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THE IMMUNE SYSTEM (II)
The immune system does not design
antibodies or T-cell receptors expressly to bind invading antigens
OVERVIEW
A) DEFENCE AGAINST MICROBIAL INVASION
B) FOUR FEATURES OF THE IMMUNE SYSTEM
C) HUMORAL IMMUNITYD) CELL-MEDIATED IMMUNITYE) DISORDERS OF THE IMMUNE SYSTEMF) TYPES OF IMMUNITYG) BLOOD GROUPS and THE RHESUS
FACTORH) ANTIBIOTICS
DEFENCE MECHANISMS
PASSIVE MECHANISMS
ACTIVE MECHANISMS
First Line of Defence1.Skin
2.Mucous membranes
NON SPECIFIC INNATE IMMUNITY
SPECIFIC ACQUIRED IMMUNITY
Second Line of Defence1.Inflammation2.Complement Proteins3.Natural Killer Cells
Third Line of Defence1.Humoral Immunity2.Cell-Mediated Immunity
CELL-MEDIATED IMMUNITY:is directed against any factor that
changes a normal cell into
an abnormal cell.
Fig. 19 T lymphocyte activation by cell surface antigen. Binding requires the
presence of both foreign and normal (self) antigens.
small peptide molecules with various functions
Lymphokines:
each type of T cell produces a different type of lymphokine
T cells attack:-
1) cells infected by microorganisms, most commonly a virus
2) transplanted organs and tissues
3) cancer-causing cells
• T cells do not release antibodies
• the whole cell is involved in the attack
T Cells arise from:
precursor cells in the bone marrow
Stem cells of the bone marrow mature in the thymus gland
Immature T cells turn either into a cytotoxic cell, helper cell or a suppressor cell
Once mature, where do T cells go?
T cells:- stay in the blood
- migrate to:
1. the tissue fluid2. lymph nodes3. other organs
e.g. spleen
Stem cells develop into thymocytes inside the thymus
at this stage any cells that recognise ‘self’ are destroyed
Why is this important?
So that the body does not attack itself
So that the body does not attack itself
T-cell receptors are : glycoproteins identical on a surface (about 105)
T-cell receptors:- recognise antigens only if they are
combined with self antigens
T-cell receptors:- recognise antigens only if they are
combined with self antigens
self antigens : are glycoproteins
produced by a group of genes called the major histocompatibility complex (MHC)
these proteins are called MHC proteins are present on the surfaces of most vertebrate
cells
Three types of MHC proteins
B ody cells M acrophagesB cellsT cells
M HC I M HC II
P roteins ofcom plem ent
M HC III
Role of MHC in T cell function
the genes encoding the MHC proteins are highly polymorphic (have many forms), so that very few individuals in a population possess the same set of alleles
MHC proteins on the tissue cells serve as self markers that enable the individual’s immune system to distinguish its cells from foreign cells, an ability called self-versus-nonself recognition
What happens to lymphocytes that bind
self-MHC?
Killed!! Otherwise they attack
the body
Antibodies bind to an
intact antigen
T cell receptors bind to a piece of the antigen displayed on the surface of an antigen-
presenting cell
T cell receptors bind to a piece of the antigen displayed on the surface of an antigen-
presenting cell
Difference between antibodies & T cell receptors :
Macrophages are antigen-
presenting cells.
Three types of T cells
1. Helper T cell
2. Cytotoxic T cell / Killer cell 3. Suppressor T cell
Types of T cells Function
Helper T cell (TH or TH-CD4) [CD4 is a surface protein]
[CD = cluster of differentiation]
Commander of the immune response.
Help B cells differentiate into antibody-secreting plasma cells by secreting lymphokines.
The HIV virus that causes AIDS preferentially infects and destroys TH cells.
Types of T cells FunctionHelper T cell (TH or TH-CD4)
Commander of the immune response
Help B cells differentiate into antibody-secreting plasma cells by secreting lymphokines.
Types of T cells Function
Helper T cell (TH or TH-CD4)
The HIV virus that causes AIDS preferentially infects and destroys TH cells.
Types of T cells FunctionKiller cell or cytotoxic cell (TC or TC-CD8)
Kill tumour cells, body cells infected with viruses and transplanted tissue.
Types of T cells Function
Killer cell or cytotoxic cell (TC or TC-CD8)
Recruited by helper T cells.
Kill by a pore-forming molecule called perforin and enzymes.
These enzymes enter the cell through the perforin channels and induce the cell to commit suicide. [see next slide]
Cytotoxic T Cells Lyse Infected Cells
Natural killer cell
Perforin Granzyme
Cancercell is killed
NK cells & TC Cells Lyse Infected Cells using perforin & granzymes
Cytotoxic T cellBUT they
recognise infected cells in a different
way…….
Natural killer cells kill cells:
Cytotoxic T cells kill cells:
possessing low levels of MHC class I
molecules
possessing antigenic fragments bound to
MHC class I molecules
Types of T cells
Function
Suppressor T cell
Dampens the activity of T and B cells, scaling back the defence after the infection has been checked.
Summary of the main
stages of the cell-mediated and humoral
immune responses.
[dendritic cell =
antigen presenting cell]
What happens when T cells are activated by contact with a specific antigenic determinant?
The cytotoxic T cell proliferates
[clonal expansion]
to produce
1.memory T cells
2.active cytotoxic T cells
OVERVIEW
A) DEFENCE AGAINST MICROBIAL INVASION
B) FOUR FEATURES OF THE IMMUNE SYSTEM
C) HUMORAL IMMUNITYD) CELL-MEDIATED IMMUNITYE) DISORDERS OF THE IMMUNE SYSTEMF) TYPES OF IMMUNITYG) BLOOD GROUPS and THE RHESUS
FACTORH) ANTIBIOTICS
Two disorders of the immune system:
Juvenile diabetes: an autoimmune disease
Juvenile diabetes: an autoimmune disease
AIDS : Helper T cell destruction
AIDS : Helper T cell destruction
Autoimmune diseases are produced as the immune system fails to:
This failure results in TWO things:
This failure results in TWO things:
recognise & tolerate self antigens
1. activation of T cells
1. activation of T cells
2. production of autoantibodies by B cells = inflammation + organ damage
2. production of autoantibodies by B cells = inflammation + organ damage
Are autoimmune diseases common?
• there are over 40 known or suspected autoimmune diseases
• affect 5% - 7% of the population
PSORIASIS
AIDS
AIDS:Stands for :Acquired Immune Deficiency Syndrome
Caused by: a retrovirus –Human Immunodeficiency Virus (HIV)
AIDS is a Pandemic disease
Pandemic: distributed worldwide and affects many people
Why does the HIV attack helper T cells?
Recognises the CD4
receptors associated with these
cells
The course of an HIV infection
When is a person considered to have AIDS?
When the TH cell level has dropped significantly
Immunosuppression results in an increase in:
opportunistic infectionscancers
AIDS The HIV virus does not kill it cripples the immune
system
Common diseases that the immune system normally could defeat become life-threatening
Can show no effects for several months all the way up to 10 years
The progression of the disease can be slowed down by:
Targeting viral
enzymes
Why is it difficult to develop a vaccine?
- lacks proofreading function
This leads to mutant viruses
It is customary to give a cocktail of drugs rather
than one drug at a time to an AIDS patient. Why ?
More chance to keep virus under control. If a viral enzyme has changed shape, at least virus is prevented from reproducing by another drug.
Question: [MAY, 2006]
Use your knowledge of biology to explain the following:
Despite great progress and advances in medical research, no drug able to effectively destroy the HIV virus has as yet been produced.
[5 marks]
OVERVIEW
A) DEFENCE AGAINST MICROBIAL INVASION
B) FOUR FEATURES OF THE IMMUNE SYSTEM
C) HUMORAL IMMUNITYD) CELL-MEDIATED IMMUNITYE) DISORDERS OF THE IMMUNE SYSTEMF) TYPES OF IMMUNITYG) BLOOD GROUPS and THE RHESUS
FACTORH) ANTIBIOTICS
Two types of acquired immunity:
Activeantigens received
Passiveantibodies received
NaturalNatural activee.g. fighting infection,rejecting transplant
Natural passivefrom mother via milk or placenta
ArtificialArtificial activevaccination (injection of antigens)
Artificial passiveinjection of antibodies
providing immunity artificially
Immunisation / Vaccination Immunisation / Vaccination :-
Immunisation Immunisation :-
• Whole live microorganism
• Dead microorganism
• Attenuated (harmless) microorganism
• Toxoid (harmless form of toxin)
A preparation containing antigenic material:
What is the source of antibodies that are used in artificial passive immunity?
1. Horse is injected with antigen.
2. Blood is taken from the horse & serum is obtained.
3. Person is injected with the horse serum that contains antibodies.
MAY 2005 Paper2
Why do immunologists use horses, as opposed to other possible choices of animal, during the production of anti-venom? (2)
Since the horse is large, a lot of blood can be removed from it. Thus a large volume of serum can be extracted.
Why are patients being treated for snake bite given a small dose of anti-venom prior to administration of the full dose?
To check for possible allergic reactions.
How long does active immunity last?• It depends on the antigen
• Some disease-causing bacteria multiply into new forms that the body does not recognise, requiring annual vaccinations, like the flu shot
• Booster shot - reminds the immune system of the antigen
How long does active immunity last?
May last for a lifetime
e.g. chicken pox
Question: [MAY, 2003]
A patient cannot be vaccinated if he or she had been taking immunosuppressive medication within the previous two months.
[5 marks]
Answer to Question: [MAY, 2003]
Vaccines rely on production of primary immune response. Antigenic molecules are injected.Individual responds by producing a primary immune response.Immunosuppressive drugs prevent responses by immune system.Especially dangerous if live attenuated forms are injected since recipient cannot respond to defend himself.
Question: [MAY, 2012]
Use your knowledge of biology to explain the following statement:
lactation is important for passive immunity;
[5 marks]
lactation is important for passive immunity;
[5 marks]
OVERVIEW
A) DEFENCE AGAINST MICROBIAL INVASION
B) FOUR FEATURES OF THE IMMUNE SYSTEM
C) HUMORAL IMMUNITYD) CELL-MEDIATED IMMUNITYE) DISORDERS OF THE IMMUNE SYSTEMF) TYPES OF IMMUNITYG) BLOOD GROUPS and THE RHESUS
FACTORH) ANTIBIOTICS
• A person’s blood type is determined by antigens found on surface of red blood cells
Blood Groups
• the most important systems include: ABO Rh (rhesus) MNSKellLewisDuffy Kidd
More than 30 Blood Grouping Systems
in syllabus
ABO system ABO blood types = Types A, B, AB and O Rh factor = Rh positive and Rh negative
the immune system: is tolerant of its own RBC antigens
makes antibodies that bind to those that differ
BUT
Antigens [agglutinogens]: are glycoproteins or
glycolipids
ABO systemAntibodies
[agglutinins]:
specific against blood group antigen
A- antigen
b- antibody
ABO System: four types of blood groups
Antigen (agglutinogen)
on RBC membrane
Agglutinin(antibody)in plasma
Blood group
A b AB a B
AB nil ABnil ab O
45%
40%
11%
4%
UNIVERSAL DONORS
-blood group O persons
-can donate blood to anybody
UNIVERSAL RECIPIENTS
-blood group AB persons
-can receive blood from anybody
Blood Transfusion
In a transfusion, blood MUST In a transfusion, blood MUST be compatible. be compatible. WHY?
Otherwise, an antigen-antibody reaction
occurs.
Donor’s antigens match
Recipient’s antibodies
Agglutination
For blood to agglutinate:
A
a
RecipientDonor
Oa+b
Ab
Ba
ABo
Oa+b - - - -Ab + - + -Ba + + - -
ABo + + + -
Key - no agglutination + agglutination
Donor (no antigen) Recipient NO
Agglutination
a b
RecipientDonor
Oa+b
Ab
Ba
ABo
Oa+b - - - -Ab + - + -Ba + + - -
ABo + + + -
Key - no agglutination + agglutination
DonorRecipient
Agglutination
A
a b
RecipientDonor
Oa+b
Ab
Ba
ABo
Oa+b - - - -Ab + - + -Ba + + - -
ABo + + + -
Key - no agglutination + agglutination
DonorRecipient NO
Agglutination
b
A
RecipientDonor
Oa+b
Ab
Ba
ABo
Oa+b - - - -Ab + - + -Ba + + - -
ABo + + + -
Key - no agglutination + agglutination
DonorRecipient
Agglutination
Aa
RecipientDonor
Oa+b
Ab
Ba
ABo
Oa+b - - - -Ab + - + -Ba + + - -
ABo + + + -
Key - no agglutination + agglutination
DonorRecipient
(no antibody) NO Agglutination
The Rhesus (Rh) Factor
Rh+
85% of the total population:
15% of the total population:
Rh-
[Rh antigens absent]
[Rh antigens present: agglutinogen D])
Why called ‘Rhesus factor?
The Rhesus factor gets its name from its having first been detected in the blood of the rhesus
monkey
Rh Dangers During PregnancyRh Dangers During Pregnancy
Rh- mother with a
Rh+ foetus
What is the probability of a child to be Rh+?
i) Father is rhesus positive (heterozygous) and mother rhesus negative?
Rhesus negative: Rh- Rh-
Rhesus positive: Rh+ Rh-
Parents: Rh+ Rh- X Rh- Rh-
Gametes: Rh+ Rh- X Rh-
F1 genotype: Rh+ Rh- Rh- Rh-
50%
What is the probability of a child to be Rh+?
ii) Father is rhesus positive (homozygous) and mother rhesus negative?
Rhesus negative: Rh- Rh-
Rhesus positive: Rh+ Rh+
Parents: Rh+ Rh+ X Rh- Rh-
Gametes: Rh+ X Rh-
F1 genotype: Rh+ Rh-
100%
Rh Dangers During PregnancyRh Dangers During Pregnancy
Mother’s blood
Foetus’s blood
Risk
Positive Positive Positive Negative Negative Negative
Negative PositiveFirst child All other children
Can RBC from foetus cross the placenta?
These RBC stimulate antibody
production in mother…….
YESYES
(antibody: anti-D)
After Protection with anti-D
Lymphocytes cannot ‘see’ RBC from foetus
Anti-D (antibody against rhesus antigen)
B cell
PlacentaRBC cells in
foetus
Rh Dangers During Pregnancy
Rh- woman with Rh+ foetus
Cells from Rh+ foetus
enter mother
Woman produces antibodies against Rh+
cells
In the next Rh+
pregnancy, antibodies
attack foetal RBC
How Rh sensitization occurs
A Rhesus Baby is usually:
premature anaemic jaundiced
Haemolytic disease of the newborn
Blood of such a baby needs to be completely replaced by a transfusion of
healthy blood.
Surfaceantigens
Haemolytic disease
Surfaceantigens
Opposingantibodies+
+
Haemolytic disease
Surfaceantigens
Opposingantibodies+
+
Agglutination (clumping)
Haemolytic disease
Surfaceantigens
Opposingantibodies+
+
Agglutination (clumping) and haemolysis
Haemolytic disease
OVERVIEW
A) DEFENCE AGAINST MICROBIAL INVASION
B) FOUR FEATURES OF THE IMMUNE SYSTEM
C) HUMORAL IMMUNITYD) CELL-MEDIATED IMMUNITYE) DISORDERS OF THE IMMUNE SYSTEMF) TYPES OF IMMUNITYG) BLOOD GROUPS and THE RHESUS
FACTORH) ANTIBIOTICS
Antibiotics:• compounds produced by a microbe
• inhibit the growth of other microbes
Sir Alexander Fleming (1955)
Penicillium
Antibiotics can harm the bodyWeaken the immune system as they suppress the body’s natural defence system Destroy the
beneficial flora in the gut
Antibiotics are effective against:
BUT NOT EFFECTIVE BUT NOT EFFECTIVE AGAINST:AGAINST: VirusesViruses
BacteriaSome fungi BacteriaSome fungi
Use your knowledge of biological processes to comment on the following scenario:
Medical practitioners sometimes prescribe antibiotics when a person is affected by a viral cold.
[MAY, 2003]
Antibiotics deal with secondary infections (opportunistic
infections) - infections that occur because of a weakened immune
system.
Question: [MAY, 2003]Use your knowledge of biological processes to comment on the following scenario:
Medical authorities often recommend that prescription of antibiotics should be carried out sparingly.Bacteria have high reproductive rates and short generation timeAntibiotics effective against normal bacteriaEmergence of mutant forms resistant to antibioticsSelection pressure through antibiotic use favours rapid increase in numbers of resistant formsEmergence of disease forms with no cure
[5 marks]
Antibiotics are not equally effective against all bacteria:
An antibiotic will affect only those bacteria
which have a particular property in common
e.g. penicillin - kills only Gram positive bacteria
WHY?
Inhibits formation of peptidoglycan walls. G+ bacteria have a thick
peptidoglycan wall.
Inhibits formation of peptidoglycan walls. G+ bacteria have a thick
peptidoglycan wall.
Gram positiveGram positive Gram negativeGram negative
BROAD SPECTRUM ANTIBIOTIC:
Affect a wide range of microbes
NARROW SPECTRUM ANTIBIOTICS:
Affect a few species
Antibiotics can be:BACTERIOSTATIC
inhibit the growth and multiplication of
microbes
BACTERIOSTATICinhibit the growth and
multiplication of microbes
BACTERICIDAL kill microbes, like penicillin
BACTERICIDAL kill microbes, like penicillin
THE END