Immunology

• Immune response


  When the body is invaded by any pathogen, a series of responses ensure that the pathogen is rapidly identified (as non self), and destroyed before too much damage is caused to the affected organism

  
• Ways pathogens cause harm/disease

  • Pathogens can produce toxins which can directly damage tissue
  • Pathogens can sometimes replicate inside and destroy host cells
• Cell surface molecules


  • Proteins that identify cells, pathogens, abnormal cells, and toxins
• Antigen


  Specifically shaped molecules on the surface of own cells (self) and foreign cells or pathogens (non self) that help identify each particular type of cell to the host organism

  
• Phagocytosis


  The process where phagocytes ingest and destroy cells/pathogens that display non-self antigens

  
• Phagocytosis of pathogens


  1. Phagocyte attracted to pathogen

  2. Phagocyte engulfs pathogen

  3. Pathogen enters phagosome

  4. Lysosomes fuse with phagosome, releasing enzymes

  5. Pathogen hydrolysed

  6. Waste materials released

  7. Antigen presented on cell surface

  
• Specific cellular response


  A specific response to a specific antigen on the surface of a cell or pathogen that has been recognised as non-self

  
• T cell response


  1. Antigen presenting cell presents antigen

  2. Specific T helper cell binds to antigen and clones

  3. Cloned T helper cells differentiate into different types

  
• T helper cell


  Releases cytokines to attract phagocytes, activate cytotoxic T cells, and activate B cells
• Cytotoxic T cell


  Locates and destroys infected body cells that present the correct antigen

  
• B cell activation


  1. Specific T helper cell binds to B cell and activates it

  2. B cell clones into plasma cells and memory cells

  
• Antibody


  Protein made in response to foreign antigen, has binding sites that bind specifically to an antigen

  
• Antibody structure


  • Has constant and variable regions, variable region determines specific binding site
• How antibodies assist in pathogen destruction

  • Agglutination
  • Opsonisation
  • Lysis
  • Anti-toxin & anti-venom
  • Prevent pathogen replication

  
• Memory cells


  Remain in circulation in case of future re-infection by the same pathogen
• Secondary response


  Rapid and extensive activation of memory cells to produce antibodies when re-exposed to the same antigen

  
• The secondary immune response is effective as most pathogens have the same antigens on their surface

  
• Secondary response


  The activation of memory cells to produce antibodies
• Secondary response


  • Rapid
  • Extensive
• The antigen is normally eliminated before it can cause disease or any symptoms develop i.e. the person is "immune" to the disease
• The secondary immune response is effective as most pathogens have the same antigens on their surface, and so are recognised by memory cells when re-infection occurs

  
• Gene mutations in pathogens may lead to a change in tertiary structure of antigens specific to the B cell, meaning memory B cell antibodies will no longer be complementary to the mutated pathogen so no antigen-antibody complex will form and the individual will not be able to initiate a secondary response

  
• Antigenic variability (drift)


  A change in the antigen that makes it difficult to develop vaccines against these pathogens

  
• Passive immunity


  No exposure to antigen, antibodies are given, no memory cells are produced, short term, fast acting

  
• Active immunity


  Exposure to antigen, antibodies are produced, memory cells produced, long term, takes time to develop

  
• Vaccination


  1. Vaccine contains antigens from dead, weakened or attenuated pathogens

  2. Pathogen is engulfed by a phagocyte and displayed on an antigen-presenting cell

  3. Specific T helper cell binds to the antigen on the antigen presenting cell

  4. Specific T helper cell stimulates a specific B cell (by releasing cytokines)

  5. B cell divides by mitosis to produce plasma cells and memory cells

  6. Plasma cells produce and release antibodies

  7. Memory cells recognise the antigen on second infection

  
• Vaccines are not effective against pathogens which show antigenic variability

  
• Ethical issues associated with vaccines and their development

  • Development and testing involve use of animals - does this infringe rights of animals?
  • Human testing - who should be tested, are they being put at possible risk? Is this justified by possible benefit to society?
  • Is it available to all or only those who can afford it? (in this country, in third world etc)
  • Balancing risk of side effects against possible benefit
  • Should vaccination programmes be compulsory, if society benefits?
  • Should we be aiming to eliminate an organism? (loss of genetic variability)

  
• Monoclonal antibodies


  Antibodies are specific proteins molecules; they bind specifically to ONE antigen (molecule) type
• Uses of monoclonal antibodies

  • Research
  • Immuno assays e.g. Pregnancy testing kits and ELISA
  • Diagnosis (showing presence of a particular antigen)
  • Targeting drugs
  • Killing specific cells
  • Isolating specific chemicals

  
• The technique of producing monoclonal antibodies involves inducing tumours in mice, and in many cases the mice are also genetically engineered to produce human antibodies

  
• There have been one or two examples of human volunteers suffering major and unexpected side effects when testing the monoclonal antibody

  
• How a vaccine leads to the production of antibodies against a disease-causing organism

  1. Vaccine contains inactivated antigen from pathogen

  2. Phagocyte/macrophage presents antigen on its surface

  3. Specific T helper cell with specific receptor binds to complementary antigen

  4. T helper cell stimulates specific B cell

  5. B cell with complementary antibody on its surface

  6. B cell divides by mitosis to form plasma cells

  7. Plasma cells secretes large amounts of antibody

  8. Formation of Memory B cells with complementary antibodies remain in blood

  
• ELISA tests


  Used to determine the presence of the antibody (indirect ELISA) or the antigen (Sandwich ELISA)
• HIV


  The 'Human immunodeficiency virus' causes the disease 'Acquired Immune Deficiency Syndrome' (AIDS)

  
• HIV replication - Using TH cells


  1. Attachment proteins on HIV binds with a protein receptor commonly found on TH cells

  2. Capsid fuses with cell-surface membrane and releases Viral RNA and enzymes into the helper TH cell

  3. The HIV's reverse transcriptase converts viral RNA into cDNA using host nucleotides and cDNA converted to dsDNA by DNA polymerase

  4. Viral cDNA moves into nucleus of T cell and is inserted into host cell genome (DNA). The person / cell is now INFECTED

  5. Transcription of viral DNA into (viral) mRNA which is translated to produce HIV proteins. The infected TH cell starts to manufacture new HIV virions / particles

  6. Particles (virions) break away from TH cell with a section of host cell surface membrane which forms their lipid envelope, with TH receptor proteins embedded (to gain access into more TH cells)

  
• Over time this leads to a reduction in the number of TH cells or reduction by inactivation of TH cells
• AIDS is not a pathogen, so cannot be detected using antigens or antibodies. AIDS can be screened for by checking the number of TH cells

  
• By replicating using the body's TH cells, HIV reduces an individual's ability to respond to pathogens, as their cell mediated immunity is compromised

  
• An uninfected person should have between 800 and 1200 TH cells mm -3 of blood, compared to a person suffering from AIDS can have as few as 200 TH cells mm -3 of blood