week 6 modified apoptosis.pdf

Apoptosis

Presented

By

Ahmed El-Rashedy

Professor & Previous Head of

Pathology Department

Al-Azhar University

Apoptosis

Def.: A Programmed cell death in which these

cells activate enzymes that degrade their own

nuclear DNA and nuclear and cytoplasmic

proteins.

Apoptotic cells break into fragments, called

apoptotic bodies, which contain portions of the

cytoplasm and nucleus.

The plasma membrane of the apoptotic cell

and bodies remains intact but its structure is

altered to become “tasty” targets for

phagocytes.

The dead cell and its fragments are rapidly

removed before the contents have leaked out.

Therefore, the apoptotic cell doesn’t produce

an inflammatory reaction in the host.

Prof. Dr. Ahmed Elrashedy

Occasionally, apoptosis and necrosis coexist and

apoptosis induced by some pathologic stimuli may

progress to necrosis.

Duration:

1. Apoptosis occurs normally both during development and

throughout adulthood.

2. Apoptosis occurs pathologically when the diseased cells

become damaged beyond repair.

Aims:

1. Removal of the unwanted, aged or harmful cells.

2. Maintenance of a steady number of various cell

populations in tissues.

3. Elimination of the diseased cells that are damaged

beyond repair.


Differences Between Necrosis and Apoptosis

Necrosis Classic Apoptosis

1. Process: Passive Active

2. Type: Pathological Physiological or Pathological

3. Chromatin: Swelling or lysis Condensation or Cross-linking

4. Cell Membrane

Integrity

Absent Present

5. Leakage of cellular

contents

Present Absent

6. Host Reaction. Present Absent

7. Inflammation: Present Absent

8. Mechanism: Externally induced

Internally or externally

induced


Examples:

A) Physiologic Apoptosis:

I) Apoptosis during embryogenesis: including:

1. Implantation.

2. Organogenesis.

3. Developmental involution.

II) Involution of hormone-dependent tissues on hormonal

withdrawal:

1. Endometrial cell breakdown during the menstrual cycle.

2. Ovarian follicular atresia in menopause.

3. Regression of the lactating breast after weaning.

III) Cell loss in cell proliferation to maintain a constant number

(homeostasis):

1) Immature lymphocytes in the bone marrow.

2) Epithelial cells in intestinal crypts.

IV) Removal of harmful self-reactive lymphocytes: to prevent

reactions against one's own tissues.


Examples:

B) Pathologic Apoptosis:

I) DNA damage (either directly or by synthesis of free radicals) in:

1) Radiation.

2) Cytotoxic anticancer drugs.

3) Hypoxia.

N.B.: These injurious stimuli (if mild) can cause apoptosis but larger doses of the same stimuli may cause necrosis.

II) Cell death in viral infections:

Loss of infected cells may be induced by either :

1. The virus (as in HIV infections) or

2. The host immune response (as in viral hepatitis) causing a

significant tissue damage: through cytotoxic T lymphocytes

specific for viral proteins.

III) Cell death in tumors and cellular rejection of transplants.

IV) Pathologic atrophy: in parenchymal organs (After duct

obstruction) occuring in the pancreas, parotid gland and kidney.


Pathology:

I) E/M:

1. Cell shrinkage: Smaller in size.

2. Plasma membranes: Remain intact during

apoptosis until the last stages (become

permeable to normally retained solutes).

3. Cytoplasm:

a) Dense

b) Organelles are more tightly packed.

c) Cytoplasmic blebs (buds) & apoptotic bodies.

d) Phagocytosis of apoptotic cells or bodies (by macrophages).

4. Nucleus:

a) Breaks into two or more fragments.

b) Chromatin condensation: The most characteristic feature of

apoptosis. The chromatin aggregates peripherally under the

nuclear membrane.


Pathology:

II) L/M:

1. The apoptotic cell appears as a

round or oval mass of intensely

eosinophilic cytoplasm with fragments of dense nuclear

chromatin.

2. Apoptosis may occur in tissues before it becomes

apparent in histologic sections because:

a) Cell shrinkage and formation of apoptotic bodies occur

rapidly.

b) The apoptotic pieces are quickly phagocytosed.

c) Apoptosis (in contrast to necrosis) doesn't produce an

inflammation. Thus, it is more difficult to be detected

histologically.


Mechanisms of Apoptosis

Two pathways of apoptosis:

I) Intrinsic (Mitochondrial) Pathway:

This pathway is the result of increased mitochondrial

permeability and release of pro-apoptotic molecules (death

inducers) into the cytoplasm.

1) Mitochondria contain proteins such as cytochrome c

(which are essential for life).

2) These proteins normally control mitochondrial

permeability and prevent leakage of mitochondrial

proteins.

3) Some of the mitochondrial proteins when released into the

cytoplasm initiate the suicide program of apoptosis.

4) The release of these mitochondrial proteins is controlled

by a balance between pro- and anti-apoptotic proteins.


Mechanisms of Apoptosis

II) Extrinsic (Death Receptor–Initiated) Pathway:

1. This pathway is initiated by entry of cell membrane

death receptors found on some cells.

2. Death receptors are members of the TNF receptor

family involved in the protein-protein interactions.

3. The best-known death receptors are the type 1 TNF

receptor (TNF R1) and its related Fas protein (CD95).

4. Fas ligand (FasL) is expressed on T- cells (that

recognize self antigens) and on some cytotoxic T-

lymphocytes (which kill virus-infected and tumor cells).


من نقص ومن خطإ فمني ومن الشيطان ما كان و ما كان من صواب فمن هللا

فأستغفر هللا إنه هو الغفور الرحيم والحمد هلل رب العالمينProf. Dr. Ahmed Elrashedy

week 6 modified apoptosis.pdf

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