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17 Cards in this Set

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What are the initiator pathways for apoptosis? Common?
a. Intrinsic: P53 and Bcl pathways
b. Extrinsic: Fas/FasL
c. Common: Caspase
Describe how apoptosis as a physiological process
a) Involution of structures during development
b) Elimination of immune cells
i) E.g., self-reactive lymphocytes
ii) E.g., neutrophils in inflammatory process
c) Involution following hormonal withdrawal
i) E.g., menstruation: shedding of endometrium
d) Cytotoxic T-cell mediated elimination of infected cells or neoplastic cells
Describe apoptosis as pathologic process
a) “Insults:” radiation; drugs; DNA damage
b) Viral infections
i) E.g., Councilman (acidophil) body: apoptotic hepatocyte in viral hepatitis
c) Autoimmunity
d) Neoplastic cells
Describe the two major pathways of apoptosis, please briefly list examples
a) Intrinsic: injury, radiation, toxins, ROS, withdrawal of growth factors
b) Extrinisc: death receptors, cytotoxic T-cell meditated
What is the common execution pathway for apoptosis?
a) Caspase enzyme cascade
From the Bcl family, what are 2 pro apoptotic regulators?
a) Bax, Bak
From the Bcl family, what are 2 anti-apoptotic regulators?
a) Bcl-2, bcl-x
What are the 2 major players in the intrinsic apoptotic pathway?
a) Injury (toxins, radiation, DNA damage)
b) Withdrawal of growth factors
Discuss the intrinsic pathway of intrinsic apoptosis
a) increase¬ p53 tumor suppressor gene product
i) Arrests cell in G1 to repair DNA
ii) If unsuccessful repair -->apoptosis
iii) increased¬ Pro-apoptotic members of Bcl family of proteins: Bax, Bak
Discuss what happens with a withdrawal of growth factors (with respect to apoptosis)
a) Alter balance in Bcl family to favor apoptosis
i) increase¬ Bax, Bak;
decrease bcl-2, bcl-x
Increased activity of Bax/Bak promotes what?
a) Apoptosis
Increased activity of bcl-2 and bcl-x promote what?
a) Anti-apoptosis
What are the 2 major players in the extrinsic pathway of apoptosis?
a) Death receptors/Ligands
b) Cytotoxic T-cell mediated cell death: granzyme B
(Granzyme-B induces apoptosis through Caspase-dependent and Caspase-independent mechanisms-- it cleaves after aspartic acid residues and thus activates Caspase-mediated apoptosis)
What are 4 examples of death receptors/ligands?
a) Fas/FasL
b) TNFR1/TNF
c) E.g. elimination of self-recognizing lymphs
Provide clinical examples for both physiologic and pathologic apoptosis
a) Pathologic: insults, radiation, drugs, viral infections (councilman bodies)
b) Physiological: self reactive lymphocytes, involution of structures during development, etc
What can happen when you have too little apoptotic activity (2 examples) i) Failure to eliminate self-reacting lymphocytes
a) Cancers
i) Neoplastic cells proliferate despite DNA damage
b) Autoimmunity
What can happen with too much apoptotic activity (3 examples)
a) Neurodegenerative disorders (e.g., Parkinson disease)
b) Ischemic injury
c) Death of virally infected cells