Apoptosis Flashcards
apoptosis is not an _____ (unlike necrosis)
inflammatory process
what are the physiological situations in which apoptosis occurs
embryogenesis and involution of hormone-dependent tissues upon hormone withdrawal
what are the pathological situations in which apoptosis occur
irreversible DNA damage (mutations, radiation, and hypoxia), accumulation of misfolded protein, and certain viral infections.`
nuclear margination
chromatin condensation
on H&E stains apoptotic cells appear
intensely eosinophilic / shrunken basophilic, surrounded by halo
caspases
enzymes that when activated lead to apoptosis
what are the types of caspases
initiators (caspase 8 & 9) and executioners (caspase 3 & 6)
what are the anti-apoptotic proteins
Bcl-2 (most imp), Bclx, and Mcl-1
what are the pro-apoptotic proteins
Bak and Bax
what stimulates the production of anti-apoptotic proteins
Growth factors
which pathway is the major mechanism of apoptosis
mitochondrial pathway (intrinsic)
BH3
inhibits anti-apoptotic and activates pro-apoptotic
mitochondrial pathway
- release of cytochrome C from the mitochondria into the cytosol
- Cytochrome C binds to Apaf-1 (apoptosis activating factor) forming apoptosome
- apoptosome binds to caspase-9
caspase-9
the critical initiator caspase
which pathway is responsible for the elimination of self-reactive lymphocytes
death receptor pathway (extrinsic)
Death receptor pathway (extrinsic)
initiated by plasma membrane death receptors (TNF) - Fas receptor
- TNF-1 (Fas receptor) binds to FasL (on activated T-cells) which activates caspases (caspase 8)
death domain
cytoplasmic structure involved in protein-protein interactions (FAAD).
execution of apoptosis
Caspases 3 & 6, activation of DNase. degradation and fragmentation of nuclei and phagocytosis
Amyloidosis
abnormal aggregation of proteins (or their fragments) into B-pleated linear sheets»_space; insoluble in fibrils
congo red stain
visualizes amyloid deposits
systemic amyloidosis
amyloid deposits in multiple organs
primary amyloidosis
systemic deposition of AL amyloid (derived from the light chain of immunoglobulin
what is primary amyloidosis associated with
plasma cell dyscrasias (multiple myeloma)
secondary amyloidosis
systemic deposition of AA amyloid which is derived from serum amyloid-associated protein (SAA)
what increases SAA
chronic inflammatory and malignancy states.
-FMF
Nephrotic syndrome
increased protein in urine (most common organ is the kidney) causes amyloidosis
macroglossia
tongue enlargement
carpal tunnel syndrome
musculoskeletal amyloidosis
what is the treatment of amyloid deposits
NO treatment: damaged organs must be transplanted
localized amyloidosis
amyloid depositions to a single organ
senile cardiac amyloidosis
non-mutated serum transthyretin (deposits in the heart)
familial A cardiomyopathy
mutated serum transthyretin
non-insulin-dependent DM (type II)
Amylin (derived from insulin) islets of the pancreas
Alzheimer disease
AB amyloid deposits in the brain forming amyloid plaques
dialysis-associated amyloidosis
B2-microglobulin joints
medullary carcinoma of the thyroid
tumor cells produce Calcitonin which deposits within the tumor
