Immunity – Definition, Types, Mechanism, Components, and Immunization

Immunity is the ability of the body to resist and protect itself from disease causing organisms. It acts against foreign substances like bacteria, viruses, toxins and other antigens.

Immunity is the ability of the body to protect itself from infectious diseases and harmful foreign substances. It helps the body to recognize and destroy pathogens like bacteria, viruses, fungi and toxins. It is mainly performed by immune cells, immune organs and some proteins such as antibodies.

The immune system works by identifying the foreign substance and removing it from the body. These foreign substances are called antigens. When antigen enters into the body, different immune cells become active and try to destroy it before it produces severe disease.

There are mainly three types of immunity. These are innate immunity, adaptive immunity and passive immunity. These types are different from each other on the basis of origin, speed of response and memory formation.

Innate immunity is the natural immunity present from birth. It is non-specific type of defence. It gives first protection against foreign substances. The examples are skin, mucous membrane, body secretions and immune cells which immediately attack the pathogens.

Adaptive immunity is also called active immunity. It develops during life after exposure to disease or after vaccination. It is specific for a particular antigen. It is slower in first exposure but becomes stronger after repeated exposure.

The important feature of adaptive immunity is immunological memory. It means the immune system can remember the same pathogen. When the same pathogen enters again, the immune response becomes faster and more effective.

Passive immunity is the immunity obtained from another source. In this type, ready-made antibodies are received by the body. It gives immediate protection but it remains for short period. The examples are antibodies passed from mother to baby during pregnancy and breastfeeding.

Community immunity is also called herd immunity. It occurs when a large number of people in a population become immune to a particular infection. Due to this, spread of pathogen becomes reduced and weak persons are indirectly protected.

Historical Background of Immunity

Historical background of immunity explains how the idea of protection against disease was developed. It mainly developed from the prevention of smallpox, discovery of antibodies and development of different vaccines.

• 10th century– In China, healers used a crude method called variolation. In this method, smallpox material was used to protect people from smallpox. It was one of the earliest practice to produce immunity.
• 1796– Edward Jenner developed the first smallpox vaccine. This is considered as the first important experiment in immunology. He used material from cowpox sores for protection against smallpox.
• Origin of vaccination– The term vaccination was introduced from the Latin word vacca, meaning cow. This name was used because Jenner’s method was based on cowpox material.
• 1890– Emil von Behring and Kitasato Shibasaburo discovered antibodies or immunoglobulins. They found neutralizing substances in blood which could act against infections like diphtheria.
• Late 19th century– Louis Pasteur developed the idea of attenuated vaccines. These vaccines were made by using weakened organisms. He prepared vaccines for rabies, anthrax and chicken cholera.
• Early 1900s– Karl Landsteiner studied small chemical groups called haptens. His work helped to explain how antibodies bind with antigens in a specific way.
• 1938– The first commercial tetanus toxoid vaccine was introduced. In this vaccine, tetanus toxin was made harmless but its ability to produce immunity was maintained.
• 1952– Immunoglobulin replacement therapy was introduced. It was used as an immunotherapy for treatment of primary immunodeficiency diseases.
• 1955– Jonas Salk developed the inactivated polio vaccine. This became possible due to progress in cell culture technique.
• 1960s– Albert Sabin developed the live attenuated oral polio vaccine. It was given by mouth and helped in control of polio infection.
• 1980– World Health Organization announced the global eradication of smallpox. It was a major success of modern immunology and vaccination.
• 1986– Hepatitis B vaccine was introduced. It used recombinant DNA technology. In this method, viral proteins were produced safely in yeast cells.
• 20th century milestone– Georges Köhler and Cesar Milstein developed the technique for production of monoclonal antibodies. These antibodies have single known specificity and can be produced in large amount.
• 21st century– Katalin Karikó and Drew Weissman worked on mRNA modification. Their discoveries helped in development of mRNA vaccine technology. This technology was used for rapid vaccine development during COVID-19 pandemic.

Basic Characteristics of Immunity

Basic characteristics of immunity means the important features by which immune system protects the body. These characters help the body to recognize foreign substance, destroy them and also remember them for future response.

• Two main branches– Immunity works through two main branches. These are innate immunity and adaptive immunity. Innate immunity gives immediate and non-specific protection, while adaptive immunity gives delayed but specific protection.
• Self and non-self recognition– The immune system can distinguish between own body cells and foreign substances. Own healthy tissues are called self and foreign pathogens are called non-self. This is a basic property of immune system.
• Specificity– Adaptive immunity is highly specific in nature. It recognizes particular antigen by special antigen receptors and antibodies. Due to this, the immune response is directed against a specific pathogen.
• Memory– The immune system can remember the antigen after first exposure. This is called immunological memory. It is produced by long lived memory B-cells and memory T-cells.
• Secondary response– When the same antigen enters again, the response becomes faster and stronger. This is because memory cells are already present in the body. This property is useful in vaccination.
• Diversity– The immune system can recognize large number of antigens. During development of lymphocytes, many different antigen binding sites are formed. This gives ability to fight against millions of microbes and foreign substances.
• Self tolerance– The immune system normally does not attack own body cells. This property is called self tolerance. Harmful lymphocytes which react with self tissues are removed or controlled.
• Prevention of autoimmunity– Due to self tolerance, autoimmune reactions are prevented. If this control fails, immune system may attack own body tissues and autoimmune disease may occur.
• Mobility of immune cells– Immune cells are not fixed in one place. They move through blood, lymph and lymphoid organs. This helps them to search antigen in different parts of body.
• Systemic coordination– Immune response is coordinated by immune cells, antibodies and chemical messengers like cytokines. These components communicate with each other and bring immune cells to the site of infection or injury.

Types of Immunity

Immunity is divided into different types according to its origin and mode of development. Some immunity is present from birth. Some immunity is formed after infection or vaccination. Some immunity is obtained from another source.

1. Innate immunity– Innate immunity is the natural immunity present from birth. It is non-specific and general defence of body. It acts as first line of defence and includes skin, mucous membrane, body secretions and general immune cells which immediately act against harmful foreign invaders.
2. Adaptive immunity (Active immunity)- Adaptive immunity is developed during life after contact with specific antigen. It is specific type of immunity and produces immunological memory. It gives long lasting protection against the same pathogen.
   • Natural active immunity– It develops naturally after infection. When the body fights against a disease and recovers, this immunity is produced.
   • Artificial active immunity– It develops after vaccination. Vaccine trains the immune system to make defence without causing severe disease.
3. Passive immunity– Passive immunity is obtained by ready-made antibodies from another source. In this immunity, the body does not make antibodies by itself first. It gives immediate protection but for short period.
   • Natural passive immunity– It is obtained from mother. Antibodies pass from mother to baby through placenta during pregnancy and through breast milk after birth.
   • Artificial passive immunity– It is given by medical treatment. The examples are antivenom for snake bite and specific immune globulin therapy.
4. Community immunity (Herd immunity)- Community immunity is also called herd immunity. It occurs when large number of people in a population become immune against an infection. Due to this, pathogen cannot spread easily and weak persons are indirectly protected.

Innate Immunity

Innate immunity is a type of immunity which is present in body from birth. It is a natural defence mechanism. It gives protection to the body before the development of specific immune response.

It is the first line defence of body. The response is rapid and general. It acts against many pathogens but it is not specific for a particular antigen.

This immunity has no memory. So after second exposure also, the response remains almost same. It does not produce strong secondary response like adaptive immunity.

The barriers of innate immunity are skin, mucous membrane and cilia. These prevent the entry of microorganisms. The secretions like tears, saliva and gastric acid also destroy many microbes.

The cells involved are neutrophils, macrophages, dendritic cells, mast cells, basophils and NK cells. These cells act immediately after entry of pathogen. Neutrophils and macrophages engulf the organisms.

The soluble factors are cytokines and complement proteins. These help in inflammation and destruction of microorganisms. Complement system also marks the pathogens for phagocytosis.

The recognition is done by pattern recognition receptors (PRRs). These receptors recognize common microbial pattern called PAMPs. Toll-like receptors (TLRs) are important example of PRRs.

Components and Functions of Innate Immunity

Innate immunity has different components. These are already present in the body before infection. They act quickly and give non-specific protection against microorganisms.

• Physical barriers– Skin, mucus layer and cilia form the physical barriers. Skin covers the body surface and prevents entry of microorganisms. Mucus traps the organisms and dust particles. Cilia moves the trapped materials outside from respiratory tract.
• Chemical barriers– Gastric acid, enzymes of tears and saliva and antimicrobial peptides form chemical barriers. The low pH of stomach kills many ingested organisms. The enzymes and peptides present in secretions destroy the microbes or inhibit their growth.
• Commensal bacteria– Commensal bacteria are normal bacteria present on skin and intestine. They are not harmful in normal condition. They compete with pathogenic bacteria for space and nutrients. Thus, they prevent the growth of harmful organisms.
• Phagocytic cells– The cells which engulf the microorganisms are called phagocytic cells. The important phagocytic cells are neutrophils, macrophages and dendritic cells.
  • Neutrophils– Neutrophils are present in large number in blood. They move rapidly towards the site of infection. They engulf the organisms and destroy them by phagocytosis.
  • Macrophages– Macrophages are tissue cells. They are long lived cells. They ingest microorganisms, dead cells and foreign particles. They also secrete cytokines which take part in inflammation.
  • Dendritic cells– Dendritic cells take up the pathogen and process its antigen. Then they present the antigen to T-lymphocytes. So they connect the innate response with adaptive response.
• Additional immune cells– Some cells help in innate immunity without mainly doing phagocytosis. These cells include natural killer cells, mast cells and basophils.
  • Natural killer cells (NK cells)- NK cells kill virus infected cells and tumour cells. They release toxic granules into the abnormal cells. This results in death of target cells.
  • Mast cells and basophils– Mast cells and basophils release inflammatory mediators. These mediators increase permeability of blood vessels. As a result, other immune cells come to the infected area.
• Soluble mediators and proteins– These are the soluble factors present in blood and tissue fluid. They help in inflammation, chemotaxis and destruction of microorganisms.
  • Cytokines and chemokines– Cytokines and chemokines are chemical messengers. They regulate the immune reaction. They attract immune cells to the site where pathogen is present.
  • Complement system– Complement system is a group of plasma proteins. It acts in cascade form. It lyses microorganisms, attracts inflammatory cells and coats the microbes for phagocytosis. This coating is called opsonization.
  • Acute phase reactants– Acute phase reactants are proteins increased during infection and inflammation. C-reactive protein (CRP) and mannose-binding lectin (MBL) bind with microorganisms. This helps in easy uptake by phagocytic cells.
• Pattern recognition receptors (PRRs)- PRRs are receptors present on cells of innate immunity. They recognize common structures present on microorganisms. Toll-like receptors (TLRs) are examples of PRRs. They recognize pathogen-associated molecular patterns (PAMPs) and start the innate immune reaction.

Adaptive (Acquired) Immunity

Adaptive immunity is a type of immunity which develops during life. It is also called acquired immunity. It is formed after the body comes in contact with a particular pathogen or after vaccination.

It is specific in nature. It does not act in same general way like innate immunity. It recognizes a particular antigen and produces response against that antigen only.

This immunity is slow in first exposure. It takes some time for activation of lymphocytes and multiplication of selected cells. This delay period is called lag phase. After this, primary immune response is produced.

The important character of adaptive immunity is immunological memory. After first exposure, some B-cells and T-cells remain in the body as memory cells. These cells remember the same antigen.

When the same pathogen enters again, the response becomes rapid and strong. This is called secondary immune response. Due to this, the pathogen is removed more effectively.

Adaptive immunity is mainly carried by B-lymphocytes and T-lymphocytes. These cells have specific receptors on their surface. These receptors bind with particular foreign antigen.

There are two main types of adaptive immunity.

1. Humoral immunity– It is mediated by B-cells. The B-cells change into plasma cells and produce antibodies. These antibodies are present in blood and body fluids. They neutralize extracellular pathogens and mark them for destruction.
2. Cell-mediated immunity– It is mediated by T-cells. Helper T-cells (CD4+) release cytokines and control the immune response. Cytotoxic T-cells (CD8+) destroy virus infected cells and cancer cells.

Adaptive immunity gives long lasting protection. This is due to the presence of memory B-cells and memory T-cells. The protection may remain for months, years or sometimes for whole life.

Humoral Immunity

Humoral immunity is a type of adaptive immunity. It is mediated by B-lymphocytes and the antibodies produced by them. These antibodies are also called immunoglobulins.

It mainly protects the extracellular spaces of body. These include blood, plasma and mucosal secretions. It acts against extracellular microorganisms and their toxins.

Main components

1. B-lymphocytes– B-cells are the main cells of humoral immunity. They recognize antigen by B-cell receptor present on their surface.
2. Plasma cells– These are formed from activated B-cells. They secrete large amount of specific antibodies into blood and body fluids.
3. Antibodies– Antibodies are specific proteins produced by plasma cells. They bind with antigen and help in removal of pathogens and toxins.
4. Memory B-cells– These cells are formed after activation of B-cells. They remain for long time in body and give rapid response during second exposure.

Mechanism of Humoral Immunity

1. First, the B-cell recognizes and binds with specific antigen by B-cell receptor (BCR).
2. After binding, the B-cell takes the antigen inside the cell.
3. The antigen is broken into small peptide fragments inside the B-cell.
4. These peptide fragments are then presented on the surface of B-cell with MHC class II molecules.
5. The helper T-cell recognizes the same antigen on MHC class II of B-cell.
6. Then the helper T-cell gives activating signal to B-cell by direct contact and by cytokines.
7. After activation, the selected B-cell divides rapidly. This is called clonal expansion.
8. Many activated B-cells change into plasma cells.
9. Plasma cells secrete large amount of specific antibodies into blood and body fluids.
10. The antibodies remove pathogens by different methods.
    • Neutralization– Antibodies bind with toxins or pathogens and prevent their attachment with host cells.
    • Opsonization– Antibodies coat the surface of pathogens. This helps macrophages and other phagocytic cells to engulf them easily.
    • Complement activation– Antibodies attached with pathogen activate complement system. It causes lysis of microbes or brings inflammatory cells to that region.
11. Some activated B-cells form memory B-cells.
12. During second exposure with same antigen, these memory B-cells produce faster and stronger antibody response.

Cell-mediated Immunity

Cell-mediated immunity is a type of adaptive immunity. It is mediated by T-lymphocytes. It does not mainly depend on antibodies.

It acts against intracellular pathogens. These pathogens live inside the host cells. The examples are viruses and some intracellular bacteria. It also acts against tumour cells and abnormal cells.

Main cells involved

• Cytotoxic T-cells (CD8+ T-cells)- These cells kill virus infected cells, tumour cells and abnormal body cells. They recognize antigen with MHC class I.
• Helper T-cells (CD4+ T-cells)- These cells do not kill directly. They secrete cytokines and activate other immune cells. They recognize antigen with MHC class II.
• Natural killer cells (NK cells)- These cells are of innate immunity, but they help in killing of virus infected and tumour cells. They act when MHC class I is reduced.
• Memory T-cells– These cells remain after infection. They give rapid and strong response when the same antigen enters again.

Mechanism of Cell-mediated Immunity

• In infected cells, the pathogen proteins are broken into small peptide fragments.
• These peptide fragments are presented on the surface of cell with MHC molecules.
• CD8+ T-cells recognize antigen with MHC class I present on infected cells.
• CD4+ T-cells recognize antigen with MHC class II present on dendritic cells, macrophages and B-cells.
• After recognition, T-cells become activated and start their function.
• Cytotoxic T-cells release perforin and granzymes.
• Perforin forms pores on the target cell membrane and granzymes enter into the cell.
• The target cell undergoes apoptosis or programmed cell death.
• Helper T-cells release cytokines. These cytokines activate macrophages, help B-cells and increase the action of cytotoxic T-cells.
• NK cells kill those abnormal cells which show reduced MHC class I. This is called missing self recognition.
• After the pathogen is cleared, most effector T-cells die. Some cells remain as memory T-cells for future response.

Active and Passive Immunity

Active immunity and passive immunity are two types of acquired immunity. These are different in source, time of action, memory and duration of protection.

Active immunity

• Source of protection– It is produced by own immune system of the body. The body itself forms antibodies and immune cells.
• Development– It develops after natural infection or after vaccination. In both cases, antigen stimulates the immune system.
• Immunological memory– It forms memory B-cells and memory T-cells. These cells remember the same pathogen for future response.
• Duration– It gives long lasting protection. It may remain for many years or sometimes for whole life.
• Speed of action– It takes time to develop. Protection appears after some days or weeks because immune system has to recognize and respond to the antigen.

Passive immunity

• Source of protection– It is obtained by ready-made antibodies from outside source. The body does not produce these antibodies by itself.
• Natural examples– Antibodies pass from mother to fetus through placenta during pregnancy. Antibodies also pass to baby through breast milk, mainly colostrum.
• Artificial examples– Ready-made antibodies are given by medical treatment. The examples are immunoglobulin injection and antivenom.
• Immunological memory– It does not produce memory cells. It does not train the immune system for later response.
• Duration– It gives short term protection only. The borrowed antibodies are slowly broken down and body cannot replace them.
• Speed of action– It gives immediate protection. It is useful when rapid protection is needed.

Cells of Immune System

Cells of immune system are the cells which take part in defence of body. These cells are formed from hematopoietic stem cells. They are present in blood, lymph and different tissue.

• Innate immune cells (Myeloid lineage)
  • Neutrophils– These are most numerous white blood cells. They reach first at infection site. They engulf and destroy pathogens by phagocytosis.
  • Macrophages– These are long lived tissue cells. They ingest microbes, dead cells and foreign particles. They also start inflammation and present antigen to other immune cells.
  • Monocytes– These are precursor cells present in blood. After entering into tissue, they change into macrophages.
  • Dendritic cells– These cells capture pathogens and process their antigens. Then they present antigen to T-cells. So they form the link between innate immunity and adaptive immunity.
  • Eosinophils– These are granulocytes. They mainly act against parasitic infection.
  • Basophils– These are granulocytes present in blood. They take part in allergic reaction and response against parasites.
  • Mast cells– These cells are present in tissue near small blood vessels. They release inflammatory substances. They increase vascular permeability and help in allergy and mucosal defence.
• Lymphocytes (Adaptive and innate)
  • B-lymphocytes (B-cells)- These are cells of adaptive immunity. They recognize specific antigen. They also present antigen to T-cells.
  • Plasma cells– These are formed from activated B-cells. They produce large amount of specific antibodies.
  • Helper T-cells (CD4+)- These cells release cytokines. They activate B-cells, macrophages and cytotoxic T-cells.
  • Cytotoxic T-cells (CD8+)- These cells kill virus infected cells and cancer cells. They act directly on abnormal cells.
  • Regulatory T-cells (Tregs)- These cells suppress immune response. They prevent excess immune reaction and attack on own body cells.
  • Memory B-cells and Memory T-cells– These cells remain after infection. They give fast and strong response when same pathogen enters again.
  • Natural killer cells (NK cells)- These are innate lymphoid cells. They kill virus infected cells and tumour cells without previous sensitization.
  • Natural killer T-cells (NKT cells)- These are rare cells. They have characters of both NK cells and T-cells. They secrete cytokines and also show cytotoxic action.

Organs of the Immune System

Organs of immune system are the organs and tissues which take part in defence of body. These organs form immune cells, mature them and help in removal of pathogens. They act against foreign substances like bacteria, viruses, toxins and other antigens.

• Bone marrow– Bone marrow is a primary lymphoid organ. It is present inside the bones. All immune cells are formed from hematopoietic stem cells in bone marrow. B-lymphocytes also complete their maturation here.
• Thymus– Thymus is also a primary lymphoid organ. It is present above the heart and behind the breast bone or sternum. Immature T-lymphocytes migrate into thymus and become mature T-cells.
• Spleen– Spleen is the largest internal organ of immune system. It filters the blood. It traps blood borne pathogens and also removes old and damaged red blood cells.
• Lymph nodes– Lymph nodes are small organized lymphoid tissues present in different parts of body. They act as filtering station of lymph. Here immune cells gather, pathogens are trapped and adaptive immune response is started.
• Lymphatic vessels– Lymphatic vessels are network of vessels which collect tissue fluid or lymph from body tissues. They transport lymph, immune cells, chemicals and pathogens towards lymph nodes for filtration.
• Mucosa-associated lymphoid tissue (MALT)- MALT is the unencapsulated lymphoid tissue present near mucosal surfaces. It protects the mucosa of respiratory tract, digestive tract and other regions. It includes BALT, GALT, tonsils, adenoids, appendix and Peyer’s patches.
• BALT– Bronchus-associated lymphoid tissue or BALT is present in the respiratory tract. It helps in defence against inhaled pathogens.
• GALT– Gut-associated lymphoid tissue or GALT is present in the digestive tract. It includes Peyer’s patches, appendix and other intestinal lymphoid tissues. It acts against ingested pathogens.
• Skin– Skin is the largest protective organ of body. It acts as first line defence. It prevents the entry of disease causing organisms into the body.

Mechanism of Immune Response

Immune response is the reaction of body against any foreign pathogen. It starts after entry of pathogen into tissue. The pathogen may be bacteria, virus, fungus or toxin. First non-specific response starts and then specific immune response is formed.

1. Barrier breach– First the pathogen crosses the body barriers. These barriers are skin, mucous membrane, cilia, tears, saliva and gastric acid. Normally these prevent entry of microbes. When they fail, the pathogen enters into tissue.
2. Innate recognition– The pathogen is first detected by tissue cells like macrophages and dendritic cells. These cells contain Pattern Recognition Receptors (PRRs). These receptors recognize common microbial structures. These structures are called Pathogen-Associated Molecular Patterns (PAMPs).
3. Inflammation and cellular recruitment– After recognition, cytokines and chemokines are released from immune cells. Inflammation starts at that place. Blood flow increases. Blood vessels become more permeable. Neutrophils, macrophages and Natural Killer cells (NK cells) are attracted to infected tissue.
4. Phagocytosis and early defence– Neutrophils and macrophages engulf the pathogens. The engulfed pathogens are digested inside the cell. This process is called phagocytosis. NK cells kill the virus infected host cells by cytotoxic granules. This early response helps to control the infection.
5. Antigen processing and presentation– When the pathogen is not completely removed, Antigen Presenting Cells (APCs) become important. Mainly dendritic cells take the pathogen and break its proteins into small fragments. These fragments are then shown on the cell surface with Major Histocompatibility Complex (MHC) molecules.
6. Activation of T-cells– The APCs move to nearby lymph node through lymphatic vessel. There the antigen is presented to naive T-cells. CD4+ helper T-cells recognize antigen with MHC class II. CD8+ cytotoxic T-cells recognize antigen with MHC class I. The matching T-cells are activated.
7. B-cell activation and antibody production– B-cells bind the antigen by B-cell receptor (BCR). The antigen is taken inside and presented to activated helper T-cells. The helper cells give signals by contact and by cytokines. Then B-cells divide and form plasma cells. These plasma cells secrete specific antibodies.
8. Targeted pathogen elimination– The antibodies bind with pathogen and toxin. They neutralize them. They also coat microbes for easy phagocytosis. This is opsonization. Complement system is also activated and helps in lysis of microbes. At the same time cytotoxic T-cells kill infected cells by apoptosis.
9. Resolution of infection– After removal of pathogen, the immune response must decrease. Otherwise normal tissue may be damaged. Regulatory T-cells (Tregs) and anti-inflammatory cytokines suppress the active immune reaction. The body returns to normal condition or homeostasis.
10. Establishment of immunological memory– Most effector cells die after the response. Some B-cells and T-cells remain as memory cells. These cells stay for long time in the body. When the same pathogen enters again, the response becomes rapid and strong.

Antigen Recognition and Antibody Production

Antigen recognition and antibody production is a process of humoral immunity. In this process the antigen is first recognized by B-cells. Then the same B-cells are activated and produce specific antibodies.

1. Initial antigen recognition– Naive B-cells continuously move through blood and lymph. When a foreign pathogen enters into body, its antigen binds with matching B-cell receptor (BCR) on the surface of B-cell. This BCR is a surface immunoglobulin. Thus, only the specific B-cell is selected.
2. Internalization and processing– After binding, the B-cell internalizes the antigen. The antigen is taken inside the cell. Then it is degraded into small peptide fragments. These fragments are required for next presentation step.
3. Antigen presentation– In this step, B-cell acts as antigen presenting cell. The peptide fragments are carried on the surface of B-cell. They are displayed with Major Histocompatibility Complex class II (MHC class II) molecules.
4. Helper T-cell interaction– An activated helper T-cell comes near the B-cell. Its T-cell receptor (TCR) recognizes the same antigen peptide present with MHC class II. This is known as linked recognition. It means B-cell and T-cell are reacting with same antigen.
5. Co-stimulatory signalling– The helper T-cell now gives second signal to the B-cell. CD40 ligand on T-cell binds with CD40 receptor on B-cell. At the same time, cytokines are released. The example is Interleukin-4 (IL-4). Due to these signals, the B-cell becomes fully activated.
6. Clonal expansion– The fully activated B-cell starts rapid division. From one selected B-cell, many identical B-cells are produced. This process is called clonal expansion. All these cells are specific for the same antigen.
7. Differentiation into plasma cells– Many newly formed B-cells become plasma cells. These cells are antibody secreting cells. They produce large amount of specific antibodies and release them into blood and body fluids.
8. Isotype switching and affinity maturation– This occurs in germinal centres. In isotype switching, antibody class changes from early IgM to IgG, IgA or IgE. In affinity maturation, those B-cells are selected which bind antigen more strongly. So better antibodies are formed.
9. Establishment of memory– Some selected B-cells do not become plasma cells. They become long lived memory B-cells. These cells remain in the body for many years. When the same antigen enters again, they give faster and stronger antibody response.

Immunological Memory

Immunological memory is the ability of adaptive immune system to remember a pathogen which has entered the body before. Due to this, the immune system gives faster and stronger response when the same pathogen enters again. It is mainly produced after infection or vaccination.

• Cellular basis– It is maintained by long lived memory B-cells and memory T-cells. These cells are formed during the first or primary immune response. After removal of pathogen, some of these cells remain in the body.
• Secondary response– When the same antigen enters again, these memory cells become active quickly. They do not need long lag phase like first response. So the second response is more rapid and more effective.
• Memory B-cells– Memory B-cells produce antibodies quickly after second exposure. These antibodies have higher affinity for antigen. They bind more strongly with the pathogen.
• Antibody class– In memory response, the antibodies are more mature type. They may be IgG, IgA or IgE. These are more effective than early IgM response.
• Memory T-cells– Memory T-cells remain in the body in greater number after infection. They are more sensitive for restimulation. After activation, they produce cytokines like IFN-γ and help in destruction of pathogen.
• Self sustaining nature– Memory cells can remain in the body without continuous presence of the same pathogen. They do not need repeated infection for their survival.
• Long lasting protection– Immunological memory gives long lasting protection. It may persist for many years or sometimes for whole life. This is the main basis of protection given by natural infection and vaccination.

Disorders of the Immune System Related to Immunity

Disorders of immune system are the diseases in which immune response is not normal. Sometimes immunity becomes weak. Sometimes it attacks own body tissue. Sometimes the response becomes more than required.

• Immunodeficiency disorders– In this disorder, immune system becomes weak or absent. So the body cannot fight against infection properly. It may be primary or secondary.
  • Primary immunodeficiency– These are genetic disorders present from birth. The examples are SCID, X-linked agammaglobulinemia, Chronic Granulomatous Disease, Wiskott-Aldrich syndrome and Hyper IgM syndrome.
  • Severe Combined Immunodeficiency (SCID)- In this disease, both T-cells and B-cells do not work properly. So severe infection occurs during infancy.
  • X-linked agammaglobulinemia– In this disorder, mature B-cells are absent. So antibodies are not formed properly.
  • Chronic Granulomatous Disease– In this disease, phagocytes cannot kill microbes properly. They fail to produce reactive oxygen substances.
  • Wiskott-Aldrich syndrome– In this disease, antibody response against polysaccharide antigen is poor. So infection by encapsulated bacteria becomes common.
  • Hyper IgM syndrome– In this disorder, B-cells cannot change IgM into other antibody classes like IgG and IgA.
  • Secondary immunodeficiency– These are acquired after birth. It may occur due to HIV/AIDS, severe malnutrition and chemotherapy.
• Autoimmune diseases– In autoimmune disease, immune system fails to recognize own body tissue. It attacks the body’s own healthy cells. This causes inflammation and tissue damage.
  • Systemic Lupus Erythematosus (SLE)- It is a systemic autoimmune disease. Many organs are affected and many types of autoantibodies are produced.
  • Type 1 diabetes mellitus– In this disease, immune system attacks the pancreatic islets. So insulin producing cells are destroyed.
  • Autoimmune thyroiditis– In this disease, thyroid gland is attacked by immune response.
  • Rheumatoid arthritis– It is an autoimmune disease mainly affecting joints. It causes inflammation and damage of joint tissue.
  • Multiple sclerosis– It is an autoimmune disease affecting nervous system. The myelin sheath is damaged.
• Hypersensitivity reactions– These are exaggerated immune reactions. They occur against harmless or less harmful antigens. These reactions may damage the tissue.
  • Type I hypersensitivity– It is immediate type reaction. It is mediated by IgE, mast cells and basophils. The examples are asthma, allergic rhinitis, hives and anaphylaxis.
  • Type II hypersensitivity– It is antibody mediated cytotoxic reaction. Antibodies bind with cell surface and destroy the cell. The example is autoimmune hemolytic anemia.
  • Type III hypersensitivity– It is immune complex mediated reaction. Antigen and antibody complexes are deposited in tissues. The examples are serum sickness and poststreptococcal glomerulonephritis.
  • Type IV hypersensitivity– It is delayed type reaction. It is mediated by T-cells. The examples are contact dermatitis and tuberculin skin reaction.
• Complement system deficiencies– In this disorder, one or more complement proteins are absent or defective. So pathogen clearance becomes poor.
  • Early complement deficiency is related with lupus like autoimmune disease.
  • Late complement deficiency causes more infection by encapsulated bacteria, specially Neisseria meningitidis.
• Transplant rejection– In this condition, recipient immune system recognizes donor tissue as foreign. The donor MHC molecules are attacked by immune cells.
  • Hyperacute rejection– It occurs within minutes or hours. It is due to pre-existing antibodies.
  • Acute rejection– It occurs within weeks or months. It is mainly due to T-cell response.
  • Chronic rejection– It occurs after months or years. It causes fibrosis and gradual failure of graft.

Clinical Significance of Immunity

Clinical significance of immunity is the importance of immunity in medical field. It is used in prevention of diseases, diagnosis of diseases and treatment of many immune related conditions. It is also important in vaccination, transplantation and cancer therapy.

• Disease prevention through vaccination– Vaccination is the use of active immunity. In this method, vaccine stimulates the immune system and produces immunological memory. It does not cause the actual severe disease. By vaccination, smallpox has been eradicated and polio, tetanus and measles are greatly reduced.
• Antibody based therapy– Ready-made antibodies are used for immediate protection. This is a form of passive immunity. It is used in snake bite as antivenom, in hepatitis B exposed newborn and in Intravenous Immunoglobulin (IVIG) therapy for primary immunodeficiency.
• Cancer immunotherapy– In this therapy, immune system is used to destroy cancer cells. Immune checkpoint inhibitors stop the cancer cells from escaping immune attack. In CAR-T cell therapy, the patient’s own T-cells are taken, modified and again infused into the body to attack tumour cells.
• Management of immunodeficiency– Immunity is important in diagnosis and treatment of weak immune condition. The examples are Severe Combined Immunodeficiency (SCID) and HIV/AIDS. Treatment may include antibiotics for prevention, bone marrow transplant, hematopoietic stem cell transplant and gene therapy.
• Treatment of autoimmune and allergic diseases– In autoimmune disease, immune system reacts against own body tissue. In allergy, immune system reacts strongly against harmless antigen. The examples are systemic lupus erythematosus, type 1 diabetes, asthma and severe allergy. Biologic therapy is used to block inflammatory cytokines and decrease tissue damage.
• Organ transplantation– In transplantation, donor tissue may be recognized as foreign by the recipient immune system. MHC matching is important in this process. Immunosuppressive drugs are given to prevent hyperacute, acute and chronic graft rejection.
• Clinical diagnosis– Antibodies are important in laboratory diagnosis. They bind specifically with antigen. So they are used in blood typing, detection of infection like HIV, hormone estimation, ELISA and radioimmunoassay.
• Community immunity– Community immunity is also called herd immunity. It is formed when large number of people become immune in a population. It reduces the spread of pathogen and protects infants, immunodeficient persons and patients under cancer treatment.

References

1. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). T cells and MHC proteins. In Molecular biology of the cell (4th ed.). Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK26926/
2. An overview of pathogen recognition receptors for innate immunity in dental pulp – PMC. (n.d.). National Center for Biotechnology Information.
3. B cells, memory B cells and plasma cells: B cell activation, development and the B cell receptor. (n.d.). Technology Networks.
4. Cell-targeted vaccines: Implications for adaptive immunity – PMC. (n.d.). National Center for Biotechnology Information.
5. Children’s Hospital of Philadelphia. (2023). Parts of the immune system.
6. Children’s Hospital of Philadelphia. (n.d.). Types of immunity.
7. Cleveland Clinic. (2023). Cytokines.
8. Cleveland Clinic. (2024). Natural immunity: What it is.
9. Conjugate vaccine mechanisms, design, and immunological memory. (n.d.). The Scientist.
10. Díaz-Dinamarca, D. A., Salazar, M. L., Castillo, B. N., Manubens, A., Vasquez, A. E., Salazar, F., & Becker, M. I. (2022). Protein-based adjuvants for vaccines as immunomodulators of the innate and adaptive immune response: Current knowledge, challenges, and future opportunities. Pharmaceutics, 14(8), 1671. https://doi.org/10.3390/pharmaceutics14081671
11. From vaccines to memory and back – PMC. (n.d.). National Center for Biotechnology Information.
12. Gao, M., Wang, J., Zang, J., An, Y., & Dong, Y. (2021). The mechanism of CD8+ T cells for reducing myofibroblasts accumulation during renal fibrosis. Biomolecules, 11(7), 990. https://doi.org/10.3390/biom11070990
13. Gupta, R. C. (2026). The immune system. Nemours KidsHealth.
14. Immunological mechanisms of vaccination – PMC. (n.d.). National Center for Biotechnology Information.
15. Janeway, C. A. Jr., Travers, P., Walport, M., et al. (2001). Appendix I. Immunologists’ toolbox. In Immunobiology: The immune system in health and disease (5th ed.). Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK10755/
16. Janeway, C. A. Jr., Travers, P., Walport, M., et al. (2001). B-cell activation by armed helper T cells. In Immunobiology: The immune system in health and disease (5th ed.). Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK27142/
17. Janeway, C. A. Jr., Travers, P., Walport, M., et al. (2001). Immunological memory. In Immunobiology: The immune system in health and disease (5th ed.). Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK27158/
18. Janeway, C. A. Jr., Travers, P., Walport, M., et al. (2001). Manipulating the immune response to fight infection. In Immunobiology: The immune system in health and disease (5th ed.). Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK27131/
19. Janeway, C. A. Jr., Travers, P., Walport, M., et al. (2001). Structural variation in immunoglobulin constant regions. In Immunobiology: The immune system in health and disease (5th ed.). Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK27106/
20. Janeway, C. A. Jr., Travers, P., Walport, M., et al. (2001). T cell-mediated cytotoxicity. In Immunobiology: The immune system in health and disease (5th ed.). Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK27101/
21. Janeway, C. A. Jr., Travers, P., Walport, M., et al. (2001). The components of the immune system. In Immunobiology: The immune system in health and disease (5th ed.). Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK27092/
22. Janeway, C. A. Jr., Travers, P., Walport, M., et al. (2001). The distribution and functions of immunoglobulin isotypes. In Immunobiology: The immune system in health and disease (5th ed.). Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK27162/
23. Janeway, C. A. Jr., Travers, P., Walport, M., et al. (2001). The humoral immune response. In Immunobiology: The immune system in health and disease (5th ed.). Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK10752/
24. Janeway, C. A. Jr., Travers, P., Walport, M., et al. (2001). The structure of a typical antibody molecule. In Immunobiology: The immune system in health and disease (5th ed.). Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK27144/
25. Leduc, C. (2026). Immunoglobulins: Types, functions, and uses. AmeriPharma Specialty Care.
26. National Cancer Institute. (n.d.). Definition of immunity. NCI Dictionary of Cancer Terms.
27. Pattern recognition receptors and the innate immune response to … (n.d.). National Center for Biotechnology Information.
28. R&D Systems. (2026). Antibody basics: What are antibodies and what are antigens? Bio-Techne.
29. Sabir, S., & Jan, A. (2025). Physiology, immune response. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK539801/
30. Shaikh, A., & Chan, G. (2026). Infection recognition molecules – PAMPs – PRRs. TeachMePhysiology.
31. Systems-level analysis of host immunity: Structural architecture, molecular signaling, cellular effector mechanisms, and immunization paradigms. (n.d.).
32. The College of Physicians of Philadelphia. (2025). Different types of vaccines. History of Vaccines.
33. The immune system | Johns Hopkins Medicine. (n.d.).
34. The lymphatic system: Integral roles in immunity – PMC. (n.d.). National Center for Biotechnology Information.
35. Vaccines | Johns Hopkins Medicine. (n.d.).
36. Vojdani, A., Koksoy, S., Vojdani, E., Engelman, M., Benzvi, C., & Lerner, A. (2024). Natural killer cells and cytotoxic T cells: Complementary partners against microorganisms and cancer. Microorganisms, 12(1), 230. https://doi.org/10.3390/microorganisms12010230
37. Wikipedia contributors. (2025). Pattern recognition receptor. In Wikipedia, The Free Encyclopedia. https://en.wikipedia.org/w/index.php?title=Pattern_recognition_receptor
38. Zaru, R. (n.d.). Pattern recognition receptor (PRRs) ligands. British Society for Immunology.