10: Disease and Immunity

• Pathogens can be bacteria, viruses or fungi.
• Pathogens cause disease by damaging host cells or releasing toxins.
• An antigen is a foreign/non-self protein that stimulates an immune response/production of antibodies.
• Lysosomes contain hydrolytic enzymes which are powerful digestive enzymes which hydrolyse cells and/or organelles.
• Phagocytosis:

  Phagocytes recognise and bind to an antigen on the pathogen.

  Phagocytes engulf pathogens.

  They are enclosed in a vesicle.

  Lysosomes fuse with the vesicle and release lysozymes which digest/destroy the pathogen by hydrolysis.

  The phagocyte then places the antigen from the pathogen on its cell surface membrane and becomes and antigen-presenting cell.
• T-cells respond to antigen-presenting cells (such as phagocyte which has become an antigen-presenting cell).

  Specific helper T cells with receptors complementary to the antigens bind to them.

  T helper cells release chemicals called cytokines.

  This activates the T cell to divide rapidly by mitosis and form a clone of genetically identical cells.

  This results in cytotoxic T cells which destroy infected body cells that are presenting the same antigen by releasing perforin which makes holes in the cell membrane of the infected cell.

  More specific helper T-cells.

  Memory T cells.
• A specific B cell is activated when its complementary receptor binds to a specific antigen.

  Specific B cells can also be activated by chemicals (cytokines) released by specific helper T cells.

  The activated B cell then divides rapidly by mitosis to form a clone .

  They will develop into either plasma cells or memory B cells.

  Plasma cells secrete antibodies specific to the antigen.

  If memory cells encounter the same antigen at a later date they will divide rapidly and produce larger numbers of both cells which means if there are more plasma cells more antibodies will be produced faster.
• The secondary response is much faster than the primary response because there are already memory cells against the antigen so it can divide more quickly by mitosis to produce much larger numbers of plasma cells(clonal selection happens faster as there isn't time waisted while a specific B lymphocyte is activated).
• Organelles in a plasma cell:

  RER - site of protein synthesis (antibodies)

  Mitochondria - produce ATP through respiration which is required for protein synthesis.

  Golgi body - needed to modify & package antibodies into vesicles to be secreted by exocytosis.
• Similarities of humoral and cellular:

  both involve mitosis, both produce memory cells, both involve lymphocytes, both activated by helper T cells.
• Differences between cellular and humoral:

  cellular involves cytotoxic T cells while humoral involves B cells, cellular acts on cells which have been infected by a pathogen while humoral acts on pathogens circulating in the blood, humoral involves production of antibodies, cellular does not.
• Antigenic variability is when the antigens on the surface of each strain are different because mutations in the genes cause antigens to have a different tertiary structure and shape which will not correspond to the memory cells from previous infections.
• Antibodies are Y-shaped proteins synthesised by plasma cells which react with antigens to form an antigen-antibody complex as they are complementary shapes.
• When an antibody binds to an antigen is causes agglutination to occur, which means all the pathogens are clumped together due to the antigen-antibody complex, meaning the clumps can be engulfed by a pathogen more easily.
• Comparison of antigens and antibodies:

  both have tertiary structure

  both involved in the immune response

  antibodies are proteins, antigens are usually proteins but sometimes glycoproteins

  antigens trigger an immune response, antibodies don't

  antibodies complementary to antigens bind to and destroy or deactivate antigens
• Passive immunity is when an individual acquires antibodies from an outside source. immunity is immediate but short-lived as when the antibodies are broken down they are not replaced by the body. e.g when a foetus acquires antibodies from the mother across the placenta.
• Active immunity is when the immune system is stimulated to produce its own antibodies. Memory cells are produced meaning the antibodies can be produced again. It takes longer but is longer lasting.
• Comparison of active and passive immunity:

  Active requires exposure to antigen, passive doesn't.

  In active, antibodies are produced but in passive they are given/acquired.

  Active takes time for the immunity to develop, in passive protection is immediate.

  In active memory cells are produced, in passive they are not.

  In active protection is long term while in passive it is short term.
• A vaccine contains antigens and stimulates the production of plasma cells, antibodies and memory cells against a particular pathogen.
• Vaccines may be killed or attenuated pathogens (treated with heat to prevent them from causing illness but preserves their antigen), or isolated antigens.
• A vaccine must:

  Have few side effects if any

  Be economically available in quantities sufficient to immunise the entire vulnerable population

  Be easily stored and transported

  Have means of administration
• It is not vital to vaccinate 100% of the population in order to stop the spread of disease (90% is usually sufficient) because the pathogen will be killed quickly in vaccinated people and people who are not vaccinated have a very low chance of coming into contact with an unvaccinated person. (herd immunity)
• It is difficult to completely eradicate a disease because:

  Some individuals may have a defective immune system so may fail to induce immunity

  The pathogen may mutate quickly and change their antigens

  There may be many varieties of the same organism each with different antigens.
• Arguments for vaccination:

  fewer people getting disease

  less spread to individuals who cannot be vaccinated
• Arguments against vaccination:

  Involves animal testing

  Vaccines may have side effects

  Don't know when to discontinue vaccination
• Monoclonal antibodies are produced by the same B cell/plasma cell or from a clone of genetically identical B cells. All have same tertiary structure and bind to one specific antigen.
• Monoclonal antibodies can be made by injecting mice with antigen you wish to identify. Mouse produces antibodies by normal immune response, and these will be specific for the injected antigen. these can b extracted and purified.
• The antigen used to make a monoclonal antibody does not have to be from a pathogen - any non-self protein will result in production of monoclonal antibodies by B cells. This means they can be used to make a specific test for a protein and are widely used in medicine.
• Monoclonal antibodies are used for:

  Medical diagnosis

  Targeted drug treatments (cancer drugs can be attached to monoclonal antibodies)

  Drug testing of athletes (monoclonal antibody can be used to identify specific drug in sample)

  Pregnancy testing kits
• The ELISA test uses monoclonal antibodies to detect the presence and amount of a specific protein in a sample. It is highly sensitive and detect a substance even in small amounts.
• ELISA test:

  Container coated with monoclonal antibodies

  Sample to be tested is added to the container

  If the specific antigen is present it will bind to antibodies

  A second antibody with an enzyme attached is added, which binds to the antigens

  Sample is washed

  Substrate for this enzyme is added

  The substrate is hydrolysed and a colour change indicates a positive result
• In the ELISA test, it is important to wash after the second antibody to remove unbound second antibody to prevent a false positive result.
• Arguments for monoclonal antibodies:

  provides new treatments for specific conditions

  has been successful in treating cancer and diabetes
• Arguments against monoclonal antibodies:

  Involves animal testing producing tumour cells by deliberately inducing cancer in mice

  There have been deaths when treating multiple sclerosis
• HIV:

  Attachment proteins bind to specific, complementary receptors on the surface of helper t cells

  The capsid containing genetic material and reverse transcriptase is released into helper T cell

  Inside the cell RNA and reverse transcriptase are released

  This is used to make a complementary strand of DNA using the viral RNA as template

  DNA is incorporated into T cell's own DNA and is used to make new viral proteins

  New HIV viruses bud from cell and infect other helper T cells
• The symptoms of AIDS are as a result of other infections, not HIV virus directly. these are due to the fact that fewer T cells means fewer B cells, Tc cells and phagocytes become activated, so body's immune response is reduced. Symptoms include infection of lungs, fever, tiredness, weight loss and diarrhoea.
• HIV cannot be treated with antibiotics because these are only effective against bacterial infections. This is because viruses are not cells so do not have the structures that the drugs target. Viruses also have a different metabolism and infect body cells, so antibiotics can't affect them without damaging host cells.
• ELISA test can be used for presence of HIV antibodies specific to HIV antigens. Container is coated with antigens, blood sample added, antibodies will bind to the antigens. A second antibody with enzyme attached is added and container is washed. Substrate is added and a colour change indicates positive result. It would be difficult to test presence of antigens as they would be inside T helper cells.