11.1 Antibody Production

• All nucleated cells of the body possess unique and distinctive surface molecules that identify it as self

  • These self-markers are called major histocompatibility complex molecules (MHC class I) and function as identification tags
  • The immune system will not normally react to cells bearing these genetically determined markers (self-tolerance)
  • The surface of our cells are made of large carbohydrates, glycoproteins and other polypeptides
• Any substance that is recognised as foreign and is capable of triggering an immune response is called an antigen (non self)

  • Antigens are recognised by lymphocytes which bind to and detect the characteristic shape of an exposed portion (epitope)
  • Lymphocytes trigger antibody production (adaptive immunity) which specifically bind to epitopes via complementary paratopes
• Antigenic determinants include: 

  • Surface markers present on foreign bodies in the blood and tissue – including bacterial, fungal, viral and parasitic markers
  • The self-markers of cells from a different organism
  • Proteins from food may be rejected unless they are first broken down into component parts by the digestive system
• Red blood cells are not nucleated and hence do not possess the same distinctive and unique self-markers as all other body cells

  • This means that red blood cells can be transferred between individuals without automatically causing immune rejection

  However, red blood cells do possess basic antigenic markers which limit the capacity for transfusion (the ABO blood system)

  • Red blood cells may possess surface glycoproteins (A and B antigens) either independently (A or B) or in combination (AB)
  • Alternatively, red blood cells may possess neither surface glycoprotein (denoted as O)
• • AB blood groups can receive blood from any other type (as they already possess both antigenic variants on their cells)
  • A blood groups cannot receive B blood or AB blood (as the B isoantigen is foreign and will stimulate antibody production - can have A or O blood)
  • B blood groups cannot receive A blood or AB blood (as the A isoantigen is foreign and will stimulate antibody production - can have B or O blood)
  • O blood groups can only receive transfusions from other O blood donor (both antigenic variants are foreign but is a universal donor)
• • All red blood cells have the H antigen on their surface which does not trigger an immune response.
  • Different molecules can be added to antigen H. For blood group A, N-acetylgalactosamine is added. For blood group B, galactose is added. Blood group AB has both modified antigens.
  • The immune system forms antibodies against the antigens not found on the self's red blood cells
  • If an antigen is presented, agglutination (clumping of blood) will occur and lead to hemolysis (rupturing)
• A pathogen is an agent that causes disease – either a microorganism (bacteria, protist, fungi or parasite), virus or prion

  • A disease is any condition that disturbs the normal functioning of the body (the body can't maintain homeostasis)
  • An illness is a deterioration in the normal state of health of an organism

  Pathogens are generally species-specific in that their capacity to cause disease (pathogenesis) is limited to a particular species

  • Polio, syphilis, measles and gonorrhoea are examples of diseases caused by pathogens that specifically affect humans 
• Certain pathogens may cross the species barrier and be able to infect and cause disease in a range of hosts

  • Diseases from animals that can be transmitted to humans are called zoonotic diseases (or zoonosis)
  • Examples of zoonotic diseases include rabies (dogs), ebola (bats) and the bubonic plague (rats)
• Transmission of infectious diseases can occur via a number of distinct mechanisms:

  • Direct contact – the transfer of pathogens via physical association or the exchange of body fluids
  • Contamination – ingestion of pathogens growing on, or in, edible food sources
  • Airborne – certain pathogens can be transferred in the air via coughing and sneezing
  • Vectors – intermediary organisms that transfer pathogens without developing disease symptoms themselves
• • Non-specific immune cells called macrophages will engulf pathogens and break them down internally and present the antigens
  • Antigenic fragments are presented to specific helper T lymphocytes that, when activated, release cytokines
  • The cytokines stimulate a specific B cell that produces antibodies to the antigen to divide and form clones (clonal selection)
  • Most of the clones will develop into short-lived plasma cells that produce large quantities of specific antibody
  • A small proportion of clones will differentiate into long-lived memory cells that function to provide long-term immunity
• 1. The antigen is ingested via phagocytosis by macrophages (white blood cells) and B cells and presented on their surfaces (antigen-presenting).
  2. Helper T cell binds to antigens. Activated T cell binds to and activates B cells.
  3. B cells form clones of plasma cells and memory cells. Plasma cells produce antibodies. Memory cells can divide quickly to plasma cells if antigen reenters. Memory cells are produced to prevent the delay of antibody production in subsequent exposures and hence prevent disease symptoms developing (immunity - secondary immune response is quicker)
• Antibodies aid in the destruction of pathogens by:

  •  Precipitation – Soluble pathogens become insoluble and precipitate 

  •  Agglutination – Cellular pathogens become clumped for easier removal 

  •  Neutralisation – Antibodies may block pathogenic regions

  •  Inflammation – Antibodies may trigger an inflammatory response within the body

  •  Complement activation – Complement proteins perforate membranes (cell lysis)

  • The constant region of antibodies can be recognised by macrophages, improving pathogen identification (opsonisation)
• An allergen is an environmental substance that triggers an immune response despite not being intrinsically harmful

  • A severe systemic allergic reaction is called anaphylaxis 
  • An allergic reaction requires a pre-sensitised immune state ( prior exposure to the allergen)
  • When a specific B cell first encounters the allergen, it differentiates into plasma cells and makes large quantities of antibody (IgE)
  • The IgE antibodies attach to mast cells (white blood cells)
  • The mast cells with IgE antibodies release large amounts of histamine which causes inflammation (allergic reaction)
• The release of histamine from IgE-primed mast cells causes an inflammatory response that results in allergic symptoms:

  • Histamine increases capillary permeability, improving leukocyte (white blood cell) mobility to infected regions and triggering vasodilation
  • Vasodilation is the widening of blood vessels to improve the circulation of blood to targeted regions causing redness and heat
  • Capillary permeability describes the capacity for leukocytes to leave the bloodstream and migrate into the body tissue to allergen causing swelling and pain 
• Vaccinations induce long-term immunity stimulating memory cells

  • A vaccine is a weakened form of the pathogen (or toxin from it) that contains antigens but is incapable of triggering disease
  • The body responds to an injected vaccine by initiating a primary immune response, which results in memory cells being made
  • When exposed to the actual pathogen, the memory cells trigger a more potent secondary immune response (no disease symptoms = immune)
  • Memory cells may not survive a lifetime and individuals may subsequently require a booster shot to maintain immunity
• Smallpox was the first infectious disease of humans to have been eradicated via vaccination

  • Vaccination programme started in 1967 and the last known case of smallpox was in 1977 but it was officially eradicated in 1980
  • Smallpox was easily identifiable due to overt clinical symptoms, transmission only occurred via direct contact, infection period was short (3 – 4 weeks), virus didn’t mutate into alternate strains
  • Edward Jenner experimented with vaccines by injecting a boy with cowpox making him immune to smallpox
• Monoclonal antibodies are artificially derived from a single B-cell clone

  • An animal is injected with an antigen and produces antigen-specific plasma cells
  • The plasma cells are removed and fused with myeloma/cancer cells capable of endless divisions
  • The resulting hybridoma cell is capable of synthesising large quantities of monoclonal antibody for the specific antigen (bind to region on antigen - epitope)
• Monoclonal antibodies can be used to test for pregnancy via the presence of human chorionic gonadotrophin (hCG) in urine

  • hCG is a hormone produced by women during foetal development
  • From the urine, hCG attaches to anti-hCG antibodies with a dye
  • The hCG and anti hCG antibodies attach to more monoclonal antibodies creating a sandwich which releases the dye
  • A third set of monoclonal antibodies will bind any unattached anti-hCG antibodies and show one line, functioning as a control