Alevel 生物 第十一章Immunity

Alevel 生物知识框架图 第十一章Immunity 主要内容包括免疫系统的组成，主动免疫及被动免疫，自身免疫疾病等

Immunity

• Defence against disease
  • External defence system
    • physical, chemical and cellular defences that prevent pathogens entering
      • the epithelia -an effective barrier to the entry of pathogens
      • hydrochloric acid in the stomach - kills many bacteria that we ingest with our food and drink
      • blood clotting - stops the loss of blood and prevents the entry of pathogens through wounds in the skin
  • Internal defence system
    • White blood cells recognise pathogens by the distinctive, large molecules that cover pathogens' surfaces and the waste materials which some pathogens produce
      • cell surface antigens
        • Each of us has molecules on the surfaces of our cells that are not found in other organisms, or even in other humans.
          • eg: the human ABO blood group system
    • immune response
      • respond by producing antibodies or killing cells that have become infected by pathogens.
• Cells of the immune system
  • originate from the bone marrow; two groups- phagocytes and lymphocytes
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  • phagocytes
    • throughout life in the bone marrow; stored there before being distributed around the body; removing any dead cells as well as invasive microorganisms
      • neutrophils
        • 60% of the white cells in the blood; short-lived cells; leaving the blood by squeezing through the walls of capillaries to 'patrol' the tissues
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      • macrophages
        • larger than neutrophils and tend to be found in organs, removing any foreign matter found there; made in the bone marrow and travel in the blood as monocytes; long-lived cells ;cut pathogens up to display antigens
  • Phagocytosis
    • If pathogens invade the body and cause an infection, some of the cells under attack respond by releasing chemicals such as histamine
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  • lymphocytes
    • smaller than phagocytes; a large nucleus that fills most of the cell; produced before birth in bone marrow
    • B-lymphocytes
      • remain in the bone marrow until they are mature;spread throughout the body( in lymph nodes and the spleen)
        • the ability to make just one type of antibody molecule; Each cell then divides to give a small number of cells that are able to make the same type of antibody(clone）
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      • Memory cells are the basis of immunological memory
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      • Antibodies
        • all globular glycoproteins with quaternary structure- immunoglobulins： two 'long' or 'heavy' chains and two 'short' or 'light' chains; two identical antigen-binding sites(formed by both light and heavy chains);The antigen-binding sites form the variable region, which is different on each type of antibody molecule produced
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    • T-lymphocytes
      • collect in the thymus where they mature;The thymus doubles in size between birth and puberty, but after puberty it shrinks
      • The display of antigens on the surface of cells--antigen presentation;helper T cells and killer T cells (cytotoxic T cells);When helper T cells are activated, they release hormone like cytokines that stimulate appropriate B cells to divide
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  • Numbers of white blood cells
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    • 1.myeloid stem cells that give rise to neutrophils, monocytes and platelets 2.lymphoid stem cells that give rise to lymphocytes, both B and T cells.
      • Leukaemias are cancers of these stem cells. The cells divide uncontrollably to give many cells which do not differentiate properly and disrupt the production of normal blood cells including red blood cells and platelets.
• Autoimmune diseases – a case of mistaken identity
  • autoimmune diseases--the immune system attacks one or more self-antigens, usually proteins
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  • eg:Myasthenia gravis (MG)-- grave (serious) muscle weakness;targets the neuromuscular junctions between motor neurones (nerve cells) and skeletal muscle cells
    • helper T cells that are specific for these cell surface receptors for acetylcholine; these cells stimulate a clone of B cells to differentiate into plasma cells and secrete antibodies that bind to the receptor so blocking the transmission of impulses from motor neurones.
      • muscle cells do not receive any stimulation;gets worse with activity and improves with rest.
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    • a drug that inhibits the enzyme in synapses that breaks down acetylcholine;Surgical removal of the thymus gland is also an effective treatment
  • Multiple sclerosis --when nerve cells in the brain and spinal cord lose the insulating myelin sheaths that surround them
    • muscle weakness, loss of sensory input from the skin and other areas, poor vision and mental problems.
  • Rheumatoid arthritis --long-term destructive process; this time occurring in the joints
    • Tendons become inflamed and there is constant muscle spasm and pain; hard to keep mobile.
  • Type 1 insulin-dependent diabetes --be caused partly by a virus infection that makes the cells that secrete insulin in the pancreas unrecognisable as self
    • Killer T cells enter the islets of Langerhans and destroy the cells that produce insulin
  • 1.people with certain alleles of genes involved in cell recognition are at a higher risk of developing MG than those without these alleles; 2.environmental factors are also very important as the increase in prevalence of these diseases in the developed world
• Monoclonal antibodies
  • Antibodies have high degrees of specificity. This specificity of antibodies has made them very desirable for use in the diagnosis and treatment of diseases.
    • This requires a very large number of cells of a particular B cell clone, all secreting identical or monoclonal antibodies (Mabs).
      • a major problem : B cells that divide by mitosis do not produce antibodies, and plasma cells that secrete antibodies do not divide.
      • The cell produced by this fusion of a plasma cell and a cancer cell is called a hybridoma(divide by mitosis and secrete antibodies)
  • Using monoclonal antibodies in diagnosis
    • eg: locate the position of blood clots in the body of a person thought to have a deep vein thrombosis
      • The plasma cells are fused with cancer cells to form hybridomas that secrete the antifibrin antibody. A radioactive chemical that produces gamma radiation is attached to each antibody molecule to make radioactively labelled antibodies--they bind to any fibrin molecules with which they come into contact;A gamma-ray camera is used to detect the exact position of the antibodies in the person's body
    • There are now many Mabs available to diagnose hundreds of different medical conditions
      • locate cancer cells
      • identify the exact strain of a virus or bacterium
      • blood typing before transfusion
      • tissue typing before transplants
  • Using monoclonal antibodies in treatment
    • Monoclonal antibodies used as a treatment need to be administered more than once, and that presents problems
      • produced by mice, rabbits or other laboratory animals ;When introduced into humans, they trigger an immune response because they are foreign (non-self) and act as antigens
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      • 1.altering the genes that code for the heavy and light polypeptide chains of the antibodies so that they code for human sequences of amino acids, rather than mouse or rabbit sequences; 2. changing the type and position of the sugar groups that are attached to the heavy chains to the arrangement found in human antibodies.
    • modifying immune responses( trastuzumab, ipilimumab, infliximab and rituximab)
      • Trastuzumab --a humanised mouse monoclonal antibody; It binds to a receptor protein that is produced in abnormal quantities in the cell surface membranes of some breast cancers and this marks them out for destruction by the immune system.
      • Ipilimumab -- a more recent cancer therapy for melanoma(a type of skin cancer);binds to a protein produced by T cells (reduce the immune response); blocking the action of the protein, an immune response can be maintained against the cancer cells
      • Infliximab -- treat rheumatoid arthritis;binds to a protein secreted by T cells that causes damage to the cartilage in joints and blocks its action
      • Rituximab --control B-lymphocytes;binds to a cell surface receptor protein found on the surface of B cells;causes a variety of changes that lead to the death of the cell--used to treat diseases in which there is an overproduction or inappropriate production of B cells(leukaemias and autoimmune diseases)--multiple sclerosis and rheumatoid arthritis,myasthenia gravis
• Active and passive immunity
  • active immunity
    • the person makes their own antibodies
      • this activation occurs naturally during an infection --natural active immunity
      • The immune response can also be activated artificially, either by injecting antigens into the body or taking them by mouth --artificial active immunity( vaccination)
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  • passive immunity
    • antitoxins provide artificial passive immunity; antibodies are injected (artificial) or pass from mother to child across the placenta or in breast milk --natural passive immunity.
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  • Vaccines
    • A vaccine is a preparation containing antigens which is used to stimulate an immune response artificially
      • a whole live microorganism；a dead one；a harmless version ；a harmless form of a toxin ；a preparation of surface antigens
        • injection into a vein or muscle, or are taken orally
      • Immunity derived from a natural infection is often extremely good at providing protection;Less effective are those vaccines that do not mimic an infection
        • highly effective--one injection may well give a lifetime's protection;Less effective vaccines need booster injections to stimulate secondary responses that give enhanced protection
  • Problems with vaccines
    • Poor response
      • a defective immune system and as a result do not develop the necessary B and T cell clones;they suffer from malnutrition, particularly protein-energy malnutrition, and do not have enough protein to make antibodies or clones of lymphocytes.
    • Live virus and herd immunity
      • People vaccinated with a live virus may pass it out in their faeces during the primary response and may infect others --it is better to vaccinate a large number of people at the same time to give herd immunity
        • Herd immunity interrupts transmission in a population
    • Antigenic variation
      • It may be impossible to develop a vaccine that protects against all type of rhinovirus
      • antigenic drift --only minor changes,memory cells will still recognise them and start a secondary response;antigenic shift --more serious are major changes,ineffective against the new one
      • There are no effective vaccines in use against the diseases that are caused by protoctists(eg:malaria and sleeping sickness)
        • eukaryotes have many more genes than bacteria and viruses have
          • many hundreds or even thousands of antigens on their cell surfaces
      • malaria(Plasmodium): three stages in its life cycle have its own specific antigens ; sleeping sickness(Trypanosoma): a thousand different antigens and changes them every four or five days
    • Antigenic concealment
      • Some parasitic worms conceal themselves by covering their bodies in host proteins; Other pathogens suppress the immune system by parasitising cells (macrophages and T cells)
        • such a short period of time for an immune response to occur before the pathogen ‘hides’
          • eg:cholera( Vibrio cholerae ):the pathogens remain in the intestine beyond the reach of many antibodies. There are oral vaccineswhich provide limited protection against cholera.
  • The eradication of smallpox
    • Smallpox was an acute, highly infectious disease caused by the variola virus and transmitted by direct contact
      • Smallpox killed 12–30% of its victims
        • The WHO started an eradication programme in 1956; two main aspects of the programme: vaccination and surveillance
          • ring vaccination :When a case of smallpox was reported, everyone in the household and the 30 surrounding households, as well as other relatives and possible contacts in the area, was vaccinated.
        • The last case of smallpox was reported in Somalia in 1977. The WHO finally declared the world free of smallpox in 1980.
    • How the eradication programme succeeded
      • The variola virus was stable; it did not mutate and change its surface antigens.
      • The vaccine was made from a harmless strain of a similar virus (vaccinia) and was effective because it was a 'live' vaccine.
      • The vaccine was freeze-dried and could be kept at high temperatures for as long as six months. This made it suitable for use in the tropics
      • Infected people were easy to identify
      • The vaccine was easy to administer and was even more effective after the development of a stainless steel, reusable needle for its delivery.
      • The smallpox virus did not linger in the body after an infection to become active later and form a reservoir of infection.
      • The virus did not infect animals, which made it easier to break the transmission cycle.
      • Many 16- to 17-year-olds became enthusiastic vaccinators and suppliers of information about cases; this was especially valuable in remote areas.
  • Preventing measles
    • Measles is a preventable disease and one that could be eradicated by a worldwide surveillance and vaccination programme
    • a very difficult disease to eradicate, even with high vaccination coverage
      • the poor response to the vaccine shown by some children who need several boosters to develop full immunity; Migrants and refugees can form reservoirs of infection
    • highly infectious
      • herd immunity of 93–95% is required to prevent transmission in a population
        • As the currently available vaccine has a success rate of 95%, this means that the whole population needs to be vaccinated
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• 1.outline how and where white blood cells originate 2.explain how the immune system distinguishes between the body's own cells (self) and anything foreign, such as pathogens and transplanted tissues (non-self) 3.describe how phagocytes and lymphocytes respond during an infection 4.describe and explain the significance of the increase in white blood cell counts in people with infections and leukaemias 5.describe how autoimmune diseases occur 6.explain how the structure of antibody molecules is related to their functions 7.outline how monoclonal antibodies are produced and used in diagnosis and treatment 8.distinguish between the four diff erent types of immunity 9.describe how vaccination is used to control some infectious diseases 10.discuss why a vaccination programme was successful in eradicating smallpox, and the reasons why measles, cholera, malaria and TB have not been eradicated