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