describe the differences between active immunity and passive immunity and between natural immunity and artificial immunity

Immunity – Classification and Key Concepts (Cambridge 9700 – Topic 11.2)

1. The Immune System (Syllabus 11.1)

• Self vs non‑self antigens – the immune system distinguishes the body’s own molecules (self‑MHC, normal proteins) from foreign structures such as bacterial surface proteins or viral capsids (non‑self).
• Phagocytes

  • Macrophages – ingest microbes, present antigen fragments on MHC II, and release cytokines that recruit other immune cells.
  • Neutrophils – rapid responders that kill bacteria by oxidative burst and release of granule enzymes.

• Primary immune response – the first encounter with a specific antigen.

  1. Antigen is taken up by a macrophage (or dendritic cell) and processed.
  2. Antigen fragments are displayed on MHC II molecules and presented to helper T‑cells (Th).
  3. Activated Th cells release cytokines that stimulate:

     • B‑cells – differentiate into plasma cells (secrete antibodies) and memory B‑cells.
     • Cytotoxic T‑cells (Tc) – recognise infected cells presenting antigen on MHC I and induce cell death.

  4. Antibodies (mainly IgM) appear after 4–7 days; the response peaks around 10–14 days.

• Memory cells – long‑lived B‑cells and T‑cells generated during the primary response. On re‑exposure they mount a rapid, high‑affinity secondary response (predominantly IgG).

2. Antibody (Immunoglobulin) Structure – Syllabus Requirement (11.2)

• Y‑shaped glycoprotein composed of two identical heavy (H) chains and two identical light (L) chains linked by disulphide bonds.
• Variable (V) regions at the tips of the Y (Fab fragments) bind specific antigenic epitopes.
• Constant (C) regions determine the antibody class (isotype) and effector function.
• The Fab (fragment antigen‑binding) region contains one V_L + C_L and one V_H + C_H domain – responsible for antigen recognition.
• The Fc (fragment crystallisable) region is formed by the remaining constant domains of the heavy chains – mediates interaction with complement and Fc receptors on phagocytes.
• Human isotypes: IgG, IgM, IgA, IgD, IgE.

  • IgM – first antibody produced, effective in primary response.
  • IgG – most abundant, provides long‑term protection and crosses the placenta.
  • IgA – secreted in mucosal surfaces (e.g., saliva, breast‑milk).
  • IgE – involved in allergy and defence against parasites.
  • IgD – receptor on naïve B‑cells, role in B‑cell activation.

3. Classification of Immunity

Immunity can be described in two independent ways:

• By the source of protective agents: active or passive immunity.
• By the way the response is acquired: natural or artificial immunity.

3.1 Active vs Passive Immunity

• Active immunity

  • Host’s own immune system is stimulated to produce antibodies and memory cells.
  • Induced by exposure to antigen – either a natural infection or a vaccine.
  • Memory B‑cells are generated → long‑term protection (years to lifelong).
  • Onset is delayed (typically 4–14 days after first exposure).

• Passive immunity

  • Pre‑formed antibodies are transferred from another source.
  • No activation of the recipient’s B‑cells → no memory cells.
  • Protection is short‑lived: days (serum therapy) to a few months (maternal IgG).
  • Provides immediate protection – useful when an active response would be too slow or when the host cannot mount one.

3.2 Natural vs Artificial Immunity

• Natural immunity

  • Acquired through everyday exposure to pathogens in the environment.
  • Can be active (infection → antibody & memory) or passive (maternal antibodies transferred to the newborn).
  • No medical intervention is involved.

• Artificial immunity

  • Obtained deliberately by medical procedures.
  • Active artificial immunity – vaccination with live‑attenuated, killed, subunit, toxoid or conjugate preparations.
  • Passive artificial immunity – administration of immune serum, hyper‑immune globulin, or monoclonal antibodies.
  • Allows control of timing, dosage and safety of the immune stimulus.

4. Primary Immune Response – Step‑by‑Step

1. Antigen capture – macrophage or dendritic cell engulfs the pathogen.
2. Processing & presentation – antigen fragments are loaded onto MHC II molecules.
3. Helper T‑cell activation – Th cell recognises the MHC II‑antigen complex, becomes activated and releases cytokines.
4. B‑cell activation – cytokines stimulate B‑cells that bind the same antigen; they differentiate into:

   • Plasma cells – secrete IgM (later class‑switch to IgG, IgA, etc.).
   • Memory B‑cells – persist for future encounters.

5. Cytotoxic T‑cell activation (cell‑mediated arm) – antigen presented on MHC I to Tc cells, which then destroy infected host cells.
6. Resolution – most plasma cells die after the antigen is cleared; memory cells remain.

5. Vaccination – Artificial Active Immunity

• Live‑attenuated vaccines – contain weakened but replicating organisms (e.g., measles, mumps, rubella).
• Killed (inactivated) vaccines – whole organisms rendered non‑viable (e.g., polio IPV).
• Subunit / toxoid vaccines – purified proteins or inactivated toxins (e.g., hepatitis B surface antigen, diphtheria toxoid).
• Conjugate vaccines – polysaccharide antigens linked to a protein carrier to enhance T‑cell help (e.g., Hib, pneumococcal).
• Booster doses are given to maintain or re‑stimulate memory.

6. Hybridoma Technique – Production of Monoclonal Antibodies (Syllabus 11.2)

1. Fusion – B‑lymphocytes from an immunised mouse are fused with an immortal myeloma cell line using polyethylene glycol (PEG).
2. Selection in HAT medium – only hybrid cells (hybridomas) survive because they inherit the hypoxanthine‑guanine phosphoribosyltransferase (HGPRT) enzyme from the B‑cell and the immortality from the myeloma.
3. Cloning – individual hybridoma colonies are isolated by limiting dilution, ensuring each line produces a single, identical antibody (monoclonal).
4. Harvesting – monoclonal antibodies are secreted into the culture medium and purified for use.

7. Applications of Monoclonal Antibodies

• Diagnostics – ELISA kits for HIV, hepatitis B surface antigen, COVID‑19 antigen detection rely on monoclonal antibodies for high specificity.
• Therapeutics

  • Trastuzumab (Herceptin) – targets HER2 receptors in breast cancer.
  • Rituximab – binds CD20 on B‑cell lymphomas.
  • Pembrolizumab – anti‑PD‑1 checkpoint inhibitor for melanoma and other cancers.
  • COVID‑19 antibody cocktails (e.g., casirivimab + imdevimab) for post‑exposure prophylaxis.

• Passive artificial immunity – administration of monoclonal antibodies such as rabies immune globulin, anti‑venom, or anti‑tetanus IgG provides immediate protection after exposure.

8. Comparison of the Four Categories of Immunity

9. Suggested Diagram

Insert a flow‑chart that starts with “Immunity” and splits into two branches – “Active” and “Passive”. Each of these then splits into “Natural” and “Artificial”. For every final box include:

• Source of antibodies (self‑produced, maternal, vaccine, serum/monoclonal).
• Whether memory cells are formed (Yes/No).
• One concise example (e.g., measles infection, MMR vaccine, maternal IgG, rabies globulin).

10. Key Points to Remember for the Exam

1. Active immunity = host manufactures antibodies + memory; passive immunity = antibodies received, no memory.
2. Natural immunity arises without medical aid; artificial immunity is deliberately induced (vaccines, immune serum, monoclonal antibodies).
3. Vaccines give active artificial immunity that mimics natural infection but without causing disease.
4. Passive artificial immunity provides immediate protection and is essential for post‑exposure prophylaxis.
5. Antibody structure (heavy/light chains, Fab/Fc, isotypes) underpins their function – a core syllabus point.
6. The hybridoma technique is the standard laboratory method for producing monoclonal antibodies, which have diagnostic and therapeutic roles.
7. Remember the steps of the primary immune response and the role of phagocytes in antigen presentation.