.

No Date TOPIC TUTOR

1 17.9 The Immune System Prof. Raj

Immunity = State of protection from infectious disease

IMMUNITY

INNATE IMMUNITY ACQUIRED IMMUNITY

Innate Immunity = Non-specific Immunity

Acquired Immunity = Specific Immunity

= Adaptive Immunity
 ACQUIRED IMMUNITY
Characteristic Features

1. Specificity – Ability to distinguish pathogens

2. Diversity – Recognize millions of molecules

3. Memory – Increased & faster second response

4. Self/Non-self Discrimination – Respond to non-self

.No Date TOPIC TUTOR

1 17.9 The Immune System Prof. Raj

2 17.9 Organs and Cells of the Immune System Dr. Raja’a

3 19.9 The Major Histocompatibility Complex Prof. Raj

 .Immune system responds to bacteria, viruses, toxins

But not to thewhole! bacterium, virus or toxin

”Immune system responds to ”ANTIGENS

Antigens = Molecules that bind to an antibody or to a T

cell receptor

Immunogens = Molecules that induce immune responses

But the immune system does not respond to the whole
antigen……just to small segments or regions of Ag

Epitope = Small immunogenic segment or region in an Ag

So, the immune system responds toepitopes on antigens

of bacteria, viruses, toxins etc

Exogenous Ag = extracellular bacteria, proteins etc

Endogenous Ag = intracellular bacteria, viruses etc

 Toxins, Bacteria, Viruses

Immune System

Immune Responses

Antibodies T cells
 Antigens areINTERNALIZED by cells

Antigens arePROCESSED within cells

Epitopes arePRESENTED on cells byMHC molecules

?What are MHC molecules

MHC = Major Histocompatibility Complex

HLA = Human Leukocyte Antigens
 )Major Histocompatibility Complex )MHC – HLA
Histocompatibility = Ability to accept grafts between individuals

MHC = Region of multiple loci that are

responsible for rejection of grafts and )1(
function in signalling between lymphocytes and cells )2(
. that present antigens

MHC )HLA( molecules recognize antigens, so MHC molecules

.)are antigen-recognition molecules )like antibody molecules

HLA moleculesPRESENT. antigens to T cells

 Large number of histocompatibility GENES in MHC

Complex ComplexMajor Histocompatibility

Class II III I
Region DP DQ DR C TNF B C A
Molecule -DP-HLA HLA-DQ HLA-DR C TNF HLA-B HLA-C HLA-A
 Large number of histocompatibility GENES in MHC

Complex ComplexMajor Histocompatibility

Class II III I
Region DP DQ DR C TNF B C A
Molecule -DP-HLA HLA-DQ HLA-DR C TNF HLA-B HLA-C HLA-A
 Large number of histocompatibility GENES in MHC

Complex ComplexMajor Histocompatibility

Class II III I
Region DP DQ DR B C A
Molecule -DP-HLA HLA-DQ HLA-DR C` TNF HLA-B HLA-C HLA-A

Where? are MHC molecules expressed

Class 1 = On almost all nucleated cells

)Class 2 = On Antigen Presenting Cells )APC

Macrophages, B cells, Dendritic Cells
 Structure of Class I MHC Molecules

HLA-A, B, C molecules have a heavy chain )α (

linked to a smallerβ2-microglobulin molecule
 HLA Class 1

α1

α2

β 2m
α3

Plasma membrane

Cytoplasm
 α chain has three HLA Class 1
“domains”α 1,α 2 andα3
α1

α2

β 2m
α3

Plasma membrane

Cytoplasm
 Theα chain is highly polymorphic)exists in
)different forms in population = different alleles

Theα 1 andα 2 domains are most polymorphic,

whileα 3 andβ2m are not polymorphic
HLA Class 1 α1

α2

β 2m
α3

Plasma membrane

Cytoplasm
 Structure of Class II MHC Molecules

HLA-DP, DQ and DR molecules are made

up of one heavy chain )α ( and one light
chain )β( each

Theα chain has two ”domains”α 1 andα

2
Theβ chain has two domainsβ 1 andβ2
 HLA Class 2

α1 β1

Theα chain has two Theα chain has two

“domains”α 1 andα2 “domains”α 1 andα2

β2
α2

Plasma membrane

Cytoplasm
Theα 1 andβ 1 domains are highlypolymorphic
Theα 2 andβ2 domains are not polymorphic
 HLA Class 2

α1 β1

β2
α2

Plasma membrane

Cytoplasm
 α1 α2

α3

β 2m
 MHC molecules are highly polymorphic
i.e., exist as many alleles in the population
i.e., are different in different individuals
 MHC molecules are highly polymorphic

i.e., many HLA alleles in the population

more than 100 types of -A, -B, -C
! as many as 400 types of HLA-B

i.e., HLA are different in different individuals

! and that is why tissue grafts are rejected..…

But, what is the FUNCTION?of the MHC

 FUNCTIONS of MHC )HLA( MOLECULES

MHC molecules PRESENTantigens to cells

Class I HLA molecules presentepitopes tocytotoxic T cells

Class II HLA molecules present epitopes to helper T cells

MHC = Cell-surface molecules that PRESENT antigen to T cells

MHC molecules are essential for immune recognition

?How many types of HLA molecules do you have

Three Class I molecules – HLA-A, HLA-B and HLA-C

Three Class II molecules – HLA-DP, HLA-DQ, HLA-DR

?6

But, we get one set of HLA genes from our mothers and
another set from our fathers
These two sets are frequently different

So, we may have as many as 12types of HLA molecules

Association of HLA with Disease
Association of HLA with Disease
Association of HLA with Disease
Association of HLA with Disease
 T cell

MHC

Epitope

TCR

APC
 Viral epitope
Class I
Tc Cell death
Kill
Target cell

B Antibodies
T help
Class II epitope

Th APC
Stimulation

Cytokines

Thus, MHC molecules”present” antigens toofcells

Killing
Act as”codes” to guide cells properly intracellular bugs
Macrophage
 Viral epitope
Class I
Tc Cell death
Kill
Target cell

B Antibodies
T help
Class II epitope

Th Stimulation APC
Cytokines

Thus, MHC molecules”present” antigens toofcells

Killing
Act as”codes” to guide cells properly intracellular bugs
Macrophage
 CD molecules

 Cluster of differentiation )CD( molecules

 Cell-surface molecules that indicate cell function
 CDs are ”markers” for cells
 CD3 : Present on all T cells
 CD4 : Present only on T helper cells
CD8 : Present only on T cytotoxic cells
Th Tc

Epitope Epitope
 Proliferation
Help

Antigen

Antibodies
 Proliferation
Help

Antigen

Antibodies
 Proliferation
Help

Antigen

Antibodies
.No Date TOPIC TUTOR

1 17.9 The Immune System Prof. Raj

2 17.9 Organs and Cells of the Immune System Dr. Raja’a

3 19.9 The Major Histocompatibility Complex Prof. Raj

4 19.9 Antigens and Antigen Presentation Prof. Raj