Pathology Basics Flashcards
(46 cards)
Cell injury; irreversible changes
- Plasma membrane damage (phospholipid membrane degradation);
- leakage of cytosolic enzymes
- Ca+ influx - Lysosomal rupture/autolysis
- Nucleus:
- shrinkage (pyknosis)
- fragmentation (karyorrhexis
- fading (karyolysis) - Mitochondria permeability/vacuolization increases. (swelling alone is reversible)
What causes nuclear fragmentation (karyorrhexis)
Endonuclease mediated cleavage
What is a sensitive indicator of apoptosis
DNA laddering
Apoptosis pathways
Intrinsic (mitochondrial) pathway
Extrinsic (death receptor) pathway
-Both pathways activate caspases (cytosolic proteases)
Intrinsic pathway stimuli
Internal stimuli;
- DNA Damage/stress
- Cytokines (decreased IL-2 after an immunological reaction)
- Injurious stimuli: Toxins, radiation, hypoxia
Extrinsic pathway stimuli
External stimuli; (2 pathways)
A. Extracellular Transmembrane ligands/receptor interaction;
- FASL binding to FAS (CD95)
- TNF-a binding to its receptor
B. T-cell release of perforin and granzyme B
Mitochondrial pathway is regulated by which family of proteins?
BCL-2.
Proapoptotic: BAX and BAK
Antiapoptotic: BCL-2 and BCL-xL
What is the function of BAX and BAK on the mitochondrial membrane?
Form pores in the membrane which allows the release of cytochrome C (leads to activation of caspases)
What is the function of BCL-2 on the mitochondrial membrane?
Keeps the membrane impermeable to keep cytochrome C from leaking out.
BCL-2 overexpression leads to decreased cascade activation which promotes tumor growth. Which malignancy is associated with this overexpression?
Follicular lymphoma t(14;18)
Extrrinsic pathway is regulated by which family of proteins?
TNF (tumor necrosis factor) family;
FAS (CD95)
What is the importance of FAS-FASL interaction in the thymic medulla?
FAS-FASL is important for the elimination of self-reacting T-cells. Normally, self reacting T-cells under go apoptosis. FAS mutation increases the number of self-reacting T cells in the circulation.
What autoimmune syndrome is associated with defective FAS-FASL interaction?
Autoimmune lymphoproliferative syndrome.
Leukocyte extravasation steps
- Margination/rolling
- Adhesion
- Transmigration
- migration
Margination/rolling: Molecules present on the blood vessel wall that serve as “speed bumps” so that rolling leukocytes can slow down to exit the blood vessel and to the site of injury.
Blood vessel:
E-selectin (in endothelial cells)
P-selectin (in platelets and endothelial cells)
Leukocyte:
L-selectin
Silly-Lewis
Adhesion molecules
Blood vessel:
- ICAM (CD54)
- VCAM (CD106)
Leukocyte:
1. CD11/18 integrins;
(LFA-1 and MAC-1)
2. VLA-4 integrin
Transmigration/Diapedesis; leukocyte squeezes through endothelial cells and exits blood vessel. Which molecules are involved in this step?
PECAM-1 (CD31)
Migration: leukocyte is guided to site of injury by ________________
Chemotactic signals
Although macrophage are the dominant mediators of chronic inflammation, they are also present in the late stages of acute inflammation (peak 2-3 days after onset) what is the role of macrophage in acute inflammation?
Influence the outcome of acute inflammation (4 outcomes; Resolution, healing by scarring, abscess formation or progression to chronic inflammation) by secreting cytokines.
Outcomes of chronic inflammation?
Scarring, amyloidosis or neoplastic transformation
Which mediators activate macrophage to create a pro inflammatory response?
INF-gamma (secreted by TH1), TNF
Which mediators activate macrophage to induce an anti-inflammatory response?
IL-4 and IL-13 (Secreted by TH2)
Oncogenes that encode Receptor Tyrosine Kinases. (With the associated neoplasm)
RET
HER2
ALK
Oncogenes that encode Non-Receptor Tyrosine Kinase
JAK2
BCR-ABL
