Health and Diseases (III) Body Defence
P.1
Health and Diseases (III)
Body Defence in Mammals
an is living in a world of micro-organisms, many of which are path_______ and can cause
diseases (Pathogens are micro-organisms that can cause diseases.). Many of these microorganisms either feed on the ti____ or liberate poi_____ substances (toxins), thereby
bringing about disease. In destroying tissues and liberating toxic substances, pathogenic microorganisms change the i_______ environment and upset the smooth running of the body. Their control
by the body's natural defence mechanisms is thus an aspect of hom__________.
M
Pathogen
virus
bacteria
unicellular protists
fungi
Disease
AIDS, influenza, poliomyelitis and the common cold,
tetanus, typhoid, diphtheria and tuberculosis
malaria and amoebic dysentery
Athlete’s foot
A healthy individual is able to protect himself from the hostile pathogens by a number of very effective
means which are referred to as defence mechanisms. Some of these prevents e____ of pathogens into
our body in the first place, while others will fi___ against those pathogens that have entered.
Defence mechanisms are thus indispensable for life. Two major types of defence mechanisms are:


Non-specific mechanisms are those that combats against any type of pathogens on their invasion.
Specific mechanisms (immune responses) refer to those that depends on specific recognition of the
invading pathogen for action.
I)
Non-specific Mechanisms
These are mechanisms that are



present from b
and
are NOT dependent upon prev
exposure to pathogens.
are simple in action and are NOT sp
against a particular type of pathogen.
1.
Mechanical Barriers:
The sk
and the mu
membranes form a natural
physical barrier that prevents the entry of pathogens
in the first place. They are referred to as the first line of
defence.
 The skin is most effective because of its relatively
imp________ horny layer (stratum corneum).
 The m
membrane of the respiratory tract
produce m____ that trap air-borne agents. The
mucus are then swept up by the beating c___ to the
throat and is then sw_______ with saliva.
 The c______ of blood at wound not only prevents
excessive bleeding but also blocks the en___ of
micro-organisms.
Health and Diseases (III) Body Defence
2.
P.2
Chemical Barriers:
Various liquids and chemicals on the surface of our body or inside our body are effective in
inhibiting or destroying pathogens. They constitute the chemical barrier mechanisms.
 The seb________ secretions and sw____ of the skin contains bactericidal and fungicidal fatty acids.
 Nasal secretions, saliva, tears, urine and other body fluids contain chemicals capable of inactivating
some viruses and tears contain ly_________ which is active against bacteria.
 Secretions from mucous membranes are bactericidal and viricidal.
 A___ in the stomach is a powerful sterilizing liquid (gastric juice).

3.
In the vagina, mutualistic bacteria produce lactic a___. This makes the vagina acidic, creating an
unfavourable environment for many pathogenic yeasts, bacteria and viruses.
Phagocytosis
Pathogens that can escape the mechanical and chemical barriers into our body are first dealt with by
white blood cells called phag____. There are two main types of phagocyte:


Neutrophils which are cells with an irregular many-lobed nucleus and a granular cytoplasm.
Macrophages which are larger cells with a regular horseshoe-shaped nucleus and a non-granular
cytoplasm.
Neutro____ are the commonest type of immune cell and make up about 60 % of all white blood cells
in the bloodstream. The bone marrow produces 80 million of these cells every minute and their
number in_______ during an infection.
Macrophages develop from another type of white cell in the blood called monocytes which make up
only 6 % of the white blood cells. Monocytes are made in the bone marrow and, after circulating in the
blood for one or two days, they squeeze through the cap______ wall and migrate into the tissues
where they become macro_____.
The macrophages wander around the tissues collecting up ‘rubbish’, which may be micro-organisms
or other for
bodies, (in the lungs dust as well as micro-organisms are collected in this manner) or
dam
or dead cell. They are particularly numerous in the lungs, liver, kidney, spleen and lymph
nodes. Although the neutrophils are the first cells to arrive at a site of inf
, the longer-lived
macrophages take over at any major site.
Health and Diseases (III) Body Defence
The eating process is called phagocytosis.




It is a non-sp
P.3
_ way of destroying pathogens :
Pseudopodia are sent out which eng
bacteria to form a phagocytic vesicle or a phagosome
Lyso
in the phagocytic cell then fuse with the phagosome and discharge their contents into it.
The lysozymes are powerful hydrolytic enzymes which di
the pathogen and destroy it.
After digestion, the residues are disch______ out of the phagocytic cell.
Phagocytosis, however, has a distinct limitation: it does not act against certain bacteria and is not very
effective against vir
because they hide in____ the body's own cells where they are protected from attack.
4.
The Inflammatory Response
At sites of infection, besides the phagocytic action just mentioned, an in____________ response may also be
elicited. This is a more powerful non-specific response to eliminate the pathogens.

Due to release of hist______ in the
infected area, large number of
pha_________ cells (neutrophils first
and macrophages later) are attr
to
the area from surrounding tissues.

At the same time, the blood vessels
dil____ and the blood flow to the area
increase. The perm__________ of the
blood vessels also increase, leading to
massive flow of fluids out from the
blood into the tissues. This causes
sw_______ in the area.

Phagocytic cells move out from the
b_______ into the infected tissue,
offering extra support to those already
there.
H ,r
,s
and p
many of which die and form p
, the inflamed area contains numerous b________ and phago____,
. Sometimes the inflamed area forms a boil.
The various non-specific mechanisms normally provide quite a good defence for the body and many
invading pathogens are destroyed by them and consequently not able to penetrate deep enough into
the body to cause disease. However, in some cases, these mechanisms are not powerful enough to
stop the invading pathogen at the site of infection. In such situations the pathogens continue to
replicate locally and increase in number. Eventually they entered the lymph and blood. Those in the
lymph will reach l
nodes and those in b______ will reach the spl
and li
At these
places the pathogens will meet the fixed Phagocytic cells there. Some of the pathogens will be
destroyed by these cells. The remaining ones, however, will multiply and turn on the s______
immune responses of the body (specific mechanisms).
II)
Specific Mechanisms
There are four major characteristics of specific mechanisms: spe_______, di_______, me______
and self-tol________.




It can recognize specific molecules and produce molecules and cells to match up with and counteract
each one of them;
The immune system displays enormous diversity of immune cells and antibodies;
It is able to remember previous exposure to an antigen and a second encounter will be met with a much
stronger response;
It can distinguish between "self" and "non-self molecules and normally launch attack on non-self
particles only.
Health and Diseases (III) Body Defence
A)
Basic Definition

Pathogens are micro-organisms that can cause d
surfaces.

Antigens are usually defined as

B)
P.4
.
Pathogens often have anti
on their cell

Substances, living or non-l
im
response.

More precisely, an antigen is a substance that specifically combines with an anti

Antigen usually takes the form of a protein or glycoprotein (protein with short chain
poly
) structure on the surface of microbial organisms or other tissue cells
(s
antigens) or as a free molecule.

Antigens may not be living path______. Large chemical molecules can also be antigenic and stimulate
specific responses. (examples of antigens: Kidney issues, Red Blood cells, bacteria, viruses, foreign
proteins, pollen grains, drugs, pollutants.)
, pathogenic or non-p
, that can stimulate a specific
.
An antibody is a prot
molecule (immunoglob____) produced by an animal in response to the
presence of foreign substance -- antigen for which it has a high affi____.
The Mammalian Immune System
There are two specific mechanisms: the H__________ Immune Response (HIR) and the Cellm_______ Immune Response (CMIR). The mammalian immune system comprises:



a)
bone marrow
- with precursors (st___ cells) of blood cells
blood and lymph - where located various types of w____ blood cells are important for specific
defence
lymphoid tissues - thymus, bone marrow (primary- where lym_________ are produced)
lymph nodes and spleen (secondary-- where they develop to maturity)
Formation of blood cells
All blood cells arise from common ancestral cells called st
The stem cells develop into :
 r__ blood cells,
 plate___,
 W____ Blood cells / Leukocytes
White Blood cells can be classified
into two major groups :
Granulocytes
 have granules in their cytoplasm
 have lobed nucleus
Agranulocytes
 no granules in their cytoplasm
 kidney-shaped nucleus
cells found in the bone m
.
Health and Diseases (III) Body Defence
i)
P.5
Different types of White Blood Cells (leukocytes)
1) Granulocytes (also called PMNs -- polymorphonuclear leukocytes)
White cells that possess gran____ in their cytoplasm are referred to as granulocytes. They all have lo___
nuclei. They have a short life span (few days).

Neutrophils: (50-70%) - the most abundant type of PMN.
 An important phag______ cell for non-specific body defence.
 Actively amoeboid, capable of loco______.
 Can leave blood ves
and enter into tissue by squeezing between cells of the capillary wall.

Eosinophils: (1-4%) - quite rare. Functions ill-defined. Associated with hypersensitivity and allergic
reaction.

Basophils: (0-1%) Non-phagocytic. Becomes mast cells when entered tissues. Contains hist_____
which when released, will cause vaso_______, increase blood flow, increased perm_______ of
blood vessels and outflow of phagocytic cells.
2) Agranulocytes
These are cells with no granules in the cytoplasm. There are two types :
b)

Lymphocytes(33%) : B and T cells are chiefly responsible for the sp
___cells (for HIR). ___cells (for CMIR).

Monocytes (2-8%):
immune responses.
phagocytic, become macro______ in tissues.
Development of B and T cells
Both B and T cells originate from stem cells in bone marrow. Some migrate via blood to the
thymus and develop into T cells / lymphocytes. These T cells then migrate to lymph nodes and
spleens where most of them reside and be ready for specific immune responses.
The lymph n___ and sp____ are where B and T cells accumulate. It is
also the place where pathogens in blood and lymph are caught.
Pathogens stim____ the B and T cells and turn on sp_____ immune
responses. Most specific responses take place at these sites. They are
therefore the battle grounds for specific mechanisms!
Lymph nodes
The lymph nodes are also called 'glands' which sometimes sw
up
when we are suffering from an infection. They are widely distributed in the
body, particularly the groin and armpits. Each lymph node consists of a
network of delicate f
through which lymph filters through. Lymph
is a colourless fluid, derived from the blood. It is brought to the node by a
lymph vessel and drained away from it by another lymph vessel. The
latter leads ultimately to a vein in the neck where the lymph rejoins the
bloodstream.
The lymph nodes contain phag
macrophages which remove
pathogens and foreign particles from the lymph. These phagocytes are
mainly fixed to the fibrous network though they can move out of the
lymph node to nearby tissues.
Health and Diseases (III) Body Defence
C)
P.6
Stimulation of Specific Responses
When pathogens reach the lymph
node or spleen, they may first be
pro
by the macrophages
at these sites (antigen processing).
The processed antigens may then
stimulate either the T or B cells
(or both in some cases) and turn
on the CMIR or HIR
respectively.
Sometimes, pathogens need not
go through “antigen processing”
and can stimulate B and T cells
directly.
a)
Humoral Immune Response (HIR)
Some antigens will turn on the humoral response. e.g. bacteria, pollen, animal fur, red blood cells etc.
The characteristics of the HIR is that B cells are involved and the process results in the production of
anti
specific for the antigen.
i)
The Primary Response
A primary response is the response that is elicited when an antigen entered into the body for the first
time. Any subsequent entry by the s
antigen will cause a different response that is called a
sec_______ response.

When the antigen reach the lymph node / spleen, it will stimulate the appr ___
specific to it.

Some antigens cannot turn on the B cell directly, they need the presence of T cells and these antigens are
called T-_________ antigens. Those which do not require T cells for stimulating B cells are called Tindependent antigens.

The stimulated B cells will then differentiate and multiply into antibody forming cells –pl
are very efficient in producing anti_______ (Ab).

The specific antibodies can then act on the specific antigen / pathogen.

Some stimulated B cells become long living ‘ m
B cell there which is
cells ’.
THE HUMORAL IMMUNE RESPONSE (HIR) (primary response)
B
antigen
‘memory cell’
B
B cell
Selected /
Stimulated B cell
Plasma cell
Specific antibodies
cells which
Health and Diseases (III) Body Defence
ii)
P.7
Secondary Response
Some activated B cells will turn into
small memory cells.

These have a l
life span and
remains for a long time in the
blood circulation.

They can be turned on more easily
and vigorously on the body's n
exposure to the same antigen.

Thus, if the antigen invades the
body a second time, the memory
cell will quickly becomes act
,
and lead to formation of anti_____producing cells and antibodies
very quickly.
This is called a Secondary Response which has Four characteristics:



a shorter l___ period.
a sh______ increase and
a h_______ level of antibodies produced.
the high antibody level stays I_______ in the body.
The response is highly sp______ for the antigen. Another antigen cannot elicit a secondary response.
As a result of the more ef______ secondary response, the level of antibody is built up very q_____
and the pathogens are destroyed so rapidly that only mild or no symptoms appear. This is called
im
.
Antibodies
They are Y-shaped structures which are also called immuno
as they are protein molecules.
The two top ends of the “Y” are specific to the particular antigen and can therefore bind to it.

Lysis
Attach to the pathogen (e.g. bacterium) and cause lysis of bacterial cell wall. Consequently, water and salts inside the
antigen (bacterium) leak out and the bacterium is killed.

Enhanced phagocytosis
Antibody attaches to the antigen (e.g. bacterium), making the antigen easier to be eaten by phagocytes.

Neutralize bacterial toxins
bacterial toxins (a harmful substance secreted by bacterium) are neutralized by the formation of antigen-antibody
complexes which are then phagocytosed.
Antibodies have a short l
blood decl_____.
span and are soon metabolized if not used. As the antibody produced is used up, its level in
Q. Vaccination is often given in multiple doses, separated by several weeks or even months. Why do you suppose the
doses are spread out over such a long period rather than given in a single dose?
5m
Health and Diseases (III) Body Defence
P.8
Q. What particular organelles do you suppose to be well-developed or especially abundant in the clones of the activated B
cells (plasma cells) ?
Reference Reading : Clonal Selection Theory (by Macfarlane Burnet -- a Nobel Prize winner)
This theory explains the mechanism whereby lymphocytes can be induced to synthesize antibodies of the
correct specificity for the antigen that triggered the immune response. The theory assumes that there is a
great diversity of lymphocytes (more than ten million different clones of B cells) at birth, genetically
programmed to produce antibodies of all different specificity. When an antigen arrives, only those relatively few
lymphocytes with specificity for the antigen are triggered to proliferate and form a lot more cells (clones).
Thus the antigen selects lymphocytes of correct specificity to respond. This theory is quite generally accepted.
It could also apply to the cell-mediated type of immune response.
How does each B lymphocyte recognise its unique antigen? The B cell carries on its surface the same kind
of antibodies that it is capable of producing. These surface antibodies act as receptors. When an
appropriate antigen comes along, it is recognised by the matching clone, which then divides rapidly to make
thousands more identical B cells (clones), all secreting that particular antibodies that bind to that antigen into the
blood and lymph.
b)
The Cell-Mediated Immune Response (CMIR)
Instead of stimulating the body to produce antibodies, some antigens (e.g. certain bacteria, viruses,
foreign cells like skin, kidney etc.) turn on the CMIR.
i)
Primary Response
When such an antigen enters the blood and eventually the spleen and lymph nodes, it will stimulate
the T cells specific to the antigen to respond. The T cells may respond in either one of the following
ways:
the stimulated T cell may become a Killer T cell which can kill the antigen directly.

Alternatively, the stimulated T cell may become an Activated T cell which liberate chemicals called
Lymphokines. The lymphokines then acti____ the macrophages in the spleen and lymph nodes into
activated macrophages which are highly efficient in eating and killing the antigen. The effector in this
mechanism is therefore the Activated Macro
.
THE CELL-MEDIATED IMMUNE RESPONSE (CMIR)
‘memory’ cell
T
T
Kill pathogen
directly
Killer T cell
Lymphokines
antigen
T
Selected
T cell
An activated
Macrophage
T
Activated T cell
Macrophage
Health and Diseases (III) Body Defence
ii)
P.9
The Secondary Response
Some stimulated T cells become me
cells instead and remain in the blood. They have a long life
span and are capable of prolif
and differ
into Killer / Activated T cells to combat
against the antigen in its second invasion.
The time course of CMIR is similar to that of HIR, except that it takes a longer time to develop.
Whether a HIR or CMIR or both are elicited depends on the type of pathogen/antigen.
Reference : Further notes on the T cells
T Lymphocytes look exactly like B lymphocytes but they do not produce antibodies. They are responsible for
what is called cell-mediated immunity.
Like B lymphocytes, they have to make contact with their matching antigen before they can start work. There
are special receptors on their surface which enable them to recognise the correct antigen. The main types of
T lymphocyte, and their functions, are as follows:

T helper cells help other cells in the immune system. For example, they stimulate B lymphocytes to
divide into antibody-producing cells (T-dependent response). If these helper cells are not present, the B
lymphocytes cannot go into action. They also enhance the action of phagocytes. It is the T helper cells
which are invaded by HIV (Human Immunodeficiency Virus) and this explains why other infections are
associated with AIDS.

T suppressor cells suppress other cells in the immune system. For example, they inhibit the production
of antibodies by the B lymphocytes, and they also suppress the action of phagocytes. They act as
brakes in the immune system, dampening it down and preventing it from over-reacting.

T killer cells destroy body cells infected with viruses before the viruses have time to proliferate. They
also attack cells from other individuals if they get into the body, and in doing so they cause the rejection
problems associated with skin grafts and transplant surgery. The T killer cells are regulated in the same
way as B cells, by the T helper and T suppressor cells.
III)
Immunity and Immunization
Types of Immunity
a)
Natural Passive Immunity
Prefo_____ antibodies from one individual are passed into another individual of the same species.
This only affords temp
protection against infection, for as the antibodies do their job, or are
broken down by the body's natural processes, their number diminishes and protection is slowly lost.
For example, antibodies from a mother can cross the pla
and enter her foetus. In this way they
provide protection for the baby until its own immune system is fully functional. Passive immunity may
also be conferred by br
feeding, the initial secretion of the mammary glands, from which
antibodies are absorbed from the intestines of the baby.
b)
Acquired Passive Immunity
Here antibodies which have been preformed in one individual are extracted and then inj
into
the blood of another individual which may or may not be of the same species. For example, specific
antibodies used for combating tetanus and diphtheria are cultured in horses and later injected into
humans. This type of immunity is again sh
-lived.
c)
Natural Active Immunity
The body manufactures its o
antibodies when exposed to an infectious agent. Because m______
cells, produced on exposure to the first infection, are able to stimulate the production of massive
quantities of antibody when exposed to the same antigen again, this type of immunity is most
effective and generally per____ for a long time, sometimes even for life.
Health and Diseases (III) Body Defence
d)
P.10
Acquired Active Immunity
This is achieved by injecting (or less commonly administering orally) small amounts of ant____,
called the vaccine, into the body of an individual. The whole process is called vaccination or
immunisation. If the whole organism is administered it should be safe because the organism is either k
or attenuated / we
. This ensures that the individual does not contract the disease itself, but is
stimulated to manufacture antibodies against the antigen. Often a second, boo
injection is given
and this stimulates a much quicker production of antibody which is long lasting and which protects
the individual from the disease for a considerable time. Several types of vaccine are currently in use.

Toxoids
Exotoxins produced by tetanus and diphtheria bacilli are detoxified with formaldehyde, yet their antigen
properties remain unimpaired. Therefore vaccination with the toxoid will stimulate antibody production
without producing symptoms of the disease.

Killed organisms
Some dead viruses and bacteria are able to provoke a normal antigen-antibody response and are used
for immunisation purposes.

Attenuated organisms
Modified but living organisms are injected into the body. They are able to multiply in the body without
producing disease. Attenuation may be achieved by culturing the organisms at higher temperatures
than normal or by adding specific chemicals to the culture medium for long periods of time. Attenuated
vaccines for tuberculosis, measles, rubella and poliomyelitis are now in general use.
IV)
Unwanted Immune Response
As the immune system of the body will react to any “foreign” antigen, this poses a problem when one
wants to purposely introduce something into the body. For example transfusion of blood of an
incomp_____ group into a person, or organ trans_____.
This is because every human being has certain cell surface antigens (e.g. A and/or B on red blood
cells, HLA antigens on human tissue cells) due to inherited g____. These antigens varies from individual to individual within the same species. Thus, if cells from one individual is transferred to
another individual whose cell surface antigens does not match with the donor, any transferred cells will
be regarded as “foreign” by the recipient's immune system. These foreign cells will then be
regarded as anti____ and either CMIR or HIR is elicited to destroy them.
In blood transf____, HIR produces antibodies to aggl_______ RBCs from incompatible donor.
Unmatched organ transplants will be rejected by CMIR reactions. If rejection is minimized,
careful note must be taken to ensure that the donor and recipient's surface antigens are as similar as
possible (matching).
Hypersensitivity / alle____ of some individuals towards things like pollen, grass etc. is another
example of immune response that is not desirable.
A)
Blood Groups and Blood Transfusion
When a patient receives a blood transfusion it is imperative that he receives blood that is compatible
with his own. If it is incompatible, a type of immune response occurs. This is because the donor’s red
cell membranes possess mucopolysaccharides which act as antigens and react with antibodies in the
recipient’s plasma. The result is that the donor’s cells are agglutinated.
Two antigens exist and they are named A and B respectively. The complementary plasma
antibodies are named anti-A and anti-B, and are present in the plasma all of the time.
Health and Diseases (III) Body Defence
Blood group
Percentage of population
Antigen
Antibodies
0
46%
Nil
Anti-A and Anti-B
A
42%
A
Anti-B
B
9%
B
Anti-A
P.11
AB
3%
A+B
Nil
When transfusion occurs it is important to know what will happen to the cells of the donor. If there is
a likelihood of them being agglutinated by the recipient's plasma Antibody then transfusion should
not take place.
Individuals with blood group O are termed universal do____ because their blood can be given to
anyone. It possesses cells which will not be agglutinated by the recipient's plasma antibodies. Although
group O possesses Anti-A and Anti-B antibodies there will be very little agglutination of the recipient's
cells because the donated plasma is dil____ so much by the recipient's blood that it is ineffective in
its agglutination activity. Individuals with group AB can receive blood from anyone and are called
universal rec_______. However, they can only donate to blood group AB.
Compatible Transfusion
A
AB
O
B
Reference Reading: - The rhesus factor (an antibody-mediated immune disorder)
Of the total population, 85% possess red cells containing an antigen called the rhesus factor and are termed
rhesus positive. The remainder of the population lack the rhesus antigen and are therefore regarded as rhesus
negative. Rhesus -ve blood does not usually contain rhesus antibodies in its plasma. However, if rhesus +ve
blood enters a rhesus -ve individual the recipient responds by manufacturing rhesus antibodies.
The practical importance of this observation is made obvious when a rhesus -ve mother bears a rhesus +ve
child. During the later stages of the pregnancy, fragments of the rhesus +ve cells of the fetus may cross the
placenta & enter the mother's circulation and cause the mother to produce rhesus antibodies.(usually of the
IgG class,) These can infiltrate to the fetus and destroy fetal red cells. Normally the antibodies are not formed
in large enough quantities to unduly affect the first-born child. However, subsequent rhesus +ve children can
suffer chronic destruction of their red cells. A rhesus baby is usually premature, and anaemic, and its blood
needs to be completely replaced by a transfusion of healthy blood. This treatment may now be undertaken whilst
the baby is still in the womb.
Although certain other red cell antigens (in addition to Rh) sometimes cause problems for a fetus, an ABO
incompatibility does not. Why is an Rh incompatibility so dangerous when ABO incompatibility is not?
It turns out that most anti-A or anti-B antibodies are of the IgM class and these do not cross the placenta. In fact,
an Rh-/type O mother carrying an Rh+/type A, B, or AB fetus is resistant to sensitization to the Rh antigen.
Presumably her anti-A and anti-B antibodies destroy any fetal cells that enter her blood before they can elicit antiRh antibodies in her.
This phenomenon has led to an extremely effective preventive measure to avoid Rh sensitization. Shortly after
each birth of an Rh+ baby, the mother is given an injection of anti-Rh antibodies. The preparation is called Rh
immune globulin (RhIG) or Rhogam. These passively acquired antibodies destroy any fetal cells that got into
her circulation before they can elicit an active immune response in her.
B)
Transplantation and Rejection
Replacement of diseased tissues or organs by healthy ones is called transplantation and is a
technique used increasingly in surgery today. However, when foreign tissue is inserted into or onto
another individual it is rejected by the recipient because it acts as an antigen, so stimulating the
immune response in the recipient.
Health and Diseases (III) Body Defence
P.12
a)
Types of Transplantation
The following terms are used for the different kinds of transplantation.
Autograft
Allograft
Xenograft
tissue grafted from one area to another on the same individual. Isograft- a graft between
two genetically identical individuals such as identical twins.
a tissue grafted from one individual to another individual of the same species but of
different genetic constitution.
a graft between individuals of different species such as from pig to human.
Only allografting will be discussed here.
b)
Rejection of graft
As blood is a fluid tissue, then simple blood transfusion can be regarded as an allograft. Here rejection
results in agglutination of the donor's red cells as discussed earlier. When rejection of tissue, such as
skin, occurs the following sequence of events takes place.



c)
The skin allograft initially develops blood vessels in the first 2-3 days and generally looks healthy.
During the next six days its vascularisation decreases, and a great number of T lymphocytes and
monocytes gather in the vicinity of the graft.
Two days later the graft cells begin to die and the graft is eventually cast off.
Prevention of Graft Rejection
There are several means of preventing graft rejection currently in use, listed as follows.

Tissue m

Exposure of bone m
and l
therefore slows down rejection.

Immunosup
- here the principle is to use agents which inhibit the entire activity of the immune
system. When this occurs graft rejection is delayed, but the main problem with this technique is that the
patient becomes susceptible to all other kinds of in
. It has also been shown that immunosuppression
may make the patients more prone to develop can
.

If the disadvantages of non-specific immunosuppression are to be overcome then ways must be found of
suppressing only the T cells response to the antigens of the graft. In this way the rest of the patient's
immune system would remain unimpaired and continue to function normally. The most promising approach
is to treat the patient (or his bone marrow) with anti____ that recognises and destroys the T lymphocytes
responsible for the graft rejection.
- this is an obvious and necessary precaution to take prior to any surgery.
tissues to X-irradiation tends to inhibit blood cell production and
Reference Reading 1 : Monoclonal antibodies ( A Nobel Prized Innovation)
When a micro-organism gets into the body, or when a vaccine is administered, antibodies are always produced.
For certain sorts of laboratory research it is useful to have a pure preparation of antibodies with single
specificity.
Until comparatively recently it was impossible to obtain such pure cultures. However, in 1975 Cesar Milstein
and Georges Kohler at Cambridge succeeded in fusing antibody-secreting cells with tumour cells. The
resulting cells, called hybridomas, secrete antibodies, and are immortal - a property of tumour cells.
These hybridoma cells can be cultured as a pure clone, and their antibodies collected. Antibodies produced
this way are, like the cells that produce them, all identical and they are called monoclonal antibodies.
Milstein and Kohler were awarded a Nobel Prize for their work in 1984.
For what specific purposes do you think monoclonal antibodies are required?


Antibodies can be labelled with dye or other materials that permit it to be traced.
It is possible to produce large quantities of pure line antibody for any targeted antigen, and cytotoxic
drugs may be delivered to the specific cells they are to kill by piggybacking the drugs with the antibody
for the cells--very promising for cancer treatment.
Health and Diseases (III) Body Defence
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Reference Reading 2 : Allergy
An allergy is a harmful immune response elicited by an antigen that is not itself intrinsically harmful.
Every year millions of people suffer bouts of sneezing, running noses and itchy eyes during the pollen season all of which are symptoms of hay fever. These unpleasant symptoms are the result of an excessive immune
response or hypersensitivity and they constitute an allergy. Allergies can be induced by a variety of agents
such as grass pollen, cat fur, fungal spores and certain drugs, or as a result of an insect bite. What
happens is that antigens from one of these sources bind with the mast cells and are then attacked by
antibodies. This causes the mast cells to produce potent chemical substances such as histamine which are
responsible for the unpleasant symptoms.
Histamine causes dilation of the capillaries, flushing of the skin, itching, and constriction of the bronchi. It also
increases the permeability of the capillaries, which results in an increase in the rate of formation of tissue fluid,
causing swelling of the organs and tissues. Many of the symptoms of allergies can be attributed to
histamine. One method of treating such allergies is to give the patient anti-histamine drugs.
Immediate Hypersensitivities.
These occur quickly after exposure to the allergen. They are usually mediated by antibodies of the IgE class.
Examples: hay fever, asthma
Asthma attacks all age groups but often starts in childhood. It is a disease characterized by recurrent attacks
of breathlessness and wheezing, which vary in severity and frequency from person to person. In an
individual, they may occur from hour to hour and day to day.
This condition is due to inflammation of the air passages in the lungs and affects the sensitivity of the nerve
endings in the airways so they become easily irritated. In an attack, the lining of the passages swell causing
the airways to narrow and reducing the flow of air in and out of the lungs.
The basophils and their tissue-equivalent the mast cell, has on their surface antibodies of the IgE types. They
have no effect until and unless they encounter allergens with antigens that can bind to their antigen-binding
sites.
When this occurs, the mast cells to which they are attached explosively discharge their granules by exocytosis.
The granules contain a variety of active agents including histamine and other substances Release of these
substances into the surrounding tissue causes local anaphylaxis: swelling, redness, and itching. In effect,
each IgE-sensitized mast cell is a tiny bomb that can be exploded by a particular antigen.
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The most common types of local anaphylaxis are:

hay fever in which airborne allergens react with IgE-sensitized mast cells in the nasal mucosa and the
tissues around the eyes;
 bronchial asthma in which the allergen reaches the lungs either by inhalation or in the blood
Some people respond to environmental antigens (e.g., pollen grains, mold spores) with an unusually
vigorous production of IgE antibodies. Why this is so is unclear; heredity certainly plays a role.
Systemic Anaphylaxis
Some allergens can precipitate such a massive IgE-mediated response that a life-threatening collapse of the
circulatory and respiratory systems may occur.
Frequent causes: insect (e.g., bee) stings, many
drugs (e.g., penicillin) a wide variety of foods
(shellfish and nuts are common offenders.)
Treatment of systemic anaphylaxis centers on the
quick administration of adrenaline, antihistamines,
and — if shock has occurred — intravenous fluid
replacement.
An example of systemic anaphylaxis
The three graphs show the physiological responses
of a physician (Dr. Vick) stung by a single bee while
on a picnic with coworkers (fortunately some with
medical training!). Dr. Vick required cardiac
massage and intravenous injections of adrenaline at
the times shown. He and his colleagues worked in a
laboratory studying bee venom, but prior to this
episode he had no idea that he had developed such
extreme susceptibility.
Desensitization
So far, the most effective preventive for IgE-mediated allergies is to inject the patient with graduallyincreasing doses of the allergen itself.
Unfortunately, this therapy takes a long time and the results are too often disappointing.
Anti-IgE Antibodies
Monoclonal antibodies specific for blocking the action of IgE are in clinical trials. They have shown some
promise against asthma and peanut allergy, but such treatment will probably have to be continued indefinitely
(and will be very expensive).
Health and Diseases (III) Body Defence
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Reference Reading 3 : Organ Transplantation
Since the first transplant operations were carried out in the 1960s, organ grafting has emerged from being a
perilous final attempt at saving life to become the standard treatment for many major diseases of vital
organs. More than 200 000 organ grafts have been performed worldwide, and results continue to improve.
I) The problem of rejection.
The greatest problem facing the transplant surgeon is rejection of the transplanted organ. Unless special
treatment is given to suppress the patient's immune system, a graft between members of the same species
is rejected after 5 to 14 days. The body destroys the foreign tissue as it would a bacterium or virus. The speed
of rejection depends on how closely matched the tissues of the donor and recipient are. Thus, grafts
between identical twins are accepted permanently, since identical twins have the same genes and are
perfectly matched. In grafts between siblings, there is a one in four chance that the main tissue types will
match each other. In grafts between unrelated people, the chance of the tissues matching is remote.
The chief factors that determine rejection are the ABO blood groups and the tissue typing of the white
blood cells. However, even if these are matched, rejection may still occur because there are minor tissue
groups that we cannot yet identify. Therefore, in all cases except identical twins, drug treatment to
prevent rejection is necessary after a transplant operation. The drugs prevent the recipient's lymphocytes
attacking the graft. Their dosage needs to be carefully watched: too low a dose results in the graft being
rejected; too high a dose suppresses the immune system to such an extent that the patient readily succumbs to
infection.
II) The surgical procedure
We can now transplant all vital organs except the brain. Of course, the grafted organ must continue to
function properly after the transplantation operation. It is therefore necessary to join up the arteries and veins
of the donor organ to those of the recipient, and if the organ has a duct this must also be dealt with. Speed is
essential, for the circulation to the organ must be reestablished before the cells die.
III) Donors
For paired organs such as the kidneys, a volunteer - usually a close relative - can be a donor, provided the
blood group and tissue match are satisfactory. The donor can manage with the one remaining organ. In the
same way, a lobe of the liver can be removed for grafting without jeopardising the donor's health.
However, most human transplants are taken from recently dead donors. Organs from patients dying of
cancer or an infectious disease cannot be used for fear of transmitting the disease to the recipient. In
practice, most donors have died from brain injury caused by trauma or haemorrhage following a ruptured
brain artery. In such patients the heart can be kept beating only by ventilating the lungs with a machine. When
tests make it absolutely certain that the donor's brain is irreversibly damaged, the ventilator should be
stopped since to continue resuscitation in these circumstances would be fruitless and very distressing for the
relatives. If permission has been given, organs may then be removed for transplantation.
IV) Which organs are transplanted?
Vital organs commonly grafted to replace those that have become diseased are the following:

Kidney. This was the first organ to be transplanted. The donor kidney is usually placed on one side of
the lower abdomen. The current success rate is encouragingly high: in cases where the donor and
recipient are unrelated 80 per cent of transplanted kidneys are functioning after one year; and in cases
where the kidney comes from a matched sibling, the figure is over 90 per cent. The longest survivor with
graft function is over 25 years. Should a kidney graft fail, the patient can be kept in a reasonable state of
health by repeated dialysis until another kidney becomes available for transplantation. Some patients
have had as many as five or six kidney transplants.

Heart and lungs. These are grafted in their normal positions after removal of the diseased organs. They
may be grafted together or separately. Heart transplants are more successful than lung transplants since
the latter are more prone to infection and rejection. Approximately 70 per cent of heart grafts, and 60 per
cent of lung grafts, are functioning after one year whether they are grafted separately or together.

Liver. This is the most difficult organ to transplant because of its multiple connections and complex blood
supply. Moreover, in liver disease, blood clotting is impaired and serious bleeding can occur, making
surgery difficult. However, the procedure has improved and 70 per cent of liver grafts are now functioning
after one year. The longest survivor had the operation 23 years ago.
V) Suppressing the immune system
Health and Diseases (III) Body Defence
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In principle, all recipients of organ grafts receive the same drugs to inhibit rejection, whatever the
transplanted organ. Each drug has particular advantages and disadvantages. Their combined action is to
inhibit the production or action of lymphocytes.
Patients generally receive small doses of azathioprine, corticosteroids and cyclosporin. This 'triple therapy'
combines the effectiveness of all three drugs but avoids most of the more serious side effects. If rejection starts
to occur, extra doses of corticosteroids or anti-lymphocyte proteins usually reverse the rejection.
For the majority of patients who respond well, their quality of life can be virtually normal. They can
participate in active sports and have children, but they need to continue taking immunosuppressive drugs
indefinitely. As a result, they are more susceptible to infection and cancer than normal people are.
VI) The future
Most transplant failures are caused by the graft being rejected, or from infection resulting from excessive
immunosuppression. No doubt safer and more effective drugs will be developed. As the results of organ
grafting within the human species improve, efforts may be made to use organs taken from other animal
species. This will introduce new moral dilemmas.
Another development will be the grafting of non-vital organs. Already, more than 2000 pancreas grafts have
been performed to combat diabetes, but there is controversy over whether this treatment is better than insulininjection. The first successful bowel grafts have been reported. Grafts of testes and ovaries will raise new
ethical debates!
But whatever the ethical problems, organ grafting is now an established and preferred treatment for many
previously fatal diseases and its continued development will form one of the main branches of surgery.
Some of the Triumphs of Vaccination
The greatest triumph is the eradication of smallpox from the planet, with no naturally-occurring cases
having been found since 1977. As far as the public knows, smallpox virus now exists only in laboratories in
the U. S. and Russia. There is currently a vigorous debate as to whether these should be destroyed. If
smallpox ever should get back out into the environment, the results could be devastating because smallpox
vaccination is no longer given and so the population fully susceptible to the disease grows year by year.
This table compares the number of cases of illness in the U.S. in a representative year (either before a vaccine
was available or before it came into widespread use) with the number of cases reported in 1994.
Disease
Total cases
Year
Cases in 1994
% Change
Diphtheria
206,939
1921
2
-99.9%
Measles
894,134
1941
963
-99.9%
Mumps
152,209
1968
1537
-99.9%
Pertussis
265,269
1934
4617
-99.9%
Poliomyelitis*
21,269
1952
0
-100%
Rubella
57,686
1969
227
-99.9%
Tetanus
1,560
1923
51
-99.9%
Problems of vaccine development
With so many triumphs, why haven't vaccines eliminated other common diseases such as malaria and HIV-1
infection (the cause of AIDS)?
One problem is that experimental vaccines often elicit an immune response that does not actually protect
against the disease. Most vaccines preferentially induce the formation of antibodies rather than cell-mediated
immunity. This is fine for those diseases caused by



toxins (diphtheria, tetanus)
extracellular bacteria (pneumococci)
even viruses that must pass through the blood to reach the tissues where they do their damage (polio,
rabies)
But viruses are intracellular parasites, out of the reach of antibodies while they reside within their target
cells. They must be attacked by the cell-mediated branch of the immune system, such as by cytotoxic T
lymphocytes (CTLs). Most vaccines do a poor job of eliciting cell-mediated immunity (CMI).
Health and Diseases (III) Body Defence
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Example: Much of the early — and so far unsuccessful — work on anti-HIV-1 vaccines has focused on the
antibody response of the test animal. Antibodies may have a role in preventing infection or minimizing its
spread, but cell-mediated responses will probably turn out to be far more important. Certainly there are
thousands of patients dying of AIDS despite their high levels of anti-HIV-1 antibodies. (The most
widespread test for HIV-1 infection does not detect the presence of the virus but the presence of antibodies
against the virus.)
V)
Chemotheraphy and Antibiotics
This is the administration of chemical substances, natural or synthetic, that kill or prevent the
reproduction of micro-organisms. The term is now extended to include the inhibition of dividing
malignant cells in cancer. The chemical substances used are called chemotherapeutic agents.
A)
Antibiotics
They are chemical substances produced by micro________ (bacteria and fungi) in low concentrations
has the capacity to inhibit growth or even destroy bacteria or other microorganisms.
They are medically important because they can kill pathogenic microorganisms without affecting
the hosts-- Human or livestocks.
One of the best-known antibiotics is penicillin which was discovered by the British bacteriologist
Alexander Fleming in 1928. Penicillin has saved countless millions of lives. Since the discovery of
penicillin many more antibiotics have been isolated from a range of micro-organisms, both bacteria
and fungi. These include erythromycin, streptomycin and chloramphenicol, and sulphonamides. Also
a number of synthetic antibiotics have been developed, including penicillins.
Although chemotherapeutic agents have had an enormous influence on the control of disease, they have
one serious drawback. Every time a new one is used, r
strains of micro-organisms arise.
Further drugs then have to be developed. New drugs should therefore be used with restraint and
discrimination.
B)
Properties of a good antibiotics

Should be able to destroyed many different species of pathogenic microorganisms

Should prevent the ready development of resistant forms of the parasites

Should not produce undesirable side effects in the host, such as sensitivity and allergy, berve damage,
irrritation to the kidneys and gastrointestinal tract.

Should not eliminate the normal microbial flora of the host. The normal microflora are usually
nonpathogenic and they help in preventing pathogenic miroorganisms from establishing colonies in our body.

Should be stable and long lasting
C)
a)
Action of Antibiotics
Bacteriostatic
- inhibiting / slowdown the growth of bacteria without killing them.
- e.g. Tetracycline is an inhibitor of protein synthesis in bacteria.
Health and Diseases (III) Body Defence
b)
P.18
Bactericidal
- stop the growth of bacteria by killing them.
- e.g. Penicillin inhibits the synthesis of new cell wall in some bacteria.
Q. Folic acid is an essential vitamin (One of the B Vitamins) for the synthesis
of nuclei acid. Human obtain its folic acid from their food.
Some bacteria manufacture its own Folic acid from P-aminobenzoic acid
(PABA), which is therefore a growth factor for the bacteria. The following
diagram shows the structure of P-aminobenzoic acid and sulphanilamide.
Sulphonamides are antibiotics derived from sulphanilamide.
a. Explain how they can be effective in inhibiting growth of the bacteria.
b. Describe a simple experiment to support your theory.
c. Assuming no other side effect of sulphonamide. Explain why it is safe to take sulphonamide as drug.
d. It is known that laboratory rodents (e.g. rats) would develop signs of Vitamin K deficiency if sulphonamide is supplied in
its food. Suggest a possible reason for the observation
Reference Reading : AIDS and the HIV
The
disease apparently originated in Africa in
the late 1960s but was not widely recognized
until the late 1970s. It may have begun in the
green monkeys which inhabit the sub-Saharan
region.
I)
The Symptoms of AIDS
It is characteristic of AIDS that symptoms may not
develop for many years. When symptoms do occur,
the most common sign is swelling of the lymph nodes.
Subsequently the person may display fever, persistent
diarrhoea, severe fatigue and drenching sweats. These
are symptoms of AIDS-related complex (ARC). Usually
this progresses to AIDS itself, characterised by a
vulnerability to unusual forms of cancer and a wide
range of infections attributable to a collapse of the
immune system.
II)
How HIV damages the immune system
Immunodeficiency is a state where part of the body's immune defence against disease becomes defective,
leading to an increased susceptibility to certain infections. The pattern of infection in these new cases
indicated that this particular defect mainly affected the cell-mediated part of the immune system.
Previously, immunodeficiency had been confined to relatively uncommon congenital disorders where a
person was born without a part of the immune system, and to situations where a previously normal immune
system had become damaged or suppressed by disease or drug therapy, such as that used to prevent
Health and Diseases (III) Body Defence
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rejection of transplanted organs. The new condition became known as AIDS (acquired immune deficiency
syndrome) and the cause turned out to be a virus, now known as human immunodeficiency virus, HIV.
HIV is a small virus consisting of RNA genes surrounded by a protein coat. The RNA codes for its own
specific proteins, one of which is an enzyme called reverse transcriptase. This enzyme reverses the usual
process of gene transcription so that a DNA copy of the virus can be made from its RNA. This DNA copy is
then spliced into the gene of the infected human cell, causing persistent infection and making the host cell
become a factory for HIV replication.
One of the virus proteins that the DNA codes for is a glycoprotein in the viral coat, called gp120. This is vital
in targeting the virus to cells of the immune system which thus become infected and damaged.
An early finding in people with AIDS was that they have a greatly reduced number of T helper lymphocytes.
These cells are characterised by a molecule on their surface membrane called CD4 which is central to
communication between cells of the immune system. The viral gp120 molecule has a region that binds to a
part of the lymphocyte CD4 molecule, rather like a key fitting into a lock. In this way the virus is able to
recognise the lymphocyte and infect it.
The loss of CD4 recognition site apparently disable the helper T cells to recognize other B or T cells, and
so unable to activate them.
For example, macrophages cannot be properly activated to kill certain
organisms, B lymphocytes are unable to develop new antibody responses, and killer T cells show
impaired function. Some of these effects are the result of reduced lymphokine signals which normally come
from CD4 lymphocytes.
All this leads to progressive impairment of the cell-mediated immune system and, to a lesser extent, the
humoral system. The net result is the development of increasing susceptibility to certain bacteria, fungi,
protists and viruses and to some rather unusual virus-induced tumours.
In parallel with immunodeficiency, HIV can damage the nervous system. This too appears to result from both a
loss of cells and defective function in those that remain.
III)
What kinds of people are easily infected with AIDS ?
The first AIDS patients in the Americas and Europe were almost exclusively male homosexuals. Later
patients included those who used unsterilized intravenous needles to inject illicit drugs; hemophiliacs
(persons with a blood-clotting disorder) and others who had received blood transfusions; females whose male
sexual partners had AIDS; and the children of such couples.
However, since 1989, heterosexual sex was found to be the fastest growing means of transmission of the
virus, with 90 percent of new cases originating from heterosexual sex.
IV)
How are AIDS transmitted ?
AIDS is transmitted by direct contamination of the bloodstream with body fluids that contain the AIDS
virus, particularly blood and semen from an HIV-infected person. The virus is usually transmitted through
various forms of sexual intercourse, the transfusion of virus-contaminated blood, or the sharing of HIVcontaminated intravenous needles.
The AIDS virus cannot penetrate intact bodily surfaces, such as skin, and quickly perishes outside the
human body. Consequently, AIDS is not spread by casual physical contact or by sneezing. The virus has
been found in tears and saliva, but it exists there in such low concentrations that transmission from these
body fluids is extremely rare. There are no known cases of AIDS transmission by insects such as mosquitoes
or by domestic animals.
The virus is usually passed to an infant close to or during delivery, rather than moving across the placenta.
Recently infected mothers can transmit the virus to their children via breast milk
V)

What are the preventive measures ?
The use of one sexual partner and the absence of promiscuity will clearly reduce the risk of infection.
Health and Diseases (III) Body Defence
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
The reduction in the spread of HIV could be brought about by the use of clean needles and sterile
syringes by drug addicts. Some health authorities in European countries, such as Holland, provide free
sterile needles and syringes for drug users, but this has been suggested that this will lead to increased drug
addiction.

All blood donated must be tested for the presence of antibodies to HIV which indicates whether or not
the donor is infected. Blood containing these antibodies is not used.

using latex condoms whenever engaging in intercourse.

Education about the disease
VI)
Detection
Usually, when the AIDS virus enters the bloodstream, the body's immune system produces antibodies to battle
the microorganism. Blood tests can detect these antibodies and therefore can indicate exposure to the virus.
However, these tests occasionally give false readings and only begin to give accurate results within two
weeks to three months after infection, during which time an infected person may pass the virus to others.
Scientists do not know exactly how the AIDS virus damages the immune system, nor do they understand why the
natural antibodies developed to destroy the virus are ineffective.
Most people recently infected by the AIDS virus look and feel healthy. In some people the virus may remain
inactive, and these people act as carriers, remaining apparently healthy but still able to infect others for up
to several years.
VII)
Why do people with HTV take so long to develop AlDS?
One of the unusual things about infection with HIV (human immunodeficiency virus) is that it typically takes years
before any symptoms are seen. Indeed, some people infected never seem to progress to AIDS.
Why does it take so long for HIV to progress to AIDS, and why do some people infected with HIV never show any
symptoms? Recent research suggests that the answer may be related to the extraordinarily high mutation rate
of HIV. HIV mutates up to a million times faster than other viruses. In a person infected with HIV, the virus
replicates and, because the mutation rate is so high, sooner or later the host's antibodies fail to recognise
the viral antigens. Eventually enough of these mutant viruses accumulate to start attacking the person's
immune system. That is approximately when the first symptoms of AIDS appear.
If this theory turns out to be correct, then finding a cure for AIDS is going to be even harder than previously
thought, and finding a vaccine virtually impossible. From the biological point of view, it is an impressive
example ofjust how rapidly evolution can take place.
VIII)
Vaccination ?
The development of a vaccine is a top priority of AIDS research and offers the best hope of stemming the AIDS
crisis. However, the production of an effective AIDS vaccine is a tremendous challenge, since the virus infects
the very cells that the vaccine needs to activate. Some of the problems to be overcome are:
a)
b)
c)
d)
HIV is a retrovirus which inserts its own genes into the cell it is infecting, thus establishing a permanent
infection. Even if a cell is not actively producing viruses, it may still harbour dormant retroviral genes.
Because no viral antigens are on the cell surface, it remains invisible to the immune system.
Retroviral genes have been found to disrupt the normal growth of a cell. In other words, retrogenes cause
cancer. So if a vaccine is made from attenuated whole viruses it could cause cancer.
HIV is constantly mutating and changing its envelope protein by altering the sequence of amino acids.
The virus has a great affinity for CD4, the T cell surface protein to which it binds. Attempts have been
made to produce antibodies to the part of the virus that binds to CD4, to try to prevent binding. This has
proved more difficult than at first thought, because it seems that a second round of antibodies is
produced against the first. These attack the CD4 and destroy the T cells themselves. These are the
very cells that are under attack from the virus.
Researchers are still trying to find a 'weak spot' by which to attack HIV and most studies have been of the
envelope protein. This is a glycoprotein, where the protein component is like string wrapped around the matrix
and covered on the outside by a 'cloud' of sugar molecules. These sugars are made by the host cell and are not
Health and Diseases (III) Body Defence
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antigenic. Scientists are trying to develop a vaccine which will expose the protein beneath the sugars,
particularly the CD4 binding sites. This should then promote an immune response.
One major problem for researchers, is that there is no good animal 'model' for the disease on which to test
or produce a vaccine. Most animals do not get AIDS from HIV. Chimpanzees can be infected with HIV but none
so far have developed AIDS. Macaque monkeys have been infected with HIV-2 which is a variant found in West
Africa, and have developed AIDS. However there has been no success with the more pathogenic and common
HIV-1.
There is also a shortage of human volunteers willing to try the many new vaccines being developed. Each one
requires up to 100 high-risk Volunteers for the first phase of trials and later, thousands of people would be
needed for testing. Yet, despite all these difficulties, scientists all over the world are working towards defeating
HIV.
END