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l:oi. D:. aii:az aiwat

l:oi. D:. |ciaa ll aw,
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Normai ceii
stress
ceii injury adaptation
Iceed iimits
Within iimit
necrosis
Apoptosis
Irreversibie ceii death
Persistence o severe stimuius
odes o ceii Death
Necrosis Apoptosis
It progresses in an uncontroiied vay
and causes iocai tissue damage or
iniammation
controiied orm o ceii death, vhere the ceii
controis its ovn termination. Iirst, it
degrades its internai structure, then dies in a
vay that is easiiy handied by iocai
phagocytotic ceiis
Necrosis = dead body
O Pathoiogicai process.
O It progresses in an uncontroiied vay and causes
iocai tissue damage or iniammation
O causes : eternai stimuii
1. hypoia
2. radiation.
1. pathogens e.g. viruses.
iochemicai changes:
1. Dc:atu:atio: o: coagulatio: oi :otci:
!. Digcstio: oi ccll |, l,sosoual c:z,ucs
1- breakdovn o the ceii membrane
2- Iniu o vater and ions rom
etraceiiuiar into the ceii
1- severe ceii sveiiing and ceii rupture
+- Denaturation or coaguiation o
proteins.
s- Irreversibie damage in the
organeiies
o- reiease o the iysosomai enzymes in
the etraceiiuiar space damage o
neighboring tissue and iniammatory
response
Necrosis
Necrosis is aivays associated vith an iniammatory process
Apoptosis
O controiied orm o ceii death, vhere the ceii controis
its ovn termination.
O It degrades its internai structure, then dies in a vay
that is easiiy handied by iocai phagocytotic ceiis.
O 1he process o apoptosis is reguiated by a number o
genes that code or a amiiy o enzymes knovn as
caspases, vhich degrade reguiatory and structurai
proteins in the nucieus and in the cytopiasm.
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1- change o ceii membrane
characters vithout ioss o its
integrity throughout the entire
process.
2- Ioss o microviiii and
interceiiuiar junctions.
1- Dramatic changes in
cytopiasmic motiiity vith
ormation o cytopiasmic
biebbing
+- Hypercondensation and
breakdovn, ragmentation o
the chromatin and its coiiapse
against the nuciear periphery.
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+- shrinkage o the cytopiasm.
s- ceii organeiies remain
normai but become ciumped
inside the cytopiasm.
o- Iragmentation o the ceii
into membrane-enciosed
apoptotic bodies that
contain remnants o the
nucieus, mitochondria, and
other organeiies.
1-1he apoptotic bodies are
rapidiy recognized and
removed by neighboring
ceiis and phagocytic ceiis.
Apoptosis occurs very quickiy and
preciseiy
Necrotic ceii Apoptotic ceiis
Chromatin clumping Chromatin condenses and migrates to
nuclear membrane.
Breakdown of cell organelles intact organelles
Plasma membrane lyses Blebbing of plasma and nuclear membranes
without membrane rupture
Cell contents released from the
cell
Cell contents are packaged in membrane
bounded bodies, to be engulfed by
neigbouring cells, specifically phagocytes
General inflammatory response
is triggered
No inflammation
Necrosis Apoptosis
A pathological process Normal physiological process
Externally induced nternally or externally induced
Cell swelling & lysis Cytoplasm shrinks with fragmentation of the
cell
Classes of cells that
undergo apoptosis
+1O11OxIx. mpor:on: n emIryoqeness
1. morpnoqeness elmno:es cells 1no: xerve No Innc:on ).
1he digits o hands and eet are connected by a tissue vebbing during embryogenesis.
ceiis in this vebbing serve no purpose in the aduit and are eiiminated by programmed ceii
death
2. xelec:on elmno:es excess cells).
Apoptosis o trunk muscies in taii
+1O11OxIx. mpor:on: n emIryoqeness
2- Immnn:y elmno:es Developmen:olly Dejec:ve cells ).
xelj on:qen
recoqnnq cell
1- Orqon se elmno:es excess cells).
+tot1o:i:. ...o- .- o1o!
1. Hormone-JepenJen: nvoln:on n :ne oJnl:
1rqn mommory qlonJ
Lo:e preqnoncy, loc:o:on
Involn:on
non-preqnon:, non-
loc:o:nq)
+pop:oss
+pop:oss
-1es:os:erone
1ros:o:e qlonJ
A

c
nJome:rol cell IreoIJown Jnrnq :ne mens:rnol cycle
Involn:on n olJ oqe
+1O11OxIx. mpor:on: n oJnl:s
2. mon:ons orqon se onJ jnnc:on.
+pop:oss
+ cell Jvson

1. cells wnose cell cycle s Js:nrIeJ or :s DN+ s

JomoqeJ IeyonJ repor
o. 1rns-njec:eJ cells onJ neoplos:c cells.
. Deo:n oj cells :no: nove serveJ :ner nsejnl
pnrpose, sncn os nen:ropnls n on ocn:e
njlommo:ory response, onJ lympnocy:es o: :ne
enJ oj on mmnne response.
o. mon:on o cons:on: nnmIer oj cells n
proljero:nq cell popnlo:ons sncn os n:es:nol
cryp: ep:nelo
hat Makes a Cell
Decide to Commit
8uicide?
Causes of Apoptosis
1here is o 8o/once 8etween them
os|t|ve s|gna|s
from other ce||s and extrace||u|ar
matr|x that |nh|b|t apoptos|s
1 growth factors
2 normones such as estrogen and
androgen
3 Neutra| am|no ac|ds and z|nc
4 |nter|euk|n2 wh|ch |s essent|a|
factor for the m|tos|s of |ymphocytes
Negat|ve s|gna|s
promote apoptos|s
ach cell receives
J|thdrawa| of
pos|t|ve s|gna|s
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ece|v|ng of
negat|ve s|gna|s
negaLlve slgnals
1|ncreased |eve|s of ox|dants w|th|n the
ce||
2damage to DNA by these ox|dants or
other agents ||ke
a)u|trav|o|et ||ght
b)xrays
c)chemotherapeut|c drugs
@ese are called death
act|vators lnclude
a)1umor necros|s
factora|pha (1NI
) LaL blnds Lo
Le 1NI receptor
b)Ias ||gand (IasL)
a molecule LaL
blnds Lo a cell
surface recepLor
named Ias
3 Spec|f|c mo|ecu|es that b|nd to
spec|f|c receptors on the ce||
surface
Mechanism of
apoptosis
Apoptosis is carried out by a proteoIytic system -
caspase
(1) Why called caspase?
Cysteine Aspartic acid
specific protease
!rocaspases activation caspase
caspases are synthesized in the ceii as inactive
precursors, or procosposes, vhich are activated to
perorm its unction
caspases activate
other procaspases
activate other
key proteins in
the ceii.
irreversibie breakdovn
o the nuciear iamina
O cieaves a protein that
normaiiy hoids a
DNA-degrading
enzyme (a DNAsej in
an inactive orm,
reeing the DNAse
ieading to breakdovn
o DNA.
:otci:
Activc
D:Aas
l:activc
D:Aas
ajor Apoptotic Pathvays
m:ocnonJrol x:ress-oc:vo:eJ or n:rnsc) po:nwoy.
O signais arising vithin the ceii (i:c:cascc lcvcls oi oxica:ts wit|i:
t|c ccll , accuuulatio: oi :otci:s t|at iailcc to iolc :oc:l,, D:A
cauagc,.
O Apoptosis is dependent on mitochondriai reiease o
cytochrome c rom the inter membranous.
Deo:n recep:or ex:rnsc) po:nwoy.
O 1riggered by death activators binding to receptors at the
ceii surace ( death receptorj:
O 1NI-
O Ias iigand (IasIj
O Apoptosis does not require cytochrome c reiease
itochondriai pathvay
O lt is uai:tai:cc |, a iauil, oi
:otci:s callcc lcl! :otci:s
w|ic| a:c closcl, associatcc wit|
uitoc|o:c:ia.
O I|c, govc:: uitoc|o:c:ial outc:
ucu|:a:c c:uca|ilit,.
O lcl! :otci:s a:c cit|c: lcl!
:otccto:s t|at :otcct cclls
agai:st aotosis ; a:tiaototic,
o: lcl! |illc:s w|ic| a:c :o
aototic :otci:s.
ci-2 kiiiers are pro-apoptotic proteins that a kiii
ceiis through the reiease o cytochrome c in to the
cytosoi
cl-2
killers
cytochrome c activates caspase-9
ieading to apoptosis
Death receptor pathvay
O Activation o this pathvay is
dependent on activation o a
certain type o ceii surace
receptors coiiectiveiy knovn
as death receptors.
O Death receptors themseives
are activated through
binding to protein iigands (
death activatorj that are
ound on the surace o other
ceiis.
death receptors
-
death activator
Activation o death receptor pathvay
Death receptor: Ias receptor
Ias receptor is
activated by
binding to its
Ias iigand on
the surace 1
iymphocyte
Activated death
receptor
254.90
iigand - speciic death receptor intermediate events
activation o procaspase 8 apoptosis.