biology topic 2.3

• what is an antigen?

  • a molecule that triggers an immune response by lymphocytes
  • all cells have specific proteins on their surface membrane that identify it called antigens
  • an antigen is a protein found on the outside of cell, that triggers an immune response
• what is an antibody?

  a protein produced by lymphocytes in response to the presence of the appropriate antigen
• what can antigens identify?

  • pathogens (micro-organisms that cause disease)
  • cells from other organisms of the same species (in transplanted organs)
  • abnormal body cells (cancerous cells)
  • toxins (poisonous molecules often released by bacteria)
• what are phagocytes and what is phagocytosis?

  • phagocytes are a type of white blood cell which carries out non-specific immune response and ingests and breaks down pathogens by phagocytosis
  • phagocytes are made in the bone marrow, travel in capillaries but can squeeze through walls into tissues
  • there are two types: neutrophils and macrophages
  • phagocytosis is the cellular process of engulfing solid particles using the cell membrane - carried out by phagocytes
• what is the process of phagocytosis?

  1. a pathogen is recognised as having foreign/non self antigens. the pathogen attaches to the phagocyte by surface receptors
  2. the pathogen is engulfed by the phagocyte by endocytosis forming a phagosome
  3. lysosomes fuse to phagosome to form a phagolysosome and release H2O2, HCl and digestive enzymes into the phagosome to digest the pathogen
  4. harmless products are removed (egested/excreted) by exocytosis or used by phagocyte
• more information on phagocytosis

  • phagocytosis is non specific and it is sometimes not enough to cope with large numbers of pathogens (e.g. the flu virus)
  • phagocytes which engulf the virus, present some of the pathogens antigens on their own cell membrane-they become antigen presenting cells (APCs)
  • this activates the T-helper cells which stimulate and recruits more phagocytes and T-cells to assist in the immune response
  • this includes cytotoxic (killer) T-cells which destroy infected or foreign cells by releasing chemicals (perforin which makes pores in the membrane) into the invaded cell
• more information on phagocytosis

  • activated T-cells can then also activate B-cells causing them to divide by mitosis, this is the start of the humoral response
• specific immune response

  • there are two types of specific immune response
  • cell mediated immune response:
  • involves specialised white blood cells called T-lymphocytes which targets pathogens inside and outside cells
  • humoral response:
  • involves specialised white blood cells called B-lymphocytes which target pathogens by producing antibodies
• cell mediated immune response

  • APCs can either be phagocytes or cells that have been invaded by the pathogen
  • once phagocytosis has taken place, pathogenic antigens are presented on the cell surface membrane
  • T-cells responds to the cell which is presenting the antigens
  • T-helper cells respond first - they have receptors which fit exactly to the presented antigens
  • this activates the T-cells and they begin to differentiate and recruit other T-cells and activate B-cells
• functions of different cells

  • phagocytes - engulfs pathogens and destroys them using lysosomes, they then become APCs
  • APC's - present pathogenic antigens on its own cell membrane signalling T-lymphocytes
  • T-helper cells - stimulates lots of cells; cytotoxic T-cells, B-cells, phagocytosis, memory T-cells
  • cytotoxic T-cells - kill infected cells through the release of an enzyme that kills the cell
• what are B-cells?

  • a B-cell or B-lymphocyte is a type of white blood cell that is produces and matures within the bone marrow
  • they produce antibodies as part of their role in immunity
  • the B-cells get the antigen from pathogens or APCs and presents the antigen on its cell surface membrane
  • T-helper cells bind to this antigen to activate the B-cells
  • the B-cells begin to divide by mitosis (clone themselves) to form plasma cells and memory cells
  • this is know as clonal selection
• what is the primary and secondary immune response?

  • primary response - plasma cells produce antibodies that are complimentary to the antigens
  • secondary response - the memory cells stay in the blood stream circulating, if they come into contact with the antigen again then they divide to form plasma cells and memory cells again
• primary and secondary response

  • in the primary response there are not many intitial B-cells to make the antibody and the antibodies only survive in the blood stream for a few days
  • in the secondary response they produce antibodies much quicker and more new memory cells enter the bloodstream to provide long term immunity from reinfection of the pathogen
• what is the structure of an antibody?

  • antibodies are proteins made up of four polypeptide chains (quaternary structure), 2 heavy and 2 light
  • each chain has a variable region and a constant region
  • the chains are connected by disulphide bridges
  • all antibodies have the same constant regions that allow them to bind to receptor on immune system cells
  • they have two variable regions which are the antigen binding sites so they will have a unique tertiary structure complementary to a specific antigen
  • one antibody can bind to two pathogens at once
• how do antibodies work?

  • agglutination:
  • antibodies bind to antigens on pathogens causing them to clump together, these clumps are then destroyed by phagocytosis
  • this makes it easier for phagocytes to engulf more pathogens at a time
  • neutralising toxins:
  • some antibodies work by neutralising the toxins released by pathogens
  • preventing viruses from entering host cells:
  • viruses have spike proteins on their surface which recognise and bind to receptors on the surface of the host cell which allow them to enter the cells
  • antibodies can bind to viruses and stop them attaching to their host cells
• what is antigenic variability?

  • memory cells explain why we generally catch some diseases only once
  • their pathogens have the same antigen
  • they are identified by the memory cells and a secondary immune response is triggered which quickly wipes out the virus
  • some pathogens can form different strains (caused by mutations in the genetic material) which often have different antigens (antigenic variation)
  • this means that if you are reinfected, the memory cells won't recognise the antigen so wont be activated and the antibodies made last time won't be complimentary so you will have to start again
• what are vaccines?

  • vaccines are a way of introducing antigens of a dead or weakened pathogen into the body to stimulate the production of antibodies and memory cells
  • one dose induces a primary immune response, multiple doese can increase the number of antibodies and memory cells in the blood stream through the secondary response
  • vaccines are long lasting because the produce memory cells which can produce complimentary antibodies to the antigen
• how are pathogens prepared for viruses made harmless?

  • killing but leaving antigens unaffected
  • weakening (attenuation-heating) but leaving antigens unaffected
  • purified antigens removed from pathogen
  • using inactivated toxins called toxoids that are harmless but trigger the same immune response
• ethical issues with vaccines

  • all vaccines are tested on animals first
  • humans in clinical trials may put themselves at risk because they believe that may be 'immune'
  • some people refuse vaccines over fears of side effects, they are protected by herd immunity in the same way as people who get cant get the vaccine
  • if there was a new disease, difficult decisions would be made about who would be the first to receive it
• why don't vaccines fully eliminate diseases?

  • fails to induce immunity in some people (immunodeficiency)
  • people get infected before enough Abs are generated by vaccine to afford protection (slow primary response)
  • antigenic variability - pathogens can mutate
  • many different strains - cant vaccinate against all
  • objections to vaccinations based on moral, religious and ethical grounds
• what is herd immunity?

  • arises when a sufficiently large proportion of the population has been vaccinated which makes it difficult for a pathogen to spread within that population
• active immunity

  • the body makes antibodies after being exposed to an antigen
  • natural active immunity - you become immune after catching the disease
  • artificial active immunity - you become immune after being given a vaccination containing harmless dose of the antigen
  • long term protection because memory cell produced
• passive immunity

  • the body is given the antibodies that have been made by a different organism
  • natural passive immunity - a baby gets antibodies through placenta and breast milk
  • artificial passive immunity - you are injected with antibodies
  • short term as no immune response involved and no memory cells are produced
• HIV structure

  • membrane envelope - outer layer
  • capsid - protects genetic information
  • RNA (can be DNA in others)
  • glycoprotein - antigens
  • reverse transcriptase enzyme - turns RNA into DNA
• how HIV replicates

  1. glycoprotein molecules on the virus bind to CD4 receptors on the surface of T-helper cells, allowing the envelope surrounding the virus to fuse with the T-helper cell membrane
  2. the capsid is release into the cell where it releases the RNA and the reverse transcriptase
  3. reverse transcriptase is used to make DNA from the HIV RNA template
  4. the DNA is inserted into the cells DNA which gets replicated when cells replicate
  5. DNA used to make HIV RNA and proteins at host ribosomes
  6. virus particles are assembles which bud off from the cell membrane and go on to infect other cells
• transmission of HIV

  • having unprotected sex with an infected person
  • close contact with an infected persons blood
  • use of infected blood in a blood transfusion
  • mother to child - a mother with HIV giving birth to a child or a child drinking the mothers milk - this is known as vertical transmission, babies must be tested at 18 months as it takes time for the virus to replicate and be detectable
• how does HIV turn into AIDS?

  • people who are HIV positive contract AIDS when their number of T-helper cells reach a critical level
  • the immune systems cannot fight off simple/opportunistic infections that the body would usually defend against and so these are often what kill the patient
• monoclonal antibodies

  • antibodies are produced by plasma cells which are all clones of one B-cell
  • they are useful because they can be produced outside the body and they are reactive with only one type of antigen
• medical uses of monoclonal antibodies

  • to target medication to specific cell types by attaching a therapeutic drug to an antibody (radioimmunotherapy)
  • pregnancy testing
  • medical diagnosis by identifying proteins or antigen presence using the ELISA test
• radioimmunotherapy

  • allows doctors to target radiation to specific sites
  • links radioactive atoms to monoclonal antibodies that deliver the radioactivity by seeking out and latching onto proteins found on cancer cells
  • doctors can concentrate radiation at tumour sites, reducing the amount of radiation that reaches healthy tissue
  • they can use it to find tumours that may have spread in the body to target therapy where it is needed
• pregnancy tests

  • antibodies complimentary to hCG proteins are bound to a coloured bead
  • hCG in urine binds to antibodies
  • urine moves up the strip carrying beads
  • immobilised antibodies which bind to hCG create first 'blue line'
  • immobilised antibodies which bind to coloured beads create second 'blue line' if hCG is present
• ELISA tests

  • Enzyme Linked ImmunoSorbent Assay
  • can be used to test for the presence of any antigen or antibody
  • an antibody is bound to an enzyme, this enzyme reacts with a substrate to produce a colour change
  • the antibody will be complementary and bind to the antigen or an antibody that the test is designed to test
  • there is a washing step which will remove any unbound antibodies (plus the attached enzyme), so the more antigen there is in the sample the more colour change there will be because the more enzymes will be present to react with the substrate
• the two types of ELISA tests

  • direct - this just involves one antibody binding to an antigen
  • indirect - this uses multiple antibodies