Pronunciation: ah-poh-toh’-sis: Greek, (1) apo- away from and (2) ptosis, a falling or dropping
‘Apoptosis’ has been derived from a Greek word that describes the falling of the leaves from a tree or petals from a flower. This term was coined to differentiate this form of programmed cell death from the accidental cell deaths caused by inflammation or injury (necrosis).
Programmed cell death is an active process, first described in 1972 and usually proceeds by a distinct series of cellular changes known as apoptosis.
Apoptosis is thus the genetically programmed death of cells that is both a natural development process and the body’s means of destroying abnormal or infected cells.
Events of apoptosis:
During apoptosis, firstly, as a result of cleavage between nucleosomes, chromosomal DNA fragmentation occurs.
Following chromatin condensation, the cell shrinks in and breaks up into membrane-enclosed fragments known as apoptotic bodies.
These apoptotic cells and cell fragments are efficiently recognized and phagocytosed by macrophages and the neighbouring cells, and thus, eventually, these cells, which die by apoptosis, are rapidly removed from tissues.
This removal of the apoptotic cells from the tissues is mediated by the expression of certain signals on the cell surface. These signals are generally known as the “eat me” and include phosphatidylserine, which is restricted normally towards the inner leaflet of the plasma membrane. However, during apoptosis, phosphatidylserine becomes expressed on the cell surface, where it is recognized by receptors expressed by phagocytic cells.
Genes involved in apoptosis:
Programmed cell death was innovatively studied during the development of C. elegans, which eventually provided the critical initial insights that led to understanding the molecular mechanism of apoptosis. These pioneering studies conducted in the laboratory of Robert Horvitz helped initially identify three genes that played key roles in regulating and executing apoptosis.
Mutagenesis of C. elegans in the year 1986 helped identify the genes involved in the developmental cell death (ced-3and ced-4). If either ced-3 or ced-4 was inactivated by mutation, the normally programmed cell deaths did not occur.
A third gene known as the ced-9 functioned as a negative regulator of apoptosis. Whenever this gene ced-9 was inactivated by mutation, the cells failed to survive and instead underwent apoptosis, leading to death. Conversely, if this gene was expressed at an abnormally high level, the normally programmed cell deaths failed to occur.
Article by- SAMPRATI PAREKH (MSIWM049)
The Cell: A Molecular Approach by Geoffrey M. Cooper – 8thEdition
Cellular and Molecular Immunology by Abul K. Abbas – 7thEdition
Irreversible cell damage leads invariably to cell death as a result of interactions with noxious stimuli. Infectious agents, oxygen deprivation or hypoxia, and extreme environmental factors such as heat, radiation, or exposure to ultraviolet irradiation are all included in these noxious stimuli. The subsequent death is referred to as necrosis, commonly distinct from the other significant consequence of permanent damage, referred to as apoptosis cell death. Apoptosis is a cell death that is programmed or structured and may be physiological or pathological. Additional knowledge is beyond the scope of this chapter about this type of cell death. A pathological process is almost always associated with necrosis as a form of cell death.
They show two main types of microscopes or macroscopic appearance as cells die from necrosis. The first is liquefactive necrosis, also referred to as colliquative necrosis, characterized by a partial or total breakdown of dead tissue and liquid, viscous mass transformation. The tissue and cellular profile degradation occur in liquefactive necrosis within hours. Coagulative necrosis, the other significant pattern, is distinguished, in contrast to liquefactive necrosis, by the preservation of typical necrotic tissue architecture for several days after cell death.
The slimy, liquid-like essence of tissues undergoing liquefactive necrosis results in liquefaction. In part, this morphological appearance is due to the activities of hydrolytic enzymes that cause cellular organelles to dissolve in a cell undergoing necrosis. Liquefaction enzymes are derived either from bacterial hydrolytic enzymes or from lysosomal hydrolytic enzymes.
Types of necrosis :
Six types of necrosis are identified based on the morphological patterns associated with cell death.
a. Liquefactive necrosis
b. coagulative necrosis
c. Caseous Necrosis
d. Fat Necrosis
e. Gangrenous Necrosis
f. Fibrinoid necrosis
Liquefactive necrosis :
The necrosis pattern that is seen with infections. The pattern is also seen in the brain following ischemic injury. The release of digestive enzymes and neutrophil constituents causes liquefaction in infections, although there is a poor understanding of the cause of liquefactive necrosis following ischemic injury in the brain.
Gross Appearance: Due to pus formation, the tissue is in a liquid state and sometimes creamy yellow.
Coagulative necrosis :
Occurs in any organ in the body but the brain; this is the default necrosis trend associated with ischemia or hypoxia.
Gross Appearance: tissue is solid, and for days after cell death, architecture is preserved.
Caseous necrosis :
A rare form of tuberculosis-related cell death.
Gross appearance: white, fluffy, cheesy-looking material (case-looking).
A granuloma is known as the entire structure formed in response to tuberculosis.
Fat necrosis :
Acute inflammation affecting tissues with multiple adipocytes, such as the pancreas and breast tissue, causes fat necrosis. Digestive enzymes that break down lipids to produce free fatty acids are released by damaged cells.
Gross Appearance: Whitish deposits as a consequence of calcium soap formation.
Gangrenous Necrosis :
Medical usage in the description of lower limb ischemic necrosis (sometimes upper limbs or digits).
Gross appearance: varying degrees of putrefaction on black skin.
Fibrinoid necrosis :
Vascular damage (autoimmunity, immune complex deposition, infections (viruses, spirochetes, rickettsiae)) is a pattern associated with this.
Gross Appearance: Not necessarily grossly discernible.
All of these reflect morphological patterns, grossly, and microscopically evident. Typically, fibrinoid necrosis is evident only microscopically. In the following paragraphs, we examine the characteristic gross and microscopic effects of liquefactive necrosis.
Difference between Apoptosis and Necrosis:
Programmed cell death
Premature cell death
Occurs through shrinkage of cytoplasm, followed by chromatin condensation
Occurs through swelling of cytoplasm along with mitochondria followed by cell lysis
Naturally occurring physiological process
The pathological process, caused by external agents such as toxins, trauma, and infections.
Plasma membrane blebbing is observed without losing integrity
The membrane integrity is loosened.
Aggregation of chromatin
No structural changes in chromatin
Mitochondria become leaky often by forming membrane pores, while lysosomes kept their integrity. Organelles still function even after cell death.
Lysosomes become leaky, while mitochondria kept their integrity. Organelles are disintegrated by swelling and do not function after cell death.
Membrane-bound vesicles called apoptotic bodies fragments the cell into small bodies
No vesicle formation. Complete cell lysis occurs and releases contents into the extracellular fluid.
Tightly regulated by its activation pathway of enzymes
Caspase dependent pathway
Caspase independent pathway
The active process occurs at 40c
The inactive process does not occur at 40c
Digestion of DNA
Non-random mono and oligonucleosomal length fragmentation of DNA and show band pattern in Agarose gel electrophoresis.
DNA in the cell is randomly digested and shows a smear in Agarose gel electrophoresis.
Timing of DNA digestion
Prelytic DNA fragmentation.
Postlytic DNA digestion.
The localized process involves destroying individual cells
Affects contiguous cell groups
Either by phagocytes or adjacent cells
Neither inflammation nor tissue damage
A significant inflammatory response is generated. May cause tissue damage
Often beneficial, but abnormal activity may lead to diseases.
Always harmful. If necrosis is untreated- it may be fatal.
Involved in regulation of the number of cells in multicellular organisms.
Involved in tissue damage and induction of the immune system, defending the body from pathogens as well.