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*By Myriams-Fotos on pixabay.com*

--- *Lately, I haven't had much time to write for Steem, mostly because my MSc program is eating up all my time with deadlines over deadlines. One of the deadlines was for an essay on the innate and the adaptive immune system. I received it back with a decent grade (which surprised me, I didn't write an essay since school), so I thought "why not share it with Steemians?". It's on a higher level than my usual science posts, obviously. I might share my other essays too, once they're graded. Don't want to get punished for plagiarism because I put my essay online too early ...* --- Introduction

Every organism exists in a constant fight for survival. The most apparent fight may be the one against being eaten by other organisms, but many threats are not as immediately visible. Pathogens in the form of bacteria, viruses, or parasites are a persistent hazard to the health of any larger organism, be it a plant or an animal. To defend themselves, humans have developed a sophisticated immune system, consisting of both an innate and adaptive part. The two parts, while often being described as separate from each other, work closely together.

The innate immune system forms the first line of defence. Barriers like the skin (Proksch et al., 2008) together with the mucociliary epithelium (Sadikot et al., 2005) in the airways and acid in the stomach (Salama et al., 2013) prevent pathogens from entering the body and infecting cells in the first place. If a pathogen manages to breach through, it is immediately met with antimicrobial proteins (Gallo and Hooper, 2012), lysozymes (Fleming, 1922; Irwin et al., 2011), and the complement system (Sarma and Ward, 2011), which are often enough to kill it quickly. The classical pathway of the complement system results in a membrane attack complex (MAC), which creates a hole in the pathogen’s membrane. (Sarma and Ward, 2011)

A survival of this immediate response is followed by the early innate response, during which innate immune cells migrate to the area of infection (Jones, 2000). The cells take up pathogens through phagocytosis, which is where their name “phagocytes” derives from, and trigger an inflammatory response, recruiting more so-called professional phagocytes (Rosales and Uribe-Querol, 2017). At the same time, a particular type of phagocyte, the dendritic cells (DCs), migrates into the lymphoid tissue to present the antigen derived from the invading pathogen to the lymphocytes, which are cells of the adaptive immune system, serving as the main link between the two systems (Banchereau and Steinman, 1998).

Upon coming into contact with an antigen, T lymphocytes (or T-cells) mature into either cytotoxic T-cells (Tc cells), which proceed to kill cells with intracellular pathogens (e.g. viruses), or T-helper cells (Th cells), which among other things help activate B-cells (Kaech and Cui, 2012). B lymphocytes (or B-cells) also recognise antigens, with each B-cell expressing receptors that match one specific antigen. An activated B-cell can secrete its receptors as Immunoglobulins, also called Antibodies (Abs) (Pernis et al., 1971), which then opsonise, aggregate or neutralise pathogens (Tomasi, 1970). They can also create a link back to the innate immune system to activate the classical pathway of the complement system, resulting in a MAC (Ochsenbein and Zinkernagel, 2000), or facilitate the death of the pathogen via antibody-dependent cell mediated cytotoxicity (ADCC). ADCC is the result of a natural killer (NK) cell, which is part of the innate immune system, recognising the pathogen-bound antibody and promptly killing the cell (Leibson, 1997).

Looking at these two crucial parts of the immune system that work very closely together, the question arises if one displays any advantages over the other and if one can be regarded as “better”.

Discussion

With the overarching goal of the immune system being to keep the body alive, healthy, and free of pathogens, an evaluation of the innate and adaptive systems must focus on which one has the highest impact on this goal. Which do humans need more to survive?

Innate immunity: Protection from the beginning

The innate immune system, as the name already suggests, is the one we are born with. It develops during gestation and functions even without previous exposure to pathogens (Ygberg and Nilsson, 2012). And while breastfed babies receive antibodies through the milk their mothers produce (Butler, 1979), innate immunity is the central defence against pathogens a new-born child has.

While the adaptive immune system does exist at birth too, research shows that the high amount of T and B lymphocytes present at birth exhibit only a very low level of functionality (Ygberg and Nilsson, 2012). Only over time does this part slowly learn to recognise pathogens and it typically takes 1.5 to 2 years until a child can produce antibodies to bacterial capsular polysaccharides (Rijkers et al., 1998).

Considering the discrepancy in the speed of development, adaptive immunity appears to be severely lacking.

Specific recognition of the pathogens that slip through

Once, however, the adaptive immune system is fully matured, it can fight pathogens that managed to escape the innate one. If a virus has successfully infected a cell, the innate immune system tends to be unable to recognise this, as long as the virus doesn’t cause the cell to go into apoptosis (Arandjelovic and Ravichandran, 2015) or stops the expression of the major histocompatibility complex class I (MHC I), the latter being a “kill signal” for NK cells (Anfossi et al., 2006). This is where Tc cells step in: They recognize viral proteins produced inside the cell and presented through the MHC I (Monaco, 1992) and react with the release of perforin, granzyme, and granulysin, which has a cytotoxic effect on the infected cell (Krensky and Clayberger, 2005; Thiery and Lieberman, 2014).

If the pathogen that evaded the innate immunity is not a virus, Th and B-cells work together to get rid of it. When an antigen-specific Th cell comes in contact with a B-cell specific for the same antigen, the B-cell differentiates into either an antibody-producing plasma cell or a memory B-cell (Lanzavecchia, 1985; Parker, 1993). While plasma cells proliferate, a process called clonal expansion, and produces antigen-specific antibodies (Lane et al., 1981), the memory B-cells migrate into the bone marrow where they store the antigen information in case of a reinfection and can survive for a long time (Manz et al., 1998; Slifka and Ahmed, 1998).

The memory and antigen-specificity are what the innate immune system is lacking, and what makes the adaptive immune system so valuable.

Less specific antigen recognition has its strengths

It is possible for B-cells to differentiate into plasma cells without Th cell stimulation, but only if the antigen possesses a highly repetitive structure, usually due to polysaccharides on its surface. Antigens of this kind are called “thymus-independent” (Stein, 1992). The problem with this pathway is the lack of “isotope switching”, a process required to create different types of antibodies. Thymus-independent differentiation only yields IgM antibodies that are excellent at activating the complement system but are not as effective in opsonisation, neutralisation, agglutination, or the facilitation of ADCC (Forthal, 2014). Th cell cytokines are required for a switch to IgG, IgE, or IgA antibodies, all of them possessing different characteristics necessary for an effective immune response (Coffman et al., 1993).

However, this is not the only weakness of the B-cell’s need for collaboration with an antigen-specific Th cell. IgM antibodies might seem like a decent defence, but as mentioned in the introduction, bacterial capsular polysaccharides are not recognised by young children’s adaptive immune systems. This lack of recognition means that not only does the less-specific antigen recognition by B-cells result in antibodies with low functional variety; it does not even necessarily function during early human life.

Innate immune cells, on the other hand, are less specific in recognising pathogens, but the broad spectrum of pathogen-associated molecular patterns (PAMPs) detected via pattern-recognition receptors (PRR) like the toll-like receptors (TLR) is often more than sufficient to trigger an inflammation response that can successfully fight pathogens (Bianchi, 2007). In fact, it is likely that that at least 98% of pathogens can be fought off by the innate immune system alone, without requiring additional help from adaptive immune cells (Jones, 2000).

A lower specificity also has the advantage of being faster, while the innate system can react immediately or within a few hours, adaptive immunity can take days to become fully functional (Borghesi and Milcarek, 2007). By the time T and B-cells have reached the point of being able to fight the infection adequately, the innate immune system might have already taken care of it.

Innate and adaptive immunity cannot be clearly separated

Looking at the weaknesses of both innate and adaptive immunity possess; it becomes apparent that they tend to complement each other. While the adaptive immune system would not be able to function without antigen presentation by innate antigen-presenting cells, it also feeds back into processes of the innate one. B-cells producing IgM antibodies as a reaction to thymus-independent antigens is one example, the fact that the adaptive immune system can suppress over the top innate responses is another (Palm and Medzhitov, 2007).

Beyond that, the difference between the innate and adaptive immune system is not even that clear-cut. B-cells have been shown to not only produce antibodies but also play a role in early inflammatory cytokine response during bacterial sepsis (Kelly-Scumpia et al., 2011), even though the early inflammatory response is typically associated with the innate immune system only. NK cells, typically counted to the innate immune system, develop from the lymphocyte lineage instead of being a granulocyte like the other innate immune cells (Lanier et al., 1992), which is why some consider them innate-like T lymphocytes instead (Van Kaer, 2007). They also appear to be able to develop memory, an ability they share with B-cells (Sun and Lanier, 2009).

Concluding remarks

The human immune system is complex; even now, we do not know all the details about how it works. One apparent fact is that innate and adaptive immunity both have strengths and weaknesses, but the way they work together makes it possible to fight of threats that either alone might miss.

While innate immunity is what infants have to rely on in their first years, works considerably faster than adaptive immunity, can react to a broad range of pathogens thanks to its low specificity, and is required for the adaptive immune system to function, it could not fulfil its purpose by itself. Even during gestation the foetus profits from the mother’s adaptive immunity through antibodies passed on through the placenta and that process continues during breastfeeding, providing protection against pathogens that are not taken care of by innate immunity.

In older children and adults, the innate immune system still does not operate in a vacuum and relies on interactions with the lymphocytes of the adaptive immune system, specifically for cases when it fails. As effective as innate immune cells might be, they are not able to protect the body from everything, and if the adaptive immune system were not there to provide a second line of defence, the result would be an untimely death.

That the adaptive immune system is dependent on the innate immune system has also been explained in detail, which leads to the conclusion that it cannot be determined which part of the immune system is “better” – as they are both equally crucial for human survival.

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