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AS Level Biology 9700

11. Immunity

Written by: Pranav I
Formatted by: Pranav I

11.1 Defense against disease

External defense system

  • Plants make their own organic food via photosynthesis (mostly in leaves)
  • Absorb inorganic mineral ions and water from the soil (extensive root systems)
  • These materials must be transported to all parts of the plant

Internal defense system (immune system)

  • Pathogens successfully enter the body in some cases 
  • Antigens: A substance that is foreign to the body and stimulates an immune response (proteins, glycoproteins, glycolipids, polysaccharides, toxins and other waste materials)
    • White blood cells recognize pathogens by their antigens
    • Antibodies: A globular glycoprotein (immunoglobulin; quaternary structure) made by specialised lymphocytes in response to the presence of a specific antigen; each type of antibody molecule has a shape that is complementary to its specific antigen 
    • Has the ability to distinguish between self and non-self 
      • Self → refers to substances produced by the body that the immune system does not recognise as foreign (do not stimulate an immune response)
      • Non-self → refers to substances or cells that are recognised by the immune system as foreign (stimulate an immune response)
  • Immune response: the complex series of responses of the body to the entry of a foreign antigen; it involves the activity of lymphocytes and phagocytes 

11.2 Cells of the immune system

  • Produced from stem cells in the bone marrow 
  • Two groups of these cells:
    • Phagocytes (neutrophils and macrophages)
    • Lymphocytes 

Phagocytes

  • Produced throughout life
  • Stored in the bone marrow before being distributed in the blood
  • Neutrophils form ~60% of the white blood cells
    • Travel throughout the body
    • Leave blood by squeezing through the walls of capillaries
    • Released in large numbers during an infection
    • Short-lived cells
  • Macrophages are larger than neutrophils and are found in organs such as the lungs, liver, spleen, kidney and lymph nodes
    • Travel in the blood as monocytes
    • Develop into macrophages once they leave blood and settle in organs
    • Long-lived cells
    • Play a crucial role in initiating immune responses
      • Do not destroy pathogens completely
      • Cut them up to display antigens that can be recognised by lymphocytes

Phagocytosis

  1. Attraction (chemotaxis)
    • Cells under attack by pathogens release chemicals such as histamine
    • Pathogens release chemicals
    • Passing neutrophils are attracted to the site
  2. Recognition and attachment
    • Neutrophils have surface receptor proteins that recognise and attach to antibody markers
    • Pathogen might also attach directly to the neutrophil membrane
  3. Endocytosis
  4. Pathogen trapped within a phagocytic vacuole
  5. Fusion of lysosomes and phagocytic vacuoles
  6. Killing and digestion
    • Pathogens digested by enzymes
    • Digested products are released by exocytosis
  • Neutrophils have a short life → die after digesting some pathogens
  • Dead neutrophils collect at a site of infection to form pus

Lymphocytes

  • Smaller than phagocytes
  • Have a large nucleus
  • Produced before birth in the bone marrow
  • Two types of lymphocytes:
    • B-lymphocytes → remain in the bone marrow until mature and spread throughout the body (concentrate in the liver, lymph nodes and the spleen)
    • T-lymphocytes → leave the bone marrow and collect in the thymus (a gland in the chest) for maturation
  • Only mature lymphocytes can carry out immune responses
  • Different types develop during maturation → each specialised to respond to one antigen
  • Circulate between the blood and the lymph → distributed throughout the body, and come into contact with pathogens & each other
  • Immune response depends on B and T cells interacting with each other

B-lymphocytes

  • Gains the ability to make just one type of antibody as it matures (genes are changed)
  • Each B cell then divides to make a small number of identical cells (clone)
  • Each B cell uses part of the antibody molecule to make receptors in the CSM
    • Can combine with one specific antigen
    • To recognise antigens when they enter the body
  • Primary immune response: the first immune response to a specific antigen
  • Clonal selection: during an immune response the only lymphocytes to respond are those with receptors specific to antigens on the surface of the invading pathogen
  • Clonal expansion: the increase in number of specific clones of lymphocytes by mitosis during an immune response
  • Plasma cells: Short-lived, activated B-lymphocytes produced during clonal expansion; produce and release antibody molecules into the blood, lymph or onto the linings of the lungs and the gut
  • Antibodies stay in the blood for longer than the plasma cells
  • Memory cells: Long-lived, activated B-lymphocytes that are specific to one antigen; activated to differentiate into plasma cells during secondary immune responses to the specific antigen
    • Divide rapidly and develop into plasma cells and more memory cells during secondary immune responses
    • Faster response due to the presence of many memory cells of the specific clone
    • Basis of immunological memory (the ability of the immune system to mount a larger and more rapid response to an antigen that has already been encountered before)
  • More antibodies are produced in the secondary immune response due to the presence of many more B cells specific to the antigen (size of clone increases during the primary immune response)
Fig 11.1 The changes in antibody concentration in the blood during a primary and secondary response to the same antigen

B cells and antibodies

  • Each antibody molecules has four polypeptide chains: two ‘long’ or ‘heavy’ chains and two ‘short’ or ‘light’ chains
    • Disulfide bonds hold the chains together
  • Each antibody molecule has two identical variable regions (has parts of both light and heavy chains)
  • Each clone of B cells makes antibodies with the same variable regions → complementary in shape to one antigen
  • ‘Hinge’ region gives the flexibility for the antibody to bind to antigens on the surface of a pathogen
  • IgG → two antigen-binding sites (four polypeptide chains) ; IgA → four antigen-binding sites ; IgM → ten antigen-binding sites
Fig 11.2 An IgG antibody molecule
  • Ways in which antibodies work to protect the body from pathogens
    • Combine with viruses, preventing them from entering or damaging cells
    • Attach to flagella of bacteria, making them less active and easier for phagocytes to engulf
    • Cause agglutination of bacteria, reducing the chances of spread throughout the body (if they have multiple antigen binding sites)
    • Perforate the cell walls of bacteria, causing them to burst when they absorb water by osmosis
    • Coat bacteria, making it easier for phagocytes to ingest them; phagocytes have receptor proteins for the constant regions of antibodies
    • Antitoxins combine with toxins, neutralising them and making them harmless

T-lymphocytes

  • Specific cell surface receptors → T-cell receptors
  • Each are specific to one antigen
  • Activated when they recognise this antigen on another host cell
  • Antigen presentation: the process of preparing antigens and exposing them on the surface of host cells for recognition by T-lymphocytes
    • Macrophages that have engulfed a pathogen
    • Body cells that have been invaded by a pathogen
  • Clonal expansion of T cells occurs
  • Types of T cells
    • T-helper cells → secretes cytokines (any signalling molecule released by cells to influence the growth and/or differentiation of cells) to coordinate activity during immune responses
      • Release cytokines
      • Stimulate appropriate B cells to divide into plasma cells (secrete antibodies) and memory cells
      • Some also stimulate macrophages to carry out phagocytosis more vigorously
      • Some also stimulate T-killer cells to divide by mitosis and to differentiate by producing vacuoles full of toxins
    • T-killer (T-cytotoxic) cells → Attaches to cells, releases toxic substances to kill infected cells and cancer cells
      • Search for antigen presenting body cells with their specific antigen
      • Punch holes in CSM of infected body cells
      • Secrete toxic substances (e.g. H2O2)
      • Kill the body cells and pathogens inside
  • Memory T-helper cells and memory T-killer cells are produced → remain in the body and become active during secondary immune responses

11.3 Active and passive immunity

  • Active immunity: immunity gained when an antigen enters the body, an immune response occurs and antibodies are produced by plasma cells
    • Natural active immunity → gained by being infected by a pathogen
    • Artificial active immunity (vaccination) → gained by putting antigens into the body, either by injection or by mouth
    • Provides permanent (long-term) immunity
    • Takes time for enough B and T cells to be produced
  • Passive immunity: the temporary immunity gained without there being an immune response
    • Natural passive immunity → gained by a fetus when maternal antibodies cross the placenta, or when an infant consumes breast milk (+ colostrum - contains IgA antibodies)
    • Artificial passive immunity (e.g. antitoxins) → gained by injecting antibodies
    • Person does not produced the antibodies themselves
    • B and T cells have not been activated
    • Provides temporary (short-term) immunity

Vaccines

  • A preparation containing antigens which is used to stimulate an immune response artificially
    • Whole live microorganism
    • Dead microorganism
    • Attenuated microorganism
    • Toxoid (harmless form of toxin)
    • Surface antigens
  • Given by injection into vein/muscle OR taken orally
  • Vaccines that do not mimic an infection (lacking live microorganisms) are less effective
    • Need booster injections to stimulate secondary responses
  • Herd immunity: vaccinating a large proportion of the population; provides protection for those not immunised as transmission of a pathogen is reduced
    • Interrupts the transmission cycle
    • 93-95% required to prevent transmission in a population

Vaccination programmes

  • Schedule of vaccinations adopted by countries across the world to their own circumstances
  • Large population of children in the target age group are vaccinated → herd immunity achieved
  • Also protects against new diseases transmitted by visitors, migrants or returning travellers
  • Used to contain outbreaks of disease → ring immunity: vaccinating all those people in contact with a person infected with a specific disease to prevent transmission in the immediate area
  • One-dose vaccinations fail to eliminate diseases despite high coverage → poor response to the vaccine shown by some children (need at least 1 booster to develop full immunity)

Monoclonal antibodies

  • Monoclonal antibodies (Mabs): antibodies made by a single clone of hybridoma cells; all the antibody molecules made by the clone have identical variable regions so are specific to one antigen
    • B cells that divide by mitosis do not secrete antibodies
    • Plasma cells that secrete antibodies do not divide
  • Specificity of antibodies has made them useful in the diagnosis and treatment of diseases
  • Hybridoma: a cell formed by the fusion of a plasma cell and a cancer cell; it can both secrete antibodies and divide by mitosis

Using monoclonal antibodies in diagnosis

  • Used to locate the position of blood clots caused by deep vein thrombosis
  • Mouse injected with human fibrin
  • Makes plasma cells that secrete antibodies against fibrin
  • Collected from the spleen of the mouse
  • Plasma cells fused with cancer cells to form hybridomas (secrete antifibrin antibodies)
  • Radioactive chemical that produces gamma radiation is attached to each antibody molecule to make radioactively labelled Mabs
  • Introduced into the patient’s blood
  • Bind to fibrin molecules present in blood clots
  • Radioactivity emitted by these labelled antibodies is used to detect their location (gamma-ray cameras are used)
  • Routinely used in blood typing and tissue typing

Using monoclonal antibodies in treatment

  • Need to be administered more than once
  • Antibodies are produced by laboratory animals → trigger an immune response because they are non-self and acts as antigens
  • Humanising Mabs in two ways:
    • 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
    • Changing the type and position of the sugar groups that are attached to the heavy chains to the arrangement found in human antibodies

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