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HBIO1 > Immune System
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Antigen

  • Usually a protein (but polysaccharides, nucleic acid and lipids also act as antigens)
  • Self-antigen
    • Only found on the host's own cells and does not trigger an immune response
    • As these are proteins, their structure depends on the amino acid sequence
    • The gene for this sequence is highly polymorphic, having several alleles at each loci
    • There is great genetic variability between individuals
    • Thus, antigen is different in other people → injection would cause an immune response
    • There is only 25% chance that siblings will possess an identical antigen (transplant will not be rejected)
  • Non-self-antigen
    • Found on cells entering the body (e.g. bacteria, viruses, another person's cell)
    • Can also be displayed by cancer cells
    • May cause an immune response

Antibody (Immunoglobin Protein)

  • Secreted by B-lymphocytes and produced in response to a specific (foreign) non-self antigen
  • B-lymphocyte's receptor site matches the non-self-antigen
  • Each antibody is produced by one type of B-lymphocyte for only one type of antigen
  • Has a Y-shape
    • The two ends of the Y are called the Fab fragments
    • The other end is called the Fc fragment
    • Fab fragments are responsible for the antigen-binding properties
    • Fc fragment triggers the immune response
  • B cells divide and form memory cells and antibody-secreting plasma cells
  • Glossary
    • Agglutination makes pathogens clump together
    • Antitoxins neutralise toxins produced by bacteria
    • Lysis digests bacterial membrane, killing the bacterium (phagocytosis)
    • Opsonisation coats pathogen in protein that identifies them as foreign cells

Phagocytosis

  • White cells (phagocytes) contain digestive enzymes within lysosomes
    • Neutrophils primarily engulf bacteria
    • Macrophages engulf larger particles; including old and infected red blood cells
  • Found in blood, lymph systems and tissues
    • Squeeze through gaps in the walls of venules to enter tissues
    • This allows them to move faster to tissues infected with pathogens
  • Mechanism
    • Phagocytes are attracted by chemotaxis
    • Opsonisation by antibodies
      • Bacteria becomes coated with antibody
      • As a result, binding between bacteria and phagocytes is improved
    • Phagocytes form pseudopodia around the particle
    • This positions the particle into a phagocytic vacuole (also called phagosome)
    • Lysosome fuses with the phagosome
    • Intracellular killing by digestive enzymes from the lysosome
    • Pus is formed at the site of infection if no extensive vasculature is present

Types of Immune Response

  • Lymphocytes undergo maturating before birth, producing different types of lymphocytes
  • Humoral response - B lymphocytes
    • Produce and release antibodies into blood plasma
    • Produce antibodies from B plasma cells
    • Direct recognition of foreign antigen
  • Cellular response - T lymphocytes
    • Bind to antigen carrying cells and destroy them and/or activate the humoral response
    • Recognize foreign antigens displayed on the surface of normal body cells
  • Primary response produces memory cells which remain in the circulation
  • Secondary response new invasion by same antigen at a lower state. Immediate recognition and distraction by memory cells - faster and larger response usually prevents harm

B-Lymphocytes: Humoral Response

  • Production of antibodies in response to antigens found on pathogens not entering cells (bacteria)
  • Each B-lymphocyte (B cell) recognizes one specific antigen
  • Primary response
    • Antigen binds to specific Fab fragment of B cell
      • This produces a short and weak response
      • T helper cells are required to trigger the true potential of B cells
    • Once activated, the B cell grow and produce many clone cells
    • Clone cells have the same Fab fragment that recognizes the same antigen
    • Most differentiate into plasma cells
      • Secrete large amounts of antibodies
      • Bind to antigens and mark them for destruction
    • Some differentiate into memory cells
  • Secondary response
    • Exposure of same antigen causes activation of memory cells
    • They immediately recognize the antigen
    • Antibodies are produced more rapidly and in larger amounts

T-Lymphocytes: Cell-Mediated Response

  • Pathogens that quickly enter cells are more difficult to remove (viruses, tuberculosis)
  • Infected cell is directly destroyed / no antibodies involved
  • This is done by binding to the self and non-self antigen
    • Prevents destruction of harmless cells
    • Self antigen is a MHC (Major Histocompability Complex) protein present on almost all body cells
    • Non-self antigen (from viruses, bacterium, cancer, foreign cell, parasite) is processed and displayed on the surface of the infected cell
  • Primary response
    • Macrophage
      • Engulfs the pathogen and processes its foreign antigen
      • Non-self antigen is transported to the plasma membrane surface of the macrophage
      • Now called an antigen presenting cell (APC)
    • T Helper cells (Th cells)
      • Recognize foreign antigen on APC
      • Activates cytotoxic T cells and B cells to destroy the infected cell
    • T killer cells (cytotoxic T cells)
      • Must recognize self and non-self antigen to attach to infected cell
      • Directly kill pathogen by injecting proteases into the infected cell
      • Detach to search for more foreign cells
    • T-Suppressor cells switch off the T and B cell responses when infection clears
  • Secondary response
    • Some T cells differentiate into T-memory cells
    • Remain in the circulation and respond quickly when same pathogen enters body again
  • HIV destroys T-helper cells
    • Other immune cells are not activated
    • Humoral response cannot be launched without Th cells / require co-stimulation of Th cells
    • No immune response in patients with AIDS

Immunity and Vaccines

  • Vaccination is an artificial active immunity
  • Types
    • Live attenuated: organism is alive but has been modified/weakened so that it is not harmful
      • MMR (measles, mumps, rubella) - vaccine does NOT cause autism!
      • BCG for tuberculosis
    • Inactivated: dead pathogen but antigen is still recognised and an immune response triggered
      • Pertussis (whooping cough)
      • Poliomyelitis
    • Toxoid: vaccine contains a toxin
      • Diphtheria
      • Tetanus
    • Subunit: contains purified antigen that is genetically engineered rather than whole organism
      • Haemophilus influenza b - causes epiglottitis, meningitis
      • Meningococcal C - causes serious septicaemia, meningitis
      • Pneumoccocal - causes meningitis which results in permanent disabilities in >30%!
  • Vaccine may cause swelling, mild fever, and malaise
  • NEVER give live vaccines to children with an impaired immune system!
  • NEVER give vaccines if a child is ill (has a fever)

 

Active (Antibodies made by the human immune system, long term acting due to memory cells)

Passive (Given-Antibodies, short term acting)

Natural

- Response to disease
- Rejecting transplant

- Acquired antibodies
(via placenta, breast milk)

Artificial (immunisation)

Vaccination
(Injection of the antigen in a weakened form)

- Injection of antibodies from an artificial source, e.g. anti venom against snake biter

Differences

- Antibody in response to antigen
- Production of memory cells
- Long lasting

- Antibodies provided
- No memory cells
- Short lasting

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Monoclonal Antibodies (Magic Bullets)

  • Hybridoma
    • B cells are fused with tumour cells in the lab
    • Divide rapidly to form a clone of identical cells
    • Specific monoclonal antibodies are continuously produced and useful as
      • Tumour markers (antigens not present on non-cancer cells / attach to cancer cells only)
      • Anti-cancer drugs attached to monoclonal antibodies - deliver drug directly to cancer cells, fewer side effects
  • ¬†Uses of monoclonal antibodies
    • Monoclonal antibody is an antibody that is of just one type
    • Used to target the treatment of cancer cells or to screen (AIDS) in contaminated blood
    • Antibody direct enzyme prodrug therapy techniques (ADEPT)
      • Monoclonal antibodies are tagged with an enzyme that converts the prodrug (inactive drug) to an active form that kills cells (i.e. is cytotoxic)
      • The prodrug is injected in high conc
      • Attached to a monoclonal antibody, enzyme activates the drug and kills only cancer cells
    • In immunoassays, they can be labelled (radioactively) making them easy to detect
    • In the enzyme-linked immunosorbant assay (ELISA) technique, they are immobilised on an inert base and a test solution is passed over them
      • Target antigen combines with immobilised monoclonal antibodies
      • Second antibody attaches with an enzyme and binds to the monoclonal antibodies
      • and to the target antigen as well
      • Substrate is added which is converted to a coloured product by the added enzyme
      • Conc. of colour tells us the amount of antigens present in the test solution
    • Used to detect drugs in urine of athletics or in home pregnancy tests (where an antigen in human chorionic gonadotrophin (hCG) is secreted by the placenta)
    • Transplanted organs have non-self-antigens triggering antibodies to attack the organ, leading to its rejecting
      • T-Lymphocytes are needed for B-lymphocytes to function
      • Monoclonal antibodies against T-lymphocytes can be used to prevent B-lymphocytes from functioning, thus blocking the rejection of transplanted organs
    • [EXAM] Helping to diagnose between two pathogens because
      • Antigens are on cell-surface membrane
      • Monoclonal antibody reacts with specific antigen only
      • Thus, detects presence of special bacteria because of a different antigen on another, different bacteria