Active Immunity – Definition, Characteristics, Types, Examples

Active immunity is the immunity in which the body produces its own antibodies and memory cells against a pathogen. It develops slowly after infection or vaccination, but gives long lasting protection.

Active immunity is the type of immunity in which the body produces its own antibodies and immune cells against a particular infectious organism. It is produced by the activity of the body’s own immune system. It gives protection for long time and sometimes for whole life.

In this immunity, the adaptive immune system is exposed to a pathogen or its antigen. After this exposure, the body takes some time, usually one to two weeks, to make a proper immune response. During this process, memory cells are also formed.

These memory cells remember the same antigen. When the same pathogen enters the body again, these cells quickly activate the immune system. Then a rapid and stronger immune response is produced, and infection may be stopped before the disease becomes severe.

Active immunity is different from passive immunity. Passive immunity gives immediate protection, but it remains for short time. Active immunity develops slowly, but it is more long lasting because the body itself forms antibodies and memory cells.

Active immunity is of two main types. They are natural active immunity and artificial active immunity.

Natural active immunity is produced when a person is naturally infected by a disease organism. For example, after infection with chickenpox, the body fights the pathogen and develops immunity against it.

Artificial active immunity is produced by vaccination. In this process, vaccine contains weakened, killed, inactive pathogen or its part. It stimulates the immune system without causing actual severe disease. As a result, antibodies and memory cells are formed and the body gets protection against future infection.

Characteristics of Active Immunity

• Active immunity is self-produced immunity. In this immunity, the body’s own immune system produces antibodies and special immune cells against the pathogen.
• It takes time to develop. It is not formed immediately like passive immunity. The body generally needs some days or weeks to make proper defence.
• It is long lasting immunity. Once it is developed, it may remain for many years, decades or sometimes for whole life.
• It produces immunological memory. During this process, memory B cells and memory T cells are formed in the body.
• These memory cells recognize the same pathogen again. When the same antigen enters the body later, the immune response becomes rapid and stronger.
• It is highly specific. The antibodies and immune cells are formed only against the particular antigen or disease organism which has stimulated the response.
• Active immunity may be acquired naturally or artificially. Natural active immunity is formed after infection and recovery, while artificial active immunity is produced by vaccination.
• In vaccination, a killed, weakened or inactive form of pathogen is introduced into the body. It stimulates immune response without producing severe disease.

Types of Active Immunity

1. Natural active immunity
   Natural active immunity is developed when the body is naturally exposed to a live pathogen. It occurs after infection with disease causing organism, such as flu virus or chickenpox virus. In this immunity, the immune system fights the pathogen and produces specific antibodies and memory cells. This protection may remain for long time and sometimes for whole life.
2. Artificial active immunity
   Artificial active immunity is produced by vaccination. In this type, a vaccine introduces killed, weakened, inactive pathogen or its genetic material into the body. It stimulates the immune system to form antibodies and memory cells without causing actual severe disease. This is also called vaccine-induced immunity.
3. Hybrid immunity
   Hybrid immunity is a form of active immunity that develops after both natural infection and vaccination. In this immunity, the body gets immune stimulation from infection and also from vaccine. It produces strong and long lasting antibodies and cellular defence. It may also give broader protection against changed or mutated forms of a virus.

A. Natural Active Immunity

• Natural active immunity is the immunity which is produced after natural infection by a pathogen. It develops when a person gets infection through normal exposure, such as influenza virus or varicella-zoster virus.
• In this immunity, the body’s own defence system fights against the invading microbes. The immune system produces specific antibodies and forms memory cells for future protection.
• Memory cells may include activated lymphocytes. These cells recognize the same pathogen again and helps to remove it more quickly when it enters the body later.
• Natural infection usually exposes the body to large amount of virus or bacteria. So it can produce strong and many sided immune response.
• The duration of this immunity is not same in all diseases. In some diseases like measles, hepatitis A and chickenpox, protection may remain for whole life.
• In some infections like common cold, influenza and COVID-19, protection remains for short time. So the same person may be infected again many times in life.
• The main disadvantage of natural active immunity is that it is formed after suffering from actual disease. The severity of disease cannot be predicted before infection.
• It may cause tissue damage, severe complications, hospitalization or even death in some cases. So getting immunity by natural infection always has clinical risk.

Step by Step Mechanism of Natural Active Immunity

1. Natural active immunity starts when a live pathogen enters into the body by natural exposure. It may enter through respiratory tract, digestive tract, skin wound or mucous membrane.
2. After entry, the innate immune system acts first. Macrophages, neutrophils and other immune cells recognize the pathogen and start inflammation and phagocytosis.
3. In phagocytosis, the pathogen is engulfed by the immune cells. It is then broken down into smaller antigenic fragments inside the cell.
4. Antigen-presenting cells (APCs) such as dendritic cells and macrophages process the pathogen. They display the antigen fragments on their surface with the help of MHC class II molecules.
5. The antigen-presenting cells move to secondary lymphoid organs. These organs include lymph nodes and spleen, where many naive T lymphocytes are present.
6. In the lymphoid organ, a naive CD4+ helper T cell binds with the MHC-antigen complex by its T-cell receptor. This binding starts the activation of helper T cell.
7. A second co-stimulatory signal is also needed for full activation. For example, B7 molecule on APC binds with CD28 receptor on T cell and helps to prevent wrong immune activation.
8. After activation, helper T cells divide rapidly. They release cytokines such as IL-2, IL-4 and IFN-gamma, which control the next immune reactions.
9. The activated helper T cells differentiate into different subsets. TH1 cells help in activating CD8+ cytotoxic T cells, while TH2 cells help in stimulating antibody response by B cells.
10. At the same time, naive B cells recognize the native antigen of the pathogen. They take the antigen inside and present it on their surface with MHC II molecules.
11. Activated helper T cells bind with these antigen-presenting B cells. They provide contact signals and cytokines which fully activate the B cells.
12. The activated B cells divide rapidly and differentiate into plasma cells. These plasma cells produce large amount of specific antibodies into blood and body fluids.
13. The produced antibodies neutralize toxins, block the entry of viruses into cells and mark pathogens for destruction. This helps in removal of the infection from the body.
14. CD8+ cytotoxic T cells also become active during this response. They identify infected host cells and destroy them by releasing proteins which cause apoptosis.
15. After the live pathogen is cleared, most active T cells and B cells die by programmed cell death. This prevents unnecessary continuation of immune response.
16. Some B cells and T cells remain in resting state as memory B cells and memory T cells. These cells remain in the body for years, decades or sometimes for whole life.
17. Some plasma cells move to special survival sites in the bone marrow. These cells become long-lived plasma cells (LLPCs) and secrete protective antibodies for long time.
18. When the same pathogen enters the body again, the memory cells recognize it quickly. They do not need the long initial activation step like first infection.
19. Memory B cells rapidly change into plasma cells and produce very high amount of antibodies. This antibody response may be tens to hundreds times more than the primary response.
20. Memory T cells also become active quickly and form effector cells. This rapid and stronger response usually removes the pathogen before clinical symptoms are produced.

B. Artificial Active Immunity

• Artificial active immunity is the immunity which is produced intentionally by vaccination. It is not formed by natural exposure to disease organism.
• In this immunity, controlled antigens are introduced into the body. These antigens may be non-infectious, killed, weakened or deactivated form of pathogen.
• Different vaccines may contain live attenuated germ, killed pathogen, inactive toxin or toxoid. Some vaccines may also contain genetic material of the pathogen such as mRNA or DNA.
• The vaccine stimulates the adaptive immune system like a real infection. As a result, the body produces specific antibodies and immune cells.
• During this process, memory cells are also formed. These cells remain in the body and recognize the same pathogen during future exposure.
• Artificial active immunity gives protection without suffering from actual disease. So it reduces the risk of severe complications which may occur during natural infection.
• When the same pathogen enters the body later, the immune system gives rapid and stronger response. This helps to prevent disease or reduce its severity.
• Some vaccines may need repeated doses. Inactivated vaccines and toxoids generally do not multiply in the body, so booster doses may be required to maintain long lasting protection.

Step by Step Mechanism of Artificial Active Immunity

1. Artificial active immunity starts by vaccination. In this process, vaccine introduces a controlled and safe form of antigen into the body without producing actual severe disease.
2. The vaccine may contain weakened live pathogen, killed pathogen, inactivated toxin or toxoid. Some vaccines may also contain genetic material of pathogen, such as mRNA or DNA.
3. Some vaccines also contain adjuvants. These substances increase the immune response by keeping the antigen for longer time at injection site and helping immune cells to take it properly.
4. After vaccine administration, antigen-presenting cells (APCs) recognize the vaccine antigen. Mainly dendritic cells and macrophages take up the antigen and process it into small fragments.
5. In mRNA vaccines, the dendritic cells take up the mRNA from the vaccine. This mRNA helps the cell to produce harmless viral protein, which is then processed as antigen.
6. The processed antigen is displayed on the surface of APCs with the help of MHC molecules. This antigen presentation is necessary for activation of T lymphocytes.
7. The antigen-presenting dendritic cells then move to secondary lymphoid organs. These include nearby lymph nodes and sometimes spleen.
8. In the lymph node, the APC comes in contact with naive T cells. A naive helper T cell binds with the MHC-antigen complex by its T-cell receptor.
9. A second co-stimulatory signal is also required for full activation of helper T cell. Without this signal, proper immune response may not be formed.
10. After activation, helper T cells multiply rapidly. They release chemical messengers called cytokines, which control and increase the immune response.
11. The activated helper T cells differentiate into special types. Some cells become T-follicular helper cells, which help B cells, and some signals also activate CD8+ cytotoxic T cells.
12. At the same time, naive B cells recognize the vaccine antigen by their specific receptor. They take up the antigen and present it on their surface through MHC II molecules.
13. Activated helper T cells bind with these antigen-presenting B cells. They give contact signals and cytokines to fully activate the B cells.
14. The activated B cells divide rapidly and change into plasma cells. These plasma cells act as antibody producing cells and secrete large amount of specific antibodies into blood.
15. The antibodies bind with the same antigen. They neutralize toxin, block viral entry and mark the pathogen for destruction if real infection occurs later.
16. Some activated CD8+ cytotoxic T cells are also produced. These cells can destroy virus infected cells by releasing proteins which cause apoptosis.
17. After the vaccine antigen is cleared, most active immune cells die by programmed cell death. This prevents unnecessary over activity of immune system.
18. Some B cells and T cells remain in resting state as memory B cells and memory T cells. These cells remain in the body for many years or decades.
19. Some plasma cells move to special survival sites in the bone marrow. These are called long-lived plasma cells (LLPCs) and they continue to secrete protective antibodies for long time.
20. When the real pathogen enters the body in future, memory cells recognize it quickly. They do not need long initial activation step.
21. The memory B cells rapidly change into plasma cells and produce more antibodies. Memory T cells also become active and help in rapid cellular response.
22. This secondary response is faster and stronger than the first response. It may stop the infection before symptoms develop, and this is the main protective mechanism of artificial active immunity.

Mechanism of Active Immunity

1. Entry of antigen
   In this step, the pathogen or its antigen enters into the body. It may enter by natural infection or by vaccination. The immune system first recognizes this antigen as foreign substance.
2. Antigen recognition and processing
   The antigen is taken up by antigen presenting cells such as dendritic cells and macrophages. These cells engulf the pathogen and break it into small antigenic parts.
3. Antigen presentation
   The processed antigen is displayed on the surface of antigen presenting cell with the help of MHC class II molecules. This makes the antigen visible to the immune cells.
4. Migration to lymphoid organs
   The antigen presenting cells then move to secondary lymphoid organs. These organs include lymph nodes and spleen. Here they come in contact with naive T lymphocytes.
5. Activation of helper T cells
   The naive CD4+ helper T cell binds with the antigen presented on MHC II molecule by its T-cell receptor. A second co-stimulatory signal is also required for proper activation. This prevents wrong activation of immune response.
6. Multiplication of T cells
   After activation, the helper T cells divide rapidly. They also release chemical substances called cytokines. These cytokines control and stimulate other immune cells.
7. Differentiation of T cells
   The activated helper T cells differentiate into different types such as TH1 cells and TH2 cells. These cells help in directing the next immune response.
8. Activation of B cells
   At the same time, B cells also recognize the same antigen. They take up the antigen and present it to activated helper T cells. The helper T cells give signals and cytokines to fully activate B cells.
9. Formation of plasma cells
   The activated B cells multiply and change into plasma cells. Plasma cells are antibody producing cells. They produce large amount of specific antibodies against that antigen.
10. Antibody action
    The produced antibodies circulate in blood and body fluids. They neutralize toxins, block virus entry and mark pathogens for destruction by phagocytic cells.
11. Cell mediated response
    During this process, helper T cells also activate CD8+ cytotoxic T cells. These cells directly destroy virus infected cells and abnormal cells. They release proteins which cause apoptosis of infected cells.
12. Removal of pathogen
    After the action of antibodies and cytotoxic T cells, the pathogen is removed from the body. Most active immune cells are then destroyed by apoptosis after their work is completed.
13. Formation of immunological memory
    Some B cells and T cells remain in the body as memory B cells and memory T cells. These cells survive for many years or decades.
14. Secondary immune response
    When the same pathogen enters again, the memory cells recognize it quickly. A rapid and stronger immune response is produced. This is the main reason of long lasting protection in active immunity.

Primary and Secondary Immune Response in Active Immunity

Primary immune response

Primary immune response is the immune response which occurs when the body is exposed to an antigen for the first time. It may occur after first infection by a pathogen or after first dose of a vaccine.

This response is slow and delayed. The immune system takes time to recognize the specific antigen and activate the required naive B cells and T cells.

In this response, naive B cells are activated and changed into plasma cells. These plasma cells produce antibodies against the antigen.

The first antibody produced is mainly IgM. After some time, IgG antibody is also produced. The amount of antibody slowly increases and then reaches a plateau.

During primary immune response, T cells are also activated. They form effector T cells which help in destroying infected cells and also help B cells for antibody production.

After the pathogen is removed, most of the effector cells die by apoptosis. But some B cells and T cells remain in the body as memory B cells and memory T cells.

Secondary immune response

Secondary immune response is the immune response which occurs when the same antigen enters the body again. It may occur during re-infection by same pathogen or after a booster dose of vaccine.

This response is very fast. It occurs because memory cells are already present in the body. So the immune system does not take much time for the initial recognition and activation.

In this response, memory B cells quickly change into plasma cells. They produce large amount of antibodies within short time.

The antibody produced in secondary immune response is mainly IgG. The amount of antibody is much higher than primary response and it also remains for longer time.

Memory T cells also become active rapidly. They change into cytotoxic T cells and other effector cells which destroy infected cells more quickly.

The secondary response is stronger and more effective. It can neutralize the pathogen before it produces severe infection.

This rapid and strong response is the main reason for long lasting protection in active immunity. It also explains why booster doses of vaccines increase protection against the same disease.

Examples of Active Immunity

• Natural active immunity
  • Natural active immunity is acquired through natural infection. In this immunity, the body is infected by the pathogen and then immune system produces antibodies and memory cells.
  • Chickenpox
    • Chickenpox is caused by varicella-zoster virus.
    • After infection, the immune system produces specific antibodies and memory cells.
    • It generally gives long lasting protection and sometimes for whole life.
  • Measles
    • Measles infection produces strong immune response after recovery.
    • The body forms antibodies and memory cells against measles virus.
    • It usually gives permanent type of protection.
  • Hepatitis A
    • Hepatitis A infection also produces natural active immunity.
    • After recovery, the body develops strong defence against hepatitis A virus.
    • This immunity may remain for long time and sometimes life long.
  • Influenza
    • Influenza infection stimulates active immune response in the body.
    • The body produces antibodies against influenza virus.
    • But this immunity is usually temporary because the virus changes its antigenic structure.
  • Common cold
    • Common cold also gives active immunity after infection.
    • But the protection is short lasting.
    • This is because many types of cold viruses are present and they can change frequently.
  • COVID-19
    • After natural COVID-19 infection, the immune system learns to recognize the virus.
    • The body forms antibodies, B cells and T cells against the virus.
    • But protection may decrease with time and new variants may escape from earlier immunity.
• Artificial active immunity
  • Artificial active immunity is acquired through vaccination. In this immunity, vaccine stimulates immune response without producing actual severe disease.
  • Live attenuated vaccines
    • MMR vaccine, yellow fever vaccine and BCG vaccine are examples of live attenuated vaccines.
    • These vaccines contain weakened form of pathogen.
    • They mimic natural infection and produce strong and long lasting immunity.
  • Inactivated vaccines
    • Polio vaccine and injectable influenza vaccine are examples of inactivated vaccines.
    • These vaccines contain killed pathogen which cannot multiply in the body.
    • They cannot cause the disease, but primary and booster doses may be needed for proper protection.
  • Toxoid vaccines
    • Tetanus vaccine and diphtheria vaccine are examples of toxoid vaccines.
    • These vaccines contain inactivated bacterial toxin.
    • They stimulate the body to produce neutralizing antibodies against the toxin.
  • Conjugate polysaccharide vaccines
    • Haemophilus influenzae type b (Hib) vaccine and pneumococcal conjugate vaccine (PCV) are examples of conjugate vaccines.
    • In these vaccines, bacterial capsule polysaccharide is joined with a protein carrier.
    • It helps to produce strong active immunity and immune memory, especially in young children.
  • Nucleic acid vaccines
    • COVID-19 mRNA vaccines are examples of nucleic acid vaccines.
    • These vaccines carry genetic code for viral spike protein.
    • Host cells produce harmless spike protein, and this stimulates B cells and T cells to form immune memory without exposing the body to actual virus.

Immunological Memory and Long-Term Protection

• Immunological memory is the ability of the adaptive immune system to recognize the same pathogen again. It gives faster and more specific immune response during second exposure.
• It is developed during the primary immune response. This may occur after natural infection or after vaccination.
• During this process, antigen specific memory B cells and memory T cells are formed in the body. These cells remain for long time even after the infection is cleared.
• Most active fighting cells die after the pathogen is removed. But some cells do not die and persist in the circulation as memory cells.
• When the same pathogen enters the body again, these memory cells become active very quickly. They do not need the long initial learning phase like first exposure.
• Memory B cells rapidly change into plasma cells. These plasma cells produce very large amount of specific antibodies.
• The antibody level in secondary response is much higher than primary response. It may be tens to hundreds times more than the first immune response.
• This strong antibody response may stop the infection before it becomes established. Sometimes the person may not feel that he was exposed to the pathogen.
• Memory T cells also become active during re-exposure. They help in activating other immune cells and also destroy infected cells by cell mediated response.
• Some plasma cells move to special survival sites, mainly in the bone marrow. These cells are called long-lived plasma cells (LLPCs).
• Long-lived plasma cells continuously secrete protective antibodies into the blood. They may remain active for months, years or even decades.
• The duration of immunological memory is not same in all diseases. In diseases like chickenpox and measles, it may give life long protection.
• In some infections, protection decreases with time. This may happen because some memory cells slowly die or the virus changes its antigenic structure.
• Booster vaccination is given to maintain long-term protection. It acts like repeat exposure to the antigen and stimulates the immune memory again.

Difference Between Active and Passive Immunity

Mediators of Active Immunity

• Antigen-presenting cells (APCs) – Antigen-presenting cells are the first cells which start active immunity. Dendritic cells and macrophages engulf the pathogen, process its antigen and present it on their surface to naïve T lymphocytes.
• CD4+ helper T cells – CD4+ helper T cells are the main coordinating cells of active immunity. After activation by antigen-presenting cells, they release cytokines which stimulate other immune cells and help B cells to change into antibody producing plasma cells.
• CD8+ cytotoxic T cells – CD8+ cytotoxic T cells are responsible for cell mediated immunity. They directly destroy virus infected cells and tumour cells by releasing proteins which cause apoptosis or programmed cell death.
• Regulatory T cells – Regulatory T cells are also called suppressor T cells. They control the strength and duration of immune response and prevent over activity of immune system against the body’s own tissues.
• B lymphocytes (B cells) – B cells recognize specific foreign antigens. With the help of activated helper T cells, they divide rapidly and mature into plasma cells and memory B cells.
• Plasma cells – Plasma cells are formed from activated B cells. They act as antibody producing cells and secrete large amount of specific antibodies into blood and body fluids.
• Antibodies or immunoglobulins – Antibodies are specific proteins produced by plasma cells. They neutralize toxins, block virus entry into cells, prevent attachment of bacteria and mark pathogens for destruction.
• Cytokines – Cytokines are chemical messengers released by activated immune cells, mainly helper T cells. Interleukins, IL-2, IL-4 and interferon-gamma help in cell to cell communication and increase immune response.
• Complement system – Complement system is a group of plasma proteins which helps antibodies in destroying microbes. It causes lysis of target cells, produces inflammation and coats pathogen by opsonization for easy phagocytosis.
• Memory B cells and memory T cells – Memory cells are formed after the pathogen is removed. They remain in the body for many years or decades and give rapid stronger immune response when the same pathogen enters again.

Advantages of Active Immunity

• Active immunity gives long lasting protection after it is fully developed. It may remain for many years, decades or sometimes for whole life.
• It produces immunological memory in the body. Specific memory B cells and memory T cells are formed which remain for long time.
• These memory cells recognize the same pathogen during second exposure. Then immune response becomes rapid and stronger than first response.
• It strengthens the body’s own natural defence system. The immune system itself produces targeted antibodies and special immune cells.
• It gives specific protection against a particular pathogen. The immune response is directed against the same antigen which has stimulated the body.
• It is useful for prevention of diseases. Due to durable and long term protection, active immunity is the main basis of successful vaccination programmes.
• It can reduce the severity of future infection. If infection occurs again, pre-existing immune memory helps the body to control the pathogen more quickly.
• It is more durable than passive immunity. Passive immunity gives short term protection, but active immunity remains for longer period because memory cells are formed.

Limitations of Active Immunity

• Active immunity does not develop immediately like passive immunity. It takes some days or weeks for the body to produce proper antibodies, immune cells and memory response, so it is not useful for immediate or emergency protection.
• Natural active immunity is formed after actual infection by pathogen. In this condition, the person has to suffer from the disease and it may cause tissue damage, severe complications, hospitalization or even death.
• Active immunity is not always permanent. In some infections and after some vaccines, the level of protection slowly decreases with time, so the person may again become susceptible to infection.
• Some vaccines need more than one primary dose and later booster doses. Booster dose is required to maintain protective antibody level and to stimulate the immune memory again.
• Vaccines do not give 100% protection in every person. In primary vaccine failure, the body does not produce proper immune response after vaccination, while in secondary vaccine failure, immunity develops first but later it becomes weak.
• Vaccination may produce some mild side effects. These include pain, swelling, fever and weakness after vaccine administration.
• Live attenuated vaccines contain weakened living pathogen. They may rarely cause mild disease and generally they are not safely given to immunocompromised individuals.
• Active immunity depends on a properly functioning immune system. So the immune response may be weak or inadequate in older adults, very young infants and immunocompromised patients.

Clinical Significance and Applications of Active Immunity

• Disease prevention and eradication – Active immunity is mainly used for prevention of infectious diseases through proper vaccination programmes. It gives long term protection in population and has helped in global eradication of smallpox and near eradication of polio.
• Herd immunity – Herd immunity develops when large number of people in a community become immune against a pathogen. It reduces the transmission of disease and gives indirect protection to very young infants, old people and severely immunocompromised patients who cannot produce proper immunity.
• Reduction of disease severity – Sometimes active immunity may not completely prevent infection, but it usually makes the disease mild. The pre-existing memory B cells and memory T cells act quickly and reduce the risk of severe complications, hospitalization and death.
• Booster vaccination schedule – Active immunity is useful in deciding the time of booster doses. Some vaccines like measles vaccine may give life long protection, while tetanus toxoid, influenza vaccine and SARS-CoV-2 vaccine need booster doses because immunity may decrease or pathogen may change.
• Maintenance of immune memory – Booster dose acts like repeated exposure to the same antigen. It stimulates memory cells again and increases the level of protective antibodies in the blood.
• Hybrid immunity – Hybrid immunity is produced when both natural infection and vaccination occur in the same person. It may produce stronger neutralizing antibodies and broader cellular defence, so protection becomes better against changed forms of virus.
• Protection of vulnerable groups – Active immunity in healthy people indirectly protects those persons who cannot take vaccine or cannot develop strong immune response. This is clinically important in newborn babies, cancer patients, transplant patients and other immunocompromised individuals.
• Application in cancer therapy – The mechanism of active immunity is also used in modern cancer treatment. Therapeutic cancer vaccines introduce tumour associated antigens into the body and stimulate the patient’s own adaptive immune system to recognize and destroy malignant cells.
• Public health importance – Active immunity is the major base of public health vaccination programmes. It reduces disease spread, decreases deaths and helps to control outbreaks in the community.

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