11.1 Defence Against Infectious Disease Human Health 11.1 Defence Against Infectious Disease 2009-2010

11.1.1 Blood clotting. Clotting is the mechanism that prevents and stops blood loss from broken blood vessels. Prothrombin Thrombin Fibrinogen Thrombin Fibrin Fibrin + RBC = Clot Clotting Factors

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.  

11.1.2 Immunity This section is a simple introduction to the complexities of the human immune system. Don’t forget: cytotoxic response barriers to infection Skin Mucous membranes Secretions 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

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

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.

Clonal Selection (d) 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.

Clonal Selection (e) 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:

Cytotoxic Response T-killer lymphocytes (aka Cytotoxic cells) are able to find and destroy cancerous cells or cells infected with a virus “Self” recognition 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. 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

11.1.3 Definitions of active and passive immunity.

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. In this diagram a B lymphocyte has already cloned to produce Plasma and Bm cells a) Plasma cells synthesize antibodies which have 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).

Immunological memory: 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

11.1.5 Monoclonal antibodies. 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

Diagnosis of HIV infection using monoclonal antibodies. The test of HIV infection is based on detecting the 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). (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

Treatment of Rabies using monoclonal antibodies Rabies infection can be quickly 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

Other applications Cancer Treatment Transplant Tissue Typing Purification of industrial products

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. 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:

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 infection) the person will produce secondary infection Levels of response. i.e. high antibody levels rapid response Recovery is therefore rapid perhaps showing little or any sign of infection with these serious diseases.

11.1.7 Benefits and dangers of vaccination.