Table of Contents
Overview
Immunization uses the immune system’s ability to “remember” pathogens to protect against future infections. In immunobiology, a key distinction is made between:
- Active immunization – the body builds its own specific immune response and memory.
- Passive immunization – ready‑made antibodies are given from outside; the body does not form memory.
Both approaches aim to prevent or mitigate infectious diseases but differ fundamentally in how protection arises and how long it lasts.
Active Immunization
Basic Principle
In active immunization, the immune system is stimulated by contact with an antigen so that it produces:
- specific antibodies,
- specific T lymphocytes,
- and long‑lasting memory cells.
This contact is intentional and controlled, usually via vaccination, and occurs before or sometimes during the early phase of infection.
Important point: In active immunization, the organism does the “immunological work” itself. Protection appears with a delay but is usually long‑lasting.
Types of Vaccines
All active immunizations introduce antigens in a harmless or less harmful form. Different vaccine types do this in different ways.
1. Live Attenuated Vaccines
Contain living pathogens that have been weakened (attenuated) so that they:
- can still replicate in the body to a limited extent,
- do not (in healthy individuals) cause the full disease.
Typical features:
- Strong, often long‑lasting immunity after few doses.
- Immune response resembles that after natural infection.
- Can induce strong cellular and humoral immunity.
Examples (subject to historical and regional use):
- Measles, mumps, rubella (MMR) vaccines
- Oral polio vaccine (OPV; largely replaced in many countries)
- Some varicella (chickenpox) and yellow fever vaccines
Disadvantages:
- Unsuitable for people with severe immune deficiency.
- Rare risk of reversion to a more virulent form or of vaccine‑induced disease.
- Sensitive to storage and temperature (cold chain required).
2. Inactivated (Killed) Vaccines
Contain pathogens that have been killed (e.g., by heat or chemicals) and cannot replicate.
Characteristics:
- Safe in terms of replication; no risk of spread.
- Often require several doses and boosters to achieve and maintain strong immunity.
- Tend to induce mainly antibody responses; cellular responses can be weaker.
Examples:
- Some influenza vaccines
- Inactivated polio vaccine (IPV)
- Many hepatitis A vaccines
- Rabies vaccines (inactivated virus)
3. Subunit, Toxoid, and Conjugate Vaccines
These vaccines use only selected components of a pathogen or its products.
Subunit Vaccines
Contain purified antigens such as:
- Proteins from the surface of viruses or bacteria,
- Or virus‑like particles (VLPs) that mimic the surface but lack genetic material.
Advantages:
- Very safe, as no complete pathogen is present.
- Fewer side effects related to other pathogen components.
Often need:
- Adjuvants (see below),
- Multiple doses and booster shots.
Examples:
- Hepatitis B surface antigen vaccines
- Some HPV (human papillomavirus) vaccines
Toxoid Vaccines
Target bacterial toxins, not the bacteria themselves. The toxins are:
- Chemically modified into toxoids,
- Still antigenic, but no longer toxic.
The immune system forms antibodies that neutralize the toxin.
Examples:
- Tetanus toxoid vaccine
- Diphtheria toxoid vaccine
Conjugate Vaccines
Some bacteria have polysaccharide capsules that are poorly recognized, especially by immature immune systems (e.g., infants). In conjugate vaccines, these polysaccharides are:
- Chemically linked (“conjugated”) to a protein carrier.
Result:
- Enhanced recognition by the immune system,
- Good antibody production, even in young children,
- Formation of immune memory.
Examples:
- Haemophilus influenzae type b (Hib) conjugate vaccines
- Many pneumococcal and meningococcal conjugate vaccines
4. Newer Platforms: mRNA and Vector Vaccines
Modern technologies focus on delivering genetic information that instructs the body’s cells to produce antigens themselves.
mRNA Vaccines
Contain messenger RNA (mRNA) coding for a specific pathogen protein:
- mRNA is taken up by host cells.
- Cells synthesize the antigen.
- The immune system recognizes and responds to this self‑produced antigen.
Key points:
- No pathogen; only genetic information for a protein.
- mRNA does not integrate into the genome and is broken down after a short time.
- Rapid manufacturing possible once the pathogen’s genetic sequence is known.
Viral Vector Vaccines
Use a harmless carrier virus (vector), often unable to replicate, that carries genes for pathogen antigens:
- Vector infects some cells.
- Cells produce the antigen.
- Immune system is activated.
Features:
- Vector itself may be recognized by the immune system, potentially affecting booster responses.
- No pathogenic form of the target virus is present; only its antigen.
Adjuvants and Formulations
Many vaccines—especially inactivated, subunit, and some mRNA vaccines—contain adjuvants.
- Adjuvants are substances that enhance the immune reaction to the antigen (e.g., aluminum salts, specific emulsions).
- They promote:
- stronger antibody production,
- longer‑lasting immune memory,
- dose‑sparing (less antigen needed).
Formulations may also contain:
- Stabilizers (e.g., sugars, amino acids),
- Preservatives (in some multi‑dose presentations),
- Buffers.
Primary and Booster Immunizations
Because the immune response builds up over time, active immunization often follows a schedule:
- Primary immunization: several doses at defined intervals.
- First dose: “primes” the immune system.
- Following doses: strengthen and consolidate immunity.
- Booster vaccinations: additional doses months or years later.
- Reactivate memory cells.
- Raise antibody levels.
- Restore or prolong protective immunity.
Intervals and number of doses depend on:
- Type of vaccine,
- Pathogen,
- Age and health status of the person.
Time Course and Duration of Protection
- Onset of protection: typically days to weeks after the first or second dose.
- Duration: can vary from several years to potentially lifelong (e.g., measles) or shorter (e.g., some influenza vaccines require annual updates).
Crucially, because memory cells are formed, the immune system reacts rapidly and strongly upon natural exposure to the pathogen.
Advantages and Limitations of Active Immunization
Advantages:
- Long‑term protection.
- Formation of immune memory.
- Often effective population‑level protection if many individuals are immunized (herd immunity).
- Reduces disease severity and transmission.
Limitations:
- Not immediately effective (delay before protection).
- Immune response may be inadequate in:
- very young infants,
- very old individuals,
- immunocompromised persons.
- Risk of local or systemic vaccine reactions (usually mild and transient).
- Very rare risk of serious side effects or allergic reactions.
Passive Immunization
Basic Principle
Passive immunization provides preformed antibodies directly to an individual. The recipient:
- does not produce these antibodies themselves (at least not initially in response to this treatment),
- does not form immune memory via this route.
Protection is immediate but temporary, because the foreign antibodies are eventually broken down.
Sources of Antibodies
Passive immunization uses antibodies from different sources:
- Human immune serum or immunoglobulin preparations
- Obtained from blood plasma of donors with high antibody titers against a given pathogen or toxin.
- Pooled, purified, and processed (e.g., specific hepatitis B immune globulin).
- Monoclonal antibodies
- Produced in cell culture from a single B cell clone (or recombinant systems).
- All molecules are identical and recognize the same specific epitope.
- Highly defined and standardized.
- Historically: animal sera
- For example, antiserum from horses immunized against a toxin.
- Now largely replaced or minimized because of higher risk of immune reactions (e.g., serum sickness).
Forms of Passive Immunization
Non‑specific Immunoglobulin Preparations
Contain a broad mixture of antibodies from many donors:
- Used for general support in some immune deficiencies.
- Can offer some temporary protection against various common pathogens.
Specific Immune Globulins
Enriched in antibodies against a particular pathogen or toxin, for instance:
- Hepatitis B immune globulin,
- Rabies immune globulin,
- Tetanus immune globulin,
- Varicella‑zoster immune globulin.
Used primarily:
- After a suspected or confirmed exposure,
- In unvaccinated or insufficiently vaccinated individuals,
- In patients with high risk for severe disease.
Monoclonal Antibodies
Target very specific structures (e.g., parts of viral proteins, bacterial toxins, host receptors):
- May be used prophylactically (e.g., in at‑risk infants for certain respiratory viruses),
- Or therapeutically to neutralize pathogens or modulate immune responses.
Time Course and Duration of Protection
- Onset of protection: practically immediate, as neutralizing antibodies are already present in the circulation.
- Duration: limited by the half‑life of antibodies (often a few weeks to a few months).
Antibody levels:
- Decline gradually as they are metabolized,
- No endogenous production is stimulated solely by passive administration.
Indications and Uses
Passive immunization is particularly important when:
- Immediate protection is necessary and active immunization would be too slow.
- There has been exposure to a dangerous pathogen or toxin, such as:
- Tetanus spores in a deep wound in an unvaccinated person,
- Rabies virus after animal bites,
- Hepatitis B exposure in certain situations,
- Certain venoms (antivenom therapy).
- The patient is unable to mount an adequate immune response (e.g., severe immunodeficiency).
- A disease is already developing and neutralization of toxin or virus can reduce severity.
Risks and Limitations
Risks:
- Allergic reactions (especially with non‑human antibodies).
- Serum sickness–like reactions (immune complexes forming against foreign proteins).
Limitations:
- No formation of immunological memory.
- Protective effect is short‑lived.
- Production can be complex and expensive (especially monoclonal antibodies).
- Availability may be limited for some rare diseases.
Comparison of Active and Passive Immunization
Key Differences
| Feature | Active Immunization | Passive Immunization |
|---|---|---|
| What is administered? | Antigens (whole, inactivated, or components) | Ready‑made antibodies (immunoglobulins) |
| Who produces antibodies? | The recipient’s own immune system | External source (other humans, animals, in vitro) |
| Onset of protection | Slow (days–weeks) | Immediate (hours–days) |
| Duration of protection | Long‑term, often years (memory cells) | Short‑term (weeks–months) |
| Immune memory | Yes | No |
| Use mainly for | Long‑term prevention (vaccination) | Immediate post‑exposure protection or therapy |
Combined Use: Simultaneous Active and Passive Immunization
In some high‑risk situations, both forms are used together:
- Passive immunization ensures instant protection via specific antibodies.
- Active immunization (vaccine) is given at the same time or shortly after to induce long‑term immunity.
To avoid interference:
- Injections are typically given at different anatomical sites (e.g., different limbs),
- And formulations are chosen so that passively administered antibodies do not completely neutralize the vaccine antigen.
Typical example scenarios include:
- Tetanus‑prone injuries in persons without adequate vaccination history.
- Rabies exposure in individuals who are not previously vaccinated.
Population‑Level Aspects and Practical Considerations
Herd Immunity and Vaccine Programs (Active Immunization)
Active immunization, when taken up by a large proportion of the population, can:
- Dramatically reduce circulation of a pathogen.
- Protect individuals who cannot be vaccinated (e.g., certain immunodeficient patients, very young infants).
- Even contribute to eradication of diseases (e.g., smallpox).
For effective herd immunity, high vaccination coverage is usually required, with the threshold depending on how easily the pathogen spreads.
Targeted Use of Passive Immunization
Passive measures are typically:
- Applied to specific people at specific times (e.g., after defined exposures),
- Not used to build population‑wide herd immunity,
- But crucial as an emergency measure or adjunct to active vaccination.
Balancing Benefits and Risks
In practice, decisions about active and passive immunization (and their combination) consider:
- Severity and transmissibility of the disease,
- Time since exposure,
- Immune status, age, and health condition of the individual,
- Availability and safety profile of vaccines and immunoglobulins,
- Current recommendations and guidelines.
Summary
- Active immunization uses vaccines to stimulate the body to build its own long‑term protection and immunological memory; it is the cornerstone of preventive control of infectious diseases.
- Passive immunization provides immediate but temporary protection by supplying preformed antibodies; it is essential in high‑risk exposures and in individuals who cannot rely on their own immune responses.
- Both strategies are complementary. Understanding when and how to use each, and when to combine them, is central to effective prevention and management of infectious diseases.