Description

This video is Part 1 of Acquired Immunity – Antigens and MHC.

All information in my immunology videos is sourced from:

• Book: Immunology, Eighth Edition by David Male, Jonathan Brostoff, David Roth, and Ivan Roitt
• Additional research: PubMed
• University lecture materials

Difference Between Innate and Acquired Immunity:

• Innate Immunity:
  • Non-specific
  • No immunological memory
  • Attacks all agents equally
• Acquired Immunity:
  • Specific defense
  • Develops immunological memory

Two Types of Acquired Immunity:

• Active Acquired Immunity:
  • Developed through natural infection by microorganisms
  • Induced through vaccination
  • Outcome: Long-lasting immunity and antibody production
• Passive Acquired Immunity:
  • Acquired by receiving antibodies (e.g., injection of antibodies)
  • Transferred from mother to fetus through the placenta
  • Outcome: Temporary immunity, as antibodies are used up over time

Two Ways Adaptive Immunity Works:

• Humoral Immune Response:
  • Antimicrobial
  • Antiviral
  • Antitoxic
• Cellular Immune Response:
  • Attacks infected cells directly

Antigens:

• Microorganisms
• Red Blood Cells
• Oncogenic Cells (Cancer Cells)
• Virus-Infected Cells
• Toxins and Venoms
• Proteins (Most immunogenic)
• Polysaccharides
• Lipoproteins

Immunogenicity vs. Antigenicity:

• Immunogenicity: Ability to induce an immune response
• Antigenicity: Ability to bind to an antibody

Epitopes:

• Multivalent antigen with different epitopes
• Multivalent antigen with repeated epitopes
• Continuous/Linear Epitopes
• Discontinuous/Conformational Epitopes

Types of Antigens:

• Complete Antigen: Can induce an immune response
• Incomplete Antigen: Can bind to antibodies but does not trigger an immune response
• Thymus-Dependent Antigen: Requires T-helper cells for activation
• Thymus-Independent Antigen: Can activate B cells without T-helper cells

Major Histocompatibility Complex (MHC):

• Human Leukocyte Antigens (HLA): MHC in humans
• Gene Location: Chromosome 6 (short arm)

MHC Classification:

• MHC Class I:
  • Includes HLA-A, HLA-B, HLA-C
  • Present on all nucleated cells
  • Structure: Alpha chain (1, 2, 3) and Beta chain 2
• MHC Class II:
  • Includes HLA-DR, HLA-DQ, HLA-DP, HLA-DM
  • Present on professional antigen-presenting cells
  • Structure: Alpha chains (1, 2) and Beta chains (1, 2)
• MHC Class III:
  • Codes for complement proteins (C2, C4, Factor B) and cytokines

MHC Class I Function:

• Recognized by: Natural Killer (NK) cells and Cytotoxic T cells (CD8+ T cells)
• Normal Function: Displays self-peptides on MHC I for immune surveillance
• Infected Cells:
  • Present altered peptides on MHC I
  • Recognized and destroyed by Cytotoxic T cells using Granzyme B and Perforin
• NK Cells: Recognize and kill cells with decreased MHC I expression

MHC Class II Function:

• Antigen-Presenting Cells (APCs): Present foreign peptides to T-helper cells (CD4+ T cells)
• Leads to immune system activation

Group Antigens:

• Enterobacteriaceae (E. coli, S. typhi): Different bacterial species share common antigens
• Antigen Types:
  • O-Antigen: Lipopolysaccharides
  • Vi-Antigen: Virulence factors
  • K-Antigen: Capsular antigen
  • H-Antigen: Flagellar antigen

Transcript

Introduction
0:00
hello and welcome to another video in
0:02
this video I’m going to talk about
0:03
acquired immunity now the immune system
0:06
uses two main strategies to defeat any
0:08
type of unwanted invaders one of them is
0:10
called the innate and other ones called
0:12
acquired so the innate immune system is
0:14
mainly present since birth and therefore
0:16
sometimes also called the natural immune
0:19
system they acquired however forms
0:21
during a person’s lifetime and it’s
0:23
therefore sometimes also called adaptive
0:24
now please don’t get this wrong this
0:26
baby also has some type of acquired
0:28
immune system I just put it there to
0:29
show you that you’ve always had innate
0:32
immune system ever since you were born
0:33
all right so let’s put this to practice
0:36
imagine there are three different types
0:37
of bacterias right the Indian immune
0:40
system is what we call nonspecific
0:42
because it’s going to attack all of
0:43
these three bacterias equally and
0:46
doesn’t differentiate between them the
0:48
acquired however is going to attack
0:50
these three microorganisms individually
0:52
and then upon defeating the
0:54
microorganisms you gotta gain some type
0:56
of an immunological memory which usually
0:58
becomes enhanced upon repeated exposure
1:01
to the same antigen all right so let’s
How Does the Acquired Immune System Work?
1:04
see how the acquired immune system works
1:06
now there are two ways to divide
1:08
acquired immunity you can either have an
1:10
active immunity where your immune system
1:12
is doing all the work and we can have
1:14
passive that means you know when your
1:15
immune system is not really active and
1:17
I’ll show you why in a second so I’ll
1:20
start with active there are mainly two
1:22
ways to initiate the active immune
1:24
response one of them is naturally by
1:27
getting infected with any type of
1:28
microorganism the other type is
1:31
artificial by injecting the inactive
1:34
macro organisms or a pep types of it
1:37
either way the reason why it’s called
1:40
active is because T lymphocyte is going
1:43
to be involved and they’re gonna help
1:46
produce antibodies and as a result from
1:49
that the active immune system is going
1:51
to form an immunological memory passive
1:54
in other hand can also be classified as
1:57
either natural or artificial the
1:59
artificial way is by actually injecting
2:02
the antibodies into the patient usually
2:04
when a person it has been bitten by a
2:07
snake for example injecting antibodies
2:10
against their venom is a quick
2:12
in effective treatments the natural way
2:15
in that hand is by receiving antibodies
2:18
from the mother through the placenta so
2:21
when this bacteria comes into our body
2:23
these antibodies received will go
2:26
against that but as soon as we use them
2:28
up we’re gonna go back to have no
2:30
immunity or start activating the immune
2:33
system so that’s why it’s not active
2:35
that’s because the immune system doesn’t
2:37
really thrive to kill that the
2:39
microorganism because it already had the
2:42
antibodies against it it’s it got lazy
2:44
so now let’s go back to the active
2:46
immunity and see how the adaptive immune
2:48
response works now there are initially
2:50
two ways the adaptive immune response
2:52
works either it works with humoral
2:55
factors which which usually involves
2:56
antibodies coming from plasma cells when
2:59
a T helper cell too helps B cells
3:02
differentiate at the lymph node I’ll get
3:04
more into that later but the humoral
3:07
immune response can work against
3:08
bacteria it’s called anti antibacterial
3:10
it can work against viruses it’s called
3:13
antiviral and they also work against
3:15
toxin so we call that antitoxic the
3:19
second type of mechanism the adaptive
3:21
immune system works with is against
3:23
bacteria or viruses that they hide
3:25
inside our own cells and these we call
3:28
intracellular microorganisms this type
3:31
of mechanism is called cellular and
3:32
often involves T helper cell one helping
3:35
T’s at the toxic cell differentiate and
3:37
get rid of these infected cells now
3:40
before I go detailed into these two
3:43
topics I need to go through the
3:45
different type of antigens we can
3:47
recognize what MHC is and why it’s
3:50
important adaptive immune response and
3:53
the different antibodies we are we have
3:55
in our body the reason is that in my
3:58
opinion and experience you could say I
4:00
believe that if you really understand
4:03
these three points the antigens major
4:05
histocompatibility complex and
4:07
antibodies you will really understand
4:09
much more of the adaptive immune
4:11
response and it will become easier to
4:13
understand the mechanism as well that’s
4:17
why in this video I’ll cover antigen add
4:20
image C while antibodies will be a
4:23
different video all right so let’s start
Antigens
4:25
with antigens antigens are the things
4:28
that actually trigger your immune
4:30
response right which can bind to
4:33
antibodies and other receptors on your
4:35
cells so it has to be foreign or
4:38
something that’s not you right
4:40
so what could that be it could be
4:42
microorganisms like bacteria fungi
4:45
viruses or even protozoa
4:47
it can also be red blood cells for
4:49
example if you’re a Type A meaning that
4:52
you have a antigens on the surface of
4:53
your red blood cells and you give it to
4:55
a type B person that’s a person who have
4:58
B antigens on the surface of the
5:00
antigens but they have antibodies
5:02
against a and so that will cause an
5:05
immunological reaction because their
5:07
antibodies will bind to your red blood
5:10
cells if they receive a from you
5:12
oncogenic cells can also be a target for
5:15
your immune system meaning cancerous
5:18
cells mainly and there can be
5:20
differentiated by their MHC one complex
5:21
as the same goes to virus infected cells
5:24
toxins and Venom’s for and from animals
5:27
and plants can also trigger our immune
5:30
response even chemicals or complex
5:33
structures can be an antigen you know on
5:36
the surface of the bacteria proteins can
5:38
be an antigen proteins are actually the
5:40
most immunogenic meaning they easily
5:42
induce an antibody production
5:45
polysaccharides can be an antigen and
5:47
also lipoproteins for example and you
5:50
know what we find as dangerous might not
5:53
be dangerous for animals for example the
5:55
reason is our genetic build-up so genes
5:58
has a lot to do with what we perceive as
6:01
antigens now there are two words that
6:04
are important to remember when it comes
6:06
to antigens
6:08
the first one is immunogenicity meaning
6:11
the ability to cause an immune response
6:13
as I told you proteins are very
6:16
immunogenic because they their ability
6:18
to cause an immune response is very high
6:21
another word is antigenicity meaning the
6:25
ability of an antigen to bind to the
6:27
antibody now our body doesn’t just bind
6:31
to the antigen you know whatever random
6:33
place it grabs it catches it doesn’t
6:35
work like that
6:36
each antigen has what we call
6:38
the tops and epitopes are any part of an
6:42
antigen that is recognized by the immune
6:45
system so one antigen can have different
6:48
epitopes right let’s say this is an
6:50
antigen right it’s gonna have three
6:52
different epitopes on your surface where
6:54
three different antibodies can bind to
6:56
this is what we call multivalent
6:58
antigens with different epitopes on it
7:01
we can also have multivariate antigens
7:03
with repeated epitopes on it where the
7:05
same type of antibody binds to it and
7:08
that’s one type of classification
7:09
another type is what called continues or
7:12
liner epitopes where we have the
7:14
continuous amino acid sequence which
7:17
actually can be recognized by an
7:19
antibody and there are discontinuous or
7:23
conformational epitopes where as you see
7:25
here are formed from different or or
7:28
several amino acids in a sequence
7:31
antibodies combined or even cells that
7:33
has the right receptors to it can also
7:35
bind now we do have a small
7:39
classification system of antigens which
7:41
I’ve actually found pretty helpful first
7:44
we can classify them by their
7:46
immunogenicity if there can be a
7:48
complete antigen as you see right here
7:49
which can induce an immunological
7:52
reaction it has to be more than two
7:55
epitopes on it or it could be an
7:57
incomplete antigen which can bind to the
8:00
antibody but nothing really happens
8:03
because it’s too weak this antigen the
8:06
other type of classification is by the
8:08
immune response where it times
8:11
dependence which means when the antigen
8:14
presenting cell activates T lymphocytes
8:17
by presenting their antigen on the MHC
8:19
class 2 molecule as you see right here
8:22
the T cells later acts on B cells and
8:25
then becomes plasma cells the other type
8:28
is thymus independent antigens where B
8:32
lymphocytes are practically activated
8:34
without the help of T lymphocytes so you
8:37
know the B cell right it has already
8:39
antibodies on the surface either rgm or
8:42
itd you’ll see why when it later on
8:44
talked about the development of the B
8:46
lymphocytes in future videos but some
8:48
repeated carbohydrate engine for example
8:51
activate the B lymphocyte without the
8:54
help of T cells although if T
8:57
lymphocytes is not included this B
8:59
lymphocyte can only differentiate into a
9:01
mu type at plasma cells which secretes
9:04
only IgM and no immunological memory
9:06
happens here since T cells were never
9:09
involved all right I’ll talk more about
9:10
this later but just to sum up if it’s a
9:14
small antigen there is a decreased
9:16
immunogenicity meaning a small chance of
9:18
inducing an immune response in contrast
9:22
that big antigen also the more complex
9:24
the antigen is higher image density
9:27
right also if the antigen has many
9:30
similarities to our own antigens it will
9:34
have decreased immunogenicity in
9:36
contrast if it’s completely different so
9:39
that was all I had for antigens now
MHC
9:42
let’s look at how the major
9:44
histocompatibility complex or MHC works
9:47
you know the antigen presenting cells
9:50
and the T lymphocytes they use this amid
9:52
C molecules to differentiate one another
9:54
and communicate now MHC is found in all
9:58
animals right and it’s very different
10:01
from one species to another that’s why
10:03
in humans we say human leukocyte
10:06
antigens but in humans the MHC region
10:09
occurs in chromosome six there’s gonna
10:11
be a lot of genes right the MHC genes is
10:14
found in a short arm of chromosome six
10:17
right here approximately around 200
10:19
genes gonna call for a HLA molecule now
10:22
in the humans we get three classes of
10:25
major histocompatibility complexes in
10:28
class one the region or gene loci called
10:32
HLA a it should I be an HLA C make up
10:37
the class one major histocompatibility
10:38
complex
10:39
we got three from father and three from
10:42
mother so you can already get a hinge
10:44
that any variations of these six gene
10:47
loci is what makes my organs different
10:50
from your organs and why do I say organs
10:53
that’s because MHC class 1 is present
10:56
and all nucleated cells in your body and
10:59
that’s why it’s much easier to receive
11:01
red blood cells they don’t have any
11:03
nucleus
11:04
meaning no MHC class
11:05
one now the MHC class 1 looks like this
11:07
it has an alpha chain composed of three
11:10
domains and for this you can just
11:12
imagine thread forming three loops
11:15
you know alpha 1 alpha 2 up there and
11:17
they’re gonna be the binding site for
11:19
MHC 1 that’s where the peptide is going
11:21
to be and the last loop alpha 3 is where
11:24
the MHC is bound to the membranes kind
11:27
of anchored to the membrane b2 however
11:29
it’s encoded by chromosome 15 if I’m not
11:32
mistaken it’s called B 2 macroglobulin
11:34
there’s gonna be constant meaning it
11:36
doesn’t really change class 2 however is
11:39
encoded by HL a dr. HLA DQ it should I
11:43
DP and HL a DM these four gene loci
11:47
forms MHC 2 MHC class 2 is mainly only
11:51
gonna be present on professional antigen
11:52
presenting cells and these are
11:54
macrophages dendritic cells and B
11:56
lymphocytes it can conditionally be
12:01
present on all cell types if it gets
12:03
stimulated by interferon gamma but don’t
12:05
worry about that it’s just as some
12:06
studies I found I can put the link in
12:08
the description if you want to but
12:10
please remember this MHC 1 all nucleated
12:12
cells MHC 2 only antigen presenting
12:15
cells professional antigen presenting
12:17
cells these are macrophages b-cells and
12:19
specifically dendritic cells all right
12:22
it has an alpha chains with two domains
12:25
and better chains with two domains Alpha
12:28
and the beta one’s gonna be the binding
12:30
site for the peptide and alpha 2 and
12:33
beta 2 is both can be anchored to the
12:35
cell membrane class 3 however it has a
12:38
quite different role than class 1 class
12:41
2 it’s just the genes that cause for it
12:43
are among here that’s why we call it
12:45
class 3 it codes for proteins of the
12:49
complement system and also some
12:51
cytokines like Tim or necrotic factor
12:53
alpha but mainly complement proteins and
12:56
that’s why we sometimes call it
12:58
complement MHC all right so even though
13:01
most of the complement proteins are made
13:04
in the liver some can actually also be
13:06
made in the macrophages like C 2 C 4 and
13:10
factor B so now let’s look at how class
13:14
1 and class 2 works I will start with
13:17
class 1 MHC
13:19
MHC class 1 as I said is present in all
13:21
cells with nucleus right now what does
13:24
it do
13:25
why do I have it in all our nucleated
13:26
cells you know the natural killer cells
13:29
and the T cytotoxic cells these two are
13:31
able to recognize the emerge C class 1
13:33
molecule T cytotoxic cells can actually
13:36
recognize the peptide on the surface by
13:38
using his t-cell receptor and the cd8
13:41
natural killer cells it cannot recognize
13:45
the peptide but they can recognize the
13:46
amount of MHC class 1 and if this cells
13:49
is infected is gonna express less of the
13:52
MHC class 1 and it’s gonna kill it
13:54
so these two cells are able to recognize
13:56
6 cells from healthy cells and what are
14:00
the sick cells those are infected cells
14:03
those are cancer cells so and even
14:05
transplanted cells tuck cells that are
14:07
not initially yours
14:08
so normally all nucleated cells present
14:12
their their own peptide rights I
14:14
remember I said that knew that natural
14:16
killer cells cannot really recognize his
14:18
pitaya can only recognize the amount of
14:20
MHC class 1 molecule it has so T
14:22
cytotoxic cells binds its TCR receptor
14:25
with the MHC class 1 and then it uses
14:28
cd8 duck to the MHC class 1 and then it
14:32
says yep I recognize it cell and then
14:34
goes away now let’s say this cell gets
14:37
infected by any type of intracellular
14:39
microorganism it will then want to
14:42
present its foreign peptide on the
14:44
surface of MHC class 1 now what happens
14:47
T cytotoxic cell binds it says no this
14:50
is not our own cell and what it does it
14:52
do it releases preference which
14:55
literally perforates the membrane of the
14:57
cell and then grants on B which
15:00
fragments the nucleic acid so so that’s
15:03
why it’s called T cytotoxic cells
15:05
because it works by killing infected
15:08
cells that presents the peptides of
15:11
intracellular macro coordinates right
15:15
alternatively you know as I said earlier
15:17
you know natural killer cells once it
15:20
binds to the MHC class 1 it works as an
15:23
inhibitory response for the cell but if
15:26
this cell is infected it expresses less
15:29
MHC class 1 molecules which means less
15:32
negative signals
15:33
sent to the to the national killer cell
15:35
which kind of stimulates the natural
15:37
killer cells to actually kill this
15:38
infected cell don’t worry about this
15:41
mechanism right now I’ll talk more about
15:43
this later as I said we want to talk
15:44
about cytotoxic immunity I just wanted
15:46
to introduce these so that you kind of
15:48
see the connection now MHC class 2
15:51
molecules you know an antigen presenting
15:53
cell this is the dendritic cell right
15:55
here
15:56
imagine there’s a bacteria out here this
15:58
cell is going to phagocytosis it by
16:00
reaching out the side the paths and then
16:03
forming a phagosome and then which is
16:05
gonna fuse it with a lysosome the hiss
16:08
forming a will lysosome it’s gonna
16:11
fragment it and then form small peptides
16:14
and then it’s gonna present these small
16:16
peptides on an image see class 2
16:19
molecule and then after that is going to
16:22
travel to a lymph nodes and this is
16:24
already there or other secondary
16:26
lymphoid organs and present it to a
16:28
naive T helper cell with with its cd4 as
16:31
support and it’s gonna activate it and
16:33
help it differentiate into either T
16:35
helper cell one which activates
16:38
macrophages and stuff or T helper cell
16:40
two which helps B cells differentiate so
16:44
that was MHC class 2 now just a quick
16:47
little thing about something we call
16:49
group antigens you know the family enter
16:51
bacteria E coli and Salmonella T V both
16:54
belong to that family and both express
16:57
their own peptides but sometimes they
17:00
can express the same type of antigen and
17:02
those are what we call group antigens
17:04
and these are gram-negative bacteria
17:07
right and what they can have in common
17:09
is what we call all antigen or Lipa
17:11
polysaccharides it could be different
17:13
virulence factors they could have in
17:14
common
17:15
those are v antigens it could be a
17:17
capsule even where I’m negative bacteria
17:19
can have capsules also which workers in
17:21
group antigens these are called k
17:23
antigens or even flood gila those are
17:25
called a each antigens do you think of
17:27
hair hair antigens so that was
17:31
everything I had for now I hope this was
17:33
a little bit helpful my next video is
17:34
going to be about antibodies