Extravasation of neutrophils from postcapillary venules at site of inflammation• Local macrophages activated by bacterial infection release proinflammatory

cytokines (TNF-alpha, IL-1).These cytokines increase expression of selectins (Selectin-P) on endothelial cells.

• Passsing neutrophils bind to endothelial cells and start to “roll” slowly.• Rolling neutrophils start to express integrins on their cell surface, which bind to

ICAM-1 (intercellular adhesion protein-1) expressed on endothelial cells. This provides strong adhesion of neutrophils to endothelium.

• Neutrophils migrate through endothelium (diapedesis) into infected Ct and destroy bacteria.

Platelet functions in coagulation• Primary aggregation (platelet plug)• Secondary aggregation• Blood coagulation (cascade) with formation of fibrin which forms thrombus

(blood clot)• Clot retraction• Clot removals

Apoptosis or Necrosis?

****DESCRIBE****

Apoptosis triggered by chemotherapy, radiation, and death of lymphocytes (*necrosis?)Apoptosis = organelles still surrounded by PMNecrosis = cell swelling resulting in PM breakdown (viral/bacterial factor can result in this)

Programmed Cell Death

• This is an energy-dependent process. The PCD plays a major role in the embryogenesis and organogenesis (central nervous system) and in homeostatic regulation of many cell types, including epithelial cells, hematopoietic cells, tumor cells and many others.

• “Apoptosis is characterized by DNA cleavage, nuclear condensation, and plasma membrane blebbing that leads to phagocytosis of the cell without inducing an inflammatory response.” (adapted from Cellular and Molecular Immunology, Abbas, Lichtman and Pober eds.). The cell undergoing apoptosis sheds apoptotic bodies containing intact organelles. Apoptosis does not induce local inflammatory response.

• In contrast, necrosis is a random process of cell death in the response to injury, such as radiation, viral and bacterial infection, exposure to chemicals and other. Necrotic cells release cytoplasmic and nuclear contents into the environment leading to inflammation.

Apoptosis: DNA fragmentation Nuclear condensation Mitochondria morphology maintained Cell condensation & blebbing Cell fragmentation & production of apoptotic bodies w/ intact organelles Intact cell membrane Phagocytosis w/o inducing inflammatory response

Necrosis Reversible swelling leads to irreversible swelling Change in mitochondria morphology Chromatin pattern conserved (in nucleus) Plasma membrane breakdown & disintegration Random process; response to injury