Immunogenicity of Immunogenic Cell Death

Immunogenic cell death is the type of cell death that educes an immune response i.e. it is the type of cell death that brings out or calls forth an immune response. The body of human being consist of billion cells (cell- the basic unit of the organization). A good number of these cells die daily and are replaced by new ones.

This process allows the conservation of the homeostasis of the whole body. Cell death can occur in the form of apoptosis (apoptosis- it is a process of cell destruction that is genetically directed). Apoptosis was rated as a non-immunogenic procedure until the knowledge of immunogenic cell deaths which challenge the former view and gave apoptosis an immunogenic ability.

Apoptosis stimulates the immune system by the ability of the dying cell to bring out an adaptive immune response against changed self-antigen or neo epitome. Autophagy which is the way the body flushes out damaged cells to generate new and healthy cells is also another way of cell death that is said to be a non-immunogenic process.

The body system and the immune system always experience cell death during injury, infection, and tissue/cellular turnover. It is one of the defense mechanism against intercellular infections which kills the infected cell preemptively and the parasite will automatically die with it.

Immunogenic cell death is determined by adjuvanticity and antigenicity. The traces of exogenic antigen in the body explain why malignant cells introduce immune response when those cells emit adjuvant signs as a result of cellular death. A lot of pathogens have a way to control cell death to stop the dying cell from sending signals.

How the immune system reacts to different cell death has been explained using two approaches. The first approach is the theory that is based on PAMPs (pathogen-associated molecular patterns).

Example of such pattern is the viral ribonucleic acid (RNA) or the component of the bacterial cell wall by the immune cell which distinguish between the cell death that occurs without a pathogen — silent cell death and the cell death which occurs in the presence of a pathogen i.e. the immunogenic cell death.

PAMPs are not the only determinant of immunogenicity and the reason being that the unaffected cell always educes an effective canter tumor immune response when they die. The remnant of the untransformed host cell can jump-start the autoimmune response.

Therefore, the concept of DAMPs — the damage-associated molecular pattern was proposed to address the immunogenic pattern of uninfected dying cells. Dying cells released DAMPs and as a result, calls forth immune responses to cell antigens regardless of what caused the death. Consequently, it was said that cell death must release the damage-associated molecular pattern to aid immune cells before it can be considered as immunogenic.

Phosphatidylserine, calreticulin, HSPs-heat shock protein and HMGB1 (the proteins released into the clear liquid of cell), and nucleic acids and its breakdown product are the immunogenic signals that are emitted from the dying cells. DAMPs that are released from the surface of dying cells such as those mentioned determine the DC activation, apoptotic bodies, DC maturation, and antigen processing.

The second approach is based on the notion that different types of cell death stimulate diseases and apoptosis. Necrosis is immunogenic and it causes swelling reactions. Further investigation shows that necrosis is not as immunogenic as the apoptosis form of immunogenic cell death.

Types of Cell Death

Pyroptosis: it is the process of cell death that occurs when pathogen-infected cells infect normal cells. It involves the contribution of inflammasomes. Cell death is caused by the mitotic catastrophe at any stage of mitosis and even after mitosis. It can be detected morphologically by mitotic arrest or micro-nucleation before the cell change into the apoptotic or necrotic aspects.

Cell fate has a great influence on the response of immune to dead or dying cells. Dead cells are either engulfed by other cells or shed from the body surface. The engulfed dead cells affect immune response unlike those that are shed from the surface of the body.

Necrosis: It can be referred to as the increase in cell volume (oncosis), the destruction of the plasma membrane, the inflammation of organelles, and the loss of intracellular content. Necrosis is said to be an accidental form of cellular death that occurs when cells are infected by pathogens.

A lot of factors are to be considered in other to know whether cell death is immunogenic or not. The factors include the process of activation before cell death, the pathway that caused the cell death, the responding cell of the immune system, and the nature of the cell.

Ingestion of Dying Cells

The cells send a find-me signal which creates a ray that attracts phagocytic cells. Lysophosphatidylcholine is an example of the signal and it is produced by phospholipase A₂ (PLA₂). PLA₂ is activated when caspases cleave.

The death of cells emit eat-me signals, the example of the signal is phosphatidylserine (PS), the difference in carbohydrate composition, and oxidized lipids. The diffusion of PS is caused by the loss of plasma membrane or ATP.

In the process of apoptosis, a sporadic botch of phospholipids membrane occurs and is consequential to the destruction of the asymmetry of phospholipids and the display of PS on the surface. The loss of the plasma membrane can be detected with the help of apoptosis and Annexin v.

Conclusion

The understanding and the manipulation of the response of the immune system and its dealings with dying cells can help us to understand and influence automatic immunity, tissue injury, and infectious diseases. The complexity of the dying cells to the immune system is due to the evolution of our immune system.

The failure to remove dying or dead cells from the body has the immunity implications but the process of removing the dead cells is hidden in organisms that have no resemblance with the inflammatory response of the unmoved dead cells. The complexity of the immune system in dealing with pathogens gives it an opportunity to educes an immune response.