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Immune system

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The Immune System (also known as the Immunlological System) is made up of all the mechanisms through which a multicellular organism defends itself from internal invaders such as bacteria, viruses or parasites.

The immune system can be divided into two main branches:

This division is useful for categorizing the different components of the immune system, but it is important to recognize that in the immune response there is continuous interplay between members of both branches.

Contents

Innate Non-specific Mechanisms

The innate system is comprised of all the mechanisms that defend an organism in non-specific form, against an invader, responding in the same fashion, regardless of what it is. It constitutes older defense strategies, some of these being found in primitive multicellular forms, in plant and fungi.

Physical Barriers

Phagocytes

Phagocytes are cells, such as neutrophils and macrophages, that have the capacity to directionally extend cellular portions (pseudopod), engulfing and overtaking a foreign particle or microorganism. This microorganism is contained inside a vacuole which is then merges with lysosomes, vacuoles rich in enzymes and acids, which digest the particle or organism. Phagocytes react to cytokines produced by lymphocytes, but also patrol the body autonomously , without stimulus, albeit in a less eficient manner. This form of defense is important against bacterial infections, as viruses typically have their own means of entering host cells and the majority of parasites too large to be consumed. Phagocytosis is also an important part of the cleaning process after cellular destruction following infection or any other process that leads to cellular death. Should many phagocytes die after phagocytosis, both phagocytes and bacteria can be trapped in a pasty liquid rich in stuctural proteins, known as pus.

Some bacteria, such as Mycobacterium tuberculosis, which causes tuberculosis, have defense mechanisms against digestion after phagocytosis, and survive within the phagocyte undetectable by lymphocytes.

Phagocytes and related cells:

Neutrophils, eosinophils and basophils are also known as polymorphonuclear leukocytes (due to their lobed nuclei) or granulocytes.

Complement System

The complement system is a biochemical cascade of the immune system that helps clear pathogens from an organism. It is derived from many small plasma proteins working together to form the primary end result of cytolysis by disrupting the target cell's plasma membrane. The proteins are sythesized in the liver, mainly by hepatocytes.

Other non-specific proteins include Protease C3-convertase, which is also sythesized in the liver and connects to other molecules that are commonly found in bacteria but non-existant in humans, stimulating the complement system and phagocytosis.

Inflammatory Response

The inflammatory response is fundamentally a non-specific reaction, despite in practice controlled by specific mechanisms (lymphocytes). It is characterized by the following quintet, defined in Greco-Roman antiquity: redness (rubor), heat (calor), swelling (tumor), pain (dolor) and dysfunction of the organs involved (functio laesa).

Inflammation is stimulated by factors released by injured cells. These factors (histamine, bradicine) sensitize pain receptors and cause dilation of the blood vessels at the scene (rubor and tumor), and also attract phagocytes, especially neutrophils. Phagocytosis causes the neutrophils to release other factors that call lymphocytes and other phagocytes.

Specific or Adaptive Immune System

The basis of specific immunity lies in the capacity of immune cells to distinguish between proteins produced by the body's own cells ("self" antigen - those of the original organism), and proteins produced by invaders or cells under control of a virus ("non-self" antigen - or, what is not recognized as the original organism). This distinction is made via T-Cell Receptors (TCR) or B-Cell Receptors (BCR). For these receptors to be efficient they must be produced in thousands of configurations, this way they are able to distinguish between many different invader proteins. This immense diversity of receptors would not fit in the genome of a cell, and millions of genes, one for each type of possible receptor, would be impractical. What happens is that there are a few families of genes, each one having a slightly different modification. Through a special process, unique to human cells, the genes in these lymphocytes recombine, one from each family, arbitrarily into a single gene.

This way, for example, each antibody or BCR of B lymphocytes has six portions, and is created from two genes unique to this lymphocyte, created by the recomniation (union) of a random gene from each family. If there are 6 families, with 50, 30, 9, 40, and 5 members, the total possible number of antibodies is 50x30x6x9x40x5 = 16 million. On top of this there are other complex processes that increase the diversity of BCR or TCR even more, by mutation of the genes in question. The variability of antibodies is practically limitless, and the immune system creates antibodies for any molecule, even artificial molecules that do not exist in nature.

Many TCR and BCR created this way will react with their own peptides. One of the functions of the thymus and bone marrow is to hold young lymphocytes until it is possible to determine which ones react to molecules of the organism itself. This is done by specialized cells in these organs that present the young lymphocytes with molecules produced by them (and effectively the body). All the lymphocytes that react to them are destroyed, and only those that show themselves to be indifferent to the body are released into the bloodstream.

The lymphocytes that do not react to the body number in the millions, each with millions of possible configurations of receptors, each with a receptor for different parts of each microbial protein possible. The vast majority of lymphocytes never find a protein that its receptor is specified for, those few that do find one are stimulated to reproduce. Effective cells are generated with the specific receptor and memory cells. These memory cells are quiescent, they have long lives and are capable of identifying this antigen some time later, multiplying themselves quickly and rapidly responding to future infections.

The specific immune system is controlled directed largely by lymphocytes. There are various types of lymphocytes:

B Lymphocytes and Antibody Production

see B cells

CD8+ T Lymphocytes and Cytotoxicity

see Cytotoxic T cells

Phagocytes

Though phagocytes are an innate mechanism, since they respond to any foreign body, they are also the first line decision makers for lymphocytes.

Phagocytes, especially macrophages, respond to cytokines generated by lymphocytes. Monocytes are the precursors to macrophages and they transform into macrophages when stimulated by CD4+ T cytokines. They are also attracted by other cytokines and factors emitted by cells in areas of active infection.

If properly stimulated by cytokines emitted in a localized and controlled manner by CD4+ T lymphocytes, the macrophages release sufficient quantities of enzymes and free radicals to completely destroy a localized area, killing both invaders and human cells.

On top of this, under control of lymphocytes, macrophages are responsible for some specific immunological reactions such as granuloma and abscesses. Granuloma occurs during an invasion of microbacteria and fungi, the most well-known example being tuberculosis. It is a reaction commanded by cytokines fro CD4+ T cells, when there is intracellular infection of the phagocytes themselves. In order to stop the invader from entering the bloodstream and spreading throughout the body in these mobile cells, the CD4+ lymphocytes secrete cytokines that call more macrophages, and make them more resistant to infection. Cytokines also provoke an adaptation in macrophages of epithelial morphology around the area of invasion, with numerous layers of immobilized cells connected by water-resistant links as to close off the invader. The tuberculosis microbacteria cannot propagate and remains stagnant. Today hundereds of millions of healthy people have microbacteria controlled in this form within their lungs (visible in x-rays). Only in those that have severely debilitated immunities do these pathogens escape and cause tuberculosis. The abscess is similar, surrounded by a cyst of pus. It is important to sequester pathogenic bacteria whose toxicity kills phagocytes (forming the pus) and does not permit efficient cleaning.

CD4+ Lymphocytes and Response Supervision

CD4+ Lymphocytes, or helper T cells, are immune response controllers. They "decide" which actions to take during an invasion, promoting or inhibiting all other immune cells via cytokines. HIV, being a virus that directly attacks the CD4+ T cells, causes a collapse of the entire system by attacking the root.

CD4+ lymphocytes are able to decide of there is an invasion due to the fact that each cell contains a randomly created TCR. All phagocytes and some other cells, such as dendrites, after digesting the proteins of an invader retain some of the peptides in a protein membrane, MHC. The TCR of the CD4+ T lymphocytes attach to the MHC II via the peptide and if the connection is effective, liberates cytokines. Almost no CD4+ T lymphocytes contain TCRs that react against self peptides, these were destroyed during the cell development in the thymus. If the levels of these cytokines are sufficiently high, and if other, less known factors exist in the blood, the CD4+ T lymphocytes "decide" that there is an invasion and what sort, beginning the specific immune response. The CD4+ T lymphocytes then produce other cytokines activating other cells for the appropriate response. As with other lymphocytes, stimulated CD4+ T lymphocytes multiply and some serve as memory cells to speed up future responses.

There are essentially two types of CD4+ T helpers, corresponding to two types of responses. The TH1 response is characterized by the production of cytokines such as IL-2, IFN-gamma and TNF-beta. Macrophages are activated, and through cytotoxic mechanisms (T lymphocytes), the infected areas are extensively destroyed. It is efficient in elimination of intracellular pathogens (intracellular viruses and bacteria). In the TH2 response there is a release of IL-4 and IL-5. It is characterized by the production of antibodies from B lymphocytes. It is effective against organisms in the blood, such as extra-cellular bacteria and parasites.

Which response (TH1 or TH2) is produced is important to the progression of the infection. For example, in leprosy, an infection caused by the intracellular Mycobacterium leprae, the TH1 response is extremely effective and the infection is kept to minimum (lepra tuberculoide) ; but if a response TH2 is activated, ineffective against intracellular organisms, common leprosy occurs causing extensive damage and loosening of the skin (lepra lepromatosa).

There is a third type of T lymphocyte, the regulatory T cells (Treg), which limit and suppress the immune reaction against self-antigens, an important mechanism considering the extreme destruction the immune system can cause.

Disorders of the human immune system

The most important function of the human immune system occurs at the cellular level of the blood and tissues. The lymphatic and blood circulation systems are paths for specialized white blood cells to travel around the body. White blood cells include B cells, T cells, natural killer cells, macrophages, and dendritic cells. Each has a different responsibility, but all function together with the primary objective of recognizing, attacking and destroying bacteria, viruses, cancer cells, and all other pathogens. Without this coordinated effort, a person would not be able to survive more than a few days before succumbing to an overwhelming infection. When a pathogen has entered the body, it sets off a chain reaction that starts with the activation of macrophages and natural killer cells that reach the site of infection and destroy as much of the pathogen as possible. While this is happening, it is the job of the dendritic cells to take “snap-shots” of the battle-ground to take to the lymph nodes in order to activate T cells which then activate B cells to produce antibodies against the pathogen.

Many disorders of the human immune system fall into two broad categories that are characterized by:

Other factors that affect immune response

Many factors can also contribute to the general weakening of the immune system:

Pharmacology

Despite high hopes, there are no medications that directly increase the activity of the immune system. Various forms of medication that activate the immune system may cause autoimmune disorders. Adjuvants (often Aluminium Hydroxide) can be used in conjuction with a vaccine to provoke a quicker immunological reaction.

Suppression of the immune system is often used to control autoimmune disorders or inflammation when this causes excessive tissue damage, and to prevent transplant rejection after an organ transplant. Commonly used immunosuppressants include glucocorticoids, azathioprine, methotrexate, ciclosporin, cyclophosphamide and mercaptopurine. In organ transplants, ciclosporin, tacrolimus, mycophenolic acid and various others are used to prevent organ rejection through selective T cell inhibition.

See also

Further reading

External links

Lymphatic system - [http://encycl.opentopia.com/ edit]
Lymph nodes > Lymph | Lymphocytes | Lymph vessels | Thoracic duct | Immune system | Bone marrow | Spleen | Thymus | Tonsils

Human organ systems
[ v]·[ d]·[ e]
Cardiovascular system | Digestive system | Endocrine system | Immune system | Integumentary system | Lymphatic system | Muscular system | Nervous system | Reproductive system | Respiratory system | Skeletal system | Urinary system

Immune system - [http://encycl.opentopia.com/ edit]
Humoral immune system | Cellular immune system | Immunological tolerance | Lymphatic system | White blood cells | Antibodies | Antigen (MHC) | Complement system | Inflammation 

 

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