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THE IMMUNE SYSTEM EXPLAINED
cells of the immune system,
picture courtesy of
National Cancer Institute
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THE IMMUNE SYSTEM EXPLAINED
- INTRODUCTION
- THE ORGANS OF THE IMMUNE SYSTEM
- THE CELLS OF THE IMMUNE SYSTEM
- THE COMPLEMENT
- SPECIFIC IMMUNE RESPONSE
- PHAGOCYTES AND THEIR RELATIVES
- B CELLS
- C CELLS
- CYTOKINES
- KILLER CELLS
- ANTIGENS
- IMMUNOGLOBULINS
- ALLERGIES
INTRODUCTION
We are constantly exposed to infectious agents, but in most cases, we are able to resist these infections because of our immune system.
The immune system is a network of cells, tissues and organs that work together to defend the body against “invaders”, which are mainly microbes – infection-causing organisms.
One has to understand the immune system as an elaborate and complex communications network, in which millions of cells pass information back and forth. To keep “foreign invaders” out or to destroy them once they have entered the body, the immune system – which can remember millions of different “enemies” – produces chemicals, which allow the cells to regulate their own growth and behaviour.
When the immune system hits the wrong target or is not functioning properly, it unleashes many diseases, like allergies, arthritis or AIDS.
The success of a healthy immune system is the ability to distinguish between the body’s own cell, SELF, and foreign cells, NONSELF. Anything that triggers an immune response is called an Antigen. An antigen can be a microbe or just a part of a microbe. Tissues or cells from another person (except identical twin) carry nonself markers and act as antigens. That explain, why tissue transplants maybe rejected.
In abnormal situations the immune system can mistake self for nonself and attacks the body’s own cells and tissues. This results in autoimmune disease. In other cases the immune system mistakes a harmless foreign substance as an attacker. The result is an allergy and the “attacker”-antigen is called an allergen.
The immune system is composed of two major subdivisions, the innate or non-specific immune system and the adaptive or specific immune system. The innate immune system is our first line of defence against invading organisms while the adaptive immune system acts as a second line of defence and also affords protection against re-exposure to the same pathogen. Each of the major subdivisions of the immune system has both cellular and humoral components by which they carry out their protective function. In addition, the innate immune system also has anatomical features that function as barriers to infection. Although these two arms of the immune system have distinct functions, there is interplay between these systems.
Although the innate and adaptive immune systems both function to protect against invading organisms, they differ in a number of ways. The adaptive immune system requires some time to react to an invading organism, whereas the innate immune system includes defences that, for the most part, are constitutively present and ready to be mobilized upon infection. Second, the adaptive immune system is antigen specific and reacts only with the organism that induced the response. In contrast, the innate system is not antigen specific and reacts equally well to a variety of organisms. Finally, the adaptive immune system demonstrates immunological memory. It “remembers” that it has encountered an invading organism and reacts more rapidly on subsequent exposure to the same organism. In contrast, the innate immune system does not demonstrate immunological memory.
Phagocytes,
picture courtesy of
National Cancer Institute
THE ORGANS OF THE IMMUNE SYSTEM
The organs of your immune system are positioned throughout your body.
They are called lymphoid organs because they are home to lymphocytes--the white blood cells that are key operatives of the immune system. Within these organs, the lymphocytes grow, develop, and are deployed.
Bone marrow, the soft tissue in the hollow center of bones, is the ultimate source of all blood cells, including the immune cells.
The thymus is an organ that lies behind the breastbone; lymphocytes known as T lymphocytes, or just T cells, mature there.
The spleen is a flattened organ at the upper left of the abdomen. Like the lymph nodes, the spleen contains specialized compartments where immune cells gather and confront antigens.
In addition to these organs, clumps of lymphoid tissue are found in many parts of the body, especially in the linings of the digestive tract and the airways and lungs--gateways to the body. These tissues include the tonsils, adenoids, and appendix.
THE CELLS OF THE IMMUNE SYSTEM
Cells destined to become immune cells, like all blood cells, arise in your body's bone marrow from stem cells. Some develop into myeloid progenitor cells while others become lymphoid progenitor cells.
The myeloid progenitors develop into the cells that respond early and non-specifically to infection. Neutrophils engulf bacteria upon contact and send out warning signals. Monocytes turn into macrophages in body tissues and gobble up foreign invaders. Granule-containing cells such as eosinophils attack parasites, while basophils release granules containing histamine and other allergy-related molecules.
Lymphoid precursors develop into the small white blood cells called lymphocytes. Lymphocytes respond later in infection. They mount a more specifically tailored attack after antigen-presenting cells such as dendritic cells (or macrophages) display their catch in the form of antigen fragments. The B cell turns into a plasma cell that produces and releases into the bloodstream thousands of specific antibodies. The T cells coordinate the entire immune response and eliminate the viruses hiding in infected cells.
THE COMPLEMENT
The COMPLEMENT (C) is known to contribute to host defences. It can opsonize bacteria for enhanced phagocytosis; it can recruit and activate various cells including macrophages, it can participate in regulation of antibody responses and it can aid in the clearance of immune complexes and apoptotic cells. Complement can also have detrimental effects for the host; it contributes to inflammation and tissue damage and it can trigger anaphylaxis.
Complement is actually composed of over 20 different serum proteins that are produced by a variety of cells including, hepatocytes, macrophages and gut epithelial cells. Some complement proteins bind to immunoglobulins or to membrane components of cells. Others are pro-enzymes that - when activated - cleave one or more other complement proteins. Upon cleavage some of the complement proteins yield fragments that activate cells, increase vascular permeability or opsonize bacteria.
THE SPECIFIC IMMUNE RESPONSE
A. Self/non-self discrimination - One characteristic feature of the specific immune system is that it normally distinguishes between self and non-self and only reacts against non-self.
B. Memory - A second feature of the specific immune response is that it demonstrates memory. The immune system "remembers" if it has seen an antigen before and it reacts to secondary exposures to an antigen in a manner different than after a primary exposure. Generally only an exposure to the same antigen will illicit this memory response.
C. Specificity - A third characteristic feature of the specific immune system is that there is a high degree of specificity in its reactions. A response to a particular antigen is specific for that antigen or a few closely related antigens.
PHAGOCYTES AND THEIR RELATIVES
Some immune cells have more than one name. For example, the name "phagocytes" is given to the large immune cells that can engulf and digest foreign invaders, and the name "granulocytes" refers to immune cells that carry granules laden with killer chemicals.
Phagocytes include monocytes, which circulate in the blood; macrophages, which are found in tissues throughout the body; dendritic cells, which are more stationary, monitoring their environment from one spot such as the skin; and neutrophils, cells that circulate in the blood but move into tissues when they are needed.
Macrophages are versatile cells; besides acting as phagocytic scavengers, they secrete a wide variety of signaling cytokines (called monokines) that are vital to the immune response.
Neutrophils are both phagocytes and granulocytes: they contain granules filled with potent chemicals. These chemicals, in addition to destroying microorganisms, play a key role in acute inflammatory reactions. Other types of granulocytes are eosinophils and basophils, which degranulate by spraying their chemicals onto harmful cells or microbes. The mast cell is a twin of the basophil, except it is not a blood cell. Rather, it is responsible for allergy symptoms in the lungs, skin, and linings of the nose and intestinal tract.
A related structure, the blood platelet, is a cell fragment. Platelets, too, contain granules. They promote blood clotting and wound repair, and activate some immune defenses.
B CELLS
B cells work chiefly by secreting soluble substances known as antibodies. They mill around a lymph node, waiting for a macrophage to bring an antigen or for an invader such as a bacteria to arrive. When an antigen-specific antibody on a B cell matches up with an antigen, a remarkable transformation occurs.
The antigen binds to the antibody receptor, the B cell engulfs it, and, after a special helper T cell joins the action, the B cell becomes a large plasma cell factory that produces identical copies of specific antibody molecules at an astonishing pace--up to 10 million copies an hour.
T CELLS
T cells contribute to your immune defences in two major ways. Some help regulate the complex workings of the overall immune response, while others are cytotoxic and directly contact infected cells and destroy them.
Chief among the regulatory T cells are helper T cells. They are needed to activate many immune cells, including B cells and other T cells.
Cytotoxic T cells (sometimes called killer T cells) help rid your body of cells that have been infected by viruses as well as cells that have been transformed by cancer but have not yet adapted to evade the immune detection system. They are also responsible for the rejection of tissue.
CYTOKINES
Cytokines are diverse and potent chemical messengers secreted by the cells of your immune system. They are the chief communication signals of your T cells. Cytokines include interleukins, growth factors, and interferons.
Lymphocytes, including both T cells and B cells, secrete cytokines called lymphokines, while the cytokines of monocytes and macrophages are dubbed monokines. Many of these cytokines are also known as interleukins because they serve as a messenger between white cells, or leukocytes.
Interferons are naturally occurring cytokines that may boost the immune system's ability to recognize cancer as a foreign invader.
Binding to specific receptors on target cells, cytokines recruit many other cells and substances to the field of action. Cytokines encourage cell growth, promote cell activation, direct cellular traffic, and destroy target cells--including cancer cells.
When cytokines attract specific cell types to an area, they are called chemokines. These are released at the site of injury or infection and call other immune cells to the region to help repair damage and defend against infection.
KILLER CELLS
At least two types of lymphocytes are killer cells--cytotoxic T cells and natural killer cells. Both types contain granules filled with potent chemicals. Both types kill on contact. They bind their targets, aim their weapons, and deliver bursts of lethal chemicals.
To attack, cytotoxic T cells need to recognize a specific antigen bound to self-MHC markers, whereas natural killer (NK) cells will recognize and attack cells lacking these. This gives NK cells the potential to attack many types of foreign cells.
ANTIGENS
A. Immunogen - A substance that induces a specific immune response.
B. Antigen (Ag) - A substance that reacts with the products of a specific immune response.
C. Hapten - A substance that is non-immunogenic but which can react with the products of a specific immune response. Haptens are small molecules which could never induce an immune response when administered by themselves but which can when coupled to a carrier molecule. Free haptens, however, can react with 2 products of the immune response after such products have been elicited. Haptens have the property of antigenicity but not immunogenicity.
D. Epitope or Antigenic Determinant - That portion of an antigen that combines with the products of a specific immune response.
E. Antibody (Ab) - A specific protein which is produced in response to an immunogen and which reacts with an antigen.
FACTORS INFLUENCING IMMUNOGENICITY
A. Contribution of the Immunogen
1. Foreignness - The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic.
2. Size - There is not absolute size above which a substance will be immunogenic. However, in general, the larger the molecule the more immunogenic it is likely to be.
3. Chemical Composition - In general, the more complex the substance is chemically the more immunogenic it will be. The antigenic determinants are created by the primary sequence of residues in the polymer and/or by the secondary, tertiary or quaternary structure of the molecule.
4. Physical form - In general particulate antigens are more immunogenic than soluble ones and denatured antigens more immunogenic than the native form.
5. Degradability - Antigens that are easily phagocytosed are generally more immunogenic. This is because for most antigens (T-dependant antigens, see below) the development of an immune response requires that the antigen be phagocytosed, processed and presented to helper T cells by an antigen presenting cell (APC).
B. Contribution of the Biological System
1. Genetic Factors - Some substances are immunogenic in one species but not in another. Similarly, some substances are immunogenic in one individual but not in others (i.e. responders and non-responders). The species or individuals may lack or have altered genes that code for the receptors for antigen on B cells and T cells or they may not have the appropriate genes needed for the APC to present antigen to the helper T cells.
2. Age - Age can also influence immunogenicity. Usually the very young and the very old have a diminished ability to mount an immune response in response to an immunogen.
C. Method of Administration
1. Dose - The dose of administration of an immunogen can influence its immunogenicity. There is a dose of antigen above or below which the immune response will not be optimal.
2. Route - Generally the subcutaneous route is better than the intravenous or intra gastric routes. The route of antigen administration can also alter the nature of the response
3. Adjuvants - Substances that can enhance the immune response to an immunogen are called adjuvants. The use of adjuvants, however, is often hampered by undesirable side effects such as fever and inflammation.
CHEMICAL NATURE OF IMMUNOGENS
A. Proteins -The vast majority of immunogens are proteins. These may be pure proteins or they may be glycoproteins or lipoproteins. In general, proteins are usually very good immunogens.
B. Polysaccharides - Pure polysaccharides and lipopolysaccharides are good immunogens.
C. Nucleic Acids - Nucleic acids are usually poorly immunogenic. However they may become immunogenic when single stranded or when complexed with proteins.
D. Lipids - In general lipids are non-immunogenic, although they may be haptens. Some glycolipids and phospholipids can stimulate T cells and produce a cell-mediated immune response.
 Immunoglobulins,
picture courtesy of
National Cancer Institute
IMMUNOGLOBULINS
Antibodies belong to a family of large protein molecules known as immunoglobulins.
Scientists have identified nine chemically distinct classes of human immunoglobulins, four kinds of IgG and two kinds of IgA, plus IgM, IgE, and IgD.
Immunoglobulins G, D, and E are similar in appearance. IgG, the major immunoglobulin in the blood, is also able to enter tissue spaces; it works efficiently to coat microorganisms, speeding their destruction by other cells in the immune system. IgD is almost exclusively found inserted into the membrane of B cells, where it somehow regulates the cell's activation. IgE is normally present in only trace amounts, but it is responsible for the symptoms of allergy.
IgA--a doublet--guards the entrance to the body. It concentrates in body fluids such as tears, saliva, and secretions of the respiratory and gastrointestinal tracts.
IgM usually combines in star-shaped clusters. It tends to remain in the bloodstream, where it is very effective in killing bacteria.
1. IgG - Gamma (γ) heavy chains
2. IgM - Mu (μ) heavy chains
3. IgA - Alpha (α) heavy chains
4. IgD - Delta (δ) heavy chains
5. IgE - Epsilon (ε) heavy chains
B. Immunoglobulin Subclasses - The classes of immunoglobulins can de divided into subclasses based on small differences in the amino acid sequences in the constant region of the heavy chains. All immunoglobulins within a subclass will 6
have very similar heavy chain constant region amino acid sequences. Again these differences are most commonly detected by serological means.
1. IgG Subclasses
a) IgG1 - Gamma 1 (γ1) heavy chains
b) IgG2 - Gamma 2 (γ2) heavy chains
c) IgG3 - Gamma 3 (γ3) heavy chains
d) IgG4 - Gamma 4 (γ4) heavy chains
2. IgA Subclasses
a) IgA1 - Alpha 1 (α1) heavy chains
b) IgA2 - Alpha 2 (α2) heavy chains
Immunity and Allergies, picture courtesy of
National Cancer Institute
ALLERGIES
When your immune system malfunctions, it can unleash a torrent of disorders and diseases.
One of the most familiar is allergy. Allergies such as hay fever and hives are related to the antibody known as IgE. The first time an allergy-prone person is exposed to an allergen--for instance, grass pollen--the individual's B cells make large amounts of grass pollen IgE antibody. These IgE molecules attach to granule-containing cells known as mast cells, which are plentiful in the lungs, skin, tongue, and linings of the nose and gastrointestinal tract. The next time that person encounters grass pollen, the IgE-primed mast cell releases powerful chemicals that cause the wheezing, sneezing, and other symptoms of allergies. |
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