Course Lecturer :

Dr. Abdi Kadir Jibril Adem

Family Medicine MD

Amoud University
College of Health Science
School of Medicine & Surgery
1st Medical Students .

Group Presentation
Course : Human Genetics
Topic : The Immune System (Immunogentics)

Group Three
 The genetics of immune system
(immunogenetics). 1. Introduction to Immunogenetics
Key Points of this Chapter
2. Immunity
3. Clonal Selection Theory of antibody formation
4. Immunological Memory
5. Antigen and Antibody
6. Cells of Immune system and organs of immune system.
7. Immune response
8. The organization of immunognolobuin Genes
9. Major Histocompatibility Gene Complex
10.HLA & transplantation , HLA and Disease association and Clinical Application of
HLA
11. Immunogenecity and immunization
12.Blood Genetics
13.Allelic exclusion and class switching
14.ABO Blood grouping system
15.The Rh system
16.Immunological Dis-orders
17.Auto immune dis – orders
18.Immunodeficiency
 Terms of the immunity you should know
 Immunology: Study of the components and function of the immune system
 Immune system : is body defense system.
 Immune response : is the action of lymphocytes to response entry antigen in the body.
 Pathogen : a bacterium, virus, or other microorganism that can cause disease.
 Antibody : is the protein made by plasma cells derived B lymphocytes, secreted in
response to an antigen
 Antigen : is substance that is foreign to the body and stimulate immune response.

1. Introduction to
immunogentics
the study of the genetics of the immune system is known as
immunogenetics.
In other hand , immunogentics is the branch of medical genetics
that explores the relationship between the immune system and
genetics .
 2. What is Immunity ?
Is the Process by which our bodies protect themselves against:
Pathogens
Cancer
Foreign Objects
Infectious Agents

Cell surfaces are covered with messages that tell the body what is “self” and what
is “foreign”
The main function of immunity are :
 Immune defense
 Immune homeostatis
3. Clonal selection theory of antibody formation
 Clonal selection theory is a scientific theory in immunology that
explains the functions of cells (lymphocytes) of the immune system
in response to specific antigens invading the body.
We know that lymphocytes have specific receptor molecules on their
membranes.
Each kind of cell has uniquely shaped receptors.
 In short the theory is an explanation of the mechanism for the
generation of diversity of antibody specificity
 4. Immunoligical Memory
When a specific antigen enter in our body for the first time, our immune
response may be too slow to prevent sickness from developing
the initial immune response has resulted in the production of a memory cells
an specially stable line of B and T lymphocytes that persist for decades
In the case many antigens our bodies retain a memory of the initial immune
response long after the antigen has disappeared.
 We refer to this persisting response as sensitization to the specific antigen
 Immunological memory explained the long term or even life-long immunity
conferred by many illnesses such as chickenpox .
 5. Antigens
 Any “foreign” signal that induces an
immune response
 Antigen has an epitope region that
binds to the paratope of antibody.
 Usually refers to the molecules on
the cell surface that are recognized
by immune system as foreign
 Usually made of:
Carbohydrates
Proteins
5.1. Antibody
Antibodies are glycoproteins that are
present on the surface of the B-cell.
Also known as immunoglobulin.
Basic antibody structure has 4
polypeptide chains
2 identical light chains
2 identical heavy chains
Regions of heavy and light chains
Variable
Constant
6. Cells of immune system
 Cells of the immune system originate in the bone Phagocytes are divided in to two types which are
marrow. a) Neutrophils b) Macrophages
 There are two types of immune cells
Neutrophils .
a) Phagocytes b)Lymphocytes Neutrophils are kind of phagocytes which travel through out
the body often leaving the blood by squeezing the walls of
a) Phagocytes capillaries to tissue.
they have short life, after killing pathogen .
 Phagocytes are produced through out of the life by
bone marrow. Macrophages
 They are stored there before being distributed Macrophages are kind of phagocytes which are lager than the
around the body in the blood. neutrophils .
 They are “scavengers” removing any dead cells . They found in organs such as ; lungs , liver , spleen.
They are long lived cells .
They kill large molecules that they recognize as foreign to the
body.
They are also responsible to clean dead neutrophils
B) Lymphocytes
 Lymphocyte are smaller than the phagocytes
Lymphocytes

B – Lymphocytes T – Lymphocytes
“ B – cells “ “ T - cells

 B – cells are made and mature in bone marrow and mature in the red bone
marrow.
 They are spread through out the body concentrating in lymph nodes and spleen
 B – cells are divided in to two : Plasma cells and Memory cells.
Plasma cells produce anti – body molecules very quickly and the secreted into the
blood.
These cells are not live long and after several weeks their number decrease.
Memory cells are circulate in the body for long time.
They responsible for retaining the shape of the antigen that attack the body once
to not come back again.
They respond if some antigen re introduced a few weeks or months after the first
infectious.
These cells divide rapidly and become plasma cells.
When an antigen invade the first time the body the primary respond is low at
this stage because there are every few B cells that are specific to an antigen .
But the second invasion the secondary respond is high because there are no
memory cells which quickly divide and differentiate into plasma cells and
produce many anti body.
T – lymphocytes (t-cells).
 They are produced in bone marrow but mature in the thymus .
 The thymus is a gland that lies in the chest jut beneath the sternum
 The T cells are divided in to four types.
1CYTOTOXIC T – CELLS : Attacks and virus infected cells
2. HELPER T – CELLS : release chemicals called CYTOKINS that activate ;
B cells , cytotoxic t cells and macrophages .
3. SUPPRESSOR T - CELLS : slow down or inhibit the activities of B & T cells
on the antigen has been destroyed.
4. MEMORY CELLS : Responsible for secondary respond.
Characteristics of B cells and T cells .
B – cells T – cells

1. Produce and mature in bone marrow.
2. B cells produce anti body
3. Reside in spleen and lymph nodes
circulate in blood and lymph
4. Directly recognize antigen and
undergo clonal selection
1. Produce in bone marrow and mature in
thymus
2. T – cells don’t produce antibodies ,
3. their T – h cells stimulates B cells to
differentiate into Plasma and memory .
Organs of the immune system
 These Organs of the immunity can
be:
Primary organs; include
the thymus and bone marrow.
Secondary Organs; include
spleen, tonsils, lymph vessels,
lymph nodes, adenoids, skin,
and liver.
Types of the immunity.
 Immunity can be divided in to two types
Innate immunity: Born in it Composition of innate immunity
eg : your normal Immune system,  Barriers
Adaptive immunity: acquired and developed Physical barrier: include skin and
mucosa
eg : Immunization.
Chemical barrier: include
1. Innate immunity antimicrobial secretion of skin and
 It is present at birth; This is our first line of defense. mucosa eg: HCl in your stomach.
 Characteristics of innate immunity are Biotic barrier: include normal
Exist naturally flora existing on the surface of the
Non-specific skin.
No-immune memory Anatomic barrier:
hereditable
 Blood-brain barrier
 Blood-placenta barrier
 Blood-thymus barrier
 Adaptive immune system

Cell-mediated immune
Humoral immune system
system

B-cells T-cells

Work together to destroy antigen

2. Adaptive immunity
the adaptive immunity includes
It is not present at birth but becomes part of
both:
our immune system as the lymphoid system
develops.  Humoral immunity, which
Three basic characteristics: combats extracellular infections
1. Diverse:
 Can handle many different types of  Cell-mediated immunity, which
pathogens fights intracellular infections.
2. Specific:
 Distinguishes with great specificity  Humoral immunity also known as
between harmful and non-harmful antigens B-lymphocytes , Cell-mediated
3. Remembers: immunity also known as cellular
 Builds and keeps antibodies for a second
immune system.
attack
 7. Immune Response
Primary response
1. This occurs as a result of primary
contact with an antigen.
2. Responding cell is native B-cell
and T-cell.
3. Lag phase is often longer (4-7
days), sometimes as long as weeks
or months
4. It takes longer time to establish
immunity
5. First antibody produced is mainly
IgM. Although small amount of
IgG are also produced.
 Secondary response
1. This occurs as a result of second
and subsequent exposure of the
same antigen
2. Responding cell is memory cell.
3. Lag phase is shorter (1-4 days) due
to the presence of memory cell
4. Takes shorter time to establish
immunity.
5. Mainly IgG antibody is produced.
Although sometimes small amount
of IgM are produced. Other
immunoglobulins such as IgA and
in the case of allergy IgE a
 7. Process of Immune response
The immune system distinguishes two groups of foreign substances.
One group consists of antigens that are freely circulating in the body.
These include molecules, viruses, and foreign cells.
A second group consists of self cells that display aberrant MHC proteins.
Aberrant MHC proteins can originate from antigens that have been engulfed
and broken down (exogenous antigens) or from virus‐infected and tumor
cells that are actively synthesizing foreign proteins (endogenous antigens).
Depending on the kind of foreign invasion, two different immune responses
occur:
 cell mediated response and Humoral immune.
Humoral respond
The humoral response or antibody‐
mediated response) involves B cells that
recognize antigens or pathogens that are
circulating in the lymph or blood
Antigens bind to B cells Interleukins or
helper T cells costimulate B cell
 B cells proliferate and produce plasma
cells
 B cells produce memory cells. Memory
cells provide future immunity
cell-mediated respond
The cell‐mediated response involves
mostly T cells and responds to any
cell that displays aberrant MHC
markers.
 including cells invaded by pathogens,
tumor cells, or transplanted cells.
 Self cells or APCs displaying foreign
antigens bind to T cells.
Interleukins (secreted by APCs or
helper T cells) costimulate activation
of T cells.
levels of protection
Two levels of protection:
1. Innate (nonspecific) immunity
 Phagocytosis, Antimicrobial proteins, fever
 Skin, mucous membranes, fever and inflammation

2. Adaptive (specific) immunity

 B cells and T cells
 Antibodies, Cytokines, etc
8. Immunoglobulins
are glycoprotein molecules produced by plasma cells (white
blood cells). They act as a critical part of the immune
response by specifically recognizing and binding to particular
antigens, such as bacteria or viruses and aiding in their
destruction.
The role of the immunoglobulins are
They prevent pathogens from entering or damaging cells.
they stimulate removal of pathogens by macrophages and other cells
by coating the pathogen.
Neutralize toxins
 Types of immunoglobulin's
immunoglobulin's are classified in to four types

A) immunoglobulin G
B) immunoglobulin M
C) immunoglobulin A
D) immunoglobulin E
 9. Major histocompatibility gene complex
Transplantation of organs and tissue has been practiced for centuries but only in recent
years has there been any notable success.
Many of transplantation failure were ascribed to physiological problems or event to
super natural force.
Early in the century how ever it was discovered that rejection of transplanted tissue and
failed blood transfusion were the result of immune reaction.
A person who has suffered a severe burn will often have skin grafted to the burn area
from another part of body. Invariably that graft will succeed.
How ever if their graft come from another person (not an identical twin) then the graft
will not succeed the body will reject it.
Transplant rejection occurs because the donor tissue carries cell surface markers or
antigens that are clearly non self and these antigen triggers an immune response from the
host.
 10. HLA and Trnasplantation
 When one person denotes an organ such as kidney or a heart to another person, the success of transplant
depends primarily on how similar the HLA systems are in the two individuals.
 The greater the similarities, the greater the chances of a success.
 Translation b/w identical twins are very successful because the two HLA genotypes are the same.
 Transplantation: is the act of transferring cells, tissue, or organs from one site to another.
 Graft: implanted cell, tissue, or organs.
 Donor: individual who provides the graft.
 Recipient or host: individual who receives the graft.
 Immune system usually recognizes replacement as foreign(non-self).
 Immunosuppressive drugs
Inhibit T-cells or production of antibody.
 Transplantation can be divided:
Autograft: grafting of cells, tissue, or organs from one site to another site of a same individual.
Isograft: transferring grafts of two identical twins.
Allograft: Tissue is transferred between two genetically different members of same species.
Xenograft: Tissue is transferred between two different species.
10.1.HLA and Disease associations
 The HLA antigens give each person a unique set of identifying cell surface makers. The body’s
immune system recognizes these markers as self.
 Another function of HLA system may be to protect against microbes in the environment. The
histocompatibility antigens from a large library of self signals on cell membranes
 One of the most intriguing roles of the HLA complex is its association with certain diseases.
 What is thee connection b/w the HLA genotype and a particular disease?
 There is increasing evidence that the antigens on certain viruses and bacteria resemble but are
still distinct from the antigen encoded by a particular HLA allele.
 These antigens instruct lymphocytes about self versus non-self making it more likely that and
invading microbe will appear as non self.
 When immune system launches its attack on the invading Microbes it inadvertently attacks self
tissues. This causes the symptoms we observe in many of these disease.
 Several inherited diseases are also physically linked to the HLA.
 10.2. Clinical applications of HLA
 There are many clinical applications of HLA system.
 HLA antigen is crucial for transplation
 HLA typing can be used to detect the diseases that are physically linked to the HLA
complex in families.
 Finally HLA typing is valuable in paternity testing and in other medicolegal situations.
11. Immunogenicity
 Is the ability of a particular substance, such as an antigen to provoke an immune
response in the body of a human.
 Factors influence immunogenecity
- Foreignness
- Molecular size
- Chemical composition and heterogeneity
- Susceptibility to antigen processing and presentation
 11.1. Immunization
 Immunization is the process whereby a person is made immune or resistant to an
infectious disease, typically by the administration of a vaccine. Vaccines stimulate the
body's own immune system to protect the person against subsequent infection or disease.
 Vaccines that contain live but weakened organisms include
 Bacille Calmette-Guérin (BCG—for tuberculosis)
 Chickenpox (varicella)
 Cholera (certain vaccines given by mouth)
 Measles-mumps-rubella. MMR vaccine
 Polio (only the oral vaccine)
 Typhoid (only the oral vaccine)
 Hepatitis B Virus (HBV)
12. Blood Genetics
. Discovered in 1901 by Dr. Karl
The human ABO gene is on chromosome 9Landsteiner
Everyone has two copies of chromosome 9 so you have two ABO genes.
One copy is inherited from our mother, the other from our father.
4 Main Phenotypes (A, B, AB, O)
13. Allelic Exclusion and class switching
 There are three versions (called “alleles”) of this blood type gene: A, B, and O.
 A person’s blood type is determined by which allele he/she inherits from each parent.
 Phenotype vs. Genotype
 The genetic makeup of an organism is called the “genotype”.
 The “phenotype” is the visible properties of an organism.
 In this case, the A, B, and O allele combination a person has is their genotype
 Their blood type is their phenotype.
 Dominant vs. Recessive Genes
 The “A” allele is dominant and so is the “B” allele.
 Together though, the “A” and “B” alleles are co-dominant.
 The “O” allele is recessive.
 Determining the Genotype

Human blood type is controlled by three alleles : IA, IB and O.

Alleles IA and IB are dominant over O . Blood Type Genotype

IA and IB are codominant A IA IA or IAIo

B IB IB or IBIo

AB IA IB

O IoIo
 Antibodies
• Blood plasma is packed with proteins called antibodies.
• The blood groups have different Antibody which include A and B
antibody.
• The A and B blood group have B and A-antibody.
• However O blood group have both A and B-antibody.
Note: AB blood group have no antibody.
 14. ABO Blood Grouping System
Blood group A
If you belong to the blood
group A, you have A antigens
on the surface of your RBCs
and B antibodies in your blood
plasma.
Blood Group B Blood group AB
If you belong to the blood If you belong to the
group B, you have B blood group AB, you
antigens on the surface of have both A and B
your RBCs and A antigens on the surface of
antibodies in your blood your RBCs and no A or B
plasma. antibodies at all in your
blood plasma.
Blood group O
If you belong to the blood group O
(null), you have neither A or B
antigens on the surface of your
RBCs but you have both A and B
antibodies in your blood plasma.
 Blood Transfusions
It is important to carefully match the donor and recipient blood types.
If the donor’s blood cells have antigen that are different from those of the
recipient, antibodies in the recipient’s blood recognize the donor blood as
foreign.
This triggers an immune response resulting in blood clotting or
agglutination.
People who are Type A blood produce antibodies to agglutinate cells which
carry Type B antigens. They recognise them as non-self
The opposite is true for people who are Type B
Neither of these people will agglutinate blood cells which are Type O as they
do not carry any antigens for the ABO system..
Donor-recipient compatibility
Recipient
Type A B AB O
A
Donor B
AB
O

Note:
• Type O blood may be transfused into all the other types =
= Agglutination the universal donor.
• Type AB blood can receive blood from all the other blood
= Safe transfusion types = the universal receivers.
 15. What is the Rh factor in blood?
Discovered in 1940 after work on Rhesus
monkeys.
RH gene located on short arm of
chromosome 1
Rhesus (Rh) factor is an inherited protein
found on the surface of red blood cells. If
your blood has the protein, you're Rh
positive. If your blood lacks the protein,
you're Rh negative. Rh positive is the most
common blood type.
Most people (about 85%) have a positive
Rh factor
Rh is expressed as either positive or
negative.
 Rhesus Factor
Positive (+) allele is dominant to negative (-) allele
Rh +: you have the protein Rh-: you don’t
Mother Father Child

Rh- Rh+ Rh+

Rh - Rh- Rh-

– If a person has either two (+)

genes for Rh or one (+) and
one (-) Rh gene, they will test
Rh(+).
– A person will be negative only
if they have 2 (-).
 P1 : Female Rh- × Male Rh+

Baby is Rh+ because father is. Mother’s blood produces

antibodies upon birth, (since blood mixes at birth).
 First baby is okay.
Second pregnancy- mom’s antibodies can now move across the
placenta and cause baby’s RBC’s to clump (agglutinate) if second
baby is also Rh+. This decreases oxygen delivery in the baby –
“blue baby.”
The “Rh Issue”… Mom = Rh- Baby #1 = Rh+
 What causes rhesus hemolytic disease of the new born
 When Rh- woman married to Rh+ man bears Rh+ foetus. Although the foetal and maternal blood
do not come in direct contact due to placental barrier, some foetal R.B.C’s manage to enter the
maternal blood stream. The Rh antigen on their surface induces formation of anti-Rh antibodies.
These antibodies then cross the placenta and enter the foetus blood circulation and cause a blood
disorder known as erythroblastosis foetalis/rhesus hemolytic disease of the new born. The
reaction of Rh-woman against her Rh+ offspring becomes progressively more severe with each
subsequent pregnancy.
 What can be done?
 Mom can be given an injection of a drug that inhibits antibody production immediately after
delivery anti D OR rhogam
 What happens if this is undetected?
 Baby could be given a blood transfusion while in the womb. Fairly uncommon.
16. Immunological Disorders

There are two types of

immunological
disorders.
1.Autoimmune
disease
2. Immunodeficiency
 17 Autoimmune disease
 1.
 In cases of immune system over activity, the body attacks and damages its own tissues.
 Autoimmune disease can be:
 Specific:
Juvenile diabetes (attacks insulin-producing cells)
Multiple sclerosis (attacks myelin coating of nerve axons)
Myasthenia gravis (attacks nerve-muscle junction)
Thyroiditis ( Inflammation of the thyroid)
 Systemic: Immune complexes accumulate in many tissues and cause inflammation
and damage.
Systemic Lupus Erythematosus (anti-nuclear antibodies): harms kidneys, heart,
brain, lungs, skin…
Rheumatoid Arthritis (anti-IgG antibodies): inflammatory disease usually presenting
in women ages 20 to 45 and it effects joints, hearts, lungs, nervous system…
 Autoimmune disease

Grave’s disease:  
Multiple sclerosis
also known as toxic diffuse goiter, is
chronic, typically progressive
disease involving damage to the an autoimmune disease that affects
sheaths of nerve cells in the brain the thyroid.
It frequently results in and is the
and spinal cord, symptoms may
include numbness, impairment of most common cause of
speech and of muscular coordination, hyperthyroidism
blurred vision, and severe fatigue.
Juvenile diabetes
Type 1 Diabetes mellitus: a lifelong
condition that causes a person's blood sugar
level to become too high. characterized by
the body's inability to produce insulin due to
the autoimmune destruction of the beta cells.
18
 2. Immunodeficiency Diseases
 This diseases occur when some components of the immune system fails to
function. These diseases are generally characterized by low resistance to
infection and to the loss of immunologic surveillance function, such as seeking
out and destroying cancer cells.
 We will take a look examples of immune deficiency diseases that reveal defects
in T-cells , B cells and both T and B cells.
 T-Cells Deficiencies: Patients with T-cells defects, we usually observe a low
resistance to bacterial infections and to intracellular viral infections. They are
especially susceptible to protozoan and fungal infections.
 The DiGeorge Syndrome: Is
characterized by the absence of the
thymus and parathyroid glands.
 Without the thymus the T-cells
cannot be induced to develop. This
diseases is caused by mutation in
long arm of chromosome 22.
AIDS (Acquired Immune Deficiency
Syndrome): It is a fatal disease caused by HIV.
This virus suppresses the ability of T-helper
cells and the patients with this disease dies for
opportunistic infections such as Pneumonia
caused primarily by a protozoan( Pneumocystis
carinii ) or virus known as cytomegalo virus.
 B-Cell Deficiencies

The absence of B cells and their

products, the circulating antibodies,
creates serious problems.
Bruton’s Disease, : (In fantile X-linked
agammaglobulinemia ) : this condition
is the result of an X-linked allele that
causes the complete absence of B cells.
The patients that this disease affects are
susceptible to bacterial infections;
however, they can live relatively
normal lives if they receive regular
injections of gamma globulins.
T-Cells and B-Cell Deficiencies
When both T cells and B cells are missing, we have a usually fatal
condition called Severe Combined Immunodeficiency Syndrome (SCIDS)
and these patients have no defence against infections or any anomaly such
as cancer that may rise in the system.
The only way this patients to survive this defect is to live in sterile
environment.