vaccines, disease and monoclonal antibodies

vaccines

• Vaccines introduce pathogenic antigens into the body, triggering a specific immune response which results in the release of antibodies by plasma cells

  • Vaccines can contain:

    • weakened forms of the pathogen

    • antigens

    • genetic material that codes for the antigens

• Vaccinations produce active immunity, as they cause memory cells to be produced

  • The immune system recognises the antigen and triggers a faster, stronger secondary response

  • This response eliminates the pathogen before symptoms develop

heard immunity

• Vaccines protect individuals and populations from disease by triggering immunity

• Herd immunity occurs when enough people are vaccinated to stop the spread of infection

• This protects unvaccinated individuals, such as babies or those with weakened immune systems

• The more infectious a disease is, the higher the proportion of the population that must be vaccinated

• If vaccination rates drop below the threshold, herd immunity is lost (e.g. measles outbreak in Swansea, Wales, 2012)

active immunity

• Active immunity occurs when the immune system is stimulated by an antigen to produce antibodies and memory cells

• It can be stimulated:

  • Naturally, from an infection

  • Artificially, from a vaccination

• Active immunity provides long-term immunity due to memory cell formation

• This means if the same antigen is encountered again, there will be a faster and stronger secondary response

passive immunity

• Passive immunity is when a person receives ready-made antibodies without producing them

• No immune response is triggered, so no memory cells are formed

  • This means that protection is short-term

• Passive immunity is useful when there is no time to wait for an immune response and immediate protection is needed

  • e.g. providing a tetanus antitoxin which contains specific antibodies that bind to the tetanus toxin

• Passive immunity can be:

  • Artificial: where antibodies are introduced via an injection(e.g. antitoxins)

  • Natural: where antibodies are passed from mother to foetus via the placenta or to a baby via breast milk (colostrum)

HIV

• HIV structure includes the following components:

  • RNA

    • HIV is a retrovirus, meaning that its genetic material is RNA rather than DNA

  • Reverse transcriptase enzyme

    • This enzyme converts RNA into DNA, which can then be transcribed by the host cell

  • A protein coat known as a capsid

  • A lipid envelope

    • The lipid bilayer is derived from the cell membrane of the host helper T cell that the particle escaped from

  • Attachment proteins

    • These allow HIV to bind to a host cell before infecting it

replication of HIV

• When the virus enters the bloodstream it infects helper T cells

• The virus uses the cell machinery of helper T-cells to replicate:

  1. viral RNA enters the cell

  2. viral reverse transcriptase enzymes produce a DNA copy of the viral RNA

  3. the DNA copy is inserted into the chromosomes of the cell

  4. each time the cell divides it copies the viral DNA

  5. HIV proteins are produced from the viral DNA

  6. the proteins are used to build new HIV particles

  7. thousands of new HIV particles are released, killing the helper T cell

  8. the new HIV particles go on to infect other helper T cells

• Gradually the virus reduces the number of helper T cells in the immune system

  • B cells are no longer activated

  • No antibodies are produced

• This decreases the body’s ability to fight off infections, eventually leading to AIDS (acquired immune deficiency syndrome)

  • Note that it takes time for a HIV infection to develop into AIDS; it is possible to be HIV positive but not yet have developed symptoms of AIDS

symptoms of AIDS

• HIV infection often causes mild flu-like symptoms initially

• A latent period follows, with no obvious symptoms

• Over time, HIV becomes active, destroying helper T cells

• Fewer T cells weakens the specific immune response:

  • Reduced B cell activation, antibody production, and phagocytosis

• When the immune system can’t respond to pathogens, the person develops AIDS

• Opportunistic infections (e.g. TB) can then occur and can be fatal

treatment of AIDS

• There is currently no cure for AIDS, but antiviral drugs can slow virus replication

• With treatment, HIV-positive individuals can have a normal life expectancy

AIDS antibiotics and viruses

• Antibiotics kill bacteria by disrupting metabolism or protein synthesis

• Viruses are not cells as they lack metabolism and the cellular structures targeted by antibiotics

• Therefore, antibiotics are ineffective against viruses like HIV

monoclonal antibodies

• Monoclonal antibodies (mAbs) are identical antibodies from a single B cell clone

• They are highly specific and so bind to one particular antigen

uses of monoclonal antibodies - targeting medication

• mAbs can be designed to bind only to specific cell types, e.g. cancer cells

  • A therapeutic drug is attached to the antibody

  • The antibody carries the drug directly to the target cells

• This increases effectiveness and reduces damage to healthy cells

uses of monoclonal antibodies - medical diagnosis

• mAbs are used to detect the presence and location of specific antigens

• They are often labelled with a radioactive, fluorescent or enzyme marker

• Common uses of monoclonal antibodies include:

  • pregnancy tests (detect hCG in urine)

  • infection detection (e.g. HIV, Streptococcus)

  • cancer screening and locating blood clots/tumours

ethical issues with the use of vaccines - use of animals

• Vaccines are first tested on animals, which some view as unethical

• Animal-derived substances may also be used in vaccine production

ethical issues with the use of vaccines - human testing

• Trial vaccines carry risks (e.g. side effects or a false sense of protection)

• Volunteers may be vulnerable if motivated by payment, raising concerns over exploitation

ethical issues with the use of vaccines - side effects

• Some avoid vaccines due to the small risk of side effects

• Herd immunity protects them, which some argue is unfair

• Ethical concern over parents refusing vaccines for children, potentially putting them at risk

ethical issues with the use of vaccines - epidemics and access

• Questions over priority groups during epidemics (e.g. priority vaccines for the elderly or healthcare workers during the COVID-19 pandemic)

• Global inequality, where wealthier countries may access vaccines before poorer nations, raises concerns over fair distribution

ethical issues with the use of monoclonal antibodies - use of animals

• Mice are used to produce mAbs: mice are injected with with an antigen before activated B cells are extracted from the spleen

• This may cause suffering or harm to the mice and raises concerns for those who oppose animal testing or genetic modification

ethical issues with the use of monoclonal antibodies - human use in treatment and trials

• mAbs are used in cancer and disease treatment, but may have serious side effects

• Informed consent is essential to ensure that patients fully understand the risks

• Trials may involve vulnerable participants (e.g. financially motivated or severely ill)

ethical issues with the use of monoclonal antibodies - accessibility and cost

• Monoclonal antibody treatments are often expensive

• Raises concerns about fair access, especially in lower-income countries or healthcare systems

what is ELISA

• (Enzyme-Linked Immunosorbent Assay) uses antibodies to detect the presence and quantity of a specific antigen or antibody in a sample

what happens in an ELISA test

• An enzyme is attached to antibodies

• When this enzyme reacts with a certain substrate, a coloured product is formed, causing the solution in the reaction vessel to change colour

• If a colour change occurs, this shows that the antigen or antibody of interest is present in the sample being tested (e.g. blood plasma)

different types of ELISA test

• Direct ELISA tests use a single antibody that is complementary to the antigen being tested for

• Indirect ELISA tests use two different antibodies (known as primary and secondary antibodies)

indirect ELISA for HIV diagnosis

• An indirect ELISA test can be used to test whether a patient has antibodies to HIV:

  1. HIV antigens are fixed to the bottom of the test well

  2. Patient's blood plasma is added – if HIV-specific antibodies are present, they bind (primary antibodies) to the HIV antigens

  3. The well is washed to remove unbound antibodies

  4. Secondary antibodies with an enzyme attached are added – they bind to the primary antibodies

  5. Another wash step removes unbound secondary antibodies

     • This step avoids a false-positive test

  6. A substrate is added – if the enzyme is present, a colour change occurs

  7. A colour change indicates the patient has HIV-specific antibodies, meaning they are infected with HIV