What is immunity? and how immune system work?

Immune system :

Immune system is a specific defence mechanism of our body. The immune system of a body is a complex network of; Cells, Tissues, Organs, and other substances. Which helps the body to resist and fight infections and other disease causing microbes. The immune system includes; White blood cells, Tissues, and Organs of the lymphatic system, such as; Thymus, Spleen, Tonsils, Lymph nodes, Lymph vessels, and Bone marrow. The most important characteristic of the immune system is that it distinguishes between self (body’s own cells) and non-self (foreign molecules or invading cells). The term immunity was coined by Burnet. Immunology is a branch of medical science which deals with the study of the immune system, immune responses to foreign substances and their role in resisting infection by pathogens. The father of immunology is Emil Von Behring, who discovered antibodies.

What is Immunity?

Immunity is also called disease resistance. Immunity is the general ability of the body to; Recognize, Neutralize, Destroy, and Eliminate. Pathogens (i.e. disease causing organisms), like; Bacteria, Virus, and Toxic substances, etc. which enters the body. The immunity is provided by the cells of the immune system. The lack of immunity is known as Susceptibility. There are two major types of immunity, viz;

1. Innate immunity, and

2. Acquired immunity.

Innate immunity :

The immunity that is inherited by the organism (i.e. genetic makeup) from the parents to the individual, and protects it from birth throughout life is called Innate immunity. The innate immunity is also known as Inborn immunity or Congenital immunity or Genetic immunity or Inherited immunity or Non-specific immunity or simply, Natural immunity. In this immunity antibodies are not generated to protect the body to any foreign agents. This immunity does not generates a specific response to any particular pathogen (i.e. It is non-specific). This immunity does not generate an immunological memory. This immunity shows a rapid response to any particular pathogen. This immunity work through three different types of barriers, viz;

1. Physical barrier,

2. Physiological barrier, and

3. Cellular barrier.

Physical barrier :

They are mechanical barriers to many microbial pathogens. These are of two types, viz;

• Skin : The skin is a physical barrier of the body. Its outer tough layer, the stratum corneum, prevents the entry of bacteria and viruses.

• Mucous membrane : Mucous  membrane secrete a mucous, which traps the microor­ganisms and immobilises them. The mucous membrane lines; Respiratory tract, G.I. tract, Urogenital tract, and Exposed part of eyeball (i.e. conjunctiva).

Physiological barrier :

Body temperature, pH of the body fluids and various body secretions prevent growth of many disease causing microorganisms. Some of the important examples of physiological barriers are as follows;

• Acid of the stomach kills most ingested microorganisms,

• Bile juice does not allow growth of microorganisms,

• Cerumen (ear wax), traps dust particles, kills bacteria and repels insects,

• Nasal Hair, they filter out microbes and dust in nose,

• Urine, It washes microbes from urethra,

• Vaginal Secretions, It is slightly acidic which discourages bacterial growth and flush microbes out of vagina,

• Sebum (sweat); It forms a protective acid film over the skin surface that inhibits growth of many microbes,

• Lysozyme is present in all tissue fluids and in almost all secretions except in cerebrospinal fluid, sweat and urine. Lysozyme is in good quantity in tears from eyes. Therefore conjunctiva is free of foreign particles by the flushing action of lacrimal secretions. Lysozyme is active only against some pathogenic Gram +ve bacteria by dissolving their cell walls.

Cellular barrier :

These are; 

• Certain leukocytes (neutrophils and monocytes), 

• Macrophages, 

• Natural killer cells (NK cells), 

• Complement system : The complement system is a part of the immune system, consisting of a series of proteins that interact with one another in a highly regulated manner, in order to eliminate pathogens. It helps antibodies and phagocytic cells to clear pathogens by promoting inflammation and attacking pathogen’s plasma membranes. Proteins that take part in the complement system are called complements (or Antimicrobial substances). Complements collectively work as a Complement cascade or biological cascade. Complements are soluble proteins and glycoproteins mostly produced by hepatocytes. More than 20 types of complements are present in serum, found circulating normally in the human body in inactive forms (called as zymogens or proenzymes). Complement activation is triggered by an antibody when it is bound to the antigen. It can also be triggered by some components of innate immunity. Thus the complement system works in both innate and acquired immunity.

• Interferons (IFNs) : Virus-infected and tumour cells secrete low molecular weight glycoproteins which protect the non-infected nearby cells from pathogen’s attack, they are known as interferons. In response to interference, non- infected cells produce Antiviral Proteins (AVPs). Interferons activate macrophages, which are natural killer cells, and prevent viral replication. They increase antigen presentation to lymphocytes which constantly multiply to eliminate foreign bodies. Based on their function and cells from which they secreted, interferons are;

• Inflammation Reaction : Inflammatory or inflammatory response is the biological response of the immune system to harmful stimuli, such as; Injured by microbes, Trauma, Toxins, andbHeat, etc. Inflammatory response is the protective response of the body against infection or injury. It involves the migration of the cells of the immune system to the site of injury or infection which result in the four characteristic signs and symptoms of inflammation; Redness (Ruber), Swelling (Tumor), Pain (Dolor), and Heat (Calor). The major events that take place in sequence during an inflammatory response are as follows; Vasodilation, Increased vascular permeability, Leakage of plasma proteins, and Leukocyte extravasation.

• Fever : A fever is a temporary increase in average body temperature of 98.6°F (37°C). It is also known as Pyrexia. It is a common sign of an infection, not an illness. When someone has a fever, they may also have; Headache, Mental confusion (i.e. difficulty in concentrating), Chills or Shivering (i.e. feelings of coldness), Fatigue (i.e. feeling of tiredness or lack of energy), Malaise (i.e. a general feeling of discomfort), Excess sweating, Dehydration, Anorexia (i.e. loss of appetite), Increased sensitivity to pain, and Feel sleepy, etc.

• Acute phase proteins (APPs) : Acute phase proteins are plasma proteins. They synthesized in the liver. The concentrations of APPs increase or decrease by 25% or more during inflammation (inflammation occurs due to infection or injury). This response is called the acute-phase reaction/response. These proteins serve as inhibitors or mediators of the inflammatory processes. These include; C Reactive Protein(CRP), Mannose binding protein, Alpha-1-acid glycoprotein, and Serum Amyloid P, etc.

• Cytokines : Cytokines are a category of signaling molecules, like hormones. The chemical nature of cytokines are; Peptides, Proteins, or Glycoproteins. They are secreted by specific cells of the immune system. Cytokines bind with specific receptors on the surface of other cells, called the cytokinin receptor. The lifespan of cytokines are shorter, therefore they are mostly acts over a short distance (i.e. autocrine and paracrine). Cytokine is a general name, other names are defined based on their; Presumed function, Cell of secretion, or Target of action. For example; lymphokines.

Acquired immunity :

The immunity that an individual acquires after the birth during lifetime due to the course of time is called Acquired immunity. The acquired immunity is also known as Adaptive immunity or Specific immunity. In this immunity antibodies are generated to protect the body from any foreign agents. Antibodies neutralize the antigens. This immunity generates a specific response to any specific pathogen (i.e. it is specific). This immunity generates an immunological memory. This immunity takes a long time to respond to any particular pathogen. There are two types of acquired immunity, viz;

1. Active Immunity, and

2. Passive Immunity.

Active Immunity :

The immunity developed by an individual as a result of antigenic stimulus, is called Active Immunity. The pathogen has direct contact with the body, in case of active immunity. Active immunity does not generate a rapid response. It is a long time immunity. It generates an immunological memory. It does not work in immunodeficient hosts, because immune cells are not functional. Active immunity may be;

• Natural : In this antibodies developed in response to an infection.

• Artificial : In this antibodies developed in response to an vaccination.

Passive Immunity :

The immunity received by an individual, directly outside the body(i.e. ready-made) , is called Passive Immunity. The pathogen has no direct contact with the body, in case of passive immunity. Passive immunity generates a rapid response. It is a short time immunity. It does not generate an immunological memory. It works in immunodeficient hosts. Passive immunity may be;

• Natural : In this antibodies are received from mother through breast milk, and through placenta.

• Artificial : In this Antibodies received from a medicine.

Unique features of Acquired immunity :

Acquired or Adaptive immunity has four unique features, viz;

• Recognition : Our body has the unique ability to differentiate between its own cells and foreign cells (i.e. differentiate between self and non-self).

• Diversity : Our body has the ability to detect vast varieties of pathogens, ranging from protozoa to viruses.

• Specificity : Our body has the ability to differentiate between different types of pathogens, whether it is harmful or not, and devise ways to destroy them.

• Memory : When the immune system encounters a specific foreign agent for the first time, it generates an immune response and eliminates the invader. This is called the first encounter. The immune system retains the memory of the first encounter. As a result, a second encounter with the same pathogen brings about a quicker and stronger immune response.

What is immunological memory?

Immunological memory is the ability of the immune system to quickly and specifically recognize an antigen that the body has previously encountered and initiate a corresponding immune response. Generally these are secondary, tertiary and other subsequent immune responses to the same antigen.

Cells of Immune System :

There are two main types of cells involved in the working of the Immune system. They are; Lymphocytes, and Antigen Presenting cells.

Lymphocytes :

Lymphocytes are the main cells of the immune system. Like other leukocytes (WBCs), lymphocytes arise from hematopoietic stem cells in bone marrow by the process called hematopoiesis (i.e. mitosis). Lymphocytes are the type of agranulocytes of leucocytes of blood. Lymphocytes are about 25-30% of total WBCs. Lymphocytes are the smallest of all WBCs. Its nucleus is large and spherically shaped. Based on the size and function, lymphocytes are;

• Natural killer lymphocytes (NK lymphocytes) : The natural killer lymphocytes are also known as Natural killer cells (NK cells) or simply Killer cells. Natural killer cells and largest lymphocytes. Nk cells are present in the spleen, lymph nodes and red bone marrow. NK cells do not have antigen receptors like T-cells and В-cells. NK cells cause cellular destruction in at least two ways; NK cells produce perforins, and Another function of NK cells is apoptosis which means natural cell death.

• T-lymphocytes : In T-lymphocytes 'T' stands for Thymus gland. T-lymphocytes are also called T-cells. T-lymphocytes arise from hematopoietic stem cells in bone marrow by the process called hematopoiesis (i.e. mitosis). Pre-mature T-lymphocytes migrate to and mature in the Thymus gland. Mature T-cells occur mostly inside the lymph nodes. T-cells form 75-80 % of total lymphocytes. They have a comparatively longer lifespan to B-cells. Microvilli are absent on the cell surface of T-cells. It has a T-cell receptor(TCR), it is a protein complex. T-cells lack surface antigens, but they bind with B-cell receptors and activate the process of Antibody production. They move to the site of infection. T-cells can only recognize viral antigens outside the infected cells. T-cells bind with foreign antigen in association with self-antigen only such as a virus-infected cell. Lymphokines are the type of cytokines, And they are the chief secretory product of T-cells. They are involved in cell-mediated immunity, i.e. cell-mediated immune system (CMIS). They are activated in response to antigen presenting cells (APCs), and APCs by antigens. After activation T-cells multiples, and differentiated into four types, which are similar in structure(i.e. clones of each other), but they perform different functions, viz;

1. Helper T-cells,

2. Killer T-cell,

3. Suppressor T-cell, and

4. Memory T-cell.

• B-lymphocytes : In B-lymphocytes 'B' stands for Bursa of fabricius in birds, but in humans the Barsha is equivalent to Bone marrow. B-lymphocytes are also called B-cells. B-lymphocytes arise from hematopoietic stem cells in bone marrow by the process called hematopoiesis (i.e. mitosis). They mature in Bone marrow, Tonsils, and Peyer’s patches of the intestine. Mature B-cells occur mostly outside the lymph node. B-cells form 20-25 % of total lymphocytes. They have a comparatively shorter lifespan to T-cells. Microvilli are present on the cell surface of B-cells. It has a B-cell receptor(BCR), it is a protein complex. B-cells have surface antigens, for T-cells. They do not move to the site of infection. B-cells bind with only all types of  extracellular antigens. B-cells can recognize the surface antigens of bacteria and viruses. Antibodies are the chief secretory product of B-cells. They are involved in humoral immunity (or antibody-mediated immunity), i.e. antibody-mediated immune system (AMIS). They are activated in response to antigen as well as Helper T-cells. After activation B-cells multiples, and differentiated into two types, which are similar in structure(i.e. clones of each other), but they perform different functions, viz;

1. Plasma B-cells, and

2. Memory B-cell.

Antigen Presenting Cells (APCs) :

Helper T-cells can identify only peptides, but antigens are large proteins. Hence, these antigens are processed by specialized antigen presenting cells. The APCs trap, engulf, and destroy antigen; and break antigens proteins into peptides. These peptides now come out on the surface of antigen presenting cells. And informs the adaptive immune response about an infection (i.e presents fragments of antigen to T-cells). There are three types of antigen presenting cells in the body, viz; 

• Macroph­ages : Monocytes circulate in the bloodstream for about 8 hours, during which time they enlarge and then migrate into the tissues and differentiate into specific tissue called Macrophages. Macrophages are long lived and are highly motile phagocytes. Macrophages engulf and destroy microbes by the process phagocytosis. Macrophages contain more cell organelles, especially lysosomes. Macrophages are of two types, viz; Fixed macrophages, and Free (or Wandering) macrophages. Both mac­rophages serve different functions in their different tissue locations. Some examples of fixed macrophages are; Pulmonary alveolar macrophages in the lung, Histiocytes in connective tissues, Kupffer cells in the liver, Glomerular Mesangial cells in the kidney, Microglial cells in the brain, Osteoclasts in bone. Nk cells are one example of macrophages.

• Dendritic Cells : These cells are characterized by long star shaped(i.e. branched appearance) cytoplasmic processes/morphology. Their primary role is to trap, engulf, destroy antigen, and inform the adaptive immune response about an infection (i.e presents fragments of antigen to T-cells). These cells are a specialised group of phagocytic cells. They are found in different locations in the body, viz; Lymph node, Spleen, Thymus, and Skin.

• B-lymphocytes : In B-lymphocytes 'B' stands for Bursa of fabricius in birds, but in humans the Barsha is equivalent to Bone marrow. B-lymphocytes are also called B-cells. B-lymphocytes arise from hematopoietic stem cells in bone marrow by the process called hematopoiesis (i.e. mitosis). They mature in Bone marrow, Tonsils, and Peyer’s patches of the intestine. Mature B-cells occur mostly outside the lymph node. B-cells form 20 to 25% of total lymphocytes. They have a comparatively shorter lifespan to T-cells. Microvilli are present on the cell surface of B-cells. It has a B-cell receptor(BCR), it is a protein complex. B-cells have surface antigens, for T-cells. They do not move to the site of infection. B-cells bind with only all types of  extracellular antigens. B-cells can recognize the surface antigens of bacteria and viruses. Antibodies are the chief secretory product of B-cells. They are involved in humoral immunity (or antibody-mediated immunity), i.e. antibody-mediated immune system (AMIS). They are activated in response to antigen as well as Helper T-cells. After activation B-cells multiples, and differentiated into two types, which are similar in structure(i.e. clones of each other), but they perform different functions, viz;

3. Plasma B-cells, and

4. Memory B-cell.

Cell-Mediated Immune System (CMIS) or Cellular Immunity :

The cell-mediated immune response is mediated by T-cells. Antibodies are not formed in cell mediated immune response. Receptors are used in cell-mediated immunity to detect antigens. This immunity product against intracellular pathogens (i.e. intracellular disease-causing bacteria, parasite viruses, etc.). The cells involved in cell-mediated immunity are; Macrophages, and T-Lymphocytes. This immunity can eliminate tumor cells. Humoral immunity response also participates in the rejection of organ transplants.

Antibody-mediated Immune System (AMIS) or Humoral immunity :

The humoral immune response is mediated by antibodies (produced by plasma B-cells). Antibodies are formed in humoral

immune response. Antibodies are used in humoral immunity to detect antigens. This immunity product against extracellular pathogens (i.e. extracellular disease-causing bacteria, parasite viruses, fungi, etc.). The cells involved in humoral immunity are; Macrophages, T-Lymphocytes, and B-Lymphocytes. This immunity cannot eliminate tumor cells. Humoral immunity may be involved in the early graft rejection due to pre- formed antibodies.

Mechanism of response of Cell-Mediated Immune System (CMIS) and Antibody-Mediated Immune System (AMIS) in 1st and Nth exposure, is as follow;