Cell recognition and the immune system

• Antigen

  Cell-surface molecule which stimulate immune response, usually (glyco)protein, sometimes (glyco)lipid or polysaccharide, enables identification of cells from other organisms of same species, pathogens, toxins & abnormal body cells
• Phagocytosis

  1. Phagocyte moves towards pathogen via chemotaxis

  2. Phagocyte engulfs pathogen via endocytosis to form a phagosome

  3. Phagosome fuses with lysosome (phagolysosome)

  4. Lysozymes digest pathogen

  5. Phagocyte absorbs the products from pathogen hydrolysis
• Antigen-presenting cells (APCs)


  Macrophage displays antigen from pathogen on its surface (after hydrolysis in phagocytosis), enhances recognition by TH cells
• Differences between specific and nonspecific immune responses

  • Nonspecific (inflammation, phagocytosis) = same for all pathogens
  • Specific (B & T lymphocytes) = complementary pathogen
  • Nonspecific = immediate
  • Specific = time lag
• Types of specific immune response

  • Cell-mediated
  • Humoral
• Cell-mediated response

  1. Complementary TH lymphocytes bind to foreign antigen on APC

  2. Release cytokines that stimulate clonal expansion of complementary TH cells (become memory cells or trigger humoral response)

  3. Release cytokines that stimulate clonal expansion of cytotoxic T cells (TC) which secrete enzyme perforin to destroy infected cells
• Humoral response

  1. Complementary TH lymphocytes bind to foreign antigen on antigen-presenting T cells

  2. Release cytokines that stimulate clonal expansion of complementary B lymphocytes

  3. B cells differentiate into plasma cells

  4. Plasma cells secrete antibodies with complementary variable region to antigen
• Antibody

  Proteins secreted by plasma cells, quaternary structure: 2 'light chains' held together by disulfide bridges, 2 longer 'heavy chains', binding sites on variable region of light chains have specific tertiary structure complementary to an antigen, the rest of the molecule is known as the constant region
• Antibodies lead to destruction of a pathogen


  Formation of antigen-antibody complex results in agglutination, which enhances phagocytosis
• Monoclonal antibodies


  A single type of antibody that can be isolated or cloned
• Memory cells

  Specialised TH/ B cells produced from primary immune response, remain in low levels in the blood, can divide very rapidly by mitosis if organism encounters the same pathogen again
• Antigen variability

  1. Random genetic mutation changes DNA base sequence

  2. Results in different sequence of codons on mRNA

  3. Different primary structure of antigen = H-bonds, ionic bonds & disulfide bridges form in different places in tertiary structure

  4. Different shape of antigen
• Antigen variability

  Memory cells no longer complementary to antigen = individual not immune = can catch the disease more than once, many varieties of a pathogen = difficult to develop vaccine containing all antigen types
• Vaccination

  1. Small amounts of dead/ inactive pathogen or antigen introduced in mouth or by injection

  2. Activates B cells to go through clonal expansion and differentiation- B cells undergo mitosis to make large numbers of cells

  3. B cells differentiate into plasma cells (make antibodies) or memory B cells (divide rapidly into plasma cells when re-infected with same pathogen) which remain in blood -so secondary response is rapid & produces higher concentration of antibodies

  4. Pathogen is destroyed before it causes symptoms
• Herd immunity


  Vaccinating large proportion of population reduces available carriers of the pathogen, protects individuals who have not been vaccinated e.g. those with a weak immune system
• Ethical issues surrounding vaccines

  • Production may involve use of animals
  • Potentially dangerous side-effects
  • Clinical tests may be fatal
  • Compulsory vs opt-out
• Structure of HIV

  -viruses replicate inside of cells so difficult to destroy them without harming host cells -no cell wall so cannot be destroyed by antibiotics -CORE= Genetic material (2 x RNA) & viral enzymes (integrase & reverse transcriptase) -CAPSID= outer protein coat ENVELOPE= derived from host cell membrane -GP120 ATTACHMENT PROTEINS= on surface enabling them to attach to helper T cells
• How HIV results in AIDS

  1. Attachment proteins bind to complementary CD4 receptor on TH cells

  2. HIV particles replicate inside TH cells, killing or damaging them

  3. AIDS develops when there are too few TH cells for the immune system to function

  4. Individuals cannot destroy other pathogens & suffer from secondary diseases/ infections
• Antibiotics are ineffective against viruses
• Clinical applications of monoclonal antibodies

  Pregnancy tests by detecting HCG hormones in urine, diagnostic procedures e.g. ELISA test, targeted treatment by attaching drug to antibody so that it only binds to cells with abnormal antigen e.g. cancer cells due to specificity of tertiary structure of binding site
• Direct ELISA test

  1. Monoclonal antibodies bind to bottom of test plate

  2. Antigen molecules in sample bind to antibody, rinse excess

  3. Mobile antibody with 'reporter enzyme' attached binds to antigens that are 'fixed' on the monoclonal antibodies, rinse excess

  4. Add substrate for reporter enzyme, positive result: colour change
• Indirect ELISA test

  1. Antigens bind to bottom of test plate

  2. Antibodies in sample bind to antigen, wash away excess

  3. Secondary antibody with 'reporter enzyme' attached binds to primary antibodies from the sample

  4. Add substrate for reporter enzyme, positive result: colour change
• Ethical issues surrounding monoclonal antibodies

  • requires use of animals to produce antibodies and tumour cells leads to ethical debates as to if this is justified for better treatments of cancer and to detect disease
  • Drug trials against arthritis & leukaemia resulted in multiple organ failure
• HIV replication

  -attachment proteins on HIV bind to complementary CD4 receptor on surface of helper T cell

  -HIV protein capsule fuses with helper T cell membrane enabling RNA and enzymes from HIV to enter

  -RNA is converted to DNA using reverse transcriptase

  -DNA is inserted into T helper cell nucleus

  -DNA undergoes transcription to make mRNA and translation creates viral proteins to make new viral particles
• ELISA test

  -add test sample from patient to base of beaker

  -wash to remove any unbound test sample

  -add antibody complementary in shape to antigen being tested for

  -wash to remove any unbound antibody

  -add second antibody complementary in shape to first antibody with enzyme attached

  -substrate for enzyme added (substrate produces colour in presence of enzyme)

  -colour change=antigen present + intensity of colour change=quantity
• Direct monoclonal antibody therapy

  -monoclonal antibodies designed with binding site complementary in shape to antigens on outside of cancer cells

  -antibodies bind to cancer antigens preventing chemicals binding to cancer cell that enables uncontrolled cell division

  -prevents cancer cell growing

  -do not cause harm to other cells
• Indirect monoclonal antibody therapy

  -monoclonal antibodies complementary in shape to antigens on outside of cancer cells which have drugs attached to them

  -cancer drugs delivered directly to cancer cells and kill them

  -reduces side effects of chemo
• Passive immunity

  -antibodies introduced into body

  -no plasma / memory cells made

  -no long-term immunity

  -passed through placenta or breast milk
• Active immunity

  -immunity created by own immune system following exposure to pathogen or its antigen

  -natural= following infection- creation of bodies own antibodies

  -artificial= vaccination
• Agglutination

  -antibodies are flexible and can bind to multiple antigens to clump them together

  -easier for phagocytes to locate and destroy pathogens