What is apoptosis and inflammation ? Difference between apoptosis vs necrosis

Apoptosis and necrosis

Ø   Apoptosis is a preprogrammed cell death Iccurring actively through internal and external sources (suicide) while necrosis is occurring passively through some external lethal sources (murder).

Ø   Usually Necrosis involve a group of cells not only one cell.

APOPTOSIS	NECROSIS
It's like a suicide	It's like a murdering
Occurs actively	Occur passively
Occurs to single cell	Involve a group of cells so its like tissue death
Pre Programmed mechanisms through special enzymes etc	Its pathological causing Lethaly severe injury to cell
No inflamatoyr response because of no surrounding injury due to formation of membranous bags	They have an inflammatory zone around them due to injury around them
Condense its cytoplasm so the apoptotic cell is shrinking	Membrane disrupting and cell swelling
	Morphological changes

Ø   After the condensation of the cell materials into small bags called apoptotic bodies in which condensed organelle and degraded materials are present these are then taken by the macrophages.

Ø   Due to these bodies a type of flip occurs in the lipids of the cell membrane which is a kinda signal for the macrophages.

Ø   Also these bodies release some molecules which cause activation of macrophages as they have receptors for these bodies.

Ø   These molecules help in phagocytosis of the apoptotic bodies with macrophages by attaching one side with macrophages and another side with the bodies, these molecules are called opsonins.

Why apoptosis occurs

(Phatophysilogically)

Physiologically:

Ø   For the development of hands and foot (interdigital area undergo apoptosis).  Mean embryogenesis which pathological

Ø   Hormonal withdrawn i.e during the menstrual cycle the withdrawal of progesterone causes the endometrial cells apoptosis. also lactating female.

Ø   Autoreactive T cells formation due to sometimes the formation of autoreactive T cells receptors formation and their deletion through apoptosis (important because it can lead to autoimmunity).

Ø   During blood cell formation by bone marrow house apoptosis occurs because to prevent the number of cells going to circulation from very high, prematurely.

Ø   Apoptosis occurs in GIT lining cells too.

Ø   Apoptosis occurs in the skin lining epidermal cells too.

Ø   Because of the above last three points cell population is very well regulated.

 

Pathologically:

(1)         Seere injured Cell

Ø   It occurs when a cell's genetic material (DNA) is damaged in such a way that it can be repaired back.

Ø   This damage can occur through radiations etc so through apoptosis this should be removed because it can cause mutations and other problems and cancer too.

Ø   Not only genetic material but a cell is damaged severely through thermal radiations or hypoxia can also cause pathological apoptosis.

Ø   Hypoxia can cause both necrosis and apoptosis, but it depends if it occurs severely to a large group of cells then it causes necrosis and if a small group of cells or one cell then apoptosis.

Ø   Another damage is endoplasmic reticulum stress  in which the endoplasmic reticulum is being filled with many unfolded proteins that trigger the apoptotic process causing the suicide of cells

Ø   In viral hepatitis HBV many hepatocytes undergo apoptosis.

(2)         Other

Ø   Obstruction in tubes

Ø   P53gene (guardian of the genome) if cell genetic material is damaged so much that can be repaired so then p53 causes the suicide of that cell.

Ø   During cancer or tumour formation the p53 gene helps destroy the cells

Molecular programs responsible for apoptotic activity

 

Ø   Molecular mechanism of apoptosis consists of two pathways one is extrinsic and the second is intrinsic which then finally combine forming a common pathway causing suicide.

Extrinsic pathway:

Ø   It depends on special receptors on the cell membrane calling as death receptors because they can trigger the death of cells through apoptosis.

Ø   Here one is the FAS ligand (death inducer molecule) and the second the death receptor called as FAS or tumour necrotic factor receptor.

Ø   Below the death receptors we have death domains to which adopter protein attach which also has its death domains.

Ø   These domains causes activation of an enzyme called as

 C  ASP ASE is a member of the proteases family containing cysteine in its active pocket and its aspartate specific cuts at aminoacids chain.

Ø   Initiator caspases activate early stage of apoptosis and executioners activated at the late stage of apoptosis.

Ø   So the caspases are activated and their inhibitory peptide is removed by the domains of the adopter protein

Ø   So procaspases (inactive) is converted to caspases (active) by themselves and through these domains.

Ø   The initiator's caspases will activate another group of caspases as the executioner caspases.

Ø   Executioner include caspases 3,6,7 and initiators includes the caspases 8 (lower primates ) humans have 10 cases

Ø   Executioner will do digest away protolysis of the cytoskeleton of cytoplasm means destroying structural support, also destroying proteins for nucleus structure.

Ø   All it activates the DNAses by digesting inhibitory component of DNAses and then it will digest away the genetic materials.

Ø   The DNASes cut the nucleosome in between destroying the genetic material.

Ø   Simply mean DNAses produce te internucleosomal digesting activities.

Ø   Now the cell membrane undergoes some specific changes and removes the genetic materials and all other substances outside n the form of a pouch and then macrophage eengulfit because these apoptotic bodies have changed lipid layer and also they have opsonin triggering it for the macrophages.

Overview of the extrinsic pathway

Death receptors> Caspases> initiator caspases>executionar caspases> starting of death >DNASes> genetic materials budded outs apoptotic bodies.

 

Intrinsic pathway:

Ø Also called as mitochondrial pathway bcz of having the major role of mitochondria

Ø There are specific groups of genes responsible for the life span of the blood cells. Called as pro-apoptotic genes/pro-death genes.

Ø These genes must be balanced with antiapoptotic genes/prolife genes.

Ø Every cell has both types of genes now those cells surviving for a long time means having long half-lie are having the prolife or antiapoptotic genes and vice versa.

Ø  Antiapoptotic have BCL genes but specially bcl2 and bclx are antihepatotoxic 

Ø Others genes the mean prodeath also called as bax gens the bak genes.

Ø Though mitochondria is the powerhouse of cells but they also have some negative functions causing cell death through some molecules.

Ø Mitohcandria two types of molecules called cyt c and apoptosis-inducing factor (AIF).

Ø When the BCL genes (bcl2 and bclx) are expressed it causes the blockage of the permeable channels (in mitochondria) for these two molecules either in homo or heterodimeric form then the cells can survive for a long time.

Ø Also the bcl2 and bclx products keep inhibited the A ACTIVATING F so that the cell can survive for long.

Ø Normally GF, cytokines and hormones are responsible for survival by controlling the anti genes positively and negatively the pro-death genes but why does this occur?.

Ø But when these hormones etc are withdrawn the reverse type occurs means the pro-death genes start activating and the bcls genes then inhibiting.

Ø Bcz the dimers of the bak genes cant plug those channels and the deadly substances start releasing to the cytoplasm.

Ø now the cyt c plus the apoptosis activating factor 1 will cause the activating of the caspases 9 initiator onee and then it will activate the executioners and then DNases, nuclear proteins destruction and cytosolic digestion of cytoskeleton.

ØInitiatorr caspases in the case of the extrinsic pathway are 8 and in intrinsic one has caspases 9.

Ø But the executioner caspases 3,6,7 are activated by the initiator caspases of both

Ø And the remaining apoptosis-inducing factor combined with apoptosis inhibiting protein/antiapoptotic proteins (bcl2 and bclx) causing neutralization.

Ø Then it causes the inhibiting effect of the BCL genes.

 

Inflammation

Ø Anything which damage/injure vascular connective tissue then the body(vascuconnconnectivetissue) will respond to that in the form of inflammation.

Ø Purpose of inflammation is to remove the cause of injury and to remove those dead cells as a result of inflamation.

Ø  It brings our defence mechanism to the focus of injury.

Ø Then it removes the dead cells and opens them for the repair process.

Ø There are two types of it acute and chronic.

Ø Rapidly developing response and for short time then it is acute inflamation.

Ø If the inflamation is for a long time and occurs gradually then it is chronic.

Ø The time difference is basic between both.

Ø There are five cardinal signs of inflamation

Swelling/tumour

Hotness/calor

Redness/report

Pain/dolour

Loss of function of tissue/function laser

Ø   Acute inflamation can be divided into two events the vascular changes and cellular/wbcs events.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Ø   At the site of acute inflamation or chronic Exudation is the moving of the fluid from the vascular compartment to toward the outside tissue/interstitial area or cavity bringing a lot of proteins in this fluid. has high specific gravity due to proteins

Ø   Transudate fluid is the protein poor fluid coming from the vascular compartment toward the interstitial compartments without the endothelial cells gaps opening mean without the microcirculation permeability. It has low specific gravity due to the non-availability of proteins.

Ø   Edema is excessive fluid in the interstitial space or cavity that may be exudate or transudate.

Ø oedema which is formed due to inflamation is due to the process of exudation.