Immunity- Mechanism, Components, and Immunization

Immunity is the ability of the body to defend itself against disease-causing organisms, such as bacteria, viruses, fungi, parasites, and toxins. These foreign agents are called pathogens or antigens, and they can trigger an immune response in the body. The immune response is a complex and coordinated system of cells, molecules, and organs that work together to eliminate or neutralize the invaders and prevent infections.

The immune system can be divided into two main branches: innate immunity and adaptive immunity. Innate immunity is the first line of defense against pathogens. It is non-specific, meaning that it does not distinguish between different types of pathogens. It consists of physical barriers, such as the skin and mucous membranes, chemical barriers, such as antimicrobial proteins and enzymes, and cellular barriers, such as phagocytes and natural killer cells. Innate immunity also activates the adaptive immunity, which is the second line of defense.

Adaptive immunity is specific, meaning that it recognizes and targets specific antigens. It involves two types of lymphocytes: B cells and T cells. B cells produce antibodies, which are proteins that bind to antigens and mark them for destruction. T cells help activate B cells and other immune cells, or directly kill infected cells or pathogens. Adaptive immunity also generates memory cells, which remember the antigens and mount a faster and stronger response upon re-exposure.

Both innate and adaptive immunity are essential for protecting the body from infections and diseases. However, sometimes the immune system can malfunction and cause problems, such as allergies, autoimmune diseases, immunodeficiencies, or cancers. Therefore, understanding the mechanism of immunity is important for developing ways to prevent or treat these conditions.

In this article, we will explore the history of immunology, the components of the immune system, and the types of immunization that can enhance or induce immunity. We will also discuss some of the challenges and opportunities in immunology research and applications.

One of the most important breakthroughs in the history of immunology was the discovery of antibodies by Emil von Behring and Shibasaburo Kitasato in 1890. Antibodies are proteins that can bind to specific antigens and neutralize their harmful effects. Antigens are any substances that can trigger an immune response, such as bacteria, viruses, toxins, or foreign cells.

Behring and Kitasato were working at the Institute of Infectious Diseases in Berlin, under the supervision of Robert Koch, a pioneer of bacteriology. They were interested in finding a way to prevent and treat two deadly diseases: diphtheria and tetanus. Both diseases are caused by bacteria that produce toxins that damage the nervous system and cause paralysis and death.

Behring and Kitasato experimented with injecting animals with small doses of the toxins, hoping to induce immunity. They found that the animals developed antibodies in their blood that could protect them from subsequent exposure to the toxins. They also found that the serum (the liquid part of the blood) containing the antibodies could be transferred from one animal to another, conferring passive immunity.

They published their results in 1890, showing that serum from rabbits immunized with tetanus toxin could protect mice from a lethal dose of tetanus bacilli . They also showed that serum from guinea pigs immunized with diphtheria toxin could protect other guinea pigs and rabbits from diphtheria infection.

Their discovery was revolutionary, as it opened a new way of preventing and treating infectious diseases by using serum therapy. Serum therapy involves injecting patients with antibodies from animals or humans that have been exposed to a specific pathogen or toxin. Serum therapy was widely used for diphtheria, tetanus, botulism, rabies, and other diseases until the development of vaccines and antibiotics.

Behring received the first Nobel Prize in Physiology or Medicine in 1901 for his work on serum therapy. He was also elevated to the Prussian nobility and became known as Emil von Behring. Kitasato returned to Japan in 1892 and founded the Institute for Infectious Diseases in Tokyo. He became a leading figure in Japanese medicine and public health. He also discovered the bacterium that causes plague (Yersinia pestis) in 1894. Both Behring and Kitasato are regarded as founders of immunology and heroes of medicine.

One of the pioneers of immunology was Elie Metchnikoff, a Russian zoologist who worked at the Pasteur Institute in Paris. He is widely regarded as the father of innate immunity and the discoverer of phagocytosis, the process by which certain cells engulf and destroy foreign particles or microorganisms.

Metchnikoff was fascinated by the phenomenon of intracellular digestion, which he observed in various animals, especially in transparent marine invertebrates. He noticed that some cells, which he called phagocytes (from Greek words meaning "eating cells"), were able to ingest food particles as well as bacteria and other foreign material.

In 1882, while studying starfish larvae under a microscope, he made a groundbreaking observation. He inserted a thorn into the body of a larva and saw that phagocytes quickly gathered around the foreign object and tried to engulf it. He then repeated the experiment with different materials, such as glass, coal, and splinters of wood, and obtained similar results.

He concluded that phagocytosis was a natural defense mechanism against infection and injury. He also hypothesized that phagocytes were not only present in invertebrates, but also in vertebrates, including humans. He proposed that phagocytes were responsible for eliminating pathogens and damaged cells from the body, thus maintaining its integrity and health.

Metchnikoff`s theory of phagocytosis was met with skepticism and criticism by many of his contemporaries, who favored the idea that immunity was mediated by soluble substances in the blood serum, such as antibodies. However, Metchnikoff persisted in his research and provided experimental evidence to support his claims.

He showed that phagocytes could be classified into two types: microphages, which were small cells derived from white blood cells called neutrophils; and macrophages, which were larger cells derived from monocytes. He also demonstrated that phagocytes could recognize and respond to different types of pathogens, such as bacteria, fungi, protozoa, and worms.

He further suggested that phagocytosis was influenced by various factors, such as temperature, pH, oxygen tension, and chemical stimuli. He also introduced the concept of opsonins, substances that coat foreign particles and make them more attractive to phagocytes.

Metchnikoff`s work on phagocytosis laid the foundation for the modern understanding of innate immunity, which is the first line of defense against infection. His discoveries also paved the way for further studies on how phagocytes interact with other cells of the immune system, such as dendritic cells and lymphocytes.

For his contributions to immunology, Metchnikoff shared the Nobel Prize in Physiology or Medicine with Paul Ehrlich in 1908 . He is remembered as one of the most influential and original scientists of his time .

The immune system is composed of various cells, tissues and organs that work together to protect the body from harmful invaders such as bacteria, viruses, parasites and fungi. The main components of the immune system are :

• White blood cells (leukocytes): These are the main cells of the immune system that search for, attack and destroy foreign agents. There are many types of white blood cells, such as macrophages, neutrophils, eosinophils, basophils, mast cells, dendritic cells, natural killer cells, B cells and T cells. Each type has a specific function and role in the immune response. White blood cells can circulate in the blood and lymphatic system or reside in certain tissues.

• The spleen: This is an organ located in the upper left area of the abdomen, behind the stomach and under the diaphragm. The spleen filters the blood and removes damaged red blood cells. It also stores platelets and white blood cells and produces antibodies. The spleen helps identify and eliminate microorganisms that may cause infection.

• The bone marrow: This is the soft tissue inside the bones where all blood cells are produced, including white blood cells. Some white blood cells, such as B cells, mature in the bone marrow before entering the circulation. Others, such as T cells, travel to the thymus for maturation.

• The thymus: This is a gland located above the heart, behind the sternum and between the lungs. The thymus produces a hormone called thymosin that stimulates the development of T cells. T cells are responsible for cell-mediated immunity and can activate B cells or kill infected cells. The thymus is only active until puberty, then it shrinks and is replaced by fat and connective tissue.

• The lymphatic system: This is a network of vessels that carry a fluid called lymph throughout the body. Lymph contains white blood cells and other substances that help fight infection. The lymphatic system also drains excess fluid from tissues and transports dietary fats from the intestines to the blood.

• The lymph nodes: These are small structures located along the lymphatic vessels that filter lymph and trap foreign particles. They contain clusters of white blood cells that can mount an immune response when they encounter antigens. Lymph nodes are found in various parts of the body, such as the neck, armpits, groin and abdomen.

• The mucosal associated lymphoid tissues (MALTs): These are lymphoid tissues found in parts of the body where mucosa is present, such as the intestines, eyes, nose, skin and mouth. They contain lymphocytes and macrophages that defend against pathogens attempting to enter from outside the body.

• The gut associated lymphoid tissues (GALTs): These are lymphoid tissues found in the mucosa and submucosa of the gastrointestinal tract, tonsils, appendix and Peyer`s patches in the small intestine. They help protect against pathogens that may enter through food or water.

These components of the immune system work together to provide innate (non-specific) and adaptive (specific) immunity. Innate immunity is the first line of defense that responds to any foreign agent, while adaptive immunity is more specialized and responds to specific antigens. For more information on innate and adaptive immunity, see the module "Innate vs. Adaptive Immune Response".

Innate immunity is considered the first line of defense against foreign agents in the host body. The components of innate immune responses are categorized into five main types:

• Removing foreign agents from body tissues by non-specific white blood cells known as macrophages. Macrophages are large phagocytic cells that can engulf and digest microbes and other foreign particles. They also secrete cytokines and chemokines that attract and activate other immune cells. Macrophages are found in various tissues and organs, such as the skin, lungs, liver, spleen, and lymph nodes.

• Attracting cells of the immune system to the site of infection by releasing anti-inflammatory mediators known as cytokines and chemokines. Cytokines are molecules that are used for cell signaling, or cell-to-cell communication. They can regulate the intensity and duration of immune responses, as well as stimulate or inhibit the proliferation, differentiation, and activation of immune cells. Chemokines are a subset of cytokines that are specialized in inducing chemotaxis, or directional movement, of immune cells towards the source of infection or inflammation. Cytokines and chemokines are produced by various cells of the innate and adaptive immune system, such as macrophages, dendritic cells, mast cells, natural killer cells, T cells, and B cells.

• Activating a sequence of immune reactions that function to clear bacteria, infected host cells, and debris known as the complement cascade. The complement system is a group of plasma proteins that can be activated by different pathways: the classical pathway (initiated by antibody binding to antigens), the alternative pathway (initiated by microbial surface molecules), and the lectin pathway (initiated by carbohydrate-binding proteins). The activation of the complement system results in three main outcomes: opsonization (coating of microbes with molecules that enhance phagocytosis), inflammation (increasing vascular permeability and attracting immune cells), and lysis (forming pores on microbial membranes that cause cell death). The complement system also links the innate and adaptive immune responses by presenting antigens to B cells and enhancing antibody production.

• Acting as a physical and chemical barrier to infectious agents; via physical measures such as skin and chemical measures such as clotting factors in blood, which are released following a contusion or other injury that breaks through the first-line physical barrier. The skin is the largest organ of the body and forms a physical barrier that is impermeable to most infectious agents. The skin also produces sweat, organic acids, and antimicrobial peptides that create an acidic and hostile environment for microbes. The mucous membranes that line the respiratory, gastrointestinal, and urogenital tracts also provide physical barriers that trap and expel microbes. The mucous membranes secrete mucus, lysozyme, defensins, and IgA antibodies that inhibit microbial growth and invasion. The blood clotting mechanism is another component of innate immunity that prevents blood loss and infection by forming a fibrin mesh at the site of injury. The fibrin mesh also serves as a scaffold for wound healing and tissue repair.

• Activating the adaptive immune system through antigen presentation. Antigen presentation is the process by which specialized cells of the innate immune system, called antigen-presenting cells (APCs), capture and process antigens from pathogens or infected host cells and display them on their surface in association with major histocompatibility complex (MHC) molecules. MHC molecules are proteins that bind to peptide fragments derived from antigens and present them to T cells, which are lymphocytes of the adaptive immune system. There are two types of MHC molecules: MHC class I (found on all nucleated cells) and MHC class II (found only on professional APCs such as dendritic cells, macrophages, and B cells). MHC class I molecules present antigens from intracellular pathogens (such as viruses) to cytotoxic T cells (CD8+ T cells), which can kill infected host cells. MHC class II molecules present antigens from extracellular pathogens (such as bacteria) to helper T cells (CD4+ T cells), which can activate B cells to produce antibodies or other effector T cells to enhance cellular immunity. Antigen presentation is essential for initiating specific and long-lasting immune responses against pathogens.

The adaptive immune system is a subsystem of the overall immune system that is composed of highly specialized cells and processes that eliminate specific pathogens and tumor cells. The adaptive immune system is activated when the innate immune system is insufficient to control an infection, and it receives signals from the innate immune system to recognize and respond to specific antigens.

There are two types of adaptive responses: the cell-mediated immune response, which is carried out by T cells, and the humoral immune response, which is controlled by activated B cells and antibodies . Activated T cells and B cells that are specific to molecular structures on the pathogen proliferate and attack the invading pathogen. Their attack can kill pathogens directly or they can secrete antibodies that enhance the phagocytosis of pathogens and disrupt the infection. Adaptive immunity also involves a memory, which gives the host long-term protection from reinfection by the same type of pathogen; upon re-exposure, this host memory will facilitate a rapid and powerful response.

B cells

B cells are lymphocytes that mature in the bone marrow and are responsible for the secretion of antibodies specific to foreign antigens . Antibodies are proteins that bind to antigens with high specificity and affinity, meaning that they recognize and attach to only one or a few molecules with a high strength of binding. Antibodies can neutralize pathogens by blocking their attachment to host cells, opsonize pathogens by marking them for phagocytosis, activate the complement cascade by forming complexes with pathogens, and agglutinate pathogens by cross-linking them into clumps.

B cells have receptors on their surface that can bind to antigens. When a B cell encounters an antigen that matches its receptor, it becomes activated and undergoes clonal expansion, meaning that it divides into many identical copies of itself. Some of these copies become plasma cells, which secrete large amounts of antibodies into the blood and lymph. Other copies become memory B cells, which persist in the body for a long time and can quickly respond to a subsequent exposure to the same antigen .

B cells can be activated by two different pathways: T-dependent or T-independent. T-dependent activation requires the help of T helper cells, which are a type of T cell that can recognize antigens presented by antigen-presenting cells (APCs) such as macrophages or dendritic cells. T helper cells can bind to B cells that have internalized and processed the same antigen, and provide signals that stimulate B cell proliferation, differentiation, and antibody class switching. Antibody class switching is the process by which a B cell can change the type of antibody it produces, such as IgM, IgG, IgA, IgE, or IgD. Different classes of antibodies have different functions and locations in the body .

T-independent activation does not require T helper cells, but instead relies on repeated or clustered antigens that can cross-link multiple B cell receptors. This type of activation usually results in the production of IgM antibodies only, and does not generate memory B cells .

T cells

T cells are lymphocytes that mature in the thymus and are responsible for both activating B cells (T helper cells) and for killing pathogens or pathogen-infected host cells (T-killer cells) . Unlike B cells, T cells do not secrete antibodies, but instead have receptors on their surface that can recognize antigens presented by major histocompatibility complex (MHC) molecules on other cells. MHC molecules are proteins that display fragments of antigens on the surface of APCs or host cells. There are two types of MHC molecules: MHC class I and MHC class II. MHC class I molecules are found on almost all nucleated cells and present antigens derived from intracellular sources, such as viruses or bacteria that infect host cells. MHC class II molecules are found only on APCs and present antigens derived from extracellular sources, such as bacteria or parasites that are phagocytosed by APCs .

T cells also have two types of receptors: CD4+ and CD8+. CD4+ receptors are found on T helper cells and can bind to MHC class II molecules on APCs. CD8+ receptors are found on T-killer cells and can bind to MHC class I molecules on infected host cells. When a T cell receptor binds to an antigen-MHC complex, it becomes activated and undergoes clonal expansion .

T helper cells can differentiate into several subtypes depending on the type of antigen they encounter and the signals they receive from APCs or other cytokines. These subtypes include Th1, Th2, Th17, Tfh, and Treg. Each subtype has a different function and role in regulating the immune response. For example, Th1 cells secrete cytokines that activate macrophages and promote cell-mediated immunity against intracellular pathogens; Th2 cells secrete cytokines that activate B cells and promote humoral immunity against extracellular pathogens; Th17 cells secrete cytokines that recruit neutrophils and enhance inflammation against fungal or bacterial infections; Tfh cells secrete cytokines that help B cells migrate to lymph nodes and produce high-affinity antibodies; Treg cells secrete cytokines that suppress other immune cells and prevent autoimmunity or excessive inflammation .

T-killer cells can directly kill infected host cells or tumor cells by releasing perforins and granzymes that induce apoptosis (programmed cell death) or by expressing Fas ligand that binds to Fas receptor on target cells and triggers apoptosis. T-killer cells can also secrete cytokines that inhibit viral replication or activate other immune cells. Like B cells, T-killer cells also generate memory T-killer cells that can quickly respond to a subsequent exposure to the same antigen .

Vaccination is the act of introducing a vaccine into the body to produce protection from a specific disease. A vaccine is a preparation that contains a weakened, killed, or inactivated form of a pathogen or its components, such as proteins or toxins . When a vaccine is administered, it stimulates the body`s immune system to recognize and eliminate the pathogen, as well as to develop memory cells that can respond faster and more effectively in case of future exposure.

Vaccination is one of the most effective ways of immunization, which is the process of acquiring immunity against a disease. Immunization can also occur naturally when a person is exposed to and recovers from an infection, but this may result in severe illness or death. Vaccination, on the other hand, provides a safer and more controlled way of inducing immunity without causing disease .

Vaccination has been used to prevent and eradicate many infectious diseases that were once common and deadly, such as smallpox, polio, measles, mumps, rubella, diphtheria, tetanus, pertussis, and hepatitis B . According to the World Health Organization (WHO), vaccination prevents 2-3 million deaths every year from diseases that can be prevented by vaccines. Vaccination also reduces the burden of disease on health systems and society, as well as contributes to global health security and equity.

Vaccination can be classified into two types: passive and active immunization. Passive immunization involves transferring preformed antibodies from another source (such as human or animal serum) to a recipient, while active immunization involves triggering the recipient`s own immune response by exposing them to a vaccine. Passive immunization provides immediate but temporary protection, whereas active immunization provides long-lasting but delayed protection. Both types of immunization have their advantages and disadvantages, depending on the situation and the disease. The following points will discuss passive and active immunization in more detail.

Passive immunization is a type of immunization that involves transferring preformed antibodies to a recipient. These antibodies can be obtained from humans or animals that have been exposed to a specific pathogen or antigen and have developed immunity. Passive immunization can provide immediate protection against a disease, but it does not stimulate the recipient`s own immune system to produce memory cells. Therefore, passive immunization is only temporary and requires repeated administration.

One example of passive immunization is the transfer of maternal antibodies to the fetus through the placenta or to the infant through breast milk. These antibodies can protect the newborn from some infections for several months, until the infant`s own immune system matures. Another example is the injection of antiserum, which is a preparation of antibodies derived from the blood of an immune individual or animal. Antiserum can be used to treat or prevent diseases caused by toxins, such as tetanus, botulism, and snake venom, or by pathogens, such as rabies, hepatitis, measles, and diphtheria.

Passive immunization has some advantages and disadvantages. The advantages include:

• It can provide immediate protection against a disease that poses a high risk of morbidity or mortality.
• It can be used in situations where active immunization is not possible or effective, such as in immunocompromised individuals, in cases of exposure to a novel pathogen, or in outbreaks of emerging infectious diseases.
• It can reduce the severity and duration of symptoms in some cases of infection.

The disadvantages include:

• It can cause adverse reactions, such as allergic reactions, serum sickness, or anaphylaxis, especially if the antibodies are derived from animals.
• It can interfere with the development of active immunity by neutralizing the antigen before it can stimulate the recipient`s immune system.
• It can be expensive and difficult to produce and store large quantities of antibodies.
• It can have a limited shelf life and may lose its potency over time.

Passive immunization is an important tool for disease prevention and treatment, but it should be used with caution and in conjunction with other measures, such as active immunization, hygiene, and isolation. Passive immunization can provide temporary protection against a disease, but it cannot replace the long-lasting immunity conferred by active immunization.

Passive immunization is the transfer of preformed antibodies to a recipient, either from a human or an animal source. It provides immediate but temporary protection against certain infections or toxins. However, passive immunization also has some drawbacks and risks that limit its use. Some of the negative effects of passive immunization are:

• Lack of immunological memory: Passive immunization does not activate the host immune system to produce its own antibodies or memory cells. Therefore, it does not confer long-lasting immunity or protection against future exposures to the same pathogen or toxin. For example, people who receive rabies immune globulin after a bite still need to get the rabies vaccine to develop active immunity.
• Risk of hypersensitivity reactions: Passive immunization can cause allergic reactions in some recipients, especially if the antibodies are derived from a different species (such as horses). These reactions can range from mild (such as rash, itching, or fever) to severe (such as anaphylaxis, a life-threatening condition that involves difficulty breathing, low blood pressure, and shock) . Even human-derived antibodies can cause hypersensitivity reactions in some cases, due to differences in allotypes (genetic variants of antibodies within the same species).
• Risk of serum sickness: Serum sickness is a type of delayed hypersensitivity reaction that occurs when the recipient`s immune system produces antibodies against the foreign antibodies. This leads to the formation of immune complexes that deposit in various tissues and organs, causing inflammation and damage. Serum sickness can cause symptoms such as fever, joint pain, rash, swelling, and kidney problems . It usually occurs 7 to 21 days after passive immunization and resolves within a few weeks.
• Risk of transmission of infections: Although rare, there is a possibility that passive immunization can transmit infectious agents from the donor to the recipient. This can happen if the donor`s blood or plasma is contaminated with viruses (such as hepatitis B or C, HIV, or parvovirus B19) or bacteria (such as syphilis or Lyme disease) . To minimize this risk, donors are screened for infections and their products are tested and treated with various methods to inactivate or remove pathogens.
• Interference with active immunization: Passive immunization can interfere with the effectiveness of some vaccines by neutralizing the antigens that stimulate the host immune system. This can result in a reduced or delayed immune response and lower levels of protection. For example, maternal antibodies transferred to infants can interfere with the measles vaccine, which is why it is not given before 12 to 15 months of age . Similarly, tetanus immune globulin can interfere with the tetanus vaccine if given at the same time. To avoid this interference, passive and active immunization should be given at different sites or at different times.

Active immunization is the process of inducing a long-lasting and specific immunity against a disease-causing pathogen by exposing the body to a harmless form of the pathogen or its antigens. Active immunization can be acquired naturally by recovering from an infection or artificially by receiving a vaccine. The main advantage of active immunization is that it stimulates the immune system to produce antibodies and memory cells that can recognize and eliminate the pathogen in future encounters. Active immunity is usually long-lasting and sometimes life-long.

Active immunization can be achieved by using different types of vaccines, depending on the nature and characteristics of the pathogen. Some of the common types of vaccines are:

• Live attenuated vaccines: These vaccines contain weakened or modified forms of the live pathogen that can replicate in the body but do not cause disease. Examples of live attenuated vaccines are measles, mumps, rubella (MMR), varicella (chickenpox), and yellow fever vaccines .
• Inactivated vaccines: These vaccines contain killed or inactivated forms of the pathogen that cannot replicate in the body but can still elicit an immune response. Examples of inactivated vaccines are polio (Salk), hepatitis A, rabies, and influenza (seasonal flu) vaccines .
• Subunit vaccines: These vaccines contain purified or recombinant antigens from the pathogen that can induce a specific immune response without exposing the body to the whole pathogen. Examples of subunit vaccines are hepatitis B, human papillomavirus (HPV), meningococcal, and pneumococcal vaccines .
• Toxoid vaccines: These vaccines contain inactivated toxins or toxoids produced by some bacteria that can cause disease. The toxoids stimulate the production of antibodies that can neutralize the toxins. Examples of toxoid vaccines are diphtheria and tetanus vaccines .
• Conjugate vaccines: These vaccines combine polysaccharides or sugars from the surface of some bacteria with proteins or toxoids to enhance their immunogenicity and elicit a stronger immune response. Examples of conjugate vaccines are Haemophilus influenzae type b (Hib), pneumococcal, and meningococcal vaccines .

Active immunization is an effective and safe way to prevent many infectious diseases that can cause serious complications and mortality. However, active immunization may have some limitations or challenges, such as:

• The need for multiple doses or boosters to maintain adequate immunity over time .
• The possibility of adverse reactions or side effects, such as pain, swelling, fever, allergic reactions, or rare serious events .
• The variability in vaccine efficacy and duration depending on individual factors, such as age, health status, genetic background, and previous exposure to the pathogen.
• The emergence of new strains or variants of the pathogen that may escape or reduce vaccine-induced immunity.
• The lack of access or availability of some vaccines in certain regions or populations due to cost, supply, distribution, or acceptance issues.

Despite these challenges, active immunization remains one of the most important public health interventions to reduce the burden of infectious diseases and improve global health outcomes.

One of the goals of immunization is to elicit long-lasting protection against diseases caused by pathogens. However, some vaccines may not provide sufficient or durable immunity after a single dose or a primary series of doses. Therefore, boosters and repeated inoculations are sometimes needed to maintain or enhance the immune response and prevent infections.

A booster dose is an additional dose of a vaccine that is given after the primary series to increase the level of immunity or extend the duration of protection. A booster dose may be recommended when the immunity from the previous vaccination declines over time, or when a new variant of the pathogen emerges that requires a modified vaccine.

A repeated inoculation is a dose of a vaccine that is given at regular intervals to provide continuous protection against a disease. A repeated inoculation may be recommended when the immunity from the previous vaccination is short-lived, or when the exposure to the pathogen is frequent or persistent.

The need for boosters and repeated inoculations depends on several factors, such as:

• The type and quality of the vaccine
• The age and health status of the recipient
• The epidemiology and evolution of the pathogen
• The availability and accessibility of the vaccine

Some examples of vaccines that require boosters and repeated inoculations for children are:

• Diphtheria-tetanus-acellular pertussis (DTaP): This vaccine protects against three bacterial diseases that can cause serious complications, such as respiratory infections, nerve damage, and bleeding disorders. Children should receive five doses of DTaP vaccine at 2, 4, 6, 15-18 months, and 4-6 years of age. A booster dose of tetanus-diphtheria-acellular pertussis (Tdap) vaccine is recommended at 11-12 years of age, and every 10 years thereafter.
• Measles-mumps-rubella (MMR): This vaccine protects against three viral diseases that can cause fever, rash, swelling of glands, and complications such as pneumonia, meningitis, and birth defects. Children should receive two doses of MMR vaccine at 12-15 months and 4-6 years of age. A third dose may be recommended during outbreaks or for travelers to areas with high risk of measles.
• Varicella (chickenpox): This vaccine protects against a viral disease that causes itchy blisters, fever, and complications such as skin infections, pneumonia, and encephalitis. Children should receive two doses of varicella vaccine at 12-15 months and 4-6 years of age. A third dose may be recommended for people who have weakened immune systems or are exposed to someone with chickenpox.
• Hepatitis A: This vaccine protects against a viral disease that causes inflammation of the liver, jaundice, nausea, and diarrhea. Children should receive two doses of hepatitis A vaccine at 12-23 months and 6-18 months apart. A booster dose may be recommended for travelers to areas with high risk of hepatitis A.
• Influenza (flu): This vaccine protects against a viral disease that causes fever, cough, sore throat, and complications such as pneumonia and ear infections. Children should receive an annual flu vaccine starting from 6 months of age. Children aged 6 months through 8 years who are getting vaccinated for the first time or who have only had one dose in their lifetime need two doses given at least four weeks apart.
• COVID-19: This vaccine protects against a viral disease that causes respiratory infections, loss of taste or smell, and complications such as blood clots and organ damage. Children aged 6 months through 5 years may need multiple doses of COVID-19 vaccine to be up to date, including at least one updated dose of Pfizer-BioNTech or Moderna COVID-19 bivalent vaccine. Children aged 6 years and older should get one updated Pfizer-BioNTech or Moderna COVID-19 bivalent vaccine. People aged 65 years and older or who are moderately or severely immunocompromised may get additional updated COVID-19 booster doses.

Boosters and repeated inoculations are important strategies to ensure optimal protection against vaccine-preventable diseases in children. Parents and caregivers should consult with their healthcare providers about the recommended vaccination schedule for their children and follow the latest guidance from public health authorities.

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