cell recognition + immune response

• Pathogens


  - an organism which causes a disease

  - eg. viruses, bacterium, fungus

  - cause disease by damaging/killing cells and tissues or by producing toxins
• Antigens


  - a molecule, usually a protein, with a specific tertiary structure

  - stimulates an immune response

  - found (mostly) on the surface of cells

  
  

  enable the immune system to identify:

  ->pathogens

  -> cells from other individuals of the same species

  -> toxins

  -> abnormal body cells eg cancer/infected cells
• Phagocytosis - non-specific immune response


  - phagocyte recognises foreign antigen on pathogen

  - phagocyte engulfs the pathogen, forming a vesicle called a phagosome

  - lysosomes fuse with the phagosome

  - lysozymes are released which hydrolyse molecules of the pathogen to destroy it

  - antigens of the pathogen are presented on the cell surface membrane of the phagocyte (can now be called an antigen-presenting cell)

  
• lymphocytes


  - white blood cells that carry out the specific immune response

  - B lymphocytes are associated with the humoral response

  - T lymphocytes are associated with the cellular response
• T cells - cellular response


  - antigen on the cell surface membrane of an antigen-presenting phagocyte binds to a complementary receptor on a specific helper T cell

  - this specific helper T cell stimulates:

  -> more phagocytes

  -> specific B cells

  -> cytotoxic T cells (which kill infected cells)
• B cells - humoral response


  - specific B cells are activated by specific helper T cells

  - B cells divide by mitosis into plasma cells and memory B cells

  - plasma cells secrete many identical antibodies (monoclonal antibodies - same tertiary structure, complimentary to one antigen)

  - antibodies bind to complementary antigens and agglutinate pathogens
• agglutination


  - antibodies bind to 2 antigens on different pathogens, causing them to clump together and be held in one area

  - this makes pathogens more easily engulfed and hydrolysed by phagocytes
• memory B cells

  when re-infected with the same antigen:

  - specific memory B cells with the complementary antibody divide by mitosis

  - to form plasma cells

  - which make many more antibodies much more quickly
• what is clonal selection?

  only the B cell with the specific antibody complementary to the antigen is cloned
• antibodies structure


  - a protein, specific to an antigen, secreted by plasma cells

  
  

  - made of 4 polypeptide chains - 2 light and 2 heavy joined by disulphide bridges

  
  

  - constant region is the same in all antibodies

  - variable region differs between antibodies from different plasma cells

  
  

  - an antibody bound to an antigen is called an antigen-antibody complex

  
• what does each antibody have?

  a specific tertiary structure with a specific variable region/binding site which is complementary and binds to only one type of antigen
• why does the structure of an antibody allow for agglutination?

  antibodies have two binding sites so they can bind to two antigens on different pathogens at the same time
• monoclonal antibodies


  - produced from identical/cloned plasma cells and have the same tertiary structure

  - therefore have the same specific bonding site/variable region which binds to the same antigen
• primary response

  - antigen infects the body for the first time

  - slower as it takes time for specific B cells to clone into plasma cells (clonal selection) = antibodies are produced slower

  - symptoms occur
• secondary response

  - body is re-exposed to the same antigen

  - bigger and faster as specific memory B cells with complementary antibody, clone much faster into plasma cells

  - plasma cells produce many more antibodies much more quickly

  - no symptoms occur (milder)
• vaccinations

  - vaccinations contain antigens of a pathogen

  - phagocyte presents the antigen on cell surface membrane

  - specific helper T cell activates specific B cells

  - B cells clone into plasma cells and memory cells

  - plasma cells secrete many antibodies with specific binding sites complementary to the antigen - antibodies agglutinate the antigen and destroy it

  - memory B cells are produced so on second exposure to the antigen, more antibodies are produced more quickly, destroying the pathogen before symptoms are displayed

  
  

  BOOSTER DOSES ARE GIVEN TO INCREASE THE NUMBER OF MEMORY CELLS OVER A LONG PERIOD OF TIME
• Herd immunity

  - if most people are vaccinated against a disease, this can provide protection for the whole population

  - those who are not vaccinated are still protected because they are less likely to come into contact with infected individuals
• Active immunity

  - primary immune response is stimulated by an antigen leading to the production of antibodies by plasma cells

  - takes more time due to slower process

  - long term immunity because memory cells are produced

  - natural = immune after infection

  - artificial = immune after vaccination

  
  

  + long term protection as memory cells made

  - artificial can only be given before getting the disease

  - takes more time to be immune, to make memory cells

  - natural will get symptoms of the disease
• Passive immunity

  - antibodies introduced into body from outside source

  - takes less time due to faster process

  - short term immunity because no memory cells are produced and antibodies are broken down

  - natural = baby receives antibodies from mother's milk

  - artificial = injected with preformed antibodies

  
  

  + can be given after exposure to antigen/pathogen

  + works straight away

  - does not last long as antibodies broken down, no memory cells produced
• Ethical issues with vaccinations

  - often involves use of animals to develop vaccine (may cause pain/suffering)

  - possible side effects

  - human testing - volunteers may be at risk

  - for vaccine to be effective - herd immunity - should vaccination be compulsory? can people opt out? If so on what grounds?

  - should expensive vaccination programmes continue when disease is almost eradicated?
• Antigenic variability


  - due to mutations in the DNA of pathogens, the tertiary structure of the antigen can change shape

  - antibodies from the specific memory cells are no longer complementary to the antigen (re-exposure)

  - each new infection causes a new primary response requiring clonal selection and production of the antibody again
• Problems with antigenic variability

  - antigen has a different tertiary structure to that of the vaccine, so the vaccine becomes ineffective

  - a new vaccine needs to be developed each time the antigen changes which takes time and is expensive

  - individuals previously protected from a disease are now susceptible
• HIV (human immunodeficiency virus) structure

  retrovirus which infects and kills helper T cells (host cell), reducing the effectiveness of the immune response

  
  

  structure:

  -> *reverse transcriptase = enzyme which converts RNA into DNA in host cell

  -> *viral RNA = genetic material of HIV

  -> protein capsid = surrounds and protects genetic material

  -> *lipid envelope = outer layer made of membrane taken from previous host cell

  -> attachment proteins = attaches virus to complementary receptor on host helper T cell

  
  

  * = only HIV

  
• HIV replication


  - attachment protein attaches to a complementary receptor molecule on the cell membrane of the host helper T cell

  - capsid is released into the cell and uncoats releasing RNA into the cytoplasm

  - reverse transcriptase is used to make a complementary strand of DNA from the RNA

  - DNA is made double stranded and is inserted into the host DNA

  - host cell enzymes and ribosomes are used
• AIDS (acquired immune deficiency syndrome)

  - HIV kills helper T cells

  - when helper T cells numbers drop significantly the immune system starts to fail

  - minor infection occur

  - then more serious infections occur (cancer becomes more common)

  - when T cell numbers become very low, serious infections can kill the patient

  - clinically diagnosed when T cell number drops below 200ml per ml of blood
• Explain how HIV leads to AIDS and patient death

  - HIV infects and kills Helper T-cells

  - Specific B-cells are not activated so do not clone into plasma cells so specific antibodies are not produced

  - Cytotoxic T-cells are not activated so do not kill infected cells;

  - Pathogens are not destroyed so continue to divide/multiply

  -And destroy host cells and produce toxins
• Why are antibiotics not effective against viruses?

  Antiviral drugs


  - target parts of a bacteria which are not found in a virus eg bacterial cell wall, ribosomes and bacterial enzymes

  
  

  - viruses are difficult to kill as they replicate inside cells and have few drugs targets such as enzymes, as they use the host cells enzymes and organelles for replication

  - one target for antiviral drugs is reverse transcriptase, but this only works if it is a retrovirus which contains reverse transcriptase
• Treating disease - cancer

  - monoclonal antibodies can be made to have specific shaped variable regions

  - which are complementary to and bind specific antigens on cancer cells

  - antibody is linked to a toxin which kills the cancer cells
• Monoclonal antibodies in diagnosis

  pregnancy tests:

  -> used to find hCG hormone in the urine of pregnant women

  
  

  diagnosing disease using tissue samples

  -> monoclonal antibodies are complementary for the antigens on cancer cells so can be used in cancer diagnosis on biopsy tissue samples. antibody complementary for the cancer antigen has a fluorescent tag on it which shows up down a microscope

  
  

  covid lateral flow tests:

  -> used to find antigen of the coronavirus present in the sample taken from saliva

  -> if antigen was present, it would bind to the complementary antibody bound to the paper at the 'T' line

  -> 'c' line = test has worked + sample taken has moved past the 'T' line
• ELISA test

  - enzyme-linked immunosorbent assay

  - used in disease diagnosis, uses monoclonal antibodies to see if body has a certain antibody (indirect) or antigen (direct)
• Indirect ELISA - used to detect an antibody


  - HIV antigen bound to bottom of a well in a well plate

  - sample of patient's blood plasma, which might contain several different antibodies is added to the well

  - if there are any HIV-specific antibodies in the plasma, these will bind to the HIV antigen in the well (primary antibodies)

  - well is then washed to remove any unbound antibodies

  - secondary antibody, that has a specific enzyme attached to it is added to the well

  - secondary antibody can bind to the HIV-specific antibody

  - well is washed out to remove unbound secondary antibodies

  - if there are no primary antibodies in blood, all secondary antibodies will be washed away as they have no primary antibodies to bind to

  - a solution is added to the well which contains a substrate, able to react with the enzyme attached to the secondary antibody and produce a coloured product
• Ethical issues with monoclonal antibodies

  - technique involves inducing tumours in mice

  - in many cases, mice are 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