February 28, 2008
iii. Lack gene for NADPH oxidase
*Chronic granulomatous (granuloma) infections
=tumor-ish granulocyte growth
*Pus- lots of dead neutrophils and bacteria
Lacked genes for NADPH oxidase and iNOs
**Killed by normal gut flora in a few weeks
iv. Diphteria
** Respiratory infections symptoms caused by exotoxins- proteins secreted by bacteria that damage your cells
Pertussis – toxins activated by low pH in phagolysosome
*Viral replication relies on degradation of its capsid by phagolysosome proteases
III. Variations
a. Rho-GTPases- actin rearrangements
*Yersinia pestis/The Black Plague: uses Rho-GTPases to force host cell to engulf it
*Salmonella use same method
Some respiratory pathogens (S. pyogenes, S. Pneumoniae) bind to epithelial cell receptors, trigger phagocytosis.
b. Apoptosis and phagocytosis
Phosphatidylserine<- on inner membrane
(recognized by PS receptor on macrophage)
Phagocytosis of apoptotic cell, expression of anti-inflammatory proteins by macrophage
C1 of complement also binds inner membrane phospholipids
C1 then bound by calreticulin on macrophage, phagocytosis
c. Microbial evasion of killing by phagocytes
*Stop fusion of phagosome with granules
*Have chemicals that disable antimicrobial contents of granules
Ex. M. Tuberculosis (engulfed by alveolar macrophages)
*Stops phagolysosome formation
*Catalase: breaks down ROS
Mycolic acid: thick, waxy cell wall, protects bacteria
I. Toll-like receptors
*Found on macrophages, dendritic cells, and some epithelial cells
a. Transmembrane proteins
*Signal Transduction- binding of microbial product to extracellular domanin of TLR- conformational change- change in shape of intracellular domain- change in interaction between cytoplasmic proteins and intracellular domain of TLR
*expression of inflammatory cytokine genes
