ALLERGIES - III

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THE IMMUNE SYSTEM

Their are 9 forms of immunoglobuline anitbodies associated with all vertabrate animals that are found in the human body. In mammals with a placenta there are five antibody isotypes known as IgA, IgD, IgE, IgG and IgM There are other antibodies associated with vertabrate animals but they are not associated with humans. The nine antibodies are all part of two main immune defense systems [1]the"Innate Immune System" and [2] the "Adaptive Immune System. TTHE IMMUNE SYSTEM

Although the two systems share some cellular components and elements of another immune element called the humoral system. Both systems have what are called natural killer cells the killer cells of both systems are not the same. Those of the innate system are called NK-cells those of the adaptive system comprise two types called simply NK and NKT and while names and the functions of these killer cells in both systems are similar, the mechanisms of the adaptive system are much more complex.

[1]the"Innate Immune System" (aka the "the non-specific immune system") is the first line of defense and

is composed of cells and mechanisms that defend the body from a wide range of organisms. This system is

immediate fast acting and non specific generally recognizing and responding to pathogens in a generic way that

does not confer long-lasting or overall protective immunity to the host. The non specific immune system is the

dominant immune system found in plants, fungi insects and primitive multicellular organisms and is considerd an

older defense simpler system utilizing innate leukocytes and associated mechanisms the primary mechanism

is innflammation. .

[2]The adaptive immune system, aka " acquired immune system ( or sometimes the "specific" immune

system") is the second line of defense and is composed of highly specialized, systemic cells and processes

that both eliminates or prevents the growth of pathogens . The activation of adaptive system is achieved through

a process known as antigen presentation. This system is supplemented by a macromolecule system known as

Humoral Immunity which in addition to antibodies uses other body chemicals to combine and create physical

and chemical barrier to infectious agents.

THE NINE FORMS OF IMMUNOBLOBULINE ANTIBODIES

The nine forms of immunoglobuline found in humans are listed below in alphabetical order. In addition to the name there is a number enclosed in brackets [1&2...] to assist in identifying the 9 forms. This number has no relationship to the NAME of the Antibody

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[1&2]

NAME: IgA IMMUNOGLOBULINE A

FORMS IgA has two forms or subclasses IgA1 and IgA2 also referred to as isotypes .

IMMUNE RESPONSE TYPE: TYPE I ALLERGY AND ATOPY* (HEREDITARY)

NON-AUTOIMMUNE

SOURCE: An antibody produced in the mucosal tissue linings and which can accumulate to levels as high as 15% of the total immunoglobuline found in the body. It is found in all mucous secretions (gastrointestinal urogenital, respiratory tracts prostate, saliva, tears, colostrum (breast milk)) as well as in the blood in small amounts. IgA1 is found in lymphoid tissues and is predominant in blood and other serums, while IgA2 is predominant in secretions.

FUNCTION: IgA provides protection against microbes in secretions, prevents colonization of pathogens, and inhibits the inflammation effects of other Ig's can survive harsh environments .

CHARACTERISTICS: A decreased IgA level is considered a significant immunodeficiency and can be caused by protease chemicals found in other diseases, and results in increased risk of infection as well as other immune diseases.

RELATED DISEASES: IgA deficiency is related to celiac disease, liver failure, streptoccus phneumoniae, gonorrhaeae and heamophilial influenzas. In addition to the deficiency being found in 2.3% of all persons with Celiac disease, having this deficiency r epresents a 10 fold increase of celiac. The nephropathy (non inflammatory damage)in tissues and linings is caused by IgA liver deposits, and the IgA changes and alterations in celiac disease are caused by the presence of antiendoymysial antibodies.

NOTES: forms a dimeric complex

*Atopy :a predisposition toward an excessive IgE reaction and developing certain allergic hypersensitivity reactions. Atopy appears to h have a hereditary component,

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[3.] NAME: IgD IMMUNOGLOBULINE D is an antibody isotype that makes up about 1% of proteins in the plasma membranes of immature B-lymphocytes where. IgD

IMMUNE RESPONSE TYPE:

SOURCE: is also produced in a secreted form that is found in very small amounts in blood serum. Secreted IgD is produced as a monomeric antibody with two heavy delta (d) class chains and two Ig light chains.

FUNCTION: IgD's function is to signal when the young B cells in the spleen are ready to be activated. Once they are activated, they are ready to take part in the defense of the body in the immune system.

CHARACTERISTICS: it is usually coexpressed with another cell surface antibody called IgM

NOTES:

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[4.]

NAME: IgE IMMUNOGLOBULINE E [4.]

IMMUNE RESPONSE TYPE: TYPE I typically known as immediate or allergic hypersensitivity reactions

involved in what are commonly known as allergies and associated with IgG1,IgG2 and IgG4 responses, .

SOURCE:

FUNCTION:

CHARACTERISTICS: causes a distinctive and excessive activation of mast cells and basophils called Atopy both types of specific white blood cells.

RELATED DISEASES: urticaria, asthma, wheat dependent exercise-induced anaphylaxis

NOTES: Forms a Monomer complex These reactions are acquired and predictable,

These reactions are acquired , predictable, and rapid. Allergy is one of four forms of hypersensitivity and is formally called type I (or immediate) hypersensitivity. Allergic reactions are distinctive because of excessive activation of certain white blood cells called mast cells and basophils by a type of antibody called Immunoglobulin E (IgE). This reaction results in an inflammatory response which can range from uncomfortable to dangerous.

Anti-gliadin IgE

The IgE antibodies are more typically found in allergy -related conditions such as urticaria , asthma , and wheat-dependent exercise-induced anaphylaxis . The target of the most allergenic antibodies are -5 gliadin , [8] that is encoded by the Gli-1B gene found on the B haplome ( Aegilops speltoides derived) of wheat. [9]

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[4.] IgE I mmunoglobuline E also known as Anti-gliadin IgE

is typically involved in what are commonly called allergies and associated with IgG1,IgG2 and IgG4 responses, .

These reactions are acquired, predictable, and rapid.

Gluten allergy may be a cause of some idiopathic gluten sensitivity and gluten allergy can be a secondary consequence of gluten-sensitivity.

Anti-gliadin IgE

enteropathy .

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[5,6,7,8.]

NAME: IgG IMMUNOGLOBULINE G refers to has 4 forms also known as subclasses named in order of their abundance in humans serum (IgG1-IgkG4) with IgG1being the most abundant).

THESE ARE TYPE II HYPERSNSITIVITY REACTIONS

IgG's is a monomeric immunoglobulin, built of two heavy chains and two light chains. Each IgG has two antigen binding sites. IgG is the most abundant immunoglobulin and is approximately equally distributed in blood and in tissue liquids, constituting 75% of serum immunoglobulins in humans.IgG molecules are synthesised and secreted by plasma B cells. IgG antibodies are predominately involved in the secondary antibody response, (the main antibody involved in primary response is (IgM ) which occurs approximately one month following antigen recognition, thus the presence of specific IgG generally corresponds to maturation of the antibody response.Pro-inflammatory cytokines have a crucial role in activation of the IgG antibody response

Anti-gliadin IgG

IgG antibodies is similar to AGA IgA , but is found at higher levels in patients with the IgA-less phenotype . It is also associated with coeliac disease and idiopathic gluten sensitivity . [5] [6] [7] and IgA-less is associated with Coeliac disease. Anti-gliadin antibodies are frequently found with anti-transglutaminase antibodies

IgG also binds and neutralizes toxins . IgG also plays an important role in antibody-dependent cell-mediated cytotoxicity (ADCC) and intracellular antibody-mediated proteolysis , in which it binds to TRIM21 (the receptor with greatest affinity to IgG in humans) in order to direct marked virions to the proteasome in the cytosol. [ 2 ] IgG is also associated with Type II and Type III Hypersensitivity .

IgG is secreted as a monomer that is small in size allowing it to easily perfuse tissues. It is the only isotype that can pass through the human placenta , thereby providing protection to the fetus in utero . Along with IgA secreted in the breast milk , residual IgG absorbed through the placenta provides the neonate with humoral immunity before its own immune system develops. Colostrum contains a high percentage of IgG, especially bovine colostrum . In individuals with prior immunity to a pathogen, IgG appears about 24–48 hours after antigenic stimulation.

There are four IgG subclasses (IgG1, 2, 3, and 4) in humans, named in order of their abundance in serum (IgG1 being the most abundant).

Name Percent Crosses placenta easily Complement activator Binds to Fc receptor on phagocytic cell

IgG1 s66% yes (1.47)† second-highest high affinit

IgG2 y23% no (0.8)† third-highest extremely low affinit

IgG3 y7% yes (1.17)† highest high affinit

IgG4 y4% yes (1.15)† no intermediate affinit

†: Quota cord/maternity concentrations blood. Based on data from a Japanese study on 228 mothers. [ 5 ]

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NAME: IgM IMMUNOGLOBULINE M [9.] is a basic antibody that is present on B cells . It is the primary antibody against and antigens on red blood cells . IgM is by far the physically largest antibody in the human circulatory system forms a pentamer complex

THESE ARE TYPE II (autoimmune)OR TYPE III (autoimmune complement) HYPERSENSITIVITIES depending on whether or not an epitope macromolecule complex is formed

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Further information: Anti-gliadin antibodies

In the late 70s it was reported that people with migraines had reactions to food allergens, like ARA, the most common reaction was to wheat (78%), orange, eggs, tea, coffee, chocolate, milk, beef, corn, cane sugar, and yeast. When 10 foods causing the most reactions were removed migranes fell precipitously, hypertension declined.Some specific instances are attributed to wheat.

The interaction between genotype and phenotype has often been conceptualized by the following relationship:

genotype + environment phenotype

Eight major food groups (milk, eggs, fish, shellfish, tree nuts, peanuts, wheat and soy) account for 90% of all food allergies.

The US FDA now requires all food manufacturers to clearly label common allergens on their product labels

It�s estimated that 12 million Americans have food allergies, with 6.9 allergic to seafood and 3.3 million allergic to peanuts or tree nuts

It is estimated that 2% of adults and 5% of infants & children have food allergies

Adults can develop food allergies at any time. Children sometimes outgrow the allergies they have as infants, but an early peanut allergy may be life long

Cow�s milk, egg, wheat and soy are the most common allergies in children, while tree nuts, fish, shellfish and peanut allergies are most likely to affect adults.

In Canada, there are ten recognized common food allergens-the eight recognized in the U.S. (milk, eggs, fish, shellfish, tree nuts, peanuts, wheat and soy) PLUS sesame and sulfites

Each year 30,000 people go to the emergency room and 150-200 people die from food allergic reactions

1) Fungal (and bacterial) Allergens and Toxins:

2) Heating, Ventilation and Air Conditioning (HVAC) Systems:

3) Dust Mite Contamination:

4) High Outdoor Airborne Particle Counts:

5) Cockroach Allergens:

6) Pet Allergens:

7) Vacuum Cleaners:

8) Vaporizers and Humidifiers:

9) Chemical Vapor (VOC) Exposure:

10) Inadequate or Unclean Ventilation:for more information 10 most common Asthmatic sources

food allergies ut not for the estimated 30,000 people each year in the U.S. who eat the wrong food and go into anaphylactic shock, a

Lactose. It�s the most common intolerance. An estimated three out of every ten Americans adults

Sulfites. These sulfur-containing additives are used as preservatives in dried fruits, wines, and dehydrated potato products like mashed potato flakes.

About one in every 100 people with asthma-some 100,000 Americans-are sensitive to sulfites

Monosodium Glutamate (MSG). This flavor-enhancer has been blamed for �Chinese Restaurant Syndrome,� the headaches and flushing some people report after eating Chinese food, which is often prepared using MSG. But linking MSG to symptoms has been difficult.

ed wine. Some people report getting headaches after drinking red-but not white-wine. The culprit probably isn�t the alcohol or the sulfites, but the phenolic flavonoids that are found in grape skins (red wine has more than white). Those same flavonoids may cut the risk of heart disease (but the evidence is sketchy).

Chocolate. Many of the ingredients used in making chocolate candy-including milk, nuts, soybeans, corn syrup, and chocolate itself-could be responsible for the headaches that some people report after eating chocolate. (No research comparable to the Harvard MSG study has ever tested people�s reactions to chocolate.)

Food Colors. Some people react with itching or hives to a synthetic yellow food coloring called tartrazine, or Yellow No. 5. That�s why the FDA requires manufacturers who use Yellow No. 5 to list it on their labels

10 most common Allergy Triggers

Pollen

Animal Dander

Dust Mites

Insect Stings

Molds

Food

Latex

Medication

Fragrance

Coachroaches

There are eight specific common allergies to food and those are milk, eggs, peanuts, tree nuts, soy, wheat, fish, as well as shellfish (crabs, lobsters). These very specific food items cause very noticeable allergic reactions. Along with these eight food items, other foods such as fruits and vegetables can give a child a certain reaction.

allergic to citric acid. That means I cannot eat, drink, or doing anything with items that have citric in it. If you think about it, that's a lot of different things. If I touch, or drink anything that has citric acid in it, I will get an instant rash and scratch for the remainder of the day. That means, no dish soap with orange scent in it, or shampoo with any kind of fruit, no orange juice in the morning, and not evening a good old vitamin C pill to keep me from getting sick

Derivative allergies

Coelic Disease

www.coeliac.co.uk

www.celiac.org

www.csaceliacs.org

www.allergyuk.org/auk_transcards.html

www.aaaai.org/patients/allergic_conditions/food_allergy.stm

www.allergysa.org

www.anaphylaxis.org.uk/mainpage_info.html

www.allergyfoundation.ca/public_information.html#Food

www.foodallergy.org

www.astmafonds.nl

www.mayoclinic.com/

www.foodallergyinitiative.org

www.allergy.org.au/aer/infobulletins/hp_allergy_milk.htm

COMMON INTOLLERANCE SYMPTOMS :

* bloating * cramps *diarrhea * fatigue *gas * headaches * heartburn *malnutrition * nausea * vomiting * weight loss * wind,

ALLERGY AND IMMUNE TERMS

Allergy: is one of the five forms of system reaction to foreign matterm known as hypersensitivities (Types 1-5). Allergies most commonly and formally called Type I (or immediate) hypersensitivity. The term was first used by Clemens von Pirquet an Austrian paediatrician in 1906 from the Greek words "allos" meaning altered and "ergia

meaning reactivity. Allergy has now come to be known as a term defining altered reactivity to specific substances, which are otherwise harmless to people.

White blood cells are a vital part of the immune system and contain cells of both the non specific and specific immune systems. The cells that are part of the the non specific innate immune system are called innate leucocytes . The cells of the specific or adaptive immune system which are a specialized subclass of leucocytes and contain cells groups called lymphocyes and are more common to the lymph system.

innate leukocytes include:Natural killer cel ls, mast cells, eosinophils, basophils, phagocytic cells macrophages, neutophils and dendritics cells and function within the immune system by identifying and eliminating pathogens that might cause infection.

lymphocytes Three distinct types of cells found in the white blood cell lymphocytes are B-cells T-cells and NK-cells found in the humoral branch of the adaptive immune system.

Atopy: a predisposition toward developing certain allergic hypersensitivity reactions as a result of an excessive IgE reaction and may be related to a hereditary component.

B cells:

are formed in the mammal bone marrow and circulate in both the blood and lymphatic system perfoming the role of surveillance. The B cells do not produce antibodies until they become activated. Each B cell has a unique recepter protien.A typical human B cell will have 50,000 to 100,000 antibodies bound to its surface

T cells: a type of lymphocyte cell in the immune system that acquired their name because they mature in the thymus. Also known as T- lymphocytes)there are several subsets of T cells, each with a specific and distinct function characterized by the receptor on the surface of the cell called a T -cell Receptor (TCR) The T-cells include :

T c Cytotoxic T cells (or CTLs) destroy virally infected cells and tumor cells, and are implicated in transplant rejection

T reg Regulatory T cells (formerly known as suppressor T cells ) are crucial in maintaining immunological tolerance

NKT Natural killer T-cells bridge the adaptive and innate immune systems and unlike conventional T cells recognize

special molecule types and once activated, these cells can perform functions ascribed to both T h and T c cells. NKT cells

are also o able to recognize and eliminate some tumor cells and cells infected with herpes viruses.

Antibodies: ( Ag ) are large proteins called glycoproteins ( because of the sugar attached to the amino acids ) that are found free in the bloodstream. The basic functional component of the antibody is the Y shaped protein Immunoglobuline(lg). If there is one Y shaped Ig component, the antibody is called a "monomer", if there are two Y shaped Ig proteins (such as IgA), it is called "dimeric" if there are 5 Y shaped components as in mammilian IgM it is called a "pentamer". It has been estimated that humans generate about 10 billion different antibodies, each capable of binding a distinct epitope of an antigen. Although each individual is capable of generating a huge range of antibodies the actual number of genes available to generate the required proteins is limited by the size of the human genome so several genetic mechanisms have evolved to genereate a large pool of antibodies from the limited number of genes. .

Immunoglobulines ( Ig ) are sometimes referred to as an antibodies but Ig is the Y shaped functional component of the Antibody. -shaped protein produced by B-cells in the humoral immune system and are used by to identify and neutralize the pathogens

plasma cells that secrete soluble antibody or memory cells that survive in the body for years afterward in order to allow the immune system to remember an antigen and respond faster upon future exposures.

Pathogens foreign objects such as bacteria viruses fungi.

Inflammation: is not a synonym for infection even if infection is the primary cause. Inflammations is one of the innate immune systems first response mechanisms to harmful stimuli such as infection or irritation to a pathogen. It is considered part of the general initial acute response to harmful stimuli by increasing the movement of plasma and leukocytes from the blood to injured tissues and promotes the healing of damaged tissue and the clearance of the pathenogens. Chronic and long term inflammation can result in a number of diseases hay fever, periodontitis aathersclerosis, rheumatioid arthritis even cancer and must be closely regulated

Humoral Immune System the main function of this system is to produce antibodies each antibody recognizes a unique part of the foreign target, called an antigen .Since antibodies exist freely in the bloodstream, they are said to be part of the humoral immune system .

called

passive immunization .

Natural Antibodies: antibodies that are produced and present in the serum of humans and higher primates, without and previous to any infectious exposure to viral, bacterial, foreign antigens or exposure to other infection by vaccination, or passive immunization. These antibodies can activate the classical complement pathway leading to lysis of enveloped virus particles long before the adaptive immune response is activated. Many natural antibodies are directed against the disaccharide galactose α(1,3)-galactose (α-Gal), which is found as a terminal sugar on glycosylated cell surface proteins, and generated in response to production of this sugar by bacteria contained in the human gut. [ 27 ] Rejection of xenotransplantated organs is thought to be, in part, the result of natural antibodies circulating in the serum of the recipient binding to α-Gal antigens expressed on the donor tissue. [ 28 ]

antigen: when speaking of immunology the term which originally came from ANTIbody GENerator is the specific substance that binds specifically to the appropriate antibody B cells.

Domain variability

The region (locus) of a chromosome that encodes an antibody is large and contains several distinct genes for each domain of the antibody—the locus containing heavy chain genes ( IGH@ ) is found on chromosome 14 , and the loci containing lambda and kappa light chain genes ( IGL@ and IGK@ ) are found on chromosomes 22 and 2 in humans. One of these domains is called the variable domain, which is present in each heavy and light chain of every antibody, but can differ in different antibodies generated from distinct B cells. Differences, between the variable domains, are located on three loops known as hypervariable regions (HV-1, HV-2 and HV-3) or complementarity determining regions (CDR1, CDR2 and CDR3). CDRs are supported within the variable domains by conserved framework regions. The heavy chain locus contains about 65 different variable domain genes that all differ in their CDRs. Combining these genes with an array of genes for other domains of the antibody generates a large cavalry of antibodies with a high degree of variability. This combination is called V(D)J recombination discussed below. [ 32 ]

Elevations in different classes of immunoglobulins are sometimes useful in determining the cause of liver damage in patients for whom the diagnosis is unclear. [ 6 ] For example, elevated IgA indicates alcoholic cirrhosis , elevated IgM indicates viral hepatitis and primary biliary cirrhosis , while IgG is elevated in viral hepatitis, autoimmune hepatitis and cirrhosis. Autoimmune disorders can often be traced to antibodies that bind the body's own epitopes ; many can be detected through blood tests .

Targeted monoclonal antibody therapy is employed to treat diseases such as rheumatoid arthritis , [ 49 ] multiple sclerosis , [ 50 ] psoriasis , [ 51 ] and many forms of cancer including non-Hodgkin's lymphoma , [ 52 ] colorectal cancer , head and neck cancer and breast cancer . [ 53 ] Some immune deficiencies, such as X-linked agammaglobulinemia and hypogammaglobulinemia , result in partial or complete lack of antibodies. [ 54 ] These diseases are often treated by inducing a short term form of immunity called passive immunity . Passive immunity is achieved through the transfer of ready-made antibodies in the form of human or animal serum , pooled immunoglobulin or monoclonal antibodies, into the affected individual. [ 55 ]

Rhesus factor , also known as Rhesus D (RhD) antigen, is an antigen found on red blood cells ; individuals that are Rhesus-positive (Rh+) have this antigen on their red blood cells and individuals that are Rhesus-negative (Rh–) do not. During normal childbirth , delivery trauma or complications during pregnancy, blood from a fetus can enter the mother's system. In the case of an Rh-incompatible mother and child, consequential blood mixing may sensitize an Rh- mother to the Rh antigen on the blood cells of the Rh+ child, putting the remainder of the pregnancy , and any subsequent pregnancies, at risk for hemolytic disease of the newborn . [ 56 ]