"Innateness" of the "innate immune system"?

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Main Question or Discussion Point

Does every macrophage (and leucocyte in general) start from “scratch” as the organism grows in terms of "knowing" which pathogens to kill or does it somehow "know" to dismantle certain pathogens "genetically" once it is created? I guess, in other words, does it have to first get "exposed" to every single "antigen" it will every meet in order "create" antibodies for "antigens"/pathogens?

I know this is super complex and maybe not answerable easily (and very much out of my field of knowledge so pardon if this is a super ignorant question), I am mainly interested in figuring out whether the “innate immune system” is actually “innate” or is it more of a situation where for example, "the mother somehow passes on the antibodies to the baby after conception and before it is born" type of a situation, which I guess wouldn’t make it “innate”, but really “adaptive” (just not adaptive “after being born”)?

Essentially, is there anything in the genes that will "directly" code against certain pathogens?

I hope I'm not totally off the mark here, just trying to figure out the label "innate" in the term "innate immune system".
 
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  • #2
jim mcnamara
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Innate is a misleading term. It implies that resistance is builtin, somehow. Antibodies pass across the placenta, so newborn humans have some immunity derived from that. Colostrum is high in immunoglobulins (antibodies). So breastfeeding also creates immunity.

http://americanpregnancy.org/breastfeeding/breastfeeding-overview/

From the very start, whatever immunity humans have then is derived from Mom. So I guess as an approximation you could call this mother-offspring connection "innate". My opinion only. But many places in the Western world diverged from breastfeeding starting in the 1950's, with the advent of widespread use of baby formula.

Also note that all immunity is ultimately derived from human exposure to antibodies or antigens - e.g., the reason we get polio inoculations. I would guess that if you look on your upper left arm you do not have a smallpox vaccination scar. Meaning you were born after 1972, when smallpox vaccinations were discontinued.
http://www.iaff.org/ET/Smallpox/What_is_the_history_of_smallpox_vaccination.htm

So some disease pathogens can go "extinct" in a sense.
 
  • #3
atyy
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Yes, the ability of the innate immune system to act against microbes is "directly" coded in the genes.

https://www.ncbi.nlm.nih.gov/books/NBK27129/
"The innate immune system uses receptors that are encoded by intact genes inherited through the germline, whereas the adaptive immune system uses antigen receptors encoded by genes that are assembled from individual gene segments during lymphocyte development, a process that leads to each individual cell expressing a receptor of unique specificity. As a result, receptors of the innate immune system are deployed nonclonally, whereas the antigen receptors of the adaptive immune system are clonally distributed on individual lymphocytes."
 
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That is super helpful, thanks atty!
 
  • #5
jim mcnamara
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Thanks @atyy for the correction. I was off target a little. Never encountered the term.
 
  • #6
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Ah somehow I totally missed your response Jim!
Checking it all now, thanks so much.

p.s. Btw I have have the vaccination scar on my right arm and was born a few after 27! But I was born in one of the "old countries" :)
 
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  • #7
BillTre
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I have frequently seen the term innate immune system used to distinguish something from the of the more familiar adaptive immune system that uses antibody based processes in their anti-pathogen responses.

I first ran into this term in graduate school in the early 1980's when I met people in a fly (Drosophila) lab were studying it.
In that case, they were working on genes that encoded enzymes that broke down the cell wall components of some common bacteria.
By breaking down a bacteria's cell wall components, the bacteria can be compromised.
Since the cell wall molecules (a basic bacterial cell component) don't change very rapidly (by evolving), a system like this can keep up with these not rapidly changing cell wall components encoded by the pathogen.
An anti-pathogen response that attacks molecules that could evolve rapidly would require something like the vertebrates adaptive immune system that can raise an immune response to almost any antigen, whether it has been encountered previously in their evolution or not.
 
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I found out about the MSR1 in macrophages (https://en.wikipedia.org/wiki/MSR1) directly coded by a gene.

I have a follow-up curiosity: although this receptor evolved to be involved in spotting and getting rid of a pathogen, what are the odds that this receptor, throughout the course of its evolution would have come across some new compound that might just happen to be beneficial to the body, but since it just happened to be "spotted" as a "pathogen", it never stood a chance?

Hope that is clear enough.
 
  • #9
BillTre
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I have a follow-up curiosity: although this receptor evolved to be involved in spotting and getting rid of a pathogen, what are the odds that this receptor, throughout the course of its evolution would have come across some new compound that might just happen to be beneficial to the body, but since it just happened to be "spotted" as a "pathogen", it never stood a chance?
Macrophages do things in addition to only attacking pathogens. They can also just clean up dead junk laying around (like dead cells) among other things. For example, your link states that it is also involved in "atherosclerosis and Alzheimer's disease" which to me implies it may be involved in the disease processes (in an auto-immune kind of way).
This may be an answer to your question. It needn't be that unlikely that the receptor would not bind some potentially useful molecule (enough negatives?), however, I am not going to give odds on it.

Evolutionarially, the receptor would be positively selected for if its benefits exceeded it adverse effects, but adverse affects for something that has not yet arisen would (it seems to me) not have much selective value one way or the other in the short term.
Over longer periods, evolutionary lineages may be limited in evolving in particular directions due to the MSR1 blocked molecule might not being able to fulfill its potential function.
This could result in a particular lineage (or an evolving clade) being less productive in generating species that could make use of, or live in, particular environments or conditions that the MSR1 blocked molecule might have otherwise enabled them to utilize.
 
  • #10
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Super helpful, thanks so much BillTre!
(Or in other words, your feedback has not ever not been helpful! :) )
 
  • #11
Laroxe
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I agree that the terms are misleading, all of our immune system is innate as in we come biologically equipped with an immune system that is capable of functioning in a variety of ways. The innate system is if you like the first responder and includes things like the physical barriers of skin and mucous membranes, chemical barriers like stomach acid or tears and some internal barriers like the blood brain barrier.
There are then cells which are capable of identifying damage or foreign proteins and attempt to remove them, basically by engulfing them, they also start the process of inflammation which sends out chemical messengers to attract other cells to the area, any damaged cells also release these chemicals, these increase the blood supply, increase the temperature and make the blood vessels more permeable.
The problem is that we have evolved alongside our pathogens and many of these are very effective at bypassing this system, viruses create specific problems, so we have a second system that generally uses chemical methods to increase the efficiency of the innate system and develop ways of preventing damage by bacterial toxins or directly attacking the pathogens. Some of these chemicals are really part of the innate system and are automatically activated by the inflammatory signals, they increase the production of immune cells and if the phagocytes (eating cells?) are having problems containing an infection, activate some secondary defences, like attempting to isolate an area, walling it off. They also attract a sort of intermediary that comes to an area and takes samples of the pathogen which it takes to specialist centres in the body. There is in fact a number of systems that appear to have their effects somewhere between the innate and adaptive systems often referred to as the complement system.
The adaptive system is where the body attempts to create various chemical defences that are specific to the threat faced, it seems to be a sort of trial and error but on a massive scale once some compounds are tested as having an effect these are selectively built upon. Your body normally produces a range of chemicals which become more specific and effective over time and then creates specific cells to produce these chemicals. This process reflects the body learning to deal with a specific threat and requires the threat to be present to activate, this is what we call the adaptive immune system. In most cases once the body has developed a specific defence this will be remembered by special cells called memory cells, how long this memory lasts varies depending on the target organism.
It might be worth looking at all the different cells involved in immunity and it may be the case that in some specific diseases there is coding for some level of immunity, this seems to be the case with diseases that are specific to humans and have evolved alongside us, TB and Syphilis come to mind there is also evidence of an evolutionary adaptation to Malaria, which is also associated with sickle cell disease. There are differences in populations that have developed where the disease was not present, measles wiped out a significant proportion of native Americans when introduced by Europeans. However generally our adaptive immunity is based on genes that allow our immune system to test large numbers of antibodies against target antigens and then mass produce the most effective, so immunity is acquired.
There are lots of different cells involved in immunity and some processes that are still not well understood but there is loads of information available.
 
  • #12
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Super helpful, thank you Laroxe!
 

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