Life Lines by Dr. Dolittle

Sponsored by the American Physiological Society

The complex interplay between pathogens and our immune system

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I read an interesting review article explaining how cells evolved the ability to kill off pathogens and, in turn, how pathogens evade death. It is kind of like a perpetual game of ‘cat and mouse’ in which the interaction between animals and pathogens drives the evolution of host defenses against infections while at the same time driving the evolution of pathogen strategies to avoid detection. According to the review article, there are three main ways an animal’s cells kill pathogens, all of which involve self-destruction of the host cells:

Apoptosis: non-inflammatory cell death that results in the cell condensing and breaking up into smaller pieces. This is a normal process that is important for growth of an organism and cancer prevention.

Pyroptosis and Necroptosis: inflammatory cell death response that forms pores in the cell membrane causing the cell to rupture.

Here is a short video explaining the difference between apoptosis (i.e. normal cell death) and necroptosis (inflammatory cell death):

In order to detect a pathogen, cells from the infected host must be able to distinguish between the pathogen and it’s own cells. Eukaryotic cells do this with the help of specialized pattern-recognition receptors on their surface that can detect pathogen-associated molecular patterns specific to various diseases. Animal cells also have what are called “death receptors” that, when activated, cause cell death. This pathway is an important host defense that prevents the spread of disease and regulates inflammatory and immune responses.

The three suicide pathways mentioned above can interact with each other and all involve the activation of specialized enzymes called caspases. All animal phyla have these enzymes and humans, in particular, have 12 different caspases (that we know of) that each play different roles in the activation of cell death responses. 

If a pathogen can evade the immune response and prevent host cells from committing suicide, then the pathogen would be able to spread more easily. Not surprisingly, pathogens have evolved strategies to disrupt self-destruction by blocking or damaging various enzymes or proteins in the pathways. In fact, large segments of DNA in viruses are dedicated to inhibiting these pathways.

I suppose we can think of the interplay between pathogens and our own cells like war games. If our cells win and can prevent pathogens from spreading, then we stay healthy. If the pathogens win, on the other hand, then we become sick.

For the record, I am on the host-team.

Wishing you all good health!

Source:

B Tummers, DR Green. The evolution of regulated cell death pathways in animals and their evasion by pathogens. Physiological Reviews.102(1): 411-454, 2022.

Categories: Bird flu, Covid, Illnesses and Injuries, Nature's Solutions

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