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5 Cards in this Set

  • Front
  • Back
Describe the basic functions of macrophages
Removal of injured tissue/debris (phagocytosis, collagenase)

Antimicrobial (ROS, NO)

Chemotaxis, prolif of fibroblasts (PGDF, TGF-beta, TNF, IL-1)

Angiogenesis

Deposition and remodeling of ECM (TNF, IL-1, collagenase)


Classically activated macrophages are induced by microbial products and cytokines, particularly IFN-gamma and are microbicidal involved in potentially harmful inflammation

Alternatively activated macrophages are induced by other cytokines and in response to helminths (not shown), and are important in tissue repair and the resolution of inflammation (and may play a role in defense against helminthic parasites).
Describe the process of phagocytosis in macrophages.
actin polymerization shapes the pseudopod that extends
along target surface

regulated by Rho GTPases --> switches on phosphoinositol
kinase leads to accumulation of PI(4,5)P2

Phagosome is sealed off - actin depolymerizes at the base
in response to accumulation of PI(3,4,5)P3

Actin contraction involves myosin X (non-muscle myosin)

Four digestive processes mediated by the lysosome
Specific receptor-mediated endocytosis
Phagocytosis
Pinocytosis (non-specific, constitutive)
Autophagy (micro- and macro- ; intracellular proteins and organelles)
Describe the mechanism of reactive oxygen and nitrogen species microbicidal activity in macrophages.
Generate a superoxide anion (reduction of oxygen)
O2->O2. -> H2O2->H2O + OH. -> H2O (hydroxyl radicals = very long lived, destroys anything like lipids, dna, rna)

Catalase normally keeps it in check by keeping H2O2 low (le chatliers)
*O2 requires 4 electrons to reduce it all the way to water
Enzymes in ROS
NADPH oxidase
NADPH + 2O2 -> NADP+ + 2O2°- + H+

Superoxide dismutase
2H+ + 2O2- -> O2 + H202

Catalase
2H202 -> 2H20 + O2

Glutathione peroxidase
(Glutathione essential for maintaining reducing potential in cytosol)
2 Glutathione-SH + H202 + -> 2H20 + Glutathione-S-S-Glutathione
Know the basic functions of nitric oxide in macrophages and blood vessels.
Functions of nitric oxide (NO) in blood vessels and macrophages. NO is produced by two NO synthase (NOS) enzymes. It causes vasodilation, and NO-derived free radicals are toxic to microbial and mammalian cells.

Sustained production of NO endows macrophages with cytostatic
or cytotoxic activity against viruses, bacteria, fungi, protozoa,
helminths, and tumor cells.