Skills to Develop
- Name the common PAMPs associated with acid-fast bacteria that stimulate cytokine production and an inflammatory response.
- Name pathogenic 2 acid-fast bacteria and state the infection each causes.
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, such as peptidoglycan monomers, teichoic acids, LPS, porins, mycolic acid, arabinogalactan, mannose-rich glycans, and flagellin 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 (def) 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, arabinogalactan, and peptidoglycan fragments (muramyl dipeptides) from their acid-fast cell wall (see Fig. 1). The mycolic acid molecules, arabinogalactan, and peptidoglycan fragments bind to pattern-recognition receptors on macrophages (def) and dendritic cells (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.
Medscape article on infections associated with organisms mentioned in this Learning Object. Registration to access this website is free.
- PAMPs associated with acid-fast bacteria include mycolic acid, arabinogalactan, and peptidoglycan fragments.
- Medically important acid-fast bacterium include Mycobacterium tuberculosis and Mycobacterium leprae.
Study the material in this section and then write out the answers to these questions. Do not just click on the answers and write them out. This will not test your understanding of this tutorial.
Dr. Gary Kaiser (COMMUNITY COLLEGE OF BALTIMORE COUNTY, CATONSVILLE CAMPUS)