VERIFIED
Major causes of cellular injury
- loss of membrane integrity
- leakage of lysosome and cell contents
- cell dissolution
Too much ROS pathological effects
-Lipid peroxidation
- Protein Modification- breakdown or misfolding
- DNA damage- mutations in genome
Coagulative necrosis
cells own enzymes are denatured so leukocytes come and degrade dead cells
- firm texture
- infarcts in solid organs
liquefactive necrosis
The tissue liquefies
- seen in bacterial and fungal infections
- CNS infarcts
caseous necrosis
- cheese-like
- fragmented of lysed cells seen
,- no visible tissue architecture
- Common in granulomas (TB)
Fat necrosis
Breast, pancreas, and other abdominal organs
Action of lipases
Fibrinoid necrosis
Immune complex disposition- when antibodies bind they make complexes and can
lodge in the vasculature of kidneys and causes inflammation or cell death.
capases
main proteases that carry out apoptosis
1st Group- initiators
2nd Group- executioners
- cleaves target and activates nucleases and proteases that attack DNA,
nucleoproteases and the cytoskeleton.
The End result is controlled cell fragmentation that results in apoptotic bodies
The Mitochondrial (intrinsic) Pathway
Sensors in BCL-2 family activate BAX and BAX which make holes in the mitochondrial
membrane. Mitochondrial Proteins (cytochrome C) escape and activate the cascade
cascade.
The Death Receptor (extrinsic) Pathway
Receptor-ligand interactions -Fas -TNF receptor.
Results in activation of cascade cascade.
Cardinal Signs of Inflammation
, heat, redness, swelling, pain, loss of function
TLR
-bind bacterial cell wall lipids/ microbial DNA/RNA
- sends inflammatory cytokine response
- pro-inflammatory protons are released
- cytokines>cell> cell signals
Inflammasome
- used when there is dead tissue that we need to clean up
- recognizes loose ATP or anything floating around that should not be.
Leukocyte Recruitment Steps
1) margination- moving WBCs towards walls of vessels
2) rolling- leukocytes roll on vessels and interact with receptors
3) leukocyte adhesion- anchor to receptors
4) diapedesis- WBCs squeeze between gaps between endothelial cells and access BM;
enter tissues
5) chemotaxis- respond to chemical gradient in tissue and move to site where needed
Margination and Rolling Molecules
- Selectins,
- Sialyl-LewisX
- IL-1
- TNF
Adhesion Molecules