Cell recognition and the immune system

• What is an antigen?

  • Foreign molecule/protein/glycoprotein/glycolipid
  • That stimulates an immune response leading to the production of antibodies
• How are cells identified by the immune system?

  • Each type of cell has specific molecules on its surface that identify it
  • Often proteins have a specific tertiary structure
• Describe the process of Phagocytosis

  1)Phagocyte is attracted to pathogen due to chemicals being released (Chemotaxis)

  2)Phagocyte binds to pathogens antigens via opsonin's and surface receptors

  3)Pathogen is engulfed via endocytosis and then forms a phagosome (Vesicle)

  4)Lysosomes fuse to phagosome (forming a phagolysosome) and releases lysozymes to hydrolyse pathogen

  5)The hydrolysed products of the pathogen are absorbed by the phagocyte or released via exocytosis
• What do macrophages do that neutrophils don't?

  1)After endocytosis, rather than fully hydrolysing the pathogen they cut it up instead

  2)They display the antigens of the pathogens on their cell surface membrane (using the major histocompatibility complex)

  3)These displayed antigens can then be recognised by lymphocytes

  4)This cell is now called an antigen-presenting cell (APC)
• What are Opsonin's?

  • Protein molecules that attach to the antigens on the surface of a pathogen
  • Enhance phagocytosis by marking an antigen for an immune response or marking dead cells for recycling
  • They are non specific - allows them to bind to a variety of pathogenic cells
• What are antigen presenting cells (APC)

  Cells that display a foreign antigen on their cell surface membrane
• T-lymphocytes (T-cells)

  • Mature in the thymus
  • Involved in cell mediated immunity (involving body cells)
• B-lymphocytes (B-cells)

  • Mature in bone marrow
  • Involved in humoral immunity (Involving antibodies present in fluids or 'humour' such as blood or plasma
• What are the 4 types of APC?

  1. Macrophages - present antigens on cell surface membrane
  2. Body cells infected by a virus - present the viral antigens on their own cell surface membrane
  3. Cancer cells - different to normal body cells, and so are their antigens
  4. Transplanted cells - other individuals have different antigens on their cell surface membrane
• Describe the response of T-lymphocytes to a foreign antigen (cell mediated immunity)

  Specific helper T lymphocytes with complimentary receptors bind to antigens on APC. They are then activated and divide by mitosis to form:

  • Cytotoxic T killer cells
  • T helper cell
  • T memory cell
• What do T-Helper cells do?

  They release cytokines which activate B-lymphocytes and macrophages
• What do T-Memory cells do?

  Remain in the blood to respond to same antigen in the future
• What do Cytotoxic T-Killer cells do?

  • Binds to infected cell
  • Releases perforin proteins which pierce holes in the infected cells membrane and enzymes enter the holes which cause apoptosis
  • Infected cell is destroyed
• Describe the response of B-lymphocytes to a foreign antigen (Humoral response)

  Clonal Selection:

  • Specific B-lymphocytes with complementary receptors binds to antigen
  • The B-lymphocyte is then activated by cytokines released from T-Helper cells
  • B-lymphocytes then divide rapidly by mitosis to form clones

  Clonal Expansion:

  • Some differentiate into B-Plasma cells - secrete large amounts of (monoclonal) antibodies
  • Some differentiate into B-Memory cells - remain in blood for secondary response
• What are antibodies?

  • Quaternary structure proteins (4 polypeptide chains)
  • Secreted by B-lymphocytes e.g. plasma cells in response to specific antigens
  • Bind specifically to antigens forming an antigen-antibody complex
• What are the key parts of an antigen?

  • Antigen binding site
  • Variable region
  • Constant region
  • Disulphide bridge
  • Hinge region
  • Heavy polypeptide chain
  • Light polypeptide chain
• What are the 3 functions of antibodies?

  1)Opsonisation - Opsonin binds to antigen on pathogen to mark it for phagocytosis

  2)Neutralisation - Antibodies bind to and block all of the receptors on the pathogen rendering it harmless until they are destroyed by phagocytosis

  3)Agglutination - Antibodies bind multiple pathogens to clump them together so a large amount can be engulfed at once
• What is a vaccine?

  • Injection of antigens from a weakened pathogen
  • Stimulating formation of memory cells
• How do vaccines provide protection to individuals against disease?

  1. Specific B-lymphocyte with complementary receptor binds to antigen
  2. Specific T-Helper cell binds to APC and stimulates B cell
  3. B-lymphocytes divide by mitosis to form clones
  4. Some differentiate into B-Plasma cells which release antibodies
  5. Some differentiate into B-Memory cells
  6. On secondary exposure to antigen, B-Memory cells rapidly divide by mitosis to produce B-Plasma cells
  7. These release antibodies faster and at a higher concentration
• What is active immunity?

  • Initial exposure to antigen e.g. vaccine or primary infection
  • Memory cells involved
  • Antibody produced and secreted by B-Plasma cells
  • Slow; takes longer to develop
  • Long term immunity as antibody ca be produced in response to a specific antigen again
• What is passive immunity?

  • No exposure to antigen
  • No memory cells involved
  • Antibody introduced from another organism e.g. breast milk/across placenta from mother
  • Faster acting
  • Short term immunity as antibody hydrolysed (endo/exo/dipeptidases)
• What are the key parts in the structure of HIV?

  • Lipid envelope
  • RNA
  • Reverse transcriptase
  • Capsid
  • Attachment proteins
• Describe the replication of HIV in T-Helper cells

  1. HIV attachment proteins attach to receptors on helper T cell
  2. Lipid envelope fuses with cell-surface membrane, releasing capsid into cell
  3. Capsid uncoats, releasing RNA and reverse transcriptase
  4. Reverse transcriptase converts viral RNA to DNA
  5. Viral DNA inserted into T-Helper cell DNA (may remain latent)
  6. Viral Protein/capsid/enzymes are produced - DNA transcribed into HIV mRNA - HIV mRNA translated into new HIV proteins
  7. Virus particles assembled and released from cell
• Explain how HIV causes the symptoms of AIDS

  1)HIV infects and kills T-Helper cells as it multiplies rapidly

  • So T-Helper cell can't stimulate Cytotoxic T-Killer cells, B cells and phagocytes
  • So B-Plasma cells can't release as many antibodies for agglutination and destruction of pathogens

  2)Immune system deteriorates - more susceptible to infections

  3)Pathogens reproduce, release toxins and damages cells
• Explain why antibiotics are ineffective against viruses

  • Viruses do not have metabolic processes/ribosomes
  • Viruses do not have bacterial enzymes/murein cell wall
• What is a monoclonal antibody?

  • Antibody produced from genetically identical/cloned B-lymphocyte/Plasma cell
  • So have same tertiary structure
• Explain how monoclonal antibodies can be used in medical treatments

  • Monoclonal antibody has a specific tertiary structure
  • Complementary to receptor found only on a specific type of cell (e.g. cancer cell)
  • Therapeutic drug attached to antibody
  • Antibody binds to specific cell, forming antigen-antibody complex, delivering drug

  Some monoclonal antibodies are also designed to block antigens/receptors on cell
• Explain how monoclonal antibodies can be used in medical diagnosis

  • Monoclonal antibody has a specific tertiary structure
  • Complementary to specific receptor/protein/antigen associated with diagnosis
  • Dye/stain/fluorescent marker attached to antibody
  • Antibody binds to receptor/protein/antigen, forming antigen-antibody complex

  Examples vary e.g. pregnancy tests
• Describe the process of DIRECT ELISA testing

  1. Attach sample with potential antigens to well
  2. Add complementary monoclonal antibodies with enzyme attached - bind to antigens if present
  3. Wash well - remove unbound antibodies (to prevent false positive)
  4. Add substrate - enzymes create products that causes a colour change (positive result)
• Describe the process of SANDWICH ELISA testing

  1. Attach specific monoclonal antibodies to well
  2. Add sample with potential antigens, then wash well
  3. Add complementary monoclonal antibodies with enzymes attached - bind to antigens if present
  4. Wash well - remove unbound antibodies
  5. Add substrate - enzymes create products that cause a colour change
• Describe the process of INDIRECT ELISA testing

  1. Attach specific antigens to well
  2. Add sample with potential antibodies, wash well
  3. Add complementary monoclonal antibodies with enzyme attached - bind to antibodies present
  4. Wash well - remove unbound antibodies
  5. Add substrate - enzyme create products that cause a colour change
• Suggest the purpose of a control well in the ELISA test

  • Compare to test to show only enzyme causes colour change
  • Compare to test to show all unbound antibodies have been washed away