Defence against infectious disease.
Clotting is the mechanism that prevents and blood loss from broken blood vessels.
a) Platelets or damaged cells release a group of proteins called clotting factors. These clotting factors are released into the plasma a wound site.
b) Clotting factors activate the enzyme Thrombin from its inactive form prothrombin
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.
This section is a simple introduction to the complexities of the human immune system. Whilst antibody production represents the more complex level of immunological response it should not be forgotten that there are other important aspects including the cytotoxic response, barriers to infection and phagocytes.
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.
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
c) The lymph node contains a wide variety of B Lymphocytes
The macrophage presents the antigen 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.
Notice the presence of T Lymphocytes that are selected in the same way at the same time.
d) In this example a corresponding B 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.
e) B lymphocytes rapidly 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:
Antibody production is covered in section 11.1.4 but another important immune response is the cytotoxic response of the T-lymphocytes:
T-killer lymphocytes also known as Cytotoxic cells are able to find and then destroy cells infected with a virus or a cancerous cell.
Tk Cells probe the surface of 'self' cells. Those that share the same surface glycoproteins are recognise 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.
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.
11.1.2 shows how the presentation of the macrophage in the lymph node results in the clonal selection of an appropriate
B lymphocyte. In this diagram a B lymphocyte has already cloned to produce Plasma and Bm cells
a) Plasma cells synthesis antibodies which has a complementary structure to that of the antigen epitope.
b) The antibody binds to the antigen (A) and then binds them to other antigen 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).
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.
There are various diagnostic and treatment technologies that use antibodies.
To produce antibodies on a large scale
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
The rest of this section deals with uses of monoclonal antibodies in the diagnosis and treatment of named diseases.
Diagnosis of HIV infection using monoclonal antibodies.
(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.
Rabies infection can be quickly an effectively treated by the direct injection of antibodies
The antibodies are synthesis ed by monoclonal antibody technology
This is an effective treatment for a very serious infection
Transplant Tissue Typing
Purification of industrial products
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.
The pathogen organism in some vaccines is dead and in others is weakened (attenuated).
These vaccines carry the pathogen antigen (epitope) and therefore stimulate clonal selection and the development of immunological memory but without developing the disease symptoms or signs.
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 infection) the person will produce secondary infection
Levels of response. i.e.
high antibody levels
Recovery is therefore rapid perhaps showing little or any sign of infection with these serious diseases.
Read and discuss.
The decision to immunise.
The decision to immunise or not is a decision based on some kind of risks-benefits analysis. The problem perhaps is that not all members of a community are in the position to carry out such an analysis, primarily as they have limited knowledge of the process. Under such circumstances people are inclined to follow some of the more sensationalist types of journalism.
The effectiveness of vaccines has resulted in generation of people who have no direct experience of disease that once commonly killed or disabled. Tuberculosis (TB) was once so serious that in the post second world war period, hospices existed in virtually ever town in the UK. In these hospices men and women would be confined with very little prospect of recovery. The older members of our communities still carry the scar of these once common diseases and their experiences are not to be ignored. Today, some consider that such disease no longer constitute a threat to the population. Yet TB has once more emerged in the homeless populations of europe and in particular the UK. As recently as August 2006 it was announced that super-resistant strains of TB had emerged against which we have no effective vaccine. This must give cause for thought amongst the ' it wont happen to me' groups.
In the UK, as in many nations there are immunisation targets for the population. These targets if achieved effectively protect the whole population, this concept is called herd immunity. The principle is to isolation those individuals who are carrying individuals by surrounding them with immune individuals. Therefore preventing the transmission of the disease through the population. Different diseases require different % immunisation's within the population.
There are those who take the decision not to immunise and they do so for a wide variety of reason. Some of these individuals will justified this decision on the rare nature of diseases, or that they have not contracted any instance of the diseases. That they have not contracted an infection is a consequence of the immunisation programmes used by the rest of the population. In other words, they have benefited form the herd immunity . It is a serious step to devolve the responsibility for vaccinate to others. Should we all follow this choice the now rare diseases will quickly spread once more through the population. There is some evidence that this has already begun in developed regions of the world.
There has been much publicity surrounding the dangers of autism as a side effect to the MMR combined vaccine. This vaccine is against measles, mumps and rubella. Each of these diseases has serious effects on the individual and are good examples of the once common serious disease which have now become rare. The reports about the complications of the MMR vaccine have received serious attention in the medical community. If there is any such risk it is statistically very low in comparison to the dangers of contracting measles, mumps or rubella. Of course statistic apply to populations they do however help informed decisions for the individual.
Currently having my own children are being immunised and I take this decision to do so by comparing the risk of death or serious disabilities from the various diseases against that of side effects and complication of the vaccines. Currently, I believe that the balance is still very much in favour of vaccination. You the students of IB will very soon face this same decisions when you come to immunise your own children. At that time you will have to balance the risks and benefits but significantly you will be taking real decisions about real people and not a theoretical exercise.
The following link to the recommended immunisation schedule for children and adolescents in the USA. The diagram is modified from the source paper Recommended Childhood and Adolescent Immunisation Schedule-United States 2006 MMWR Jan 6,2000/Vol 54/Nos 51 &52