Transcript Body Defence

Body Defence
BODY DEFENCE MECHANISMS
The body defends itself against physical
injuries and invasion by harmful
materials and organisms in various ways.
These ways can be divided into
PREVENTION and
CURE.
1. PREVENTION
secretions
mechanical barriers
1. PREVENTION
(a) Against physical injuries
(i) Tough outer coating
- keratinised compound squamous epithelium of skin.
The skin is thickest in areas where physical injury is most common
e.g. palms of hands, soles of feet.
(ii) Adipose tissue
- forms a cushion between skin and underlying organs.
Some delicate organs, e.g. kidneys, may be further protected by a
coat of fat.
(iii) Bones
- the delicate haemopoietic (blood forming) tissues are encased in
the shafts of long bones of the limbs and the sternum (red bone
marrow).
The brain, spinal cord, heart and lungs are also protected by bones.
(b) Against invasion by harmful materials and organisms
(i) Intact skin
- relatively few chemicals and organisms are able to penetrate intact
skin.
(ii) Cilia
- beating of cilia on the outer surface of epithelial cells in the
respiratory tract he1ps to prevent harmful dust/bacteria etc. reaching
the lungs.
(iii) Secretions
- many body secretions contain chemicals which are harmful to
many pathogenic organisms.
e.g. gastric juice (pH 2)
tears (from lachrymal glands)
mucus - respiratory tract, vagina
sebaceous secretions
lysozyme in tissue fluid
2 CURE
There are two important mechanisms by which the
body can remove harmful materials / organisms
once they have entered the body.
These mechanisms are:
I. INFLAMMATORY RESPONSE
II. SPECIFIC IMMUNE RESPONSE
The inflammatory response is a local response to
tissue damage and invasion by harmful materials
and/or organisms.
The response is often described as being “non-specific”
as the response is much the same regardless of the
nature of the issue damage or foreign material/
organisms.
The strength of an inflammatory response does, however,
vary according to the severity of an injury.
The inflammatory response can:
- remove dead and damaged body cells
- remove harmful materials and cells
Specific
immune
responses
differ from
inflammatory responses in that an immune response is
a ‘specific’ response to invasion by harmful materials
and/or cells.
Thus a particular immune response will deal specifically
with the material or organism which stimulated the
response.
Immune responses cannot deal with dead or damaged
body cells, however certain cells of the immune
system can ‘remember’ a particular harmful material
or organism and can react very quickly to a second or
subsequent invasion by that substance.
I. INFLAMMATORY RESPONSE
Events during localized infection (a non-specific mechanism):
 permeability,  blood flow, vasodilation
Histamine is
released from
mast cells
WBCs emerge
from blood
vessel
I. INFLAMMATORY RESPONSE
When connective tissues and blood vessel walls are damaged by
physical injury or the presence of harmful materials/cells, certain
cells respond by liberating a variety of chemicals.
These chemicals have two major functions:
(a) Capillary dilation,
resulting in increased blood flow in the damage area.
(b) Increase in capillary permeability, allowing blood plasma and
neutrophil phagocytes to pass into the surrounding fluid.
(a) and (b) cause the inflamed area to become:
(i) red
(ii) swollen
(iii) warmer than surrounding tissues
(iv) painful (due to pressure of increased fluid on local
endings)
The phagocytes which have migrated from blood vessels
engulf dead and damaged cells, thus cleaning the
wound, and also phagocytose harmful materials and
organisms.
Once cell debris and ‘foreign’ materials are removed
tissue repair can take place.
The inflammatory response is not always sufficient to
destroy and remove harmful materials and organisms,
and these may migrate from the site of injury to other
parts of the body via the blood and lymph.
It is in such situations that a specific immune response
occurs.
To lymph node
To spleen
II SPECIFIC IMMUNE RESPONSE
Lymphocytes are the most important cells in immune
responses, although other cells are also involved, such
as macrophages.
Lymphocytes are found in the blood (20-25% of white
blood cells) and in lymphoid organs such as the bone
marrow, thymus, lymph nodes (often called glands) and
spleen.
Any substance which is recognized as ‘foreign’ by
the body and which can stimulate an immune
response is called an ANTIGEN (Ag).
Antigens may be soluble macromolecules, cell
surface components or chemicals synthesized by
foreign cells.
Commonly encountered antigens include:
Bacteria ( components of cell walls and flagellae, toxins)
Viruses ( protein ‘coat’ subunits)
Fungi and protozoa ( cell surface components)
Macromolecules ( especially proteins)
Less frequently encountered antigens include:
RBC’s (‘blood group substances’ on membranes)
grafted cells (cell membrane proteins or glyco-proteins)
There are two kinds of immune responses:
- ANTIBODY response (or humoral immune response)
- CELLULAR response (or cell-mediated immune response)
In general, ANTIBODY responses deal with bacterial
and RBC antigens and possibly fungal and
protozoal antigens,
whilst the CELLULAR response deals with viral
antigens, grafted cells and possibly fungal and
protozoal antigens.
(a)
Development of immune responsiveness
(i) Lymphocytes develop in the bone marrow from haemopoietic
precursor cells.
(ii) Some lymphocytes nature fully in the bone marrow to
become B lymphocytes (B cells).
(iii)Other, immature, lymphocytes pass from the bone marrow to
the thymus where they mature into T lymphocytes (T cells).
(iv)Both B and T cells pass to the lymph nodes and spleen via the
blood stream.
(N.B. Lymph nodes and spleen can be regarded as a complex
organization of three types of cell involved in the initiation of
the immune reaction - lymphocytes, plasma cells and
phagocytic cells of the mono-nuclear phagocyte system.
Different types of white blood cells
Stem cell
leucocytes
agranulocytes
Granulocytes
(polymorphonuclear
Leucocytes-PMN)
lymphocytes
RBS platelets T cell B cell
33%
erythrocytes
Macrophage
phagocytic
Neutrophile Basophil
Monocyte 50-70%
0-1%
2-8%
phagocytic
Eosinophil
1-4%
Allergic?
Mast cell
Releases histamine
Different types of white blood cells
1) Granulocytes (polymorphonuclear leucocytes or cells)
- White blood cells that possess GRANULES in their cytoplasm,
with nuclei & a few days of life span,
- a) Neutrophils:
- the most abundant PMN, an important PHAGOCYTIC cell for
NON-SPECIFIC body defence;
- amoeboid, can leave blood vessels & enter into tissue.
b) Eosinophils:
quite rare, functions uncertain but probably phagocytic &
associated with hypersensitivity & allergic reactions.
c) Basophils:
- smallest number, NON-PHAGOCYTIC but becomes MAST
CELLS when entered tissues;
- contains HISTAMINES which when released, will cause vasodilation, increased blood flow, increased permeability of blood
vessels & outflow of cells.
2) Agranulocytes (no granules in the cytoplasm)
a) lymphocytes (33%):
B CELLS & T CELLS which are small cells with large
nucleus;
b) monocytes (2-8%):
Phagocytic, becomes macrophage in tissues & have
kidney-shaped nucleus
**Development of B & T cells
Both B & T cells originate from a stem cell in
haemopoietic tissues (yolk sac & liver in foetus; bone
marrow in adults).
Some migrate via blood to the thymus & develop into T
cells/lymphocytes.
These T cells then migrate to lymph nodes & spleens
where most of them reside and be ready for specific
immure responses.
Thymus, being an important organ for the differentiation
of stem cells into specific lymphocytes, is called the
PRIMARY LYMPHOID TISSUE while lymph nodes &
spleen where the mature immunocompetent cells lie are
called SECONDARY LYMPHOID TISSUES
In birds, some stem cells migrate from haemopoietic
tissues to an organ called Bursa of Fabricius and
develop into B cells/lymphocytes.
The B cells then migrate to the lymph nodes &
spleen and reside there for specific immune
responses.
The bursa equivalent for mammals is unknown. The
bone marrow is thought to be a likely place.
When B & T cells arrive at the secondary lymphoid
organs (lymph nodes & spleen), they settle in
separate specific areas.
There are specific T & B areas in these organs.
Primary
lymphoid
tissues
Secondary
lymphoid
tissues
/spleen
The secondary lymphoid organs are the places
where B & T cells accumulate.
It is also the place where pathogens in blood
& lymph are caught.
It is in these places that pathogens stimulate
the B & T cells and TURN ON specific
immune responses.
Most specific responses take place at these
sites. They are therefore the battle grounds
for specific mechanisms!
**antigen processing
**
T cell
response
or
B cell response
STIMULATION OF SPECIFIC RESPONSES
When pathogens reach the lymph node or spleen,
they may be first processed 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.
(b) Reaction of lymphocytes to antigen
(i) In the lymph nodes or spleen the antigen stimulates B
and / or T lymphocytes as follows:
(ii) ( I ) Humoral response:
antigen
Memory cell
Blast
cell
antibodies
OR T-helper cell for
T-dependent antigens
Antibody
forming
cell
Plasma cell
Primary immune response
Secondary immune response
antigen
B cell
Same antigen
Blast cell
Antibody forming cell
Plasma cell which produce antibodies
Differentiation of B cells
The characteristics of the humoral response is that B
cells are involved & the process results in the
production of ANTIBODIES specific for the
antigen.
THE PRIMARY RESPONSE (elicited when an
antigen entered into the body for the FIRST TIME):
When an antigen reaches the lymph node/spleen, it
will stimulate the appropriate B cell there which is
specific to it.
Some antigens cannot turn on the B cell directly, they
need the presence of T cells & these antigens are
called T-dependent antigens (in contrast to Tindependent antigens).
The stimulated B cell will then differentiate &
multiply into BLAST CELLS.
These in turn proliferate & differentiate into
ANTI-BODY FORMING CELLS and then
plasma cells which are very efficient in
producing ANTI-BODIES which can then act
on the antigen.
Receptor sites
for antigens
High affinity for
PMNs, macrophage
The antibodies are Y-shaped structures which are also called
IMMJJNOGLOBULINS as they are protein molecules.
The top ends of the “Y” are specific to the particular antigen & can
therefore bind to it.
The antibodies can help to destroy antigens in
three main ways:
1) Bacterial lysis by antibody
bacterium
antibodies
Attachment of antibodies
Complement attached to bacterium-antibody complex
A hole is drilled by the complex,
resulting in lysis
Lysis and death
The antibodies can help to destroy antigens in
three main ways:
1) Bacterial lysis by antibody
2) Enhanced phagocytosis
Enhanced phagocytosis:
Bacterium is “slippery”
Phagocyte cannot grasp it
coat
bacterium
Antibodies attached to coat of
bacterium
Since end of antibody has high
affinity for phagocyte,
phagocyte can now grasp
bacterium through antibody
The antibodies can help to destroy antigens in
three main ways:
1) Bacterial lysis by antibody
2) Enhanced phagocytosis
3) Certain antibodies can neutralize bacterial toxins by
forming antigen-antibody complexes which are then
phagocytosed.
Eosinophils are especially active in phagocytosing
antigen-antibody complexes.
SECONDARY RESPONSE:
Memory B lymphocytes are long-lived cells which
remain dormant in lymphoid tissues for many
months or years, until the antigen which
stimulated their production is encountered again.
If and when this occurs the memory B Lymphocytes
respond immediately to antigen by dividing and
differentiating into more plasma cells and memory
B lymphocytes.
Stronger and
faster
Latent period
1st injection
Primary response
Latent period
Re-injection
Secondary response
Compared with the original, or primary
response to antigen the secondary immune
response is:
- larger
- faster
- longer lasting, as once stimulated, the
memory cells continue to divide for months
or years.
(II) Cellular response
T lymphocytes
cell divisions and differentiation
cytotoxic T lymphocytes
and
activated T lymphocytes
+ ‘memory’ T lymphocytes
The cell-mediated immune response (CMIR)
Memory
cell
Killer T cell (cytotoxic T cell)
Kill antigen directly
lymphokines
antigen
Activated T cell
*No antibodies are involved
monocyte
macrophage
Activated
macrophage
kills antigen
Cytotoxic T lymphocytes
- these migrate (if necessary) to the site of the
antigen, which is normally a cell with
antigen on its surface.
- The cytotoxic T cells are capable of killing
cells with antigen on their surfaces.
- These ‘target’ cells then lyse and the
fragments are phagocytosed.
- As ‘in the antibody response, cytotoxic T
cells have a particular specificity, only
reacting with cells bearing the antigen
which stimulated their production.
Activated T lymphocytes
- these liberate chemicals called lymphokines.
The lymphokines then activate the macrophages into
activated macrophages which are highly efficient in
eating and killing the antigens.
Memory T lymphocytes are very similar to memory B
lymphocytes, except that subsequent stimulation by
antigen results in rapid production of more cytotoxic T
lymphocytes and memory T lymphocytes.
The same graph showing primary and secondary
responses applies except that the y axis becomes
‘number of cytotoxic T lymphocytes’.
(I) IMMUNITY ANY IHM1UNITSATOIN
Immunity of the body refers to “all those
physiologic mechanisms that endow the
animal with the capacity to recognize
materials as foreign to itself and to
neutralize, eliminate, or metabolize them
with or without injury to its own tissues”.
Immunity to a disease may be acquired
naturally or artificially.
Natural Immunity
1. Natural passive immunity is important in young babies
when antibodies in the mother’s blood diffuse across
the placenta before birth.
Maternal antibodies are also present in breast milk.
As antibodies are catabolised in a few months the
protective effect is short-lived.
2. Natural active immunity results from infection with a
pathogen, resulting in the individual producing his own
antibodies etc.
If the disease has a long incubation period then both
primary and secondary responses occur, resulting longterm immunity, e.g. mumps, chicken pox.
Artificial Immunity
1. Artificial passive immunity involves an injection of
‘ready-made’ antibodies, usually obtained from animals
immunised with the antigen.
The immunity is short-lived (3-6 months) as the
antibodies are catabolised, however this is a good
method of immunisation if instant immunity is required.
2. Artificial active immunity involves the
introduction of killed or non-virulent strains
of disease-causing organisms into the body.
Humoral and/or cellular responses then
take place.
Generally at least two doses of antigen
are given at suitable intervals, so that the
secondary immune response is stimulated.
There are three main types of bacterial and viral
antigen preparations in current use:
(a) Toxoids
Soluble toxins of bacteria such as diphtheria and
tetanus, modified and made less toxic by adding
formalin or gentle-beating.
Treatment destroys the toxic parts of the antigen
molecule, leaving the antigenic sites unchanged.
(b) Killed organisms
Cultured organisms killed by heat, UV light or
chemicals, e.g. whooping cough (pertussis),
poliomyelitis (Salk), cholera, typhoid.
(c) Live, “attenuated” organisms
Vaccines made from strains of organisms that have lost
their virulence.
The emergence of an attenuated strain is a combination
of science and luck
e.g. BCG - a virulent strain of Mycobacterium
tuberculosis was grown in a medium containing bile
salts which resulted in the production of an attenuated
strain - Bacillus Calmette - Guerin (1908).
Other examples of vaccines prepared from attenuated
organisms are poliomyelitis (Sabin), measles, rubella,
yellow fever.
Virtually all countries tog have a Standard
immnunisation schedule for babies and children.
There is no doubt that childhood immunisation has
had a dramatic effect on the incidence of many often fatal - viral and bacterial diseases, many of
which are virtually unheard of in Hong Kong
today.
Perhaps the greatest success story is the result of the
WHO’s efforts to eradicate smallpox by rigorous
immunisation programmes world-wide.
At present considerable efforts are being made to develop
vaccines for the prevention of protozoal diseases such
as malaria, trypanosomiasis and schistosomiasis, these
diseases being common causes of illness and death in
developing countries.
The reason why no, successful vaccines have been
developed so far seems to be that protozoan pathogens
have evolved a variety of complex mechanisms for
evading the immune responses of their human hosts.
Additionally there are a number of bacterial and viral
diseases for which vaccines are not yet available, either
because the killed organisms are not antigenic or
because a safe (non-virulent) strain of a particular
organism has not yet beep developed, e.g. viral hepatitis
– new and better vaccines are not available.
(II) TRANSPLANTION
Grafted skin and transplanted organs such as kidneys may be
rejected by the recipient - unless the donor is an identical twin or
possibly a sibling.
The rejection mechanism is basically a cellular immune response
against ‘foreign antigens’ on the membranes of the transplanted
cells.
On virtually all our cells, except RBCs and the cornea, are
genetically-coded glyco-proteins called transplantation antigens
or histo-compatibility antigens.
In a population possibly one hundred or more of these antigens
exist, but one individual only possesses eight of these.
The number of combinations is therefore enormous!
The recipient’s immune system will recognise transplanted cells as
foreign if one or more tissue antigens on the donor cells differ
from those on the recipient’s own cells.
Fortunately it is now possible to ‘type’ the cells of
potential donors and recipients in the laboratory
for the most important of these antigens.
A good ‘tissue-match’ between donor and recipient
(i.e. most or all antigens the same) indicates that
the transplant has a good chance of survival and
vice-versa.
DRUGS
In the broadest sense, a drug is any chemical that can
effect an alteration in the function or structure of
living tissue.
As commonly used, the word ‘drugs’ implies
medicinal chemicals - those substances that, in
carefully regulated doses, produce desirable
changes in the human body, counteracting disease
or relieving distress.
Antibiotics
Antibiotics refer to drugs obtained from
microorganisms, and are often used to kill other
microorganisms.
They may be anti-bacterial and/or anti-fungal.
One of the best known antibiotics is penicillin, which
acts on growing bacteria, killing them and
preventing their growth.
However, its precise mode of action is unknown, as
is the case with the majority of antibiotics.
Sulphonamides
Sulphonamides are complex organic ring compounds
with a powerful antibacterial action.
The sulphonamides are similar in their chemical
structure to para-aminobenzoic acid, an essential
metabolite in the reproduction of certain bacteria.
They are believed to compete with paraaminobenzoic acid for the active site of an enzyme.
In this way, though they do not actually kill the
active site of an enzyme.
In this way, though they do not actually kill the
bacteria, they stop them reproducing.