Monoclonal Antibodies and Vaccines

Immunoglobulins (antibodies)
1. Y-shaped proteins
  1. Locate and neutralise foreign particles in the body
2. Each specific to a unique part of a foreign object
  1. Antigens
3. Conserved and variable regions
  1. Each tip contains a paratope
    1. Specific for a particular epitope on an antigen
      1. Key
      2. Allows precise binding of antigens and antibodies, which tags foreign particles for attack by the immune system
    2. Lock
4. Formed from two heavy polypeptide chains and two light polypeptide chains, with two variable sites for antigen recognition
Polyclonal antibodies
1. Derived from many B cell lines and were first used to treat infectious diseases
  1. Tetanus and diphtheria
2. Use limited due to low reproducibility and consistency and variable toxicity
Monoclonal Antibodies
1. Derived from identical B cells that are clones of a parent cell
  1. Monospecific for a certain antigen
  2. Can be produced in bulk to identify, bind to or eliminate a target substance in the blood
    1. Used massively in biochemistry and medicine
2. Currently 21 human therapeutic monoclonal antibodies, with over 100 more in clinical trials
3. Produced by injecting a mouse with an antigen, causing its immune cells to produce the complementary antibody, immunising the animal
  1. Immune cells that produce the antibody are isolated, extracted and fused with tumour cells, making hybridomas
    1. Unfused cells die as they lack the HGPRT enzyme to survive in a HAT medium
    2. Hybridomas are screened for antibody production and then are cloned, making many cells which all produce the desired antibody
4. Used in the treatment of cancer, autoimmune diseases, eye disorders and cardiovascular systems
Chimeric Antibodies
1. Fusion Antibodies
2. Produced from the recombination of genes coding for antibodies
  1. An all-rodent antibody the would not function in a human can be fused with an all-human antibody
    1. Creates a chimeric humanised antibody
      1. Originally produced in the mouse but is fully functional in humans, with around 90% human sequence
3. Less immunogenic
  1. Less able to produce an immune response
4. Examples
  1. Rituxan
    1. Used for treating Non-Hodgkins lymphoma
  2. Remicale
    1. Used for treating rheumatoid arthritis and Crohn's disease
5. Human antibody libraries
  1. Created by obtaining immune serum from patients
    1. Or by mutagenesis with PCR techniques that are more prone to mutations
      1. Increases the variability of the antigens
Vaccines
1. Biological preparations that boost the immune system to protect agains pathogens
2. Types
  1. Live attenuated
    1. Pathogen grown in culture, usually as a less virulent form
  2. Killed/inactive
    1. Pathogen is chemically inactivated
      1. Inactivated by things such as formaldehyde
  3. Subunit
    1. Use antigenic parts of the pathogen, which can still illicit a response
3. Under development
  1. Recombinant adenoviral vectors
    1. Efficient delivery system into human cells
    2. Viruses genetically altered to carry foreign proteins, which elicit an immune response
      1. By combining the physiology of one pathogen and the DNA of another, vaccinations can be carried out for diseases with complex infection methods
  2. Recombinant BCG vaccines
    1. Made up of genes of various strains of pathogen
      1. Very efficient B and T cell responses
  3. DNA vaccines
    1. Plasmid DNA (antigenic transgenes) are injected with an immunomodulator to increase their transcription and efficacy
4. Adjuvant
  1. Added to a vaccine to boost the resulting immune response to the antigen
  2. Act in various ways
    1. As an antigen store - releases slowly to maximise response
    2. As an irritant - causes the body to recruit and amplify response
    3. Activates T cells and lymphocytes
  3. Many different types, from inorganic compounds such as aluminium hydroxide to emulsifying oils
  4. Some side effects include inflammation
5. Toll-like receptors
  1. Key role in the immune response
  2. Detect foreign particles and elicit a response
  3. Receptors in dendritic cells
    1. Provide early detection of things such as ssRNA (viral particles) and LPS (bacterial membrane proteins)
      1. Understanding of this mechanism allows specific targeting of parts of the immune response and allows for a more versatile vaccine design
        Adjuvants could be added to the vaccine to activate certain TLRs
Viruses mutate and evolve, so vaccinations often need to protect from multiple strains of the same infection
1. The Avian Influenza virus crossed the species barrier in 1918, infecting humans
  1. H1N1
    1. Main antigens are referred to in the name
      1. Haemaglutinin (HA)
      2. Neuraminidase (NA)
  2. This virus has mutated many times since, changing the gene sequence which codes for the antigens
    1. Given rise to new strains
      1. H2N2
      2. H3N2
      3. Vaccination must therefore protect against all of these strains, as all of them still exist

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Monoclonal Antibodies and Vaccines

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	Criado por Lydia Buckmaster quase 11 anos atrás