cell recognition and the immune system

• defense mechanisms 


  some are general and immediate deffences like the skin forming a barrier to the entry of pathogens and phagocytosis. some are more specific, less rapid but longer lasting. these responses involve a type of white blood cell called a lymphocyte and take 2 forms;

  • cell mediated responses involving T lymphocyes
  • humoral responses involving B lymphocytes
• recognising self cells


  each cell has specific molecules on its surface that identify it, the proteins are the most important. proteins have enormous variety and a highly specific tertiary structure, which distinguishes one cell from another. these allow the immune system to identify:

  • pathogens eg HIV
  • non self materials eg cells from other organism of the same species
  • toxins eg bacterium that causes cholera
  • abnormal body cells eg cancer cells
• non self cells in transplants 


  all these cells are potentially harmful and identification is the first stage of removal. this response in beneficial to the organism, but has implications for humans who have had tissue or organ transplants as the immune system recognises these cells as non self, so attemps to destroy them. to minimise this effect, donor tissues are matched as close as possible to those of the recipient. in addition, immunosuppressant drugs are often administered to reduce the level of immune response that still occurs ~
• how lymphocytes recognise self cells in the fetus

  • many present in body at one time
  • in the fetus, they constantly collide with other cells
  • infection in the fetus is rare due to protection from the placenta, so will collide mostly with self cells
  • some lymphocytes have receptors that fit self cells, these either die or are suppressed
  • the remaining are those that may fit non self cells
• how lymphocytes recognise self cells in adults

  • lymphocytes produced in the bone marrow initially only encounter self-antigens
  • any lymphocytes that show an immune response to these self-antigens undergo programmed cell death (apoptosis) before they can differentiate into mature lymphocytes
  • no clones of these anti-self lymphocytes will appear in the blood, leaving only those that might respond to non-self antigens
• types of white blood cell

  • phagocytes
  • lymphocytes
• phagocytosis

  1. chemical products of pathogens or dead/damaged cells act as attractants, phagocytes move towards them
  2. phagocytes have receptors on their cell-surface membrane that recognise and attach to chemical on the pathogens surface
  3. they engulf the pathogen, for a vesicle (phagosome
  4. lysosomes fuse with it
  5. lysosomes contain lysozymes which destroy ingested bacteria by the hydrolysis of their cell walls
  6. the soluble products from the breakdown absorbed into the phagocyte cytoplasm
• antigens

  any part of an organism or substance that is recognised as foreign by the immune system and stimulates an immune response.

  • they are usually proteins part of the cell-surface membrane or cell wall of invading cells.
  • the presence of an antigen triggers the production of an antibody as part of the bodies defence system
• B lymphocytes


  they mature in the bone marrow. they are associated with humoral immunity (immunity involving antibodies antibodies that are present in body fluids, or "humour" such as blood plasma).
• T lymphocytes 


  they mature in the thymus gland. they are associated with cell-mediated immunity (immunity involving body cells)
• T lymphocytes can distinguish invader cells from normal cells because...

  • phagocytes that have engulfed and hydrolysed a pathogen present some of a pathogen's antigens on their own cell-surface membrane
  • body cells invaded by a virus present some of the viral antigen one their membrane
  • transplanted cells from individuals of the same species have different antigens on their membrane
  • cancer cells are different from normal body cells and present antigens on their membrane
• antigen presenting cells


  cells that display foreign antigens on their surface
• cell-mediated immunity 


  where T lymphocytes only respond to antigens present on a body cell rather than antigens in body fluids
• response of T lymphocytes to infection by a pathogen

  1. pathogens invade body cells or are taken in by phagocytes
  2. the phagocyte places antigens from the pathogen on its membrane
  3. receptors on a specific T-helper cell fit exactly onto these antigens
  4. this attachment activates the T cell to divide rapidly by mitosis and form a clone of genetically identical cells
  5. the cloned T cells:
• the cloned T cells:

  • develop into memory cells that enable a rapid response to future infections by the same pathogen
  • stimulate phagocytes to engulf pathogens by phagocytosis
  • stimulate B cells to divide and secrete their antibody
  • active cytotoxic T cells
• how cytotoxic T cells kill infected cells 


  produce a protein called perforin that makes holes in the cell-surface membrane, so the membrane becomes freely permeable to all substances, so the cells dies.
• what are (cytotoxic) T cells most effective against


  viruses as they replicate inside cells. as viruses use living cells to replicate, the killing of these cells prevents viruses multiplying and infecting more cells
• in each monoclonal antibody, the cells produced develop into one of two types of cell:

  • plasma cells - secrete antibodies into blood plasma, which destroy antigens. the production of memory cells and antibodies is the primary immune response
  • memory cells - responsible for secondary immune response. circulate in blood and tissue fluid, live longer than plasma cells. when they encounter same pathogen later, they divide rapidly and develop into plasma and more memory cells. plasma cells produce antibodies, new memory cells circulate for future infection
• B cells in humoral immunity

  1. surface antigens of invading pathogen taken up by B cell
  2. B cell processes antigens and presents them on its surface
  3. helper T cells attach to processed antigens, activating the B cell
  4. B cell divides by mitosis to give a clone of plasma cells
  5. the plasma cells produce and secrete the specific antibody that fits the antigen on the pathogen's surface
  6. the antibody attaches to the antigens and destroys them
  7. some B cells develop into memory cells
• antibodies 


  proteins with specific binding sites synthesised by B cells. has two identical binding sites complementary to a specific antigen. made up of 4 polypeptide chains:

  one pair of long chains called heavy chains

  one shorter pair of chains called light chains

  the binding sites on different antibodies are different so are known as the variable region. each binding sites consists of a squence of amino acids forming a 3D shape which binds directly to a specific antigen. the rest of the antibody is known as the constant region
• do antibodies destroy antigens


  No, they prepare the antigen for destruction
• antibodies assist destruction in 2 ways:

  • cause the agglutination of the pathogen. in this way clumps of the pathogen are formed, making it easier for phagocytes to locate them as they are less spreas out in the body
  • they then serve as markers that stimulate phagocytes to engulf the pathogend to which they are attached
• monoclonal antibodies


  a single type of antibody that can be isolated and cloned
• direct monoclonal antibody therapy for treating cancer

  • monoclonal antibodes are produced that are specific to antigens on cancer cells
  • these are given to a patient and attach themselves to the receptors on their cancer cells
  • they attach to the surface of their cancer cells and block the chemical signals that stimulate their uncontrolled growth
• advantage of direct monoclonal antibody therapy


  the antibodies are highly specific and not toxic, so have fewer side effects
• diseases diagnosed using monoclonal antibodies

  • influenza
  • hepatitis
  • chlamydia
  • certain cancer
• monoclonal antibodies in pregnancy testing 


  monoclonal antibodies present on the test strip of a pregnancy test are linked to coloured particles. if the hormone hCG (produced by the placenta) is present in the urine, it binds to these antibodies the hCG-antibody-colour complex move along the strip until trapped by a different type of antibody, creating a coloured line
• ethical use of monoclonal antibodies

  • production invloves the use of mice
  • there have been some deaths associated with their use in the treatment of multiple sclerosis. patients should have informed consent of benefits and risks of the treatment
  • dangers in testing - march 2004, healthy volunteers took part in a monoclonal antibody trial, within minutes, multiple suffered organ failure
• production of monoclonal antibodies

  • a mouse is injected with the antigen
  • B cells in the mouse produce a mixture of antibodies, which are extracted from the spleen
  • they are then fused with tumour cells to produce hybridoma cells.
  • the antibody-producing hybridoma cells are cloned through clonal expansion
  • the monoclonal antibodies are extracted
• immunity 


  the ability of an organism to resist infection
• two forms of immunity:

  • passive immunity
  • active immunity
• passive immunity 


  produced by the introduction of antibodies into individuals from an outside source. immunity is aquired immediately and no contact from the pathogen or its antigens are required. the immunity is not long lasting as the individual did not produce the antibodies themselves, so they are not being replaced when broken down, so no memory cells are formed. an example includes the anti-venom given to snake bite victims
• active immunity 


  produced by stimulating the production of antibodies by the individuals' own immune system. direct contact with the pathogen or its antigen is necessary. immunity takes time to develop. it is generally long-lasting, and is of two types:

  • natural active immunity - individual becomes infected with the disease naturally and the body produces its own antibodies
  • artificial active immunity - involved vaccination. induces an immune response without suffering symptoms
• vaccination

  • the intoduction of the appropriate disease antigens into the body, either by injection or by mouth to stimulate an immune response.
  • contains one or more types of antigen from the pathogen
  • the response is slight as only a small amount of antigen has been introduced.
  • memory cells are produced which remain in the blood if the same pathogen infects the body again, so the correct antibodies are produced rapidly to rapidly overcome the pathogen
• factors which dictate vaccination success

  • vaccine must be economically available in sufficient quantities to immune most of the vunerable population
  • must be few side effects, as unpleasant side effects may discourage people from being vaccinated
  • appropraite means of producing, storing and transporting the vaccine must be available
  • must be means of administering the vaccine properly at the appropriate time. involves staff training
  • must be possible to vaccinate most of vunerable population to produce herd immunity
• herd immunity 


  a sufficiently large proportion of the population has been vaccinated to make in difficult for pathogens to spread within that population.
• why vaccination may not eliminate a disease

  • fails to induce immunity in certain individuals, eg those with a defective immune system
  • individuals may develop disease straight after vaccination before immunity levels are high enough to protect them
  • pathogen may mutate quickly, making the vaccine ineffective. this causes antigenic variability (eg influenza)
  • may be many varieties of a pathogen that make in almost impossibe to produce a vaccine
  • certain pathogens conceal themselves in body cells to remain undected by the immune system eg cholera
  • may be religious, ethical or medical objections
• ethics of vaccination

  • testing often involves animals
  • vaccines can have side effects that cause long term harm
  • trials can be dangerous as many side effects are unknown
• HIV structure

  -

  A) attachment protein

  B) reverse transcriptase

  C) genetic matrial (RNa)

  D) capsid

  E) matrix

  F) lipid envelope

  
• HIV replication

  1. HIV enters bloodstream and circulates around body
  2. a protein on the HIV readily binds to a protein called CD4. although it occurs on many different cells, HIV mostly attaches to T helper cells
  3. the protein capsid fuses with the cell-surface membrane. the RNA and enzymes of HIV enter the helper T cell
  4. the HIV reverse transcriptase converts the virus's RNA into DNA
  5. the DNA is moved into helper T cell's nucleus and inserted into the cell's DNA