Immune Modulation Flashcards
(102 cards)
What are ways of boosting the immune system?
Vaccination
Replacement of missing components
Blocking immune checkpoints
Cytokine therapy
What are features of the adaptive immune response?
Wide repertoire of antigen receptors: Receptor repertoire not entirely genetically encoded.
Genes for segments of receptors are rearranged + nucleic acids deleted/ added at the sites of rearrangement almost randomly.
Potential to create in order of 10^11 to 10^12 receptors.
Autoreactive cells are likely to be generated.
Mechanisms must exist to delete or tolerise these autoreactive cells.
Exquisite specificity: Able to discriminate between very small differences in molecular structure.
What are antigen presenting cells?
Cells that can present peptides to T lymphocytes to initiate an acquired immune response.
Include:
- Dendritic cell
- Macrophage
- B lymphocyte
What are 5 types of osteoclasts?
Langerhans cells
Mesangial cells
Kupffer cells
Osteoclasts
Microglia
What is clonal expansion after exposure to an antigen?
T cells with appropriate specificity will proliferate + differentiate into effector cells (cytokine secreting, cytotoxic).
B cells with appropriate specificity will proliferate +
differentiate to T cell independent (IgM) (memory) plasma cells
undergo germinal centre reaction + differentiate to T cell dependent IgG/A/E(M) memory + plasma cells.
Plasma cells secrete high affinity specific antibodies.
What is immunological memory?
Pre-formed pool of high affinity specific antibodies.
Residual pool of specific T + B cells with enhanced capacity to respond if re-infection occurs.
What are features of T-cell memory?
Longevity: Memory T cells are maintained for a long time without antigen by continual low-level proliferation in response to cytokines.
Different pattern of expression of cell surface proteins involved in chemotaxis/cell adhesion: Allow memory cells to access non-lymphoid tissues, the sites of microbial entry.
Rapid, robust response to subsequent antigen exposure: There are more memory cells. These cells are more easily activated than naïve cells.
What are features of B-cell memory?
Pre-formed antibody: Circulating high affinity IgG antibodies.
Longevity: Long lived memory B cells + plasma cells.
Rapid, robust response to subsequent antigen exposure: Memory B cells are more easily + rapidly activated than naïve cells.
How do vaccines promote immunity against influenza?
CD8 T cells control virus load AFTER infection
Neutralising antibody provides a protective response to prevent infection.
Hemagglutinin (HA) is the receptor-binding + membrane fusion glycoprotein of influenza + the target for infectivity-neutralizing antibodies.
Clear correlation between resistance to infection + levels of IgG antibody to HA.
How is the BCG effective at mounting a protective response?
Attenuated, strain of bovine tuberculosis
Some protection against primary infection
Some protection against progression to active TB
T cell response is important in protection
What is the test for immunity against TB?
Mantoux test
Inject 0.1ml of 5 tuberculin units of liquid tuberculin intradermally.
The tuberculin used in the Mantoux skin test is AKA purified protein derivative, or PPD.
Patient’s arm is examined 48-72h after the tuberculin is injected.
Reaction is an area of induration (swelling that can be felt) around the site of the injection.
What are the different types of vaccines?
- Live vaccines
- Inactivated/ Component vaccines
(Conjugates + Adjuvants increase immunogenicity) - RNA vaccines
- Adenoviral vector vaccines
- Dendritic cell vaccines
What are 7 examples of live attenuated vaccines?
MMR
BCG
Yellow fever
Zostavax
Typhoid (oral)
Polio (Sabin oral)
Influenza (Fluenz tetra for children 2-17y)
How do live attenuated vaccines work?
Induce immune response
Modified (attenuated) organism to limit pathogenesis
Avoid if immunosuppressed
What are advantages of live attenuated vaccinations?
Establishes infection: Ideally mild Sx.
Raises broad immune response to multiple antigens: More likely to protect against different strains.
Activates all phases of immune system. T cells, B cells: With local IgA, humoral IgG.
May confer lifelong immunity, sometimes just after 1 dose.
What are disadvantages of live attenuated vaccines?
Possible reversion to virulence (recombination, mutation): Vaccine associated paralytic poliomyelitis (VAPP, ca.1:750,000 recipients).
Spread to contacts: Spread to immunosuppressed/ immunodeficient patients.
Storage problems.
What are 7 examples of inactivated viruses?
Influenza (inactivated quadrivalent)
Cholera
Bubonic plague
Polio (Salk)
Hepatitis A
Pertussis
Rabies
What are 3 examples of component/ subunit vaccines?
Hepatitis B (HbS antigen)
HPV (capsid)
Influenza (recombinant quadrivalent- less commonly used)
What are 2 examples of toxoid (inactivated toxin) vaccines?
Diphtheria
Tetanus
What are 4 advantages of inactivated/ component vaccines?
No risk of reversion to virulent form
Can be used with immunodeficient patients
Storage easier
Lower cost
What are 4 disadvantages of inactivated/component vaccines?
Often do not follow normal route of infection.
Some components have poor immunogenicity.
May need multiple injections.
May require modification to enhance immunogenicity.
* Conjugate to protein carrier
* Adjuvant
What are conjugate vaccines made of?
Conjugate vaccines (often used in children)
Polysaccharide plus protein carrier.
Polysaccharide alone induces a T cell independent B cell response – transient.
Addition of protein carrier promotes T cell immunity which enhances the B cell/ antibody response.
What are 3 examples of conjugate vaccines?
Haemophilus Influenzae B
Meningococcus
Pneumococcus (Prevenar)
(Remember NHS for polysaccharide encapsulated bacteria)
What is an adjuvant to a vaccine?
Adjuvant increases the immune response without altering its specificity.
Mimic action of PAMPs (pathogen associated molecular patterns) on TLR (toll-like receptors) + other PRR (pattern recognition receptors).