Innate Immunity and Elegant Worms

Whether it be from ads on TV selling products that claim to boost your immune system or some terrifying statistic about how many bacteria humans are constantly exposed to, everyone has probably at least heard of the immune system.  Truth is, no amount of multi-vitamins or disinfectants are going to protect us from getting sick – our immune system is already doing a tremendous amount. What most people don’t know is that all vertebrate animals, humans included, have two immune systems, the adaptive (or acquired) immune system and the innate immune system.

The adaptive immune system is what most people think of when they think of immunity. It is composed of highly specialized, circulating cells (B and T cells) that process and eliminate an infection once the body has been infected. In adaptive immunity, pathogen-specific receptors are acquired during the lifetime of the organism. This response is said to be adaptive because this recognition of past infection prepares the body’s immune system for future infections from that specific pathogen.

adaptive

The adaptive immune system, however, is only present in vertebrate. The innate immune system on the other hand is evolutionarily conserved and is present in all multicellular organisms. It serves as the body’s first line of defense against pathogenic microorganisms, including bacterial or fungal pathogens. The innate immune system has many facets including anatomical barriers, inflammation, and pathogen recognition. Anatomical barriers are physical, chemical, and biological barriers whose job is to prevent microorganisms from entering the body in the first place, or from entering sterile cavities of the body (such as the blood stream) from a non-sterile cavity (like the intestine). Examples of anatomical barriers would be sweating, gastric acid, digestive enzymes, mucus, saliva, tears, and, most importantly, skin and epithelial cells. Inflammation is stimulated by chemicals released by injured cells which establishes a barrier against the spread of infection, and promotes healing of any damaged tissue following the elimination of pathogen from an area. Inflammation occurs when a cell recognizes a pathogen.

Pathogen recognition is a major component of the innate immune response, and indeed innate immune recognition of a pathogen is required for the adaptive immune response to learn what is and is not a pathogen. In many organisms innate pathogen recognition is accomplished using pattern recognition receptors (PRRs), which recognize toxins and other chemicals that are broadly shared by pathogens but are distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). Pathogen recognition is necessary in innate immunity because although innate immunity does not involve memory of specific pathogens, the innate immune system has slightly different responses for different broad classes of pathogens. For instance, in flies, there are distinctly different responses for gram negative and gram positive pathogens. It is also essential that the innate immune system can distinguish between pathogen, non-pathogen, or commensal bacteria which are required for the health of the host. The immune response is resource intensive and can cause damage to the organism so improper activation is detrimental to the host.

adavptivevsinnate

Schematic of the innate and adaptive immune systems and how they interact with each other.

In short, the innate immune system is very important! All multicellular organisms have an innate immune system, while only vertebrates have developed an adaptive immune system. The adaptive immune system is a comparatively recent development to immune responses. However, there is much more known about the adaptive immune system than the innate immune system because adaptive immunity is very relevant to human health and vaccine production (So don’t feel bad if you haven’t heard of innate immunity!). Considering the innate immune system is crucial to not only our survival, but the survival of all organisms, it is important that the innate immune system is studied to the extent that the adaptive immune system has been which is where we (the Powell lab) come in.

In the Powell lab, we use C. elegans as a model host organism to study innate immunity. C. elegans make a good model host for a variety of reasons. C. elegans are bacterivores and are thus exposed to a diversity of bacteria – some of which are used as nutrition while others are pathogenic.  Another important reason is that they are invertebrates and therefore lack an adaptive immune response which allows us to study only the innate immune response. C. elegans also have a digestive tract comparable to that of humans which is able to be infected by human pathogens. This could lead to better understanding of how bacterial infections are combatted in human intestine. C. elegans are also very good lab specimen because they are small and easy to maintain which allows us to work with them in large numbers and they have a short life span which allows experiments to be completed in a relatively short time period.

C. elegan anatomy.

C. elegan anatomy.

In C. elegans there are a variety of known genes involved in innate immune response pathways, including one which Dr. Powell discovered as a post-doc: fshr-1. The gene fshr-1 codes for a G-protein coupled receptor that is required for the innate immune response for most pathogens. A G-protein coupled receptor is a type of protein that binds to small molecules such as neurotransmitters, neuropeptides, and odorants. This type of protein activates other proteins which can induce neuronal or transcriptional activity. Our work in her lab focuses on characterizing fshr-1. Our goal is to determine all of the facets of immunity in which fshr-1is involved, stresses it responds to, as well as the immune pathways it is part of.

C Elegans are the most elegant of all the model organisms. ;)

C Elegans are the most elegant of all the model organisms. 😉

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