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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.
Prof. Dr. Ahmed Elrashedy
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
Prof. Dr. Ahmed Elrashedy
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.
Prof. Dr. Ahmed Elrashedy
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.
Prof. Dr. Ahmed Elrashedy
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.
Prof. Dr. Ahmed Elrashedy
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.
Prof. Dr. Ahmed Elrashedy
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.
Prof. Dr. Ahmed Elrashedy
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).
Prof. Dr. Ahmed Elrashedy
Prof. Dr. Ahmed Elrashedy
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