Transcript Human Health

Human Health
11.1 Defence Against Infectious Disease
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2009-2010
11.1.1 Blood clotting.
Clotting is the mechanism
that prevents and stops
blood loss from broken
blood vessels.
Prothrombin
Fibrinogen
Clotting
Factors
Thrombin
Fibrin + RBC = Clot
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Thrombin
Fibrin
Clotting Mechanism
a) Platelets or damaged cells release
a group of proteins called clotting
factors. These clotting factors are
released into the plasma at the
wound site.
b) Clotting factors convert inactive
prothrombin to thrombin
c) Thrombin turns the soluble plasma
protein fibrinogen into its
insoluble fibrous form Fibrin.
d) Fibrin binds together platelets and
blood cells to form a solid 'plug'
for the4 wound. This plug is called
a clot.
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11.1.2 Immunity
 This section is a simple introduction to the
complexities of the human immune system.
 Don’t forget:
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cytotoxic response
barriers to infection
 Skin
 Mucous membranes
 Secretions
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phagocytes
Clonal Selection theory:
 a) A in the diagram represents an
antigen (These could be viruses,
bacteria, protozoa, fragments of cell
membrane or simply molecules)
 Notice the surface molecules called
EPITOPES represented by the green
and red shapes.
 Epitopes are the molecules that are
recognised by the leucocytes which
in turn triggers the immune
response
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Clonal Selection (b)
 b) The antigen epitope is
detected by the large white
cell blood cell called a
macrophage
 The macrophage engulfs the
antigen, digests it and then
incorporates the epitope into
its own cell membrane
 The macrophage migrates to
the lymph node
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Clonal Selection (c)
 c) The lymph node contains a wide
variety of B Lymphocytes
 The macrophage presents the
antigen’s epitope and selects a B
lymphocyte that has a
complementary surface epitope.
Polyclonal Selection: As the
macrophage may have a number of
molecules in its membrane it is
possible for more than one (poly) B
Lymphocyte to be selected.
 T Lymphocytes are selected in the
same way at the same time.
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Clonal Selection (d)
 d) In this example a corresponding B
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lymphocyte and T Lymphocyte have
been selected.
A T Helper cell with the corresponding
epitope has also been selected.
The T-Helper cell has a synergistic effect
of both the selected B and
T lymphocyte.
This synergy involves stimulating both
the B and T Lymphocyte to divide
rapidly.
The T Helper cell plays a crucial
coordinating role in the immune
response.
Clonal Selection (e)
 e) B lymphocytes rapidly
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divide to form a clone of
Plasma cells (P) and B
memory cells (Bm).
T cells also rapidly clone
and produce other cells
called T Killer cells (Tk),
T Killer memory cells
(Tkm).
Summary of the cells produced during
clonal selection:
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Cytotoxic Response
 T-killer lymphocytes (aka Cytotoxic cells) are
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able to find and destroy cancerous cells or
cells infected with a virus
“Self” recognition
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Those that share the same surface
glycoproteins are recognised as 'self' from
the same organisms and the T -cells leave
them alone.
 Cancer cells and virus infected cells carry
antigen epitope on their plasma membrane.
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Tk Cytotoxic cells detect this and destroy
the infected cell.
 This will also destroy the virus or cancer cell
reducing or preventing the spread of
infection within the tissue
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11.1.3 Definitions of active and passive
immunity.
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11.1.4 Antibody production
This shows how the presentation of the macrophage
in the lymph node results in the clonal selection
of an appropriate B lymphocyte.
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In this diagram a B lymphocyte has already
cloned to produce Plasma and Bm cells
 a) Plasma cells synthesize antibodies which have
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a complementary structure to that of the
antigen’ss epitope.
b) The antibody binds to the antigen (A) and then
binds them to other antigens in what is called
agglutination.
c) This concentrates the antigen and makes it
easier to engulf by phagocytic lymphocytes.
The binding of the antibody may inactivate the
antigen directly.
The immune system has memory of the antigen in the
Bm cell (and Tkm).
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Immunological memory:
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a) Primary exposure to the antigen with the resulting clonal selection and antibody
production. During this time the individual will develop disease symptoms and
signs
b) The individual has recovered from the infection. The level of plasma antibodies
is raised and this protects from immediate, short term re-infection. There will be
significant numbers of Bm cells present in the various lymph nodes.
c) Second Infection with the same antigen
d) The result is a rapid production of antibodies to higher levels. The rapid
response is due to increased probability of antigen encountering the specific Bm
lymphocyte. The high levels of antibody might be accounted for by the large
number of Bm which are stimulated to form plasma cells
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11.1.5 Monoclonal antibodies.
There are various diagnostic and treatment
technologies that use antibodies.
 To produce antibodies on a large scale
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A specific B cell is selected that can
produce the required antibody'
A tumour cell is selected which is
capable of endless cell division
(immortal).
The two cells are joined together
(hydridised)
The resulting HYBRIDOMA is capable
of synthesising large quantities of
antibodies that can be used in various
technologies
Diagnosis of HIV infection using
monoclonal antibodies.
 The test of HIV infection is based on detecting the
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presence of HIV antibody in the patients blood serum.
The test uses results in a qualitative colour change an
is an example of ELISA (Enzyme linked Immunosorbant
assay).
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(a) HIV antigen is attached to the plate.
b) Patients serum passed over the plate. Any HIV
antibody in the patients serum will attached to the
antigen already on the plate. This is a very specific
attachment.
c) A second antibody which is specific to the HIV
antibody is passed over the plate. This antibody will
attach to the concentrated HIV antibody on the plate.
This second antibody has an enzyme attached to its
structure.
d) Chromagen dye is passed over the complex of
concentrated HIV antibody/ conjugated antibody
e) The enzyme will turn the chromagen to a more
intense colour. The more intense the colour the greater
the HIV antibody level. This would be the a positive
result for a HIV test
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Treatment of Rabies using monoclonal
antibodies
 Rabies infection can be quickly
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and effectively treated by the
direct injection of antibodies
The antibodies are synthesized
by monoclonal antibody
technology
This is an effective treatment
for a very serious infection
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Other applications
 Cancer Treatment
 Transplant Tissue Typing
 Purification of industrial products
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11.1.6 Vaccination.
There are many diseases in which the primary infection stage can do
considerable damage to the body. Some of these are serious enough to
be fatal.
 Vaccination (immunisation) uses modified pathogens (Antigen) which
have significantly reduced pathogenicity.
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The pathogen organism in some vaccines is dead and in others is
weakened (attenuated).
These vaccines carry the pathogen’s antigen (epitope) and therefore
stimulate clonal selection and the development of immunological
memory without developing the disease symptoms or signs.
Alternative diagram:
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Vaccination, cont’d
 The immune system therefore produces Bm and Tkm cells as per the primary
response.
 If an infection with the disease causing organism actually occurs (primary
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infection) the person will produce secondary infection
Levels of response.
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i.e.
 high antibody levels
 rapid response
Recovery is therefore rapid
perhaps showing little
or any sign of infection
with these serious diseases.
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11.1.7 Benefits and dangers of
vaccination.
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