Friday, 3 April 2015

Human immune system




  

Immunity

Immunity can be defined as the defensive mechanism of the body that acts against foreign proteins, toxins produced by the invading pathogens or microorganisms and micro organisms.Natural immunity can be defined as the immunity that is present since birth in a human to any of the pathogens, microbial proteins and toxins. We resist many of the diseases by our own immune system and need no external vaccine or drug for the resistance. This is so because we have the necessary antibodies for resisting such diseases.

Types of immunity found in humans
Immunity can be either generated inside the body or the body can also acquire the immunity from outside sources.

Active Immunity

Active acquired immunity is the immunity which we acquire later in life when we are exposed to some pathogen. When the body successfully resists an attack from the below given factors, then active acquired immunity is attained. The immunity provided by the T cells and B cells are types of active immunity. The factors are:

A particular microorganism

A closely similar micro organism

A modified toxin

A killed microorganism

A micro organism that has been artificially made less hostile

Artificially acquired active immunity

A vaccine can induce artificially acquired immunity. Vaccine contains the necessary antigen due to which the body creates specific vaccine for resisting a particular pathogen.

Passive immunity

If we inject the serum of any animal that has antitoxins (produced because as a result of active immunity) into a human being, then the antitoxins produce passive immunity for that particular organism inside the human being.

Artificially acquired passive immunity

There are some antibodies that the human body cannot produce. When these antibodies are directly injected through short term immunization vaccines, the body attains passive immunity for those diseases of which antibodies have been injected.

Naturally acquired passive immunity

This immunity is developed in the body during pregnancy when some antibodies are directly passed form the maternal blood to the fetal blood.

Terms of immunity for familiarization

Antigen

The foreign bodies, proteins or bacteria that enter into the blood are called antigens. An antigen’s body can divided into 2 parts viz. hapten and protein nucleus. Hapten can be a mono or a polysaccharide.

Antibody

When an antigen enters the body, the body reacts to this invasion by secreting antibodies or immune bodies. These antibodies are part of the plasma proteins and are classified under the gamma globulin fraction of plasma proteins. The antibodies can be classified in 4 groups. These 4 groups are given below.

Antitoxins- These are released when toxic substances enter inside the body.

Agglutinins- These antibodies clump together the antigens and then destroy them.

Precipitins- They cause the precipitation of foreign proteins.

Haemolysins or cytolysins- They cause the haemolysis of old RBC’s.

MALT

The abbreviation malt stands for mucosa associated lymphoid tissue. Some parts of the human body like skin, eye,  salivary glands, lung , breast, thyroid and gastrointestinal tract contain MALT which is diffuse system containing small amounts of lymphoid tissue. MALT contains high amounts of B cells, macrophages, plasma cells and T cells. These immunity cells resist and destroy the antigens that pass through the mucosal lining.

GALT

GALT stands for gut associated lymphoid tissue. GALT is found in esophagus, tonsils, adenoids stomach and other areas of the gut. GALT also contains T and B cells which resist and destroy pathogens.

Similarly, other areas of the body also have lymphoid tissues that contain numerous T and B cells for resisting attack of pathogens/antigens. These are:

BALT or bronchus associated lymphoid tissue,

NALT or nasal associated lymphoid tissue,

CALT or conjuctival associated lymphoid tissue,

LALT or larynx associated lymphoid tissue, and

MALT or mucosa related lymphoid tissues are found in the body.

Mechanism of human immune system

The human body has a 3 layer immune defense mechanism against the foreign pathogens and toxins. The primary layer is called the physical barrier, the secondary layer is called the innate human system and the tertiary barrier is the adaptive immune system.

The surface immune barrier or the primary barrier

This is the first barrier of the body against the harmful foreign pathogens and toxins and is made of skin. The human skin does not allow the intrusion of any foreign particle inside the human body. But it is not possible to completely cut off the body from all foreign exchanges. The air we breathe can carry many pathogens. Pathogens can also travel inside the body through contaminated water and food. Thus it is not possible to have a total shield for the human body through which no pathogen or toxin can penetrate. Fortunately the body has certain mechanism which helps in protecting the body against pathogens. Some of the primary barriers of the body to pathogens are given below.

Cilia or tiny hairs are found in the respiratory tract that causes sneezing and coughing. Sneezing and coughing helps to eject many foreign harmful pathogens outside the respiratory tract.

Urine and tears flush out many harmful pathogens outside the body.

The human gastrointestinal tract or the GI tract and the respiratory tract secrete many mucous elements that trap, entangle and then cause the destruction of pathogens.

Skin is a water proof mechanical barrier that stops pathogens form entering the body.

Stomach acid (Hcl) kills many harmful bacteria and pathogens.

Chemical components of the physical barrier

Human secretions have certain chemicals that serve as the primary defense barriers of the body. The enzymes lysosome and phospholipase that are found in tears, saliva and breast milk are bactericidal in nature. Beta defensins is an antimicrobial peptide secreted in the skin and respiratory tract

The human semen has defensins and zinc that can kill the pathogens. Many pathogens enter the body through the food we intake. The proteases enzymes and gastric acid destroy these pathogens. The human gut has the commensal flora or friendly microorganisms that help the GI tract and the gastro urinary tract to fight against the harmful foreign pathogens. The commensal flora may alter the ph balance of the gut to make it non inhabitable for the pathogen. It can reduce the availability of iron and can also compete with the pathogen for space and food inside the gut.

Inflammation

When the body tissues are infected by some foreign pathogens or are injured, then the tissues of that area become inflamed. The inflamed swollen, red area can be distinguished from other normal areas. These changes occur as there is enhanced blood flow to the infected or injured areas. There is pain and heat in the inflamed area.  The infected /injured cells release cytokines and eicosanoids.

 Cytokines are cell signaling proteins. They include interleukins that mediate communication between WBC’s, interferons (proteins) that act against pathogenic bacteria and chemokines that help cause chemotaxis or response of the organism to chemicals.

 Eicosanoids are oxidized fatty acids that also act as signalers. Prostaglandins are eicosanoids that cause the inflammed blood vessels to dilate. Prostaglandins also produce fever in the affected organism. Leukotrienes are eicosanoids that attract other leukocytes to the affected area.

Human Innate Immune System or the secondary barrier

Those pathogens and toxins that cannot be dealt by the primary barrier are subsequently engaged by the secondary barrier or innate immune system. The different parts of innate immune system are described below.
a.Complement System

The complement system is the first arm of innate immune system. A series of chemical reactions (also called biochemical cascade or complementary system) are initiated inside the bodies which result in the attacking of the surfaces of foreign cells. The complementary system is so called as it complements the antibodies in destroying foreign pathogens. The complementary system consists of 20 proteins. The component system is humoral in nature. Unlike the cell mediated immunity which acts by activation of T-Lymphocytes and phagocytes, the humoral immunity acts by the action of macromolecules like peptides, proteins and antibodies. These peptides, proteins and antibodies are also called as the components of the complementary system. The component attaches itself to the pathogen and kills them.

b.Cellular barriers

The second arm of human innate immune system consists of leucocytes or white blood cells. Neutrophils, Basophils, Eosinophils, Mast Cells, Macrophages, Dendritic Cells and Natural Killer Cells comprise the cellular barriers. These cellular barriers engulf and destroy the pathogens by a process called Phagocytosis. The cellular barriers may also cause activation of the adaptive immune system which is the third immune barrier.

c.Phagocytosis

Phagocytosis is the process in which the pathogen is engulfed by any one of the phagocytes. Phagocytes comprise neutrophils, macrophages and dendritic cells. The entrapment occurs in phagosome which is a vesicle. The phagosome combines with the lysosome enzyme and forms phagolysosome. The digestive enzymes kill the pathogen. A respiratory burst (release of oxygen species) can also kill the pathogen.

Macrophages and neutrophils flow in the bloodstream and are carried throughout the body by blood. They locate and destroy the pathogens in all parts of the body. Macrophages also destroy the debris and old cells and thus act as scavengers. The Dendritic macrophages are found in tissue of nose, lungs, skin, stomach and intestines. Many of them come in contact to external environment and are not carried in bloodstream.

Cells of human innate immune system

The different cells of innate immune system are described below.
1.Granular leucocytes or granulocytes

These cells have granular cytoplasm. They are formed in the red bone marrow after birth. They are of 3 types.
Neutrophil

They have a multi- lobed nucleus. Their strength is 60 to 70% and count varies from 3000 to 6000 per cubic mm of blood. They are around 10 to 12 µm in diameter. The number of nucleus lobes can be more than 7 in a neutrophil. They are also called polymorphs as they have multi-lobed nucleus. Generally 3 to 4 lobed nucleus cells are found. With maturity the number of lobes increases. The cytoplasms of these cells have neutrophilic granules. These cells are amoeboid and phagocytic in nature. The enzymes found in these cells are lipase, protease, nucleotidase, phosphates etc.  Also lutathione, glycogen, ascorbic acid etc are found. The enzyme and other content of the neutrophils help them in their phagocytic activity.

Eosinophil

They have 2 or 3 lobed nucleus. Their strength is 1 to 4% and count varies from 150 to 400 per cubic mm of blood. They have a diameter ranging from 10 to 12 µm. The cytoplasm has course granules and the nucleus has 2 lobes. The eosinophils do not show any phagocytic activity. They are amoeboid though. They contain histamine.

Basophil

 the nucleus is lobed and the diameter of the cells varies from 8 to 10µm. The cytoplasm contains granules like all other granulocytes. The cell’s granules contain 5 hydroxytryptamine and histamine.

Macrophages

They develop from monocytes. Monocytes vary from 5-10% in strength. Their count varies from 350 to 800 per cu. mm. They have larger diameter which varies from 16 to 18 µm. The young nucleus is round or oval. The older cells have convoluted nucleus that can be kidney or horse shaped. The cells have non granular cytoplasm and an eccentric nucleus. These monocytes turn into macrophages when they enter the damaged tissue through the endothelium.

Fixed leukocytes

Some of the WBC’s do not keep roaming in the blood but take a place in the tissues. These are called fixed leukocytes. The mast cells and dendritic cells fall under this category.

Mast cells

Mast cells are oval or round and are large cells. The cytoplasm of mast cells consists of course granules. If we study the mast cells under an electron microscope, we will find freely roaming RNA and some amount of granular cytoplasmic reticulum. There size is similar to the basophils.

Dendritic cell

The Dendritic cells mediate between the innate and adaptive immune system. They process the pathogen material and carry them to the helper T cells. They are formed in the red bone marrow.

Natural killer cells lymphocytes

Natural killer cells are those cells that do not destroy foreign pathogens. They destroy those cells of the human body that are infected with the pathogens. They therefore destroy the virus infected cells and the tumor cells. These natural killer cells are cytotoxic lymphocytes. Lymphocytes can be small or large. The lymphocyte strength is 1500 to 2700 per cubic mm of blood and the count varies from 1500 to 2700 per cubic mm.

The Adaptive Immune System

In response to invasion by a particular antigen/pathogen, a particular and specific antibody is created in the human body. This particular antibody destroys the specific antigen. The particular characteristic of adaptive immune system is that it remembers that specific antibody and whenever that antigen invades again, it has that particular antibody ready as an immunological response. The adaptive immune system has memory cells for the purpose. The adaptive immune system also has a stronger response for the pathogens than the innate immune system.

The adaptive immune system consists of specialized leukocytes called lymphocytes. The 2 special types of lymphocytes are B cells and T cells. These cells are produced in the haemopoietic stem cells of the red bone marrow. Lymphocytes can be small or large. The lymphocyte strength is 1500 to 2700 per cubic mm of blood and the count varies from 1500 to 2700 per cubic mm.

Development of lymphocytes

Thymus is the main source of production of lymphocytes though they are produced in the spleen and red bone marrow also. The reticulum cells of the germinal center (found in the central part of lymph node) multiply and form the lymphoblasts. The lymphoblast has a diameter of 15 to 20µm. They have a non granular cytoplasm and a round or oval nucleus. The lymphoblasts proliferate to form the large lymphocyte. These cells do not mature further and are found in circulation. Those which mature form the small lymphocytes.

T cells and B cells

The 2 specialized lymphocytes of the Adaptive Immune System are T cells and B cells.

T cells

 The T cells recognize the pathogen material once it has been processed and presented by dendritic cells. The T cells have receptors for recognizing the pathogen material. The antigen/pathogen material is combined with a receptor and the combination results in the formation of major histocompatibility complex or MHC molecule. The T cells are of 3 types viz. the Killer T cells, the Helper T cells and the Suppressor T cells.

Killer T cells

These cells recognize and destroy the class 1 MHC.  All cells of body can from class 1 MHC molecules. MHC is nucleated pathogens combined with cell receptors.  In the class 1 MHC are categorized some bacteria like reickettsia, mycoplama, bacterial l forms and viruses. The killer T cells are antigen specific like B cells. The T cell receptor binds to the MHC class 1 molecule. There is also another co-receptor on the killer T cells, called CD8 which helps in identification of the specific antigen MHC1 complex. After contacting with the MHC1-antigen complex, the Killer T cells secrete cytoxins such as perforin and granulysin.  These cytoxins form pores in the pathogens cell wall and pass toxins through the pore. This causes apoptosis or programmed cell death.

Helper T cells

They recognize MHC class 2 molecules and consist of cells of the immune system. Pathogen cells presented by B cells, dendritic cells, professional antigen presenting cells (APC’s) and macrophages come under this classification. The helper T cells regulate the immune response in both innate and adaptive immune system. The helper T cells do not have cytoxic activity and hence do not kill pathogens directly. They direct other immune cells of the body for killing the pathogens. The helper T cell receptors recognize the antigen MHC class 2 molecules. Another receptor on helper T cells that helps in recognition of MHC 2 molecules is CD4. The helper T cell then release cytokins that signal the other immune cells like killer T cells and macrophages to act on the pathogen and destroy them.

Suppressor T cells – They modulate immune response.

B cells

The B cells are a class of lymphocytes that have antibody on their cell surface. These cells are antigen specific and do not require any processing of the antigen material by any cells for their recognition. They recognize the whole pathogen on their own and destroy them subsequently.

The antibody of the B cells attaches to the antigen. The antigen antibody complex is then processed by the B cells by proteolysis. Proteolysis leads to formation of peptides. These antigenic peptides are then displayed on the cell walls of the B cell in the form of MHC class 2 molecules. The helper T cells recognize these MHC class 2 molecules and release lymphokines. The lymphokines signal other B cells to form more antibodies, which subsequently leads to the destruction of other antigens.

Humoral and Cell mediated immunity

A foreign pathogen invasion in the human body can occur in 2 ways. The pathogens/antigens like foreign cells, bacteria, fungus, parasites, other foreign molecules and viruses can freely circulate in the body or the antigen may be broken down into MHC. MHC’s are mostly formed of exogenous antigens, tumor infected cells and virus cells.

For freely roaming antigens, the body creates the humoral response. Humoral response is an antibody mediated response. In humoral response, B cells are activated which directly engulf the antigens and destroy them.

The cell mediated immune response of the bodyworks by the activation of phagocytes, T lymphocytes, and the release of cytokines in response to an antigen which is the MHC molecule and not freely roaming pathogen. Therefore cell mediated does not involve antibodies.

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