Cell Recognition and the Immune System

• Pathogens:

  a pathogen is a microorganism that causes infectious disease. Pathogens can be;

  • bacteria
  • viruses
  • fungi
  • protists

  pathogens cause disease by;

  • damaging host cells
  • releasing toxins
• Antigens:

  • all cells have a specific molecule on their surface which are used in cell recognition. These molecules are called antigens
  • antigens are proteins on a cell membrane which can cause an immune response
  • antigens are specific to each group of cells in each organism. The immune system can identify foreign, or non-self antigens. These antigens all the immune system to identify;
  • pathogens
  • cells from other organisms of the same species (e.g transplants)
  • abnormal body cells (e.g cancer cells)
  • toxins
• The immune system:

  • the immune system is responsible for resisting infectious disease and can be divided into the non-specific and the specific immune system
  • if the pathogen manages to overwhelm the body's defences, the person will die. The elderly, young and those in ill health are more likely to suffer more severely from pathogens as they have a weakened immune system
• Non-specific immune response:

  • the non-specific immune response is present from birth and is effective against a wide range of pathogens and foreign substances
  • the response is always the same
• Specific immune response:

  • the specific immune response is slow and is only effective against specific pathogens; however, the response is faster after re-infection (immunological memory)
• Non-specific defence:

  • physical barriers
  • phagocytosis
• Physical barriers:

  the non-specific immune response consists of physical barriers including;

  • a protective covering - the skin covers the body's surface, creating a barrier that is hard for pathogens to penetrate
  • ciliated epithelia covered in the mucus - many epithelia produce mucus. In the lungs pathogens are often caught in the mucus and moved by the cilia
• Physical barriers:

  • hydrochloric acid in the stomach - provides a low pH that denatures the pathogen's enzymes
  • tears are salty and contain lysozymes - lysozymes (hydrolytic enzymes) digest pathogens trying to enter through the eyes. The saltiness of tears creates a low water potential so water moves out of the bacterial cells by osmosis, causing them to shrivel and die
• Phagocytosis:

  • first stage of the immune response
  • phagocytosis is the term used to describe how a phagocyte engulfs a foreign substance such as a bacterium within a vesicle and then digests it
  • phagocytes alone are not enough to be able to overwhelm a pathogen. However, they play a crucial role in alerting other cells to infection
  • the antigen-presenting cells are essential to triggering the specific immune response
• Process of phagocytosis:

  • a phagocyte recognises the antigens on a pathogen are foreign (due to receptors on the surface of the phagocyte)
  • the cytoplasm moves around the pathogen, engulfing it (endocytosis)
  • the pathogen is now contained in the phagocytic vacuole (phagosome)
  • a lysosome fuses with the phagosome and releases it's lysozymes (hydrolytic enzymes)
  • the lysozymes hydrolyse the pathogen and soluble products are absorbed into the cytoplasm
  • the phagocyte displays the antigens from the pathogen on it's cell membrane - it's now an antigen-presenting cell
• Specific immune response:

  • the cellular response (cell-mediated)
  • the humoral response
• The cellular response (cell-mediated):

  • T lymphocytes (T cells) carry out the cellular response as they recognise non-self antigens presented on the surface of other body cells (antigen-presenting cells made at the end of phagocytosis)
  • there are millions of different T cells in the body, each with slightly different receptors, so each will only be activated when a cell with a complimentary antigen has entered the body, and its antigens have been presented on an antigen presenting cells
• The cellular response (cell-mediated)

  • antigen-presenting cell was produced in phagocytosis
  • receptors on specific T cells fit exactly with these antigens (complimentary shapes)
  • this activates these T cells to divide rapidly by mitosis and form genetically identical cells
• T cells:

  • there are 3 different types of T cells produced, with different functions;
  • some are cytotoxic T cells (Tc cells) which destroy infected body cells (also called killer T cells). They produce a protein (perforin) which makes holes in cell membranes
  • some develop into memory T cells (Tm cells) that enable a rapid response to future infections by the same pathogen (they recognise the specific antigen)
  • some are helper T cells (Th cells) that release chemical signals (cytokines) which stimulate other cells of the immune system such as phagocytes, B cells and Tc cells
• The humoral response:

  • this response involves B cells and antibody production
  • the cell surface membrane of B cells contains specific antibodies. A specific B cell with a complementary antibody binds to an antigen on a pathogen
  • this along with the cytokines (chemicals) released from the Th cells activates the B cell
  • activated B cells divide rapidly by mitosis. This process is called clonal selection
  • the daughter cells are then able to produce antibodies which are complementary to the specific antigen. The daughter cells will develop into one of two types of cell; plasma cells or memory cells
• Plasma cells:

  • secrete antibodies directly
  • these cells only survive for a relatively short time, but in that time release many antibodies
  • these enter the blood and bind to complementary antigens, leading to the destruction of circulating pathogens or toxins
  • this is known as the primary immune response and typically takes a few days
• Memory cells:

  • these usually survive for years in the body
  • if they encounter the same antigen at a later date they divide rapidly and produce large numbers of plasma cells and antibodies quickly
• Antibodies:

  • antibodies are quaternary proteins synthesised by B cells
  • they bind with antigens precisely forming an antigen-antibody complex as they are complementary shapes. Antibodies are therefore very specific
  • each type of antibody has a different tertiary structured antigen-binding sites
  • each antibody has 2 x antigen binding sites
  • monoclonal antibodies are those antibodies that are secreted from the same group of plasma cells - they have the same tertiary structured variable region (antigen binding site)
• Agglutination:

  • when an antibody binds to an antigen it causes agglutination to occur. This is when all the pathogens are clumped together
  • the clumps of pathogens can then be engulfed by a phagocyte more easily, and the phagocyte can more efficiently destroy the pathogen
• Primary and secondary response:

  • primary - the antigen enters the body. Takes a while to make antibodies as time is needed to activate a specific B lymphocyte which then has to clone itself, produce plasma cells, antibodies and memory cells
  • secondary - the same pathogen and therefore antigens enter the body again. There are already memory cells against this antigen
• Secondary response:

  • memory T cells recognise the particular antigen so undergo mitosis quicker
  • memory B cells are activated quicker and have the correct antibody on their surface - they can divide by mitosis to produce larger numbers of plasma cells and therefore larger number of specific antibodies more quickly (clonal selection happens faster)
• Passive immunity:

  • this is when individuals acquire antibodies from an outside source
  • these antibodies bind to the toxin/venom/antigen and cause its destruction
  • immunity is immediate, however it is short lived as the antibodies will be broken down and not replaced by the body, and no memory cells have been made
• Examples of passive immunity:

  • one example is when the foetus acquires antibodies from the mother across the placenta or during breastfeeding (natural)
  • doctors may inject someone with antibodies if they think they have been exposed to a certain infection (artificial)
• Active immunity:

  • this is when the immune system is stimulated to produce its own antibodies
  • memory cells are produced which means antibodies can be produced again in higher amounts and more quickly
  • active immunity takes longer to occur but is longer lasting
• Examples of active immunity:

  • active immunity can be acquired naturally by an individual becoming infected by a disease and producing its own antibodies
  • active immunity can also be acquired artificially by vaccination which again causes an individual to produce an immune response
• Vaccination:

  • vaccination is the introduction of a vaccine into an organism, with the intention of making them immune to a specific disease
  • a vaccine contains antigens and this stimulates the production of specific plasma cells, antibodies and memory cells against a particular pathogen. If carried out on a large scale it can also protect whole populations
• Vaccines:

  vaccines may be;

  • killed or attenuated (weakened) pathogens
  • isolated antigens
  • new mRNA vaccines (Pfizer and Moderna vaccines for COVID)
  • booster vaccinations may need to be given a couple weeks later to increase the amount of memory cells in the body. Boosters can also be given months or years later in order to ensure the supply of memory cells remains in the body
• Successful vaccination programmes:

  • the vaccine must have few side affects if any
  • the vaccine must be economically available in quantities sufficient to immunise the entire vulnerable population
  • must be easily stored and transported
  • must have means of administration (nasal spray, injection etc)
• Herd immunity:

  • it is not vital to vaccinate 100% of the population in order to stop the spread of disease, this is because;
  • the pathogen will be killed quickly in vaccinated people
  • people who are not vaccinated have a very low chance of coming into contact with another unvaccinated person
• Ethical issues with vaccines:

  • who should the vaccine be tested upon?
  • should expensive vaccinations carry on even when disease is eradicated?
  • animal testing?
  • side effects vs disease?
  • if beneficial all population must be vaccinated? Can people opt out? Under what grounds? Should it be compulsory?
• Antigenic variability:

  • the way that memory cells work explains why we only ever develop disease such as chicken pox once in our lives
  • the pathogens are of one type (so have the same antigens) and are therefore quickly identified by memory cells during any subsequent invasion, stimulating the rapid secondary immune response
  • in contrast, influenza viruses (the cause of flu) and some other pathogens have lots of different strains
• Antigenic variability:

  • the antigens on the surface of each strain are different and this is known as antigenic variability
  • this is caused by mutations in the DNA
  • subsequent infections are likely to be caused by the same pathogen but with different antigens on the surface
  • these will not correspond to the memory cells from previous infections and so the body reacts to the organism as a new infection and stimulates a primary response, with new memory cells, specific to the antigens of the new strain, being made
  • this is much slower and, in the meantime, we develop symptoms of the infection
• Monoclonal antibodies:

  • monoclonal antibodies are produced by the same B plasma cell, or from a clone of genetically identical B cells
  • they all have the same tertiary structure antigen binding sites and will therefore bind to one specific antigen or protein
  • we can engineer monoclonal antibodies to specifically bind to antigens/proteins of interest and use them in medicine
• Uses of monoclonal antibodies:

  • targeted drug treatments for cancer
  • drug testing of athletes where a monoclonal antibody can be used to identify a specific drug in a urine or blood sample
  • they are also used in pregnancy testing kits where they detect a specific pregnancy hormone
  • medical diagnosis (e.g of HIV)
• Targeted cancer treatments:

  • cancer cells have different antigens to those on other cells in your body known as tumour markers
  • if you make an antibody that is complimentary to these tumour markers, it will only bind to the tumour markers on cells, not to antigens on other cells, as they aren't complimentary
  • you can attach an anti-cancer drug to the antibodies and inject them. The antibodies will circulate in the blood and bind only to the cancer cells, accumulating in tumour regions
  • the drug is delivered in a targeted way to the cancer cells
• Benefits of targeted cancer treatments:

  • less healthy cells are damaged and there are fewer side effects, as the treatment is localised

  different cancer cells have different tumour markers, so each type of cancer requires different monoclonal antibodies
• Pregnancy tests:

  pregnancy tests show the presence of the hormone hCG

  • urine is applied and travels up the stick. As it moves it encounters mAbs that are complimentary to hCG with blue beads attached
  • if the urine contains the hCG hormone, it binds to the antibodies
  • this complex moves down the the stick to the test area carrying the blue bead with it
  • the hCG antibody complex binds to a set of immobilised antibodies stuck in the test window, the blue beads get stuck and a blue line appears
  • if there is no hCG hormone then nothing binds to the immobilised antibodies, a blue line never appears
• Pregnancy tests:

  • in order to ensure the test works there will also need to be a control zone. This prevents a false negative
  • the control zone contains immobilised mAbs that will bind to the mAbs with the blue bead, regardless of whether it contains the hormone
  • the test zone will only bind to the mAbs with the hormone attached, and therefore only changes colour if the woman is pregnant
• ELISA (enzyme linked immunosorbent assay) test:

  • this uses monoclonal antibodies to detect the presence and amount of a specific protein in a sample
  • the test is highly sensitive and can detect the presence of a substance even in very small amounts
  • this is often used to detect antibodies or antigens within a patient's sample, but it can be used to detect any protein
  • the antigen test can be used to see if the patient is currently ill, whereas the antibody test can be used to see if the patient has previously had the illness
• The antigen test process (the direct ELISA test):

  • patient's blood plasma sample is collected and added to well. Antigens from plasma are stuck to the bottom of the well
  • monoclonal antibody with enzyme attached is added. The binding site is complimentary to the antigen of interest so will bind if the antigen is present. Sample washed to remove unbound antibody
  • colourless substrate solution is added. If antibody bound and present, the enzyme attached will convert substrate into a coloured solution