Apoptosis or Cell Death

Introduction

Every living entity needs to be periodically cleansed by destroying the redundant and old cells and replace them with young and active ones. In order to fulfil this, a natural and sustainable process is necessary and the process is called apoptosis.  The term apoptosis is derived from the Greek origin meaning dropping or falling off. It was first introduced by Kerr, Wyllie, and Currie. Apoptosis helps to remove the old cells during development. It also eliminates pre-cancerous and some infected cells thereby help in maintaining the balance of cells in the human body and is particularly important in the immune system.Body, tissues and cells undergo periodic wear as a consequence of our day-to-day biological activities. Though it is a normal process, sometimes, our body cells need to be voluntarily destroyed by a process called apoptosis. Apoptosis should take a course , failure to comply with proper and systematic apoptosis  can sometimes affect our body adversely.  "Apoptosis is the term used to describe the natural biological process of programmed cell death in which the cells destroy themselves for maintaining the smooth functioning of the body.” This post is intended to explore in detail the process of apoptosis.

 

Changes due to apoptosis

1. Physiological changes

In our body, a number of morphological alterations can occur as a result of natural cell death. It is mostly  concerned with the nuclear and the cytoplasmic changes of a cell. Normally, apoptosis is a lengthy process as  it takes more time from the point of  initiation of cell death till the final cellular fragmentation. Nevertheless, the time taken depends on the cell type, the stimulus that causes apoptosis, and the apoptotic pathway.  During the process, cells exhibit a clear-cut  chromatin condensation and nuclear fragmentation along with sphering of the cellular shape. Furthermore, the cellular volume gets depleted (pyknosis). Chromatin condensation begins at the outer surface  of the nuclear membrane . Consequently, a crescent or ring-like structure is formed. The chromatin further undergoes condensation until they are broken down while leaving behind  an intact membrane called  karyorrhexis. The phagocytic cells that help in the process engulfs the apoptotic cells at the very early stage itself therefore, apoptosis cannot be discovered in the early stage.

 2. Biochemical changes

3 major biochemical changes that are observed during apoptosis includes the activation of capsases, DNA and protein breakdown along with  the membrane changes and recognition by phagocytic cells . There is a characteristic breakdown of DNA into a large 50 to 300 kilo base pieces. The internucleosomal cleavage of DNA into oligonucleosomes in multiples of 180 to 200 base pairs by endonucleases.

  

Difference between cell necrosis and apoptosis

A sequential wave of programmed cell death is necessary for normal development of an embryo during embryogenesis, or during any cell injury and infections . Cell necrosis or death of tissues is a passive form of cell death that is induced by non-physiologic agents (not from within). The following table briefs the major differences between apoptosis and necrosis.

 

Apoptosis

Necrosis

Apoptosis is initiated by our body cells and it is a routine process necessary to keep our    cells healthy and refreshed .                                                                                                                                            

Necrosis is not a  normal phenomenon as it can occur  only when our body  cells are encountered by a dangerous situation due to the entry of pathogens or some toxins. For example, necrosis occur in diabetes patients 

Apoptosis results in the formation of new cells once the old cells are shed away.

Necrosis is an irreversible process causing permanent loss of cells  with no scope for replacement of cells.

The cell membrane breaks into several apoptotic bodies

The cell membrane undergoes lysis to release its contents

It is an essential process to safeguard our body

Necrosis is harmful to health

Apoptosis is driven by  a fixed pathway and sequence.

It follows different sequences depending upon the causes of necrosis.

Apoptosis is triggered as a result of the natural defence mechanism by our body

It is triggered as a result of infections, antigens, toxins  and injuries.

It is a passive process does not demand energy

This is an active process requires energy

 

Need for apoptosis 

Cells need a periodic cleaning by which the set of old and redundant group of cells are being assassinated, to replace them with young and active ones. On a daily basis, 50 – 80 billion cells die as a result of apoptosis. The process helps to rejuvenate and refresh the body by removing the infected cells, aged cells and many pre-cancerous cells. Hence, apoptosis is essential for bringing in the balance within a system.

 

Apoptosis in animals

Some animals undergo apoptosis in an attempt to shed their outer shell. You might have observed a dry, scaled skin of a cobra in the wild. Snake sheds its outer layer for at least 4-6 times in a year. This is a significant process for them to clean their outer skin that is being accumulated with the redundant cells. Another classic example of apoptosis is the loss of the tail of a tadpole when the attains its maturity to become a frog.

 

Mechanism of apoptosis

There are 2 separate  pathways that  initiate apoptosis namely, the intrinsic and extrinsic pathways.  Intrinsic Pathway, as the name suggests, is a response to the biochemical stress, damage, infections,  cancerous cells, etc. On the contrary, the extrinsic Pathway triggers apoptosis in response to some external stimuli like mechanical injuries. Apoptosis is initiated with  DNA damage ( genetic errors as shown in the image) which can activate the p-53 gene resulting in cessation of the cell cycle. In the next phase, the cell automatically initiates  DNA repair. If the DNA repair fails, the ultimate result could be an induced apoptosis. 

 

 

 

         Review questions        

  1. Explain the 2 pathways of apoptosis

  2. Distinguish between apoptosis and the necrosis

  3. Why is apoptosis important?  

  4. Give one example of a natural apoptosis in animals.

  5. Define karyorrhexis.

 

 

More readings 

1.

WBCs

2.

Structure and functions of cell  

3.

Meiosis

4.

Cell cycle

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