explain that vaccines contain antigens that stimulate immune responses to provide long-term immunity

Antibodies and Vaccination

Learning Objective (AO1)

Explain that vaccines contain antigens that stimulate immune responses to provide long‑term immunity.

Key Definitions (AO1)

  • Antigen: Any molecule (usually a protein or polysaccharide) that can be recognised by the immune system.
  • Antibody (Immunoglobulin, Ig): Y‑shaped protein produced by plasma B‑cells. Each antibody consists of:

    • Two identical heavy chains and two identical light chains.
    • Variable (V) regions at the tips of the “arms” (Fab) that bind a specific epitope.
    • Constant (C) regions forming the stem (Fc) that interact with complement and Fc‑receptors.

    Class‑switch recombination changes the isotype (IgM → IgG, IgA, IgE) to give specialised effector functions.

  • Vaccination (Artificial active immunity): Deliberate introduction of a harmless form of an antigen to provoke an immune response without causing disease.
  • Immunological memory: Long‑term protection generated by memory B‑cells and memory T‑cells after the first exposure to an antigen.
  • Active immunity: Immunity generated by the body’s own response (e.g., vaccination, natural infection).
  • Passive immunity: Immunity supplied by pre‑formed antibodies (e.g., maternal IgG, monoclonal‑antibody therapy).
  • Natural immunity: Immunity acquired after infection or by transfer of maternal antibodies.
  • Artificial immunity: Immunity obtained through vaccination (active) or through injection of antibodies (passive).

Comparison of Immunity Types

FeatureActive – NaturalActive – Artificial (Vaccination)Passive – Natural (Maternal)Passive – Artificial (Therapeutic)
Source of immunityLive infectionHarmless antigen preparationMaternal IgG transferred across placenta or via breast‑milkInjected antibodies (e.g., monoclonal, antivenom)
Duration of protectionYears to lifelong (memory cells)Years to lifelong (memory cells) – may need boostersWeeks to a few monthsDays to weeks
Typical examplesMeasles infection, chicken‑poxMMR vaccine, COVID‑19 mRNA vaccineMaternal antibodies protecting newbornsRituximab, antivenom, COVID‑19 monoclonal‑antibody cocktail

How Vaccines Work (AO2)

  1. Delivery of an antigenic component – live‑attenuated, inactivated (killed), sub‑unit/recombinant, mRNA, or viral‑vector.
  2. Uptake by antigen‑presenting cells (APCs) – dendritic cells, macrophages or B‑cells ingest the antigen.
  3. Processing and presentation

    • Extracellular antigens → degraded in endosomes → displayed on MHC‑II (activates CD4⁺ helper T‑cells).
    • Intracellular antigens (e.g., from mRNA or viral‑vector vaccines) → processed by the proteasome → displayed on MHC‑I (activates CD8⁺ cytotoxic T‑cells).

  4. Helper T‑cell activation – CD4⁺ T‑cells recognise antigen‑MHC‑II, bind via the T‑cell receptor (TCR) and secrete cytokines (IL‑2, IL‑4, IL‑5, IFN‑γ) that drive B‑cell proliferation and isotype switching.
  5. B‑cell activation and differentiation

    • Activated B‑cells become plasma cells that secrete antibodies (initially IgM, later switched to IgG, IgA or IgE).
    • A proportion become memory B‑cells that persist for years.

  6. Generation of memory T‑cells – both CD4⁺ helper and CD8⁺ cytotoxic memory cells are formed, ready for rapid response on re‑exposure.
  7. Booster dose (if required) – re‑exposes the immune system, allowing further affinity maturation and expansion of memory cell pools.

Types of Vaccines and Their Antigenic Forms

Vaccine TypeAntigenic ComponentTypical Immune ResponseExample
Live‑attenuatedWeakened whole organismStrong cellular (MHC‑I & MHC‑II) and humoral immunity; often lifelong protectionMMR, oral polio (Sabin)
Inactivated (killed)Whole organism rendered non‑viablePredominantly humoral (MHC‑II) response; boosters usually neededInactivated polio, hepatitis A
Sub‑unit / RecombinantPurified protein or polysaccharide (often with adjuvant)Targeted antibody response; safe for immunocompromised patientsHepatitis B surface antigen, pneumococcal polysaccharide
mRNAmRNA encoding a specific viral protein (e.g., spike protein)Protein produced inside host cells → presented on MHC‑I and MHC‑II; both cellular and humoral immunityCOVID‑19 mRNA vaccines (Pfizer‑BioNTech, Moderna)
Viral vectorNon‑replicating virus carrying a gene for the antigenic proteinRobust cellular (MHC‑I) and humoral (MHC‑II) responsesAstraZeneca COVID‑19 vaccine (chimpanzee adenovirus vector)

Adjuvants, Boosters and Safety Considerations

  • Adjuvants (e.g., aluminium salts, MF59) are added to many sub‑unit vaccines to enhance antigen uptake, stimulate cytokine release and increase the magnitude of the antibody response.
  • Booster doses re‑expose the immune system, allowing further affinity maturation of antibodies and extending the lifespan of memory B‑ and T‑cells.
  • Safety notes

    • Live‑attenuated vaccines can replicate; they are contraindicated in immunocompromised individuals (e.g., HIV, chemotherapy patients) because the weakened pathogen may cause disease.
    • Inactivated and sub‑unit vaccines are generally safe for these groups, but may require additional boosters.

Long‑Term Immunity: Role of Memory Cells (AO2)

After vaccination two principal memory populations are established:

  • Memory B‑cells: Remain in circulation or secondary lymphoid tissue; on re‑exposure they rapidly differentiate into plasma cells that secrete high‑affinity IgG (or IgA/IgE) antibodies.
  • Memory T‑cells: Include CD4⁺ helper cells that accelerate B‑cell responses and CD8⁺ cytotoxic cells that can directly kill infected cells.

The combined action of these cells produces a faster, larger, and more specific secondary immune response, often neutralising the pathogen before clinical disease develops.

Hybridoma Technique and Monoclonal Antibodies (AO1/AO2)

The hybridoma method is used to produce monoclonal antibodies (mAbs) for diagnosis or therapy:

  1. Isolate B‑cells from an immunised mouse (or other animal) that produce the desired antibody.
  2. Fuse these B‑cells with an immortal myeloma cell line → hybridoma cells that combine antibody specificity with unlimited growth.
  3. Select hybridomas that secrete the antibody of interest and clone them to obtain a pure population.
  4. Harvest the monoclonal antibody from culture medium or ascites fluid.

Examples:

  • Rituximab – a chimeric anti‑CD20 monoclonal antibody used to treat non‑Hodgkin lymphoma.
  • ELISA kits that use monoclonal antibodies to detect HIV p24 antigen or SARS‑CoV‑2 spike protein.

Key Points to Remember

  • Vaccines are antigenic preparations that mimic natural infection without causing disease.
  • Antibodies have a Y‑shaped structure (2 heavy + 2 light chains; variable Fab region for binding, constant Fc region for effector functions).
  • The primary response generates antibodies, cytokines, and memory cells.
  • Booster doses strengthen and prolong immunity through affinity maturation.
  • Different vaccine platforms present antigens via MHC‑I (intracellular) or MHC‑II (extracellular) pathways, influencing the balance of cellular and humoral immunity.
  • Hybridoma‑derived monoclonal antibodies are valuable tools for diagnosis and therapy, illustrating the practical use of antibody specificity.
  • Adjuvants, safety profiles and the choice of vaccine type are critical for effective immunisation programmes.

Suggested diagram: Flowchart – Vaccine administration → APC uptake → MHC presentation → T‑cell activation → B‑cell differentiation → Plasma cells & memory cells → Long‑term immunity.