Pathology Lecture 8 Cell Injury II

what are the 4 steps of apoptosis

1. Cell SHRINKS cytoplasm becomes dense

2. chromatin aggregates and nucleus breaks into fragments (most characteristic feature), fragments neat nuclear membrane

3. apoptotic bodies form

4. macrophages phagocytize apoptotic bodies

The lack of inflammation is thanks to the presence of which type of cell, and the absence of which cells

The presence of Macrophages prevent inflammation

The absence of Neutrophils and lymphocytes

Explain why apoptosis is important in embryologic development. what are some examples of what can happen if apoptosis fails? if it is over exaggerated?

Because… it is responsible for the appearance and regression of anatomical features.

Failure: redundant tissue is not removed. failure can result in syndactyly

Exaggeration: cleft plate and spina bifida

Role of p53

P53 is “guardian of the genome”

activates in response to DNA damage and assesses if DNA can be repaired. If DNA damage is severe p53 will initiate apoptosis

What are some extracellular signals that can trigger death receptors for apoptosis

toxins, hormones, growth factors, and cytokines

FasR is a _____ receptor and it is a member of the ______ receptor family

death ; TNF receptor family

In the extrinsic pathway of apoptosis, the FasL (fas ligand) binds to the ___

FasR (fas receptor)

Roles of caspase 8 and 10

They are initiator caspases that help lead to the activation of the executioner phase

When a cell is irreversibly damaged, what activates the intrinsic pathway

p53

In the intrinsic pathway, p53 acts on which specific Bcl-2 proteins? Where are the these proteins found?

Bak and Bax.

They are found in the mitochondria (Bak and Bax) and cytosol (Bax)

Activated Bak and Bax form what? What does it release into the cytosol

MAC (mitochondrial apoptosis-included channel). MAC mediates the release of Cytochrome C.

In the intrinsic pathway, After MAC released cytochrome, what does it bind to? This stimulates the formation of ____

1. Cytochrome C bind to a protein called Apaf-1 (apoptosis activating factor)

2. It stimulates the formation of the Apoptosome ( 1 molecule of Apaf-1 and 7 molecules of cyt C

In the intrinsic pathway of apoptosis, Caspase is activated within the apoptosome. This then activates caspases __ and __

Caspase 9, which then activates caspases 3 and 7

What are the initiator caspases of the Extrinsic pathway?

Caspase 8 & 10

What are the initiator caspases of the intrinsic pathway?

Caspase 9

1. What are the three caspases of the executioner family?

2. Which of these caspases is the primary executioner caspase that is responsible for the cleavage of nuclear lamins, DNA fragmentation, chromatin margination, and nuclear collapse

1. Caspases 3, 6, and 7

2. Caspase 3

In healthy cells __________ is present on the inner leaflet of the plasma membrane. In apoptotic cells, it then flips out, so macrophages can recognize it.

phosphatidylserine

caspase 3 activates endonucleases, which….

cleave the phosphodiester bond, and cleave chromosomal DNA into oligonucleosomal sized fragments.

which staining method allows the recognition of apoptotic nuclei in tissue sections

TUNEL Assay

Describe some differences between apoptosis and necrosis.

Necrosis: always pathological, passive process, cell swells, membrane ruptures, inflammation

Apoptosis, physiological and sometimes pathological, active process, cell shrinks, intact plasma membrane, NO inflammation