2.6 - Defects in WBCs and Outcomes of Inflammation

Normal inflammation requires every WBC step to work. Defects can produce increased susceptibility to infection.

WBC defects

• acquired:

  • iatrogenic → medication/chemotherapy, radiation therapy

  • infectious → human immunodeficiency virus (HIV)

• inherited:

  • leukocyte adhesion deficiency type I and II → defective adhesion/recruitment machinery

  • chronic granulomatous disease → NADPH oxidase does not functional normally

    • impaired ROS generation that impairs intracellular microbial killing

  • Chediak-Higashi syndrome → impaired lysosome-phagosome fusion, impaired secretion of lytic granules from cytotoxic T cells

  • Toll-like receptor pathway signaling defects → unable to activate inflammatory response

  • inflammasome gain-of-function → excessive IL-1 activity that causes repeated inflammation and fever

    • example — cryoprinin and cryoprinin-associated periodic fever syndromes

      • unrelenting fevers that logically respond to IL-1 antagonists because IL-1 is a major downstream product of inflammasome activation

outcomes of acute inflammation

1. resolution — restoration of tissue form and function

   • neutrophils undergo apoptosis

   • macrophages remove microorganisms, necrotic tissue, debris

   • lymphatics drain edema

   • WBCs release self-limiting cytokines to reduce inflammation

   • pro-repair cytokines promote healing

     • angiogenesis stimulated to supply oxygen and nutrients

     • fibroblast proliferation stimulated for collagen deposition

2. progression to chronic inflammation — acute inflammation cannot eliminate problem

   • chronic from the beginning if illness was autoimmune or viral

3. scarring and fibrosis — damage exceeds regenerative capacity to return to normal form and function

   • replaced by collagen-rich fibrous tissue

   • example — myocardial infarction

     • dead cardiomyocytes are replaced by fibrous scar, but scar tissue does not contract and has lost function

granulation tissue

repair tissue that consists of inflammatory cells, newly formed blood vessels, young fibroblasts

• tissue has granular appearance but is not a granuloma

abscess

collection containing large number of neutrophils, necrotic tissue, purulent material / pus

• substantial tissue destruction may result in fibrosis during healing