inflammatory Cytokines and Chemokines
d. Acid-Fast Cell Wall Components: Mycolic Acid and Peptidoglycan Fragments (Muramyl Dipeptides)
In order to protect against infection, one of the things the body must initially do is detect the presence of microorganisms. The body does this by recognizing molecules unique to microorganisms that are not associated with human cells. These unique molecules are called pathogen-associated molecular patterns or PAMPs. (Because all microbes, not just pathogenic microbes, possess PAMPs, pathogen-associated molecular patterns are sometimes referred to as microbe-associated molecular patterns or MAMPs.)
Molecules unique to bacterial cell walls, such as peptidoglycan monomers, teichoic acids, LPS, mycolic acid, and mannose, are PAMPs that bind to pattern-recognition receptors on a variety of defense cells of the body causing them to synthesize and secrete a variety of proteins called cytokines. These cytokines can, in turn promote innate immune defenses such as inflammation, fever, and phagocytosis. PAMPS binding to PRRs also lead to activation of the complement pathways and activation of the coagulation pathway.
Cytokines are intercellular regulatory proteins produced by one cell that subsequently bind to other cells in the area and influence their activity in some manner.Cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8) are known as inflammatory cytokines because they promote inflammation. Some cytokines, such as IL-8, are also known as chemokines. They promote an inflammatory response by enabling white blood cells to leave the blood vessels and enter the surrounding tissue, by chemotactically attracting these white blood cells to the infection site, and by triggering neutrophils to release killing agents for extracellular killing.
The lysis of pathogenic Mycobacterium species, such as Mycobacterium tuberculosis (inf) and Mycobacterium leprae (inf), releases mycolic acid and peptidoglycan fragments (muramyl dipeptides) from their acid-fast cell wall (see Fig. 1). The mycolic acid molecules and peptidoglycan fragments bind to pattern-reconition receptors on macrophages (def) causing them to release cytokines such as tumor necrosis factor-alpha (TNF-alpha). Most of the damage in the lungs during tuberculosis is thought to be due to the effects TNF-alpha along with the release of toxic lysosomal components of the macrophages trying to kill the Mycobacterium tuberculosis.
E-Medicine article on infections associated with organisms mentioned in this Learning Object. Registration to access this website is free.
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