Immunity: Definition, Types of Immunity to a Disease

Definition And Types Of Immunity

Immunity is defined as the capacity of the body to resist, the pathogenic agents. It is the ability of the body to resist the entry of different types of foreign bodies like bacteria, viruses, toxic substances, etc.

Immunity is of two types:

1. Innate immunity
2. Acquired immunity.

1. Innate Immunity Or Nonspecific Immunity

• Innate immunity is the inborn capacity of the body to resist pathogens. By chance, if the organisms enter the body, innate immunity eliminates them before the development of any disease. It is otherwise called natural or nonspecific immunity.

Read And Learn More: Medical Physiology Notes

• This type of immunity represents the first line of defense against any type of pathogens. Therefore, it is also called nonspecific immunity.
• Mechanisms of Innate Immunity: The various mechanisms of innate immunity are given in Table.

2. Acquired Immunity Or Specific Immunity

1. Acquired immunity is the resistance developed in the body against any specific foreign body like bacteria, viruses, toxins, vaccines, or transplanted tissues. So, this type of immunity is also known as specific immunity.
2. It is the most powerful immune mechanism that protects the body from the invading organisms or toxic substances. Lymphocytes are responsible for acquired immunity.

Types of Acquired Immunity: Two types of acquired immunity develop in the body:

1. Cellular immunity
2. Humoral immunity.

Development And Processing Of Lymphocytes

In the fetus, lymphocytes develop from bone marrow. All the lymphocytes are released in the circulation and are differentiated into two categories:

1. The lymphocytes designed to develop cellular immunity migrate into the thymus gland and are transformed into T lymphocytes
2. The lymphocytes designed to develop humoral immunity are processed in liver (during fetal life) and bone marrow (after birth) and are transformed into B lymphocytes.

1. T Lymphocytes

• T lymphocytes are processed in thymus. The processing occurs mostly during the period between just before birth and the few months after birth.
• Thymosin is a hormone secreted by thymus and released into circulation. It plays an important role in immunity. It accelerates the proliferation and activation of lymphocytes in thymus. It also increases the activity of lymphocytes in lymphoid tissues.

Types of T Lymphocytes: During the processing, T lymphocytes are transformed into four types:

1. Helper T cells or inducer T cells
2. Cytotoxic T cells or killer T cells
3. Suppressor T cells
4. Memory T cells.

Storage of T Lymphocytes: After the transformation, all the types of T lymphocytes leave the thymus and are stored in lymphoid tissues of lymph nodes, spleen, bone marrow, and the Gl tract.

2. B Lymphocytes: B lymphocytes were first discovered in the bursa of Fabricius in birds hence the name B lymphocytes. The bursa of Fabricius is a lymphoid organ situated near the cloaca of birds. The bursa is absent in mammals, and the processing of B lymphocytes takes place in bone marrow and liver.

Types of B Lymphocytes: After processing, the B lymphocytes are transformed into two types

1. Plasma cells
2. Memory cells.

Storage of B Lymphocytes: After the transformation, B lymphocytes are stored in the lymphoid tissues of lymph nodes, spleen, bone marrow, and the Gl tract.

Antigens

Antigens Definition And Types: The antigens are the substances, which induce specific immune reactions in the body. Antigens are of two types:

1. Autoantigens or self-antigens: The antigens present on the body’s own cells like ‘A’ antigen and ‘B’ antigen on the RBCs
2. Foreign antigens or nonself antigens: The antigens entering the body from outside.

Nonself Antigens: Following are the nonself antigens

1. The receptors on the cell membrane of microbial organisms such as bacteria, viruses, and fungi
2. The toxins from microbial organisms
3. The materials from transplanted organs or incompatible blood cells
4. Allergens or allergic substances like pollen grains.

Types of Nonself Antigens: The nonself antigens are classified into two types depending upon the response developed against them in the body

1. The antigens, which induce the development of immunity or production of antibodies (immunogenicity)
2. The antigens, which react with specific antibodies and produce allergic reactions (allergic reactivity).

Chemical Nature Of The Antigens: The antigens are mostly conjugated proteins like lipoproteins, glycoproteins, and nucleoproteins.

Development Of Cell Mediated Immunity

Development Of Cell-Mediated Immunity Introduction

• The cell-mediated immunity is the immunity that is developed by the cell-mediated response. This type of immunity does not involve antibodies.
• But it involves several types of cells such as macrophages, T lymphocytes, and natural killer cells and hence the name cell-mediated immunity. It is also called cellular immunity or T cell immunity.
• Cellular immunity is the major defense mechanism against infections by viruses, fungi, and few bacteria like tubercle bacillus. It is also responsible for delayed allergic reactions and the rejection of transplanted tissues.
• Cell-mediated immunity is offered by T lymphocytes and it starts developing when T cells come in contact with the antigens. Usually, the invading microbial or nonmicrobial organisms carry the antigenic materials.
• These antigenic materials are released from invading organisms and presented to the helper T cells by antigen-presenting cells.

Antigen-Presenting Cells: Antigen-presenting cells are the special type of cells in the body that induce the release of antigenic materials, from invading organisms and later present these materials to the helper T cells.

Types of Antigen-Presenting Cells: Two types of antigen-presenting cells are available in the body:

1. Macrophages
2. Dendritic cells
3. B lymphocytes.

1. Macrophages: The macrophages are the large phagocytic cells, which digest the invading organisms to release the antigen. The macrophages are present along with lymphocytes in almost all lymphoid tissues.

2. Dendritic Cells: The dendritic cells are nonphagocytic in nature. Based on the location, the dendritic cells are classified into three categories:

1. Dendritic cells of the spleen, which trap the antigen in blood
2. Follicular dendritic cells in lymph nodes which trap the antigen in the lymph
3. Langerhans dendritic cells in the skin, which trap the organisms coming in contact with body surface.

3. B Lymphocytes: Recently, it is found that B lymphocytes (B cells) also act as antigen-presenting cells. Thus, the B cells function as both antigen-presenting cells and antigen-receiving cells. However, B cells are the least efficient antigen-presenting cells and need to be activated by helper T cells.

Role of Antigen Presenting Cells

• Invading foreign organisms are either engulfed by macrophages through phagocytosis or trapped by dendritic cells. Later, the antigen from these organisms is digested into small peptides.
• The antigenic peptide products are moved toward the surface of the antigen-presenting cells and loaded on a genetic matter of the antigen-presenting cells called human leukocyte antigen (HLA).
• HLA is present in the molecule of class II major histocompatibility complex (MHC) which is situated on the surface of the antigen-presenting cells.
• B cells ingest the foreign bodies by means of pinocytosis. The role of B cells as antigen-presenting cells in the body is not fully understood.

MHC And HLA

• MHC is a large molecule present in the short arm of chromosome 6. It is made up of a group of genes which are involved in immune system. It has more than 200 genes including HLA genes. HLA is made up of genes with small molecules. It encodes antigen-presenting proteins on the cell surface.
• Though MHC molecules and HLA genes are distinct terms, both are used interchangeably. Particularly in human, the MHC molecules are often referred as HLA molecules. MHC molecules in human beings are divided into two types:

1. Class 1 MHC molecule: It is found on every cell in the human body. It is specifically responsible for the presentation of endogenous antigens (antigens produced intracellularly such as viral proteins and tumor antigens) to cytotoxic T cells.
2. Class 2 MHC molecule: It is found on B cells, macrophages, and other antigen presenting cells. It is responsible for presenting the exogenous antigens (antigens of bacteria or viruses which are engulfed by antigen-presenting cells to helper T cells.

Presentation of Antigen: The antigen-presenting cells present their class II MHC molecules together with antigen-bound HLA to the helper T cells. This activates the helper T cells through series of events.

The sequence of Events during Activation of Helper T Cells

• Helper T cell recognizes the antigen bound to class 2 MHC molecule which is displayed on the surface of the antigen-presenting cell. It recognizes the antigen with the help of its own surface receptor protein called T cell receptor.
• The recognition of the antigen by the helper T cell favorites a complex interaction between the helper V cell receptor and the antigen. This reaction activates helper T cells.
• At the same time macrophages (the antigen-presenting cells) release interleukin-1 which facilitates the activation and proliferation of helper T cells.
• The activated helper T cells proliferate and the proliferated helper T cells enter the circulation for further actions.
• Simultaneously the antigen bound to class 2 MHC molecules activates the B cells also resulting in the development of humoral immunity.

Role Of Helper T Cells: The helper T cells that enter the circulation activate all the other T cells and B cells. The helper T cells are of two types:

1. Helper-1 (TH1) cells
2. Helper-2 (TH2) cells.

Role of TH1 Cells: TH1 cells are concerned with cellular immunity and secrete two substances:

1. Interleukin-2 which activates the other T cells
2. Gamma interferon which stimulates the phagocytic activity of cytotoxic cells, macrophages, and natural killer (NK) cells.

Role of TH2 Cells: TH2 cells are concerned with humoral immunity and secrete interleukin-4 and interleukin-5 which are concerned with:

1. Activation of B cells
2. The proliferation of plasma cells
3. Production of antibodies by plasma cell

Role Of Cytotoxic T Cells: The cytotoxic T cells that are activated by helper T cells circulate through blood, lymph, and lymphatic tissues and destroy the invading organisms by attacking them directly.

Mechanism of Action of Cytotoxic T Cells

1. The receptors situated on the outer membrane of cytotoxic T cells bind the antigens or organisms tightly with cytotoxic T cells.
2. Then, the cytotoxic T cells enlarge and release cytotoxic substances like the lysosomal enzymes.
3. These substances destroy the invaded organisms.
4. Like this, each cytotoxic T cell can destroy a large number of microorganisms one after another.

Other Actions of Cytotoxic T Cells

1. The cytotoxic T cells also destroy cancer cells, transplanted cells such as those of transplanted heart or kidney or any other cells, which are foreign bodies.
2. Cytotoxic T cells destroy even the body’s own tissues which are affected by foreign bodies, particularly viruses. Many viruses are entrapped in the membrane of affected cells. The antigen of the viruses attracts the T cells. And the cytotoxic T cells kill the affected cells also along with viruses. Because of this cytotoxic T cell is called killer cell.

Role Of Suppressor T Cells:

• The suppressor T cells are also called regulatory T cells. These T cells suppress the activities of the killer T cells.
• Thus, the suppressor T cells play an important role in preventing the killer T cells from destroying the body’s own tissues along with invaded organisms. The suppressor cells suppress the activities of helper T cells also.

Role Of Memory T Cells:

• Some of the T cells activated by an antigen do not enter the circulation but remain in lymphoid tissue. These T cells are called memory T cells.
• In later periods, the memory cells migrate to various lymphoid tissues throughout the body. When the body is exposed to the same organism for the second time, the memory cells identify the organism and immediately activate the other T cells. So, the invading organism is destroyed very quickly. The response of the T cells is also more powerful this time.

Specificity Of T Cells: Each T cell is designed to be activated only by one type of antigen. It is capable of developing immunity against that antigen only. This property is called the specificity of T cells.

Development Of Humoral Immunity

Development Of Humoral Immunity Introduction

• Humoral immunity is the immunity mediated by antibodies which are secreted by B lymphocytes.
• B lymphocytes secrete the antibodies into the blood and lymph. The blood and lymph are the body fluids (humours or humors in Latin).
• Since the B lymphocytes provide immunity through humors, this type of immunity is called humoral immunity or B cell immunity.
• The antibodies are the gamma globulins produced by B lymphocytes. These antibodies fight against invading organisms. Humoral immunity is the major defense mechanism against bacterial infection.
• As in the case of cell-mediated immunity, the macrophages and other antigen presenting cells play an important role in the development of humoral immunity also.

Role Of Antigen-Presenting Cells: The ingestion of foreign organisms and digestion of their antigen by the antigen-presenting cells are already explained.

Presentation of Antigen: The antigen-presenting cells present their class 2 MHC molecules together with antigen-bound HLA to B cells. This activates the B cells through series of events.

Sequence of Events during Activation of B Cells

1. The B cell recognizes the antigen bound to class 2 MHC molecule which is displayed on the surface of the antigen-presenting cell. It recognizes the antigen with the help of its own surface receptor protein called B cell receptor.
2. The recognition of the antigen by the B cell initiates a complex interaction between the B cell receptor and the antigen. This reaction activates B cells.
3. At the same time macrophages (the antigen-presenting cells) release interleukin-1 which facilitates the activation and proliferation of B cells.
4. The activated B cells proliferate and the proliferated B cells carry out further actions.
5. Simultaneously the antigen bound to class 2 MHC molecules activates the helper T cells also resulting in development of cell-mediated immunity.

Transformation B Cells: The proliferated B cells are transformed into two types of cells:

1. Plasma cells
2. Memory cells.

Role Of Plasma Cells

• The plasma cells destroy the foreign organisms by producing the antibodies.
• Antibodies are globulin in nature. The rate of antibody production is very high, i.e. each plasma cell produces about 2000 molecules of anti- f bodies per second.
• The antibodies are also called immunoglobulins.
• The antibodies are released into lymph and then transported into the circulation.
• The antibodies are produced until the end of lifespan of each plasma cell which may be from several days to several weeks.

Role Of Memory B Cells

• Memory B cells occupy the lymphoid tissues throughout the body. The memory cells are in inactive condition until the body is exposed to the same organism for the second time.
• During the second exposure, the memory cells are stimulated by the antigen and produce more quantity of antibodies at a faster rate, than in the first exposure.
• The antibodies produced during the second exposure to the foreign antigen are also more potent than those produced during first exposure.
• This phenomenon forms the basic principle of vaccination against infections.

Role Of Helper T Cells: Helper T cells are simultaneously activated by antigen. The activated helper T cells secrete two substances called interleukin 2 and B cell growth factor, which promote:

1. Activation of more B lymphocytes
2. Proliferation of plasma cells
3. Production of antibodies.

Antibodies:

• An antibody is defined as a protein that is produced by B lymphocytes in response to the presence of an antigen.
• Antibody is Υ globulin in nature and it is also called immunoglobulin (Ig). The immunoglobulins form 20% of the total plasma proteins. The antibodies enter almost all the tissues of the body.

Types of Antibodies: Five types of antibodies are identified:

1. IgA (Ig alpha)
2. IgD (Ig delta)
3. IgE (Ig epsilon)
4. IgG (Ig gamma)
5. IgM (Ig mu).

Among these antibodies, IgG forms 75% of the antibodies in the body.

Structure of Antibodies

• Antibodies are gamma globulins with a molecular weight of 1, 50,000 to 9,00,000. The antibodies are formed by two pairs of chains namely, one pair of heavy or long chains and one pair of light or short chains.
• Each heavy chain consists of about 400 amino acids and sa;ch light chain consists of about 200 amino acids.
• Actually, each antibody has two halves, which are identical. The two halves are held together by disulfide bonds (S—S). Each half of the antibody consists of one heavy chain (H) and one light chain (L).
• The two chains in each half are also joined by disulfide bonds (S—S). The disulfide bonds allow the movement of amino acid chains.
• In each antibody, the light chain is parallel to one end of the heavy chain. The light chain and the part of heavy chain parallel to it form one arm.
• The remaining part of the heavy chain forms another arm. A hinge joins both the arms. Each chain of the antibody includes two regions:

1. Constant region
2. Variable region.

1. Constant Region

• The amino acids present in this region are similar in number and placement (sequence) in all the antibodies of each type. So, this region is called constant region or Fc (Fragment crystalline) region.
• Thus, the identification and the functions of different types of immunoglobulins depend upon the constant region. This region binds to the antibody receptor situated on the surface of the cell membrane. It also causes complement fixation.
• So, this region is also called the complement binding region.

2. Variable Region

• It is smaller compared to constant region. Amino acids occupying this region are different in number and placement (sequence) in each antibody.
• So, it is called variable region. This region enables the antibody to recognize the specific antigen and to bind itself with the antigen.
• Because of this, this region of the chain is called antigen binding region or Fab (Fragment antigen binding) region.

Mechanism of Actions of Antibodies: The antibodies protect the body from the invading organisms in two ways

1. By direct actions
2. Through complement system.

1. Direct Actions of Antibodies: Antibodies directly inactivate the invading organism by any one of the following methods:

1. Agglutination: In this, the foreign bodies like RBCs or bacteria with antigens on their surfaces are held together in a clump by the antibodies.
2. Precipitation: In this, the soluble antigens like tetanus toxin are converted into insoluble forms and then precipitated.
3. Neutralization: During this, the antibodies cover the toxic sites of antigenic products.
4. Lysis: It is done by the most potent antibodies. These antibodies rupture the cell membrane of the organisms and then destroy them.

2. Actions of Antibodies through Complement System

• The indirect actions of antibodies are stronger than the direct actions and play more important role in defense mechanism of the body than the direct actions.
• The complement system is the one that enhances or accelerates various activities during the fight against the invading organisms, it is a system of plasma enzymes, which are identified by numbers from C₁, to C₉.
• Including the three subunits of C₁ (C_1q C_1r C_1s), there are 11 enzymes in total. Normally, these enzymes are in inactive form and are activated in two ways:

1. Classical pathway
2. Alternate pathway.

1. Classical pathway: In this the C₁, binds with the antibodies and triggers a series of events in which other enzymes are activated in sequence. These enzymes or the byproducts formed during these events produce the following activities:

1. Opsonization: Activation of neutrophils and macrophages to engulf the bacteria, which are bound with a protein in plasma called opsonin
2. Lysis: Destruction of bacteria by rupturing the cell membrane
3. Chemotaxis: Attraction of leukocytes to the site of antigen-antibody reaction
4. Agglutination: By causing clumping of foreign bodies like RBCs or bacteria
5. Neutralization: Covering the toxic sites of antigenic products
6. Activation of mast cells and basophils, which liberate histamine: Histamine dilates the blood vessels and increases capillary permeability. So, plasma proteins from blood enter the tissues and inactivate the antigenic products.

2. Alternate pathway

• The complementary system is also activated by another way, which is called alternate pathway. It is due to a protein in circulation called factor 1.
• It binds with polysaccharides present in the cell membrane of the invading organisms. This binding activates C₃ and C₅, which ultimately attack the antigenic products of invading organisms.

Specificity of B Lymphocytes

• Each B lymphocyte is designed to be activated only by one type of antigen. It is also capable of producing antibodies against that antigen only.
• This property of B lymphocyte is called specificity. In lymphoid tissues, the lymphocytes, which produce specific antibody, are together called the clone of lymphocytes.

Functions of Different Antibodies

• IgA plays a role in localized defense mechanism in external secretions like tear
• IgD is involved in recognition of the antigen by B lymphocytes
• IgE is involved in allergic reactions
• IgG is responsible for complement fixation
• IgM is also responsible for complement fixation.

Natural Killer Cell

• Natural Kdier (NK) cell is a large granular cell with indented nucleus. It is considered as the third type of lympLcryiif and it is often called the non-T, non-B cell.
• NK cell kills the invading organisms or the cells of the body without prior sensitization. It is not a phagocytic cell but its granules contain hydrolytic enzymes. Hydrolytic enzymes play an important role in the lysis of cells of invading organisms.
• NK cell is said to be the first line of defense in specific immunity particularly against viruses.

Functions of NK Cell: The NK cell

1. Destroys the viruses
2. Destroys the viral infected or damaged cells, which might form tumors
3. Destroys the malignant cells and prevents the development of cancerous tumors
4. Secretes cytokines such as interleukin-2, interferons, colony-stimulating factor (GM-CSF), and tumor necrosis factor-a.

Cytokines

• Cytokines are the hormone-like small proteins acting as intercellular messengers (cell signaling molecules) by binding to specific receptors of target cells.
• These non-antibody proteins are secreted by WBCs and some other types of cells. Their major function is the activation and regulation of general immune system of the body.
• Cytokines are distinct from the other cell signaling molecules such as growth factors and hormones.
• Depending upon the source of secretion and effects, the cytokines are classified into several types:

1. Interleukins
2. Interferons
3. Tumor necrosis factors
4. Chemokines
5. Defensins
6. Cathelicidins
7. Platelet-activating factor

1. Interleukins: Interleukins (IL) are the polypeptide cytokines which are produced mainly by the leukocytes and act on other leukocytes. These cytokines are secreted by helper T cells, other T cells, B cells, eosinophils, basophils, monocytes, NK cells, mast cells, and macrophages. The actions of interleukins:

1. Activation of T cells, macrophages, and NK cells
2. Promotion of growth of hemopoietic cells and B cells
3. Acceleration of inflammatory response by activating eosinophils
4. Chemotaxis of neutrophils, eosinophils, basophils, and T cells
5. Killing the invading organisms.

So far, about 16 types of interleukins are identified. IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, and IL-8 play important role in the process of immunity. Recently IL-12 (otherwise called natural killer cell stimulatory factor) and IL-11 are also considered as important cytokines.

2. Interferons: The interferons (IFN) are the glycoprotein molecules secreted by WBCs, NK cells, and fibroblasts. These cytokines are considered as antiviral agents. Actions of interferons:

1. Fighting against the viral infection by suppressing the virus multiplication in the target cells
2. Inhibition of multiplication of parasites and cancer cells
3. Promotion of phagocytosis by monocytes and macrophages
4. Activation of NK cells

Interferons are of three types namely, INF-α, INF-βand INF-Υ

3. Tumor Necrosis Factors: The tumor necrosis factors (TNF) are secreted by T cells, B cells, mast cells, macrophages, NK cells, and platelets. The three types of tumor necrosis factors identified so far are TNF-α (cachectin), TNF-β (lymphotoxin), and TNF-γ.

Actions of tumor necrosis factors:

1. Causing necrosis of tumor
2. Activation of general immune system
3. Production of vascular effects
4. Promotion of inflammation.

4. Chemokines: Cytokines having chemoattractant action are called chemokines. These proteins are secreted by T cells, B cells, monocytes, and macrophages. Their function is to attract the WBCs towards the site of inflammation.

5. Defensins: Defensins are antimicrobial peptides. Two types of defensins are identified in human:

1. α defensins secreted by neutrophils, macrophages, and paneth cells in small intestine
2. β defensins secreted by airway epithelial cells (respiratory tract), salivary glands, and cutaneous cells.

Actions of defensins:

1. Role in innate immunity in airway surface and lungs
2. Killing the phagocytozed bacteria
3. Antiinflammatory actions
4. Promotion of wound healing
5. Attraction of monocytes and T cells by chemotaxis.

6. Cathelicidins: Cathelicidins are also antimicrobial peptides which are secreted by epithelial cells lining the airway, macrophages, and neutrophils. These peptides play an important role in a wide range of antimicrobial activity in air passage and lungs.

7. Platelet Activating Factor: Platelet-activating factor (PAF) is secreted by neutrophils and monocytes. It accelerates the agglutination and aggregation of platelets.

Immunization

• Immunization is defined as the procedure by which the body is prepared to fight against a specific disease.
• It is used to induce the immune resistance of the body to a specific disease. Immunization is of two types:

1. Passive immunization
2. Active immunization

1. Passive Immunization:

• Passive immunization or immunity is produced without challenging the immune system of the body.
• It is done by administration of serum or gamma globulins from a person who is already immunized (affected by the disease) to a nonimmune person.
• Passive immunization is acquired either naturally or artificially.

Passive Natural Immunization

• It is acquired from the mother before and after birth. Before birth, immunity is transferred from mother to the fetus in the form of maternal antibodies (mainly IgG) through placenta. After birth, the antibodies (IgA) are transferred through breast milk.
• The lymphocytes of the child are not activated. In addition, the antibodies received from the mother are metabolized soon. Therefore, the passive immunity is short lived.
• The significance of passive immunity that is obtained before birth is the prevention of Rh incompatibility in pregnancy.

Passive Artificial Immunization

• It is developed by injecting previously prepared antibodies using serum from humans or animals. The antibodies are obtained from the persons affected by the disease or from animals particularly horses which have been immunized artificially.
• The serum containing the antibody (antiserum) is administered to people who have developed the disease (therapeutic). It is also used as a prophylactic measure.
• Prophylaxis refers to medical or public health procedures to prevent a disease in people who may be exposed to the disease in a later period.
• This type of immunity is useful for providing immediate protection against acute infections like tetanus, measles, diphtheria, etc., and for poisoning by insects, snakes, and venom from other animals.
• It is also used as prophylactic measure. However, this may result in complications and anaphylaxis. There is risk of transmitting HIV and hepatitis.

2. Active Immunization: Active immunization or immunity is acquired by activating immune system of the body. The body develops resistance against disease by producing antibodies following exposure to antigens. Active immunity is acquired either naturally or artificially.

Active Natural Immunization

• Naturally, acquired active immunity involves activation of immune system in the body to produce antibodies. It is achieved in both clinical and subclinical infections.
• Clinical infection: During the disease, the plasma cells produce immunoglobulins to destroy the invading antigens. Later, due to the activity of memory cells, body retains the ability to produce the antibodies against the specific antigens invaded previously.
• Subclinical infection: Sometimes the disease may not be severe to develop any manifestations. However, it causes the activation of B lymphocytes resulting in production of antibodies.

Active Artificial Immunization: This type of immunization is achieved by administration of vaccines or toxoids.

• Vaccines:
  • Vaccine Is a substance that is introduced into the body to prevent the disease produced by certain pathogens. Vaccine consists of dead pathogens or live but attenuated (artificially weakened) organisms.
  • The vaccine induces immunity against the pathogen either by production of antibodies or by activation of T lymphocytes.
  • Edward Jenner produced the first live vaccine. He produced the vaccine for smallpox from cowpox virus.
  • Nowadays, vaccines are used to prevent many diseases like measles, mumps, poliomyelitis, tuberculosis, smallpox, rubella, yellow fever, rabies, typhoid, influenza, hepatitis B, etc.
• Toxoids:
  • Toxoid is a substance which is normally toxic but has been processed to destroy its toxicity but retains its capacity to induce antibody production by immune system.
  • Toxoid consists of weakened components or toxins secreted by pathogens. Toxoids are used to develop immunity against diseases like diphtheria, tetanus, cholera, etc.
  • The active artificial immunity may be effective lifelong or for short period. It is effective lifelong against the diseases such as mumps, measles, smallpox, tuberculosis and yellow fever. It is effective only for short period against some diseases like cholera (about six months) and tetanus (about one year).

Immune Deficiency Diseases

• Immune deficiency diseases are group of diseases in which some components of immune system is missing or defective. Normally, the defense mechanism protects the body from invading pathogenic organism.
• When the defense mechanism fails or becomes faulty (defective), the organisms of even low virulence produce severe disease. The organisms, which take advantage of defective defense mechanism, are called opportunists.
• The immune deficiency diseases caused by such opportunists are of two types:

1. Congenital immune deficiency diseases
2. Acquired immune deficiency diseases.

1. Congenital Immune Deficiency Diseases:

• Congenital diseases are inherited and occur due to defects in B cells, T cell, or both.
• The common examples are Di George’s syndrome (due to absence of thymus) and severe combined immune deficiency (due to lymphopenia or the absence of lymphoid tissue).

2. Acquired Immune Deficiency Diseases: Acquired immune deficiency diseases occur due to infection by some organisms. The most common disease of this type is acquired immune deficiency syndrome (AIDS).

Acquired Immune Deficiency Syndrome (AIDS)

• It is an infectious disease caused by immune deficiency virus (HIV). AIDS is the most common problem throughout the world because of the rapid increase in the number of victims.
• Infection occurs when a glycoprotein from HIV binds to surface receptors of T lymphocytes, monocytes, macrophages, and dendritic cells leading to destruction of these cells.
• It causes slow progressive decrease in immune function resulting in opportunistic infections of various types. The common opportunistic infections, which kill the AIDS patient are pneumonia (Pneumocystis carinii) and malignant skin cancer (Kaposi’s sarcoma).
• After entering the body of the host, the HIV activates the enzyme called reverse transcriptase. HIV utilizes this enzyme and converts its own viral RNA into viral DNA with the help of host cell DNA itself.
• Now, the viral DNA gets incorporated into the host cell DNA and prevents the normal activities of the host cell DNA. At the same time, the HIV increases in number inside the host’s body. The infected host cell ruptures and releases more number of HIV into the bloodstream.
• After exposure to HIV, no symptoms develop for several weeks. This is the incubation period. The patient develops symptoms only when a sufficient number of infected cells is ruptured.
• The common symptoms are fatigue, loss of weight, chronic diarrhea, low-grade fever, night sweats, oral ulcers, vaginal ulcers, etc. This phase prolongs for about three years before the disease is diagnosed.
• Mode of transmission: The HIV infection spreads when secretions from the body of infected individual come in contact with blood of the recipient through the damaged skin or mucus membrane. The most common ways of infection are contaminated blood transfusion, contaminated needles or other invasive instruments, transmission from mother to fetus during pregnancy, transmission from mother to child during delivery or breastfeeding and vaginal sexual intercourse.
• Prevention: The prevention of AIDS is essential because the authentic treatment for this disease has not been established so far. Progress in the development of effective treatment is very slow. Moreover, the maximum duration of survival after initial infection is only about 10-15 years. So, it is necessany to prevent this disease.The following safety measures should be followed to prevent AIDS:

1. Public must be educated about the seriousness and prevention of the disease
2. The HIV infected persons should be educated to avoid spreading the disease to others
3. The blood should be screened for HIV before transfusion
4. Intravenous drug users should not share the needles
5. Pregnant women should get their blood tested for HIV.
6. If the mother is infected, the treatment with zidovudine may reduce incidence of infection in infants. The baby must be given zidovudine for 6 weeks after birth
7. Young adults and teenagers must be informed about the safer sex techniques and use of condoms. And the need for limitation of sexual partners must be emphasized.

Autoimmune Diseases

• Autoimmune disease is defined as condition in which the immune system mistakenly attacks the body’s own cells and tissues.
• Normally, an antigen induces the immune response in the body. The condition in which the immune system fails to give response to an antigen is called tolerance.
• This is true with respect to the body’s own antigens that are called self-antigens or autoantigens. Normally, body has a tolerance against the self antigens.
• However, in some occasions, the tolerance fails or becomes incomplete against self antigen. This state is called autoimmunity and it leads to the activation of T lymphocytes or production of autoantibodies from B lymphocytes.
• The T lymphocytes (cytotoxic T cells) or autoantibodies attack the body’s normal cells whose surface contains the self-antigen or autoantigen.
• Thus, the autoimmune disease is produced when the body’s normal tolerance decreases and the immune system fails to recognize the body’s own tissues as “self. Autoimmune diseases are of two types:

1. Organ-specific diseases which affect only one organ
2. Organ nonspecific or multisystemic diseases, which affect many organs or systems.

Human Leukocyte Antigen System And Autoimmune Diseases

• Human leukocyte antigen (HLA) is a group of genes on human chromosome 6. These genes encode the proteins which function in the cells to transport the antigens from within the cell towards the cell surface.
• HLA is the product of a major histocompatibility complex. The HLA system monitors the immune system in the body (see above). The HLA molecules are recognized by the T and B lymphocytes and hence the name called antigens.
• HLA is distributed in almost all the tissues of the body. The antibodies are directed against the tissues possessing the HLA leading to autoimmune diseases. Most of the autoimmune diseases are HLA linked.

Common Autoimmune Diseases

1. Insulin-dependent diabetes mellitus
2. Myasthenia gravis
3. Hashimoto’s thyroiditis
4. Graves’ disease
5. Rheumatoid arthritis.

1. Insulin-Dependent Diabetes Mellitus: Insulin-dependent diabetes mellitus (IDDM) is very common in childhood and it is due to HLA-linked autoimmunity. Common causes for IDDM:

1. Development of islet cell autoantibody against (3 cells in the islets of Langerhans in pancreas
2. Development of antibody against insulin and glutamic acid decarboxylase
3. Activation of T cells against islets

2. Myasthenia Gravis: This neuromuscular disease occurs due to the development of autoantibodies against the receptors acetylcholine in neuromuscular junction.

3. Hashimoto’s Thyroiditis: It is common in the late middle aged women. The autoantibodies impair the activity of thyroid follicles leading to hypothyroidism.

4. Graves Disease: In some cases, the autoantibodies activate TSH receptors leading to hyperthyroidism.

5. Rheumatoid Arthritis:

• It is the disease due to the chronic inflammation of synovial lining of joints (synovitis). The synovium becomes thick leading to the development of swelling around joint and tendons. The characteristic symptoms are the pain and stiffness of joints.
• Chronic inflammation occurs due to the continuous production of autoantibodies called rheumatoid arthritis factors (RA factors).

Allergy And Immunological Hypersensitivity Reactions

• The term allergy means hypersensitivity. It is defined as abnormal immune response to a chemical or physical agent.
• During the first exposure to an allergen, the immune response does not normally produce any reaction in the body.
• Sensitization or an initial exposure to the allergen is required for the reaction. So the subsequent exposure to the allergen causes a variety of inflammatory responses.
• These responses are called allergic reactions or immunological hypersensitivity reactions.
• The immunological hypersensitivity reactions may be innate or acquired. These reactions are mediated by mostly by antibodies. In some conditions, T cells are involved.
• Common symptoms include sneezing, itching, and skin rashes. However, in some persons the symptoms may be severe. The common allergic conditions are:

1. Food allergy
2. Allergic rhinitis
3. Bronchial asthma
4. Urticaria

Allergens: Any substance that produces the manifestations of allergy is called an allergen. It may be an antigen or a protein or any other type of substance. Even physical agents can develop allergy. Allergens are introduced by

1. Contact (example – chemical substance)
2. Inhalation (example – pollen)
3. Ingestion (example – food)
4. Injection (example – drug)

Common Allergens: The common types of allergens are

1. Food substances: Wheat, egg, milk, and chocolate
2. Inhalants: Pollen grains, fungi, dust, smoke, perfumes, and disagreeable odor
3. Contacts: Chemical substances, metals, animals, and plants
4. Infectious agents: Parasites, bacteria, viruses, and fungi
5. Drugs: Aspirin and antibiotics
6. Physical agents: Cold, heat, light, pressure, and radiation.

Immunological Hypersensitive Reactions

Immunological Hypersensitive Reactions: The immunological hypersensitive reactions to an agent give rise to several allergic conditions and autoimmune diseases.

Hypersensitive reactions are classified into five types: Type 1 or anaphylactic reactions Type 2 or cytotoxic reactions Type 3 or antibody-mediated reactions Type 4 or cell-mediated reactions Type 5 or stimulatory/blocking reactions.

Type 1 or Anaphylactic Reactions

• Anaphylaxis means exaggerated reactions of the body to an antigen or any other agent to which the body has got sensitized already.
• It is also called immediate hypersensitive reaction because it develops within few minutes of exposure to an allergen.
• Anaphylactic reactions are mediated by IgE and other factors involved in inflammation (inflammation means the protective response of the tissues to the damage or destruction of cells).
• When the body is exposed to an allergen, the IgE immunoglobulins are produced. Also called reagins or sensitizing antibodies, these immunoglobulins bind with the surface receptors of mast cells and circulating basophils.
• Mast cells are the granulated wandering cells found in connective tissue and beneath the mucus membrane in the throat, lungs, and eyes.
• During the subsequent exposure of the body to the same allergen, the allergenlgE antibody reaction takes place. This leads to degranulation of mast cells and basophils with the release of some chemical mediators such as histamine.
• The chemical mediators produce the hypersensitivity reactions. Most serious reactions are fall in blood pressure (due to vasodilatation), obstruction of air passage and difficulty in breathing (due to broncho-constriction), and shock.

Type 2 or Cytotoxic Reactions

• The cytotoxic reactions involve mainly the IgG antibodies, which bind with antigens on the surface of the cells, particularly the blood cells.
• The affected cells are destroyed. Sometimes, IgM and IgA antibodies are also involved. The diseases developed due to cytotoxic reactions are hemolytic diseases of newborns in case of Rh incompatibility and autoimmune hemolytic anemia.

Type 3 or Antibody Mediated Reactions: Excess amounts of antibodies like IgG or IgM are produced in this type. The antigen-antibody complexes are precipitated and deposited in localized areas like joints causing arthritis, heart-causing myocarditis, and glomeruli of kidney producing glomerulonephritis.

Type 4 or Cell Mediated Reactions: This type of hypersensitivity is also called delayed or slow type of hypersensitivity. It is found in allergic reactions due to the bacteria, viruses, and fungi.

• It is also seen in contact dermatitis caused by chemical allergens and during rejection of transplanted tissues. An example of type 4 reaction is the delayed reaction after intradermal injection of tuberculin in persons who are previously affected by tuberculosis (tuberculosis skin test or Mantoux test).
• The important feature of the delayed type of hypersensitivity is the involvement of T lymphocytes rather than antibodies.

Type 5 or Stimulatory/Blocking Reactions: It is seen in autoimmune diseases like Graves’ disease (stimulatory reactions) and myasthenia gravis (blocking reactions).

Graves’ disease:

• Normally, thyroid stimulating hormone (TSH) combines with surface receptors of thyroid cells and causes synthesis and secretion of thyroid hormones.
• The secretion of thyroid hormones can be increased by thyroid-stimulating antibodies (TSAB) produced by plasma cells (B lymphocytes).
• The excess secretion of thyroid hormone leads to Graves’ disease.

Myasthenia gravis: It is due to the development of IgG autoantibodies.