Histology/Cell Biology Flashcards

1
Q

Name 9 targets of Apoptosis that occur in the body.

For example, infected cells are killing via apoptosis by NK/CD8-T cells.

A
  1. Infected cells
  2. Thymocytes that recognize self in Thymus
  3. DNA damaged cells (ie - p53 triggers apoptosis during cell cycle)
  4. Unecessary cells during development (ie - finger/toe formation)
  5. Excess/Obsolete Cells (neurons that are not used in brain)
  6. Tissue involution (shrinkage) due to l_oss of growth factors_. (ie - uterus after pregnancy)
  7. Chemotherapeutic Killing
  8. _Defective Lymphocytes _
  9. _Damaged Cell_s - Hypoxic, Nutrient deficient, etc.
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2
Q

What are some morpholigica features of apoptotic cells?

A
  1. Chromatin Condensation
  2. Progressive Cell shrinkage
  3. Nuclear Shrinkage (pyknosis)
  4. Nuclear Fragmentation (karyorrhexis)
  5. Plasma Membrane Blebbing
  6. Apoptotic Bodies (vesicle-like bodies shedding from cell) - these are phagocytosed
  7. Phagocytosis without inflammation
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3
Q

Name 3 disease linked to suppression of Apoptosis.

A
  1. Cancer
  2. Atherosclerosis
  3. Autoimmune disorders
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4
Q

Name 5 diseases linked to increased apoptosis.

A
  1. Viral Infections (AIDS)
  2. Neurodegenerative Diseases (Alzheimers)
  3. Multiple Sclerosis
  4. Ischemi Injuries (myocardial infaction)
  5. Toxic-induced diseases (alcohol-induced hepatitis)
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5
Q

How many total proteins make up the apoptosis genes (both pro and anti apoptotic)?

How many are pro and how many are anti?

What are the family of proteins called?

A

24 total protiens

  • 6 anti-apoptotic
  • 18 pro-apoptotic

Bcl-2 Family Regulatory Proteins

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6
Q

What are the 2 main protein families involved in being pro-apoptotic?

A
  1. BH3-only
  2. Bax Family
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7
Q

Name at 3 proteins in the Bax family?

A

Bax, Bak, Box

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8
Q

Name 8 proteins in the BH3-only family

A

Bid, Bim, Bik

Bad, Bmf, Hrk

Noxa, Puma

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9
Q

Name 5 proteins in the Anti-apoptitic family.

A

Bcl-2, Bcl-X, A1, Bcl-w, Mcl-1

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10
Q

Which BH3-only protein does Granzyme B and/or Death receptors trigger

A

Bid

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11
Q

An intrinsic apoptotic signal (ie-DNA damage) will release sequestered ________ proteins which will release sequested ________ proteins from _______ proteins. The ________ proteins will then create channels in mitochondria which releases ____________.

A

An apoptotic signal (ie-DNA damage) will release sequestered BH3-ONLY proteins which will release sequested BAK proteins from BCL-2 proteins. The BAK proteins will then create channels in mitochondria which releases CYTOCHROME C.

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12
Q

During an intrinsic apoptotic event, _________ is released from the mitochondria where it binds to ________. _________ then binds to that molecule forming a _________ initiator. The _________ initiator then triggers a ________ effector which degrades the cellular components.

A

During an intrinsic apoptotic event, Cytohrome C** is released from the mitochondria where it binds to **Apaf-1. Procaspase-9 then binds to that molecule forming a caspase initiator. The caspase initiator then triggers a caspase effector which degrades the cellular components.

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13
Q

What do IAPs inhibit?

A

Ihibitor of Apoptosis (IAPs) are proteins that inhibit caspases.

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14
Q

What does Smac inhibit?

A

Smac (aka -Diablo) inhibits IAPs. It is released with cytochrome C during an apoptotic event. It allows apoptosis to occur.

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15
Q

How many human caspases are there?

A

14

  • 4 initiators (2,8,9,10)
  • 3 effectors (3,6,7)
  • 7 others not related to apoptosis
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16
Q

Can withdrawl of certain growth factors trigger apoptosis?

A

Yes.

PI3K-Akt pathway is stimulated by growth factors like insulin. Akt inactivates Bad which usually trigger apoptosis.

17
Q

What are the 2 extrinsic apoptotic pathways?

A
  1. Death Receptors
  2. Granzyme B
18
Q

During extrinsic apoptosis, a ligand binds to a death receptor. The death receptors intracelluar domain, called the _____ ______ binds to a _________ (FADD). The FADD’s second domain called the _____ ____ domain recruits _________ and allows for its activation.

A

During extrinsic apoptosis, a ligand binds to a death receptor. The death receptors intracelluar domain, called the death domain binds to a Fas-Associated Death Domain (FADD). The FADD second domain called the death effector domain recruits procaspase-8 and allows for its activation.

19
Q

How does the Granzyme B pathway work in apoptosis?

What other molecule is usually associated with the release of Granzyme B?

Which cell types release it?

A

Granzyme B is released from Cytotoxic T-Cells and NK cells.

Granzyme B is released with another protein called perforin. Perforin puts holes in the cellular membrane. Granzyme B then activates BH3-only protein Bid. It can also directly activate procaspase 3 and 8.

20
Q

Does cytochrome C ALWAYS need to be activated to trigger apoptosis?

A

No.

Death receptors and granzyme B pathways can trigger effector capsases without the use of cytochrome C and caspase 9.