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
