2. Immmunity

• Describe and explain how the structure of an antibody relates to its function?

  The structure of an antibody consists of two heavy chains and two light chains that form a Y-shaped molecule. The variable regions of the antibody bind to specific antigens, while the constant regions determine the antibody's function, such as activating immune responses or neutralizing pathogens.
• Describe and explain how the structure of an antibody relates to its function?

  Primary structure of protein = sequence of amino acids in a polypeptide chain

  Determines the folds in the secondary structure as R groups interact

  • Determines the specific shape of the tertiary structure and position of hydrogen, ionic and

  disulfide bonds
• What is structure of antibody ? Quaternary structure is comprised of 4 polypeptide chains (tertiary structured) held

  together by hydrogen, ionic and disulfide bonds

  Enables the specific shaped variable region (binding site) to form which is a complementary

  shape to a specific antigen

  • Enables antigen-antibody complex to form
• How do antibodies work to destroy pathogens e.g. bacterial cells?

  Binds to two pathogens at a time (at variable region/binding site) forming an antigenantibody complex

  Enables antibodies to clump the pathogens together – agglutination

  Phagocytes bind to the antibodies and phagocytose many pathogens at once

  • Note: the hinge region means an antibody can bind to antigens / pathogens different distances part
• What is a vaccination?

  • Injection of antigens
  • From attenuated (dead or weakened) pathogens

  Stimulates the formation of memory cells

  • A vaccine can lead to symptoms because some of the pathogens might be alive / active /

  viable; therefore, the pathogen could reproduce and release toxins, which can kill cells
• The use of vaccines to provide protection for individuals against disease

  Normal immune response but the important part is that memory cells are produced

  On reinfection / secondary exposure to the same antigen, the secondary response therefore

  produces antibodies faster and at a higher concentration

  • Leading to the destruction of a pathogen/antigen (e.g. agglutination and phagocytosis)

  before it can cause harm / symptoms = immunity
• The use of vaccines to provide protection for populations against disease (herd immunity)

  • Large proportion but not 100% of population vaccinated against a disease – herd immunity

  Makes it more difficult for the pathogen to spread through the population because...

  • More people are immune so fewer people in the population carry the pathogen / are infected

  - Fewer susceptible so less likely that a susceptible / non-vaccinated individual will come into contact with an infected person and pass on the disease
• Ethical issues associated with the use of vaccines

  Tested on animals before use on humans  animals have a central nervous system so feel pain (some animal based substances are also used to produce vaccines)

  Tested on humans  volunteers may put themselves at unnecessary risk of contracting the disease because they think they’re fully protected e.g. HIV vaccine so have unprotected sex  vaccine might not work

  Can have side effects

  • Expensive – less money spent on research and treatments of other diseases
• Antigen variability is often an explanation for why...

  New vaccines against a disease need to be developed more frequently e.g. influenza

  Vaccines against a disease may be hard to develop or can’t be developed in the first place

  e.g. HIV

  • May experience a disease more than once e.g. common cold
• Explain the effect of antigen variability on disease

  Change in antigen shape (due to a genetic mutation)

  Not recognised by B memory cell  no plasma cells / antibodies

  Not immune

  Must re-undergo primary immune response  slower / releases lower concentration of

  antibodies

  • Disease symptoms felt
• Explain the effect of antigen variability on disease prevention (vaccines)

  Change in antigen shape (due to a genetic mutation)

  - Existing antibodies with a specific shape unable to bind to changed antigens / form antigen-antibody complex

  • Immune system i.e. memory cells won’t recognise different antigens (strain)
• Evaluate methodology, evidence and data relating to the use of vaccinations

  A successful vaccination programme:

  Produce suitable vaccine

  Effective – make memory cells

  No major side effects  side effects discourage individuals from being vaccinated

  Low cost / economically viable

  Easily produced / transported / stored / administered - Provides herd immunit
• Evaluating a conclusion that’s been made from a set of data / study

  If there is a scatter graph, the relationship between two variables may be a positive /

  negative correlation, or no correlation

  But correlation between two variables doesn’t always mean there’s a causal

  relationship – correlation could be due to change or another variable / factor

  Repeatability (when an experiment is repeated using the same method and

  equipment and obtains the same results)
• The use of monoclonal antibodies

  Monoclonal antibody = antibody produced from a single group of genetically identical (clones) B cells / plasma cells

  Identical structure

  Bind to specific complimentary antigen

  • Have a binding site / variable region with a specific tertiary structure / shape - Only one

  complementary antigen will fit
• Why are monoclonal antibodies useful in medicine?

  Only bind to specific target molecules / antigens because...

  • Antibodies have a specific tertiary structure (binding site / variable region) that’s

  complementary to a specific antigen which can bind/fit to the antibody
• Monoclonal antibodies: targeting medication to specific cell types by attaching a therapeutic drug to an antibody

  Example: cancer cell

  1. Monoclonal antibodies made to be complementary to antigens specific to cancer cells  cancer cells are abnormal body cells with different antigens (tumour markers)

  2. Anti-cancer drug attached to antibody

  3. Antibody binds / attaches to cancer cells (forming antigen-antibody complex)

  4. Delivers attached anti-cancer drug directly to specific cancer cells so drug accumulates 

  fewer side effects e.g. fewer normal body cells killed
• Exam question example: some cancer cells have a receptor protein in their cell-surface membrane that binds to a hormone called growth factor. This stimulates the cancer cells to divide. Scientists have produced a monoclonal antibody that stops this stimulation. Use your knowledge of monoclonal antibodies to suggest how this antibody stops the growth of a tumour (3 marks)

  Antibody has specific tertiary structure / binding site / variable region Complementary (shape / fit) to receptor protein / GF / binds to receptor protein Prevents GF binding (to receptor)
• Ethical issues associated with the use of monoclonal antibody

  Animals are involved in the production of monoclonal antibodies i.e. by producing cancer in mice who have a CNS so feel pain, and it is unfair to give them a disease

  Although effective treatment for cancer and diabetes has caused deaths when used in treatment of Multiple Sclerosis

  • Patients need to be informed of risk and benefits before treatment so they can make informed decisions
• Why antibiotics are ineffective against viruses

  Antibiotics can’t enter human calls – but viruses exists in its host cell (they are acellular)

  Viruses don’t have own metabolic reactions e.g. ribosomes (use of the host cell’s) which

  antibiotics target

  • If we did use them... act as a selection pressure + gene mutation = resistant strain of

  bacteria via natural selection  reducing effectiveness of antibiotics and waste money
• How HIV causes the symptoms of AIDS – acquired immune deficiency syndrome

  Infects and kills helper T cells (host cell) as it multiplies rapidly

  T helper cells then can’t stimulate cytotoxic T cells, B cells and phagocytes 

  impaired immune response

  E.g. B plasma cells can’t secrete antibodies for agglutination and destruction of

  pathogens by phagocytosis

  Immune system deteriorates

  More susceptible to infections

  • Diseases that wouldn’t cause serious problems in healthy immune system are deadly

  (opportunistic infections) e.g. pneumonia
• Secondary response – same antigen enters body again (role of memory cells)

  Produces antibodies faster and at a higher concentration because

  B and T memory cells present

  • B memory cells undergo mitosis quicker / quicker clonal selection

  
• Primary response – antigen enters body for the first time (role of plasma cells)

  Produces antibodies slower and at a lower concentration because

  Not many B cells available that can make the required antibody

  • T helpers need to activate B plasma cells to make the antibodies (takes time) - So

  infected individual will express symptoms
• The humoral response (the response of B lymphocytes to a foreign antigen e.g. in blood/tissues)

  Clonal selection:

  1. Specific B cell binds to antigen presenting cell and is stimulated by helper T cells which

  releases cytokines

  b) Dividesrapidlybymitosistoformclones(clonalexpansion)

  2. Some become B plasma cells for the primary immune response – secrete large amounts of monoclonal antibody into blood

  3. Some become B memory cells for the secondary immune response
• The cellular response (the response of T lymphocytes to a foreign antigen e.g. infected cells, cells of the same species)

  1. T lymphocytes recognises antigen presenting cells after phagocytosis (foreign antigen)

  2. Specific T helper cell with receptor complementary to specific antigen binds to it, becoming

  activated and dividing rapidly by mitosis to form clones which: a) Stimulate B cells for the humoral response

  b) Stimulate cytotoxic T cells to kill infected cells by producing perforin

  c) Stimulate phagocytes to engulf pathogens by phagocytosis
• Phagocyte e.g. macrophage recognises foreign antigens on the pathogen and binds to the antigen

  2. Phagocyte engulfs pathogen by surrounding it with its cell surface membrane / cytoplasm

  3. Pathogen contained in vacuole/vesicle/phagosome in cytoplasm of phagocyte

  4. Lysosome fuses with phagosome and releases lysozymes (hydrolytic enzymes) into the

  phagosome

  5. These hydrolyse / digest the pathogen

  6. Phagocyte becomes antigen presenting and stimulates specific immune response
• Antigens are specific so allow the immune system to identify...

  Pathogens (disease causing organisms) e.g. viruses, fungi, bacteria

  Cells from other organisms of the same species e.g. organ transplant, blood transfusion

  Abnormal body cells e.g. cancerous cells / tumours

  • Toxins released from bacteria
• Antigen definition

  Molecules which, when recognised as non-self/foreign by the immune system, can stimulate an immune response and lead to the production of antibodies

  Often proteins on the surface of cells

  • Note: proteins have a specific tertiary structure / shape allowing different proteins to act as specific antigens
• Cell recognition and the immune system

  All cells have antigens on their surfaces that allows them to be recognised by other cells

  The immune system can distinguish antigens on body cells (self) and antigens on foreign objects (non-self) The immune system can identify pathogens (diseasecausing organisms), abnormal body cells (cancerous/ infected cells), cells from other individuals of the same species (eg organ transplants) and toxins.
• Cell mediated response

  • There are two types of T cells: helper T cells and cytotoxic T cells
  • Receptors on specific helper T cells are complementary to the antigens the APC is presenting and this causes the helper T cell to undergo clonal expansion (clones itself) and release cytokines (chemical signals)
  • The helper T cells activate cytotoxic T cells which search for infected body cells
  • When they find an infected cell, they inject it with perforin which causes the cell membrane to disintegrate and the cell to die
• The cytokines from the helper T cells activate B cells that are specific to the antigens on the APC.
• The B-cell undergoes clonal expansion and differentiation (specialisation) into plasma cells and memory B cells.
• Plasma cells produce antibodies that fit the antigens on the APC.
• Antibodies are proteins made by B-cells that have a binding site complementary to antigens on a specific pathogen.
• Antibodies are made of four polypeptide chains, two called heavy chains and two called light chains.
• Each antibody has two binding sites.
• Antibodies have a variable region (the binding sites) and a constant region that is the same for all antibodies.
• Antibodies bind to antigens to create a antigen-antibody complex.
• Antibodies can cause agglutination (pathogens stick together so they can be engulfed easier).
• Antibodies can act as markers to stimulate the phagocytes to engulf the pathogen.
• Antibodies can neutralise the pathogen so it can't enter any body cells.