First Aid for the USMLE Step 1, IMMUNOLOGY + 01 = Overview of the immune system

hello again this is Peter Gayed with the
USMLE RX Express team and today we’re going to start with
immunology specifically will be talking about
lymphocytes which are the T&B cells or the adaptive cells up the
immune system the adaptive system is what makes
vertebrate species humans included unique from invertebrate
species while vertebrate and invertebrate
species both have an innate system only the job vertebrates have an
adaptive system and possible we’ll be talking about will
be the adaptive system in the clinic it’s usually deficiencies
are problems in the adaptive system there were concerned with but this is not to say that the innate
immune system is an important quite the contrary deficiencies in the innate immune system
are so rare and so infrequently seen because without
an innate immune system a species would be unable to survive and
as you might expect because the innate immune system shared
by vertebrates and invertebrates it is actually the
more ancient up the two systems meaning that it developed first in the
evolution of species now of course is not much evolution on
the US Emily step 1: but understanding this concept will help
you keep the differences between the inmate system and the adaptive system straight okay so what are the innate immune cells but these are the innate immune cells
include new turf fields macrophages dendritic cells NK cells and also a set of proteins known as
complement proteins which are actually produced by the liver the adaptive system on the other hand
consists of B cells and T cells and some other derivatives we can also
include here antibodies like complement proteins antibodies also sir it freely in the blood and throughout
the tissues of the body but of course not produced by the liver by B cells okay now here’s the major major
distinction between adaptive and innate immune cells and it def cell makes a receptor and the case for
the b-cell it’s called the b-cell receptor course and in the case for the T cells
called the T cell receptor in these receptors I mean I B cells and
T cells they specifically recognize one part a pathogen that is they recognize very
specific antigen or at the top as a drug here you see that the diesel
is showing one piece %uh receptor T-cell showing one piece %uh receptor
but of course there are many many copies the receptor all over the surface of the
t-cell and their many copies the b-cell
receptor all over the b-cell but the point is that each cell produces a single unique
receptor which recognizes a single unique at the
top the innate cells on the other hand have
receptors over their surface which recognize brought in general
patterns a variety of pathogens so for example the new to fill the
macrophage the dendritic cell and even the NK cell has receptors over
its surface we can recognize patterns which are common to all gram-negative
bacteria have receptors which recognize patterns
that are common to all gram-positive bacteria they have other receptors that can
recognize patterns in are in a virus is patterns that are common in DNA viruses
and even patterns that are common among parasites so in a way the innate
immune system provides broad general protection against pathogens
that is quote unquote nonspecific we mean by nonspecific is that when any of the receptors that I
just mentioned the ones I recognize gram-negative bacteria gram-positive
bacteria the different kinds of viruses parasites when any of those receptors are
triggered the innate cells will launch a general attack typically by releasing enzymes which
kill pathogens but also do damage to host tissues when you get a cut your skin that gets
inflamed when you break out in acting because you’re stressing out over the
boards those things hurt because the eight
cells are releasing enzymes which are also damaging your own tissues in causing pain dnt cells on the other hand only
recognize very specific parts of pathogens and so when they launch their
attack it is very very specific they themselves do not damage host
tissue instead they’re specifically targeted onto the pathogen and this is really the essential and
functional difference between these two systems now perhaps the most remarkable thing
about the adaptive immune system is that it can recognize almost any
pathogen that it comes into contact with not only can the adaptive system
recognize almost any pathogen their B cells and T cells that will
recognize different parts up that pathogen via their receptors the question is how is this possible
because they’re essentially more pathogens in more parts of pathogens that are
recognized by BNP self then there is space in the genome to
encode for all those different receptors even long ago immunologists realize that
it was highly unlikely that the human genome already contain
all the receptors they could recognize all the potential
pathogens to one human can come into contact with not too long ago scientists actually
found out that the genes which encode for the b-cell receptor in the T cell
receptor actually look a little bit something like this it’s not at all a single gene but many
gene segments which encode for different part of the
receptor for example Porter the b-cell receptor
which ex he recognizes antigen the so-called variable region here is
encoded by gene that actually looks like this b-cell receptor heavy chain abbreviated H which in our familiar and
body structures actually the larger polypeptide which have
pointed out here this for the sake of completeness is called the late change and of course the antibody molecule
symmetrical meaning that the two heavy chains that you see here the same and the tool a chance that you see in
the same but in any case two-parter the b-cell receptor that
binds to antigen is created when one of these segments
here which we called TV segments is combined with one other segments here
which we call the D segments and also combine with many segments here
which we call the che segments and actually in the B cell receptor
heavy chain gene they’re actually not one not to not three but actually sixty five
different the segments they could choose from and of course have abbreviated the
intervening be segments with the ellipsis here also in the D second to be some receptor
can choose from not one not to not three or four but actually twenty-seven different the
segments and finally there are total love 6 J segments to be some receptor can
choose from you can see that as the B cell receptors being formed
there are many many combinations all these gene segments in each combination is going to
recognize a different part of the pathogen this amazing diversity the result in a
process called VDJ recombination and there are very
specific enzymes which allowed the cell to pick on a TV
segments wanna d segment when a BJ segments and put it all
together to create a receptor that recognizes a very unique and very
specific part of the pathogen again for the sake of completeness it’s
worthwhile knowing that the late chain up to be so receptor operates by the same mechanism it also
has many different gene segments from which
to pick and of course the two chains which make up the T cell receptor you can see here they’re known as the T
cell receptor beta chain and the T cell receptor after chain but they also have the same
number options available to them as well the numbers are important but just as an
example the T cell receptor beta chain has 52 different the segments has two
different D segments and his thirteen different J segments and again these can be combined in
different ways to create a unique receptor in fact as an infant ages here she is
producing brand new B cells in brand new T cells that are combining their gene segments
in different ways so that by the time the child reaches adulthood many many B cells are formed in many
many T cells are formed in the each recognize something
different in eight cells on the other hand while
important are not as fancy they contain genes in the more
conventional way that we think it jeans for example they contain one gene that produces a scepter which recognizes double-stranded
RNAs which does not animals but rather occurs in viruses the
also contain a gene encodes for receptor which recognizes methylated DNA which again is not seen
in animals or plants but is instead more common to bacteria and it says also have receptors for for
John LPS have to look like it all very common components a bacterial species all the
genes for these receptors like most other genes that were familiar
with did not at all shuffle and change in the way that the b-cell
receptor gene in the T cell receptor genes shuffling change these jeans are fixed
and do not change during the lifetime of the shell where
the individual and so we call these genes germ-line encoded meaning that these
genes were present in their full form as soon as the zygote was formed where is the ultimate product at BTG a
combination in abuse of for example will be a gene that looks something like
this: perhaps it’ll have the segment 35 NJ segment number two some other
arbitrary combination this mature gene well not a Justin any other celeb the body because
it the randomness that included in this process have gene shuffling in gene changing
this diesel receptor will even be different from the
receptors formed by other B cells the other main difference between innate
and adaptive immune cells is where they are found in the body in eight other sensually found all over
the body they found in many prefer all tissues
and just beneath the mucosa in the GI and respiratory tracts in the
reproductive tracts they’re essentially in every location of
the body that a pathogen might try to invade naive B&T cells that is being T-cells which have not yet met the pathogen for
which there specific are not found in the peripheral tissues
they circulate in the blood and enter and exit lymph nodes that are
found throughout the body Nash it’s the innate immune cells which
respond first to an invading pathogen they’re also the cells that signal to
the B&T cells that infection is going on essentially when the time is right they
recruit B&T cells to come to the peripheral tissues where
an infection is ongoing thus the innate response is fast and as
you mentioned before nonspecific meaning that any an 8-cell
can recognize and begin attacking a very broad range of
pathogens although this attack will also damage
host tissues the other thing to realize again another
important difference between the innate and adaptive systems is that an eight cells produce such a
vigorous response against the pathogen that the even kill
themself it’s almost as if they’re on a kamikaze
mission in scientific terms the innate immune cells have not evolved
to be long-lived have relatively short half-lives and I B&T cells on the other hand are able to
produce a memory response what this means is that after they’ve
recognized the pathogen to which their specific they help in the clearance so that
pathogen but then even when that pathogen is gone the B&T cells will persist in very small
numbers and become poised to respond again and
more quickly if the host re encounters the same or
similar pathogen because innate immune cells die so
quickly they don’t have any memory properties I know there was quite a bit but in the
slide we really talked about the fundamental and important differences between innate and adaptive immune cells just one thing ever have to point out in
addition to being able to recognize viruses three kinds of bacteria and parasites in
eight cells also have receptors which recognize patterns for common to fund a thus you
can see that the innate immune system really can recognize and respond to all the major
pathogens that we know about

11 comments

  1. Hey man, found your videos really helpful. They were awesome. I was devastated when I found that you didn't have a series on hematology. I was wondering if you had any recommendations for something similar?

  2. Thanks Dr. Gayed! The videos are super helpful. I just purchased a subscription to the UMSLERx Express video set. The videos are helpful but I find that I like your lecture style a little more. That is, I really like the way you lecture straight from the book and add in relevant info/simple hand-drawn diagrams as you go along. It may seem trite but even the fact that your videos show the actual physical pages that you're discussing makes a big difference. There's less translating of information that I need to do on my end in order to get the notes in my book. Any chance your friends at First Aid might make a separate video series that sticks more directly with the book? Thanks for your work!

  3. Thanks a lot. Found it really helpful. The happiness when you just understand something new, and hence can connect the dots in the head is amazing..thanks again.

  4. from todays point of view do you think the videos are still up to date? i got an upcoming immunology exam at my university and thus would like to use these videos for my studies in case you approve of the content 🙂

    greez hudi

  5. Hey Pete, your videos and teaching mode not among the best, but among the VERY BEST in the industry! Any site or portal for downloading of them…even if for a fee?

    Thanks for all the handwork and time in putting them together

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