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Trying to provide all necessary information about IMMUNITY and IMMUNE SYSTEM

The factors that promotes Oxygen binding as well as Oxygen dissociation with respect to Hb are as follows:                                                                                                                                                   

1. Hb and partial pressure of Oxygen:
         The most important factor that  determine how much Oxygen combines with Hb is partialpressure of Oxygen.When the partial pressure is high i.e., in the pulmonary blood capillaries where partial pressure of Oxygen is low hold as much Oxygen and so Oxygen is released to the tissue cells.The relationship between saturation of Hb with respect to partial pressure can be illustrated by Oxygen-Hydrogen dissociative curve.

2. Hb and Acidity(Hb+pH):
         In an acidic environment,Hb affinity for Oxygen is low as a result Oxygen spilts more easily from Hb (Bohr effect).When hydrogen ions bind to certain AAs in the polypeptide chain of Hb .They alter its structure and thereby decrease Hb's Oxygen carrying capacity.Thus a low pH (acidic medium)will always drive Oxygen away from Hb making available for the tissue cells.
3. Hb and BPG ( 2,3-Bisphosphoglycerate):
           BPG is found in RBCs and is an important regulation og Hb function.It decreases affinity of Hb for Oxygen and thus helps to release Oxygen from Hb. BPG is formed in RBCs when they breakdown glucose for energy by the process called glycolysis.when BPG combines with Hb,Hb binds to Oxygen less tightly.The greater the level of BPG,the more will be the Oxygen released from Hb.
4. Hb and partial carbondioxide:
          Carbondioxide can also bind to the Hb and the effect is similar like hydrogen ions.In the tissue bloodcapillary more acidic,this is because carbondioxide is temporarily converted into carbonic acid.This conversion is catalysed by the enzyme carbonic anhydrase,while formed in the RBCs.Carbonic acid being a weak acid dissociates into bicarbonate and hydrogen ions.As the hydrogen concentration increases,the pH decreases.As a result the blood becomes more acidic .In an acidic environment,Oxygen will spilt from Hb.
5. Temperature: 
           As the temperature increases the amount of Oxygen released from Hb also increases.Heat energy which is a by product of metabolic reaction of all the cells results in active cells,liberating more heat and requiring more Oxygen.The more active the cell,the more metabolic will be the state.In other words,more Carbondioxide will be released and more acidic will be the environment.the acid and the heat thus promote release of Oxygen from Hb.

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Structure of Hemoglobin:
            The heme prosthetic group associated with each chain is held in position by a coordinate covalent bond between the ion atom and a nitrogen atom in the side chain of His residue.The 4 heme groups serve as the sites for Oxygen binding.Hence each Hb molecule is able to bind reversibly with four molecule of Oxygen.The heme 'Fe' must be maintained in the ferrous state because Ferric ion is unable to bind to Oxygen.
3D Structure of Hemoglobin.
                       Binding of Oxygen with Hb follows a 'binding pattern' called cooperative binding which results from changes in hemoglobin 3D structure  that are initiative when the 1st Oxygen binds.The binding of 1st Oxygen molecule facilitates binding of remaining 3 Oxygen molecules
When the 1 st Oxygen molecule binds to a particular heme site,a message is communicated via conformational changes in the protein chains to the other heme sites.This subtle conformational changes as Allosteric interactions.
             The Hb molecules as far as structural  conformation is concerned is often referred as oxygenated Hb in R or relaxed state while deoxygenated Hb in T or taut state.
Hb alternates between these 2 stable conformations namely R and T states.In the lungs where Oxygen tension is high Hb gets quickly saturated and as a result gets coverted into 'R' state.
             In the tissues where Oxygen tension is low Hb becomes unsaturated and gets converted into 'T' state.
             The co-operative binding of Oxygen to Hb is influenced by Carbon dioxide and hydrogen ions.This observation was made by the biochemist Christian Bohr and therefore called 'Bohr effect'. Carbon dioxide and hydrogen ions bind to Hb molecule causing changes in its quaternary structure that stabilise deoxygenated form and destabilise oxygenated form.This binding process reduces affinity of Oxygen for Hb and enhances release of Oxygen for Hb.The action of carbondioxide and hydrogen ions are caused by allosteric effect i.e., carbondioxide and hydrogen bind to Hb causing subtle conformational changes throughout the Hb structure thereby influencing Oxygen affinity at the heme site.                                                                                                                                                                                                                                                                                                                                                                                                                                                                      

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WBC Life span and Number|Immune system|Hematology

Posted by Mumtaz khan Monday, 27 February 2012 0 comments

WBC Life Span and Number:
         WBC are far less numerous than RBCc averaging from 5,000-10,000 per cubicmm of blood.The ratio of RBCs to WBCs is around 700:1. The term leucocytosis refers to increase in the number of WBCs.The term Leucopenia refers to an abnormally low levels of WBCs(below 5000 per cubic mm). The term Leukemia refers to a very abnormal increase in specific type of WBC.

         Since bacteria exist everywhere in the environment and have easy continuous acces to the body especially through mouth,nose and skin pores. Many cells especially the cells of Epithelial tissue are subjected to aging and death and their remains must be disposed off by phagocytes that actively injest bacteria and debris.In a healthy body some WBCs especially lymphocytes can live for several months or even years but on an average there is no fixed life span for WBCs.Life span is decided by the period of infection e.g.,During severe infection phagocytic WBCs may live or survive only for a few hours.

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Antigen-Antibody Interactions: Strength or Antigen-Antibody Interactions.
         The noncovalent interactions that form the basis of antigen-antibody(Ag-Ab)binding include hydrogen bonds,ionic bonds,hydrophobic interactions,and van der waals interactions.Because these interactions are individually weak(compared with a covalent bond),a large number of such interactions are required to form a strong Ag-Ab interactions.Furthermore,each of these noncovalent interactions operates over a very short distance,generally about 1 angstorms;consequently,a strong Ag-Ab interaction depends on a very close fit between the antigen and antibody.Such fits require a high degree of complementarity between antigen and antibody,a requirement that underlies the exquisite specificity that characterizes antigen-antibody interactions.

Antibody Affinity Is a Quantitative Measure of Binding Strength.
        The combined strength of a noncovalent interactions between a single antigen-binding site on an antibody and a single epitope is the affinity of the antibody for that epitope.Low-affinity of the antibodies bind antigen weakly and tend to dissociate readily,whereas high-affinity antibodies bind antigen more tightly and remain bound longer.The association between a binding site on an antibody(Ab)with a monovalent antigen(Ag)can be described by the equation.
Ag + Ab--------> Ag-Ab


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WBC Physiology:
             Once pathogens enter the body,the general function of WBC is to fight or combat by phagocytosis or immune responses.Neutrophils and macrophages are active in phagocytosis.Several different chemicals in the inflammed tissue attract phagocytes towards the tissue,this phenomenon is called chemotaxis.Among the substances that provide stimuli for chemotaxis are toxins produced by microbes,specialised products of damaged tissues called Kinins.

             Most Leucocytes possess the ability to squiz through walls of capillaries and this movement through walls is called Diapedes.Among the WBCs neutrophils respond tissue destruction by bacteria most quickly.After engulfing a pathogen during phagocytosis neutrophils releases several destructive chemicals such as antibacterial enzyme Lysozyme and strong oxidants like  hydrogen peroxide.Neutrophils also contain Defensins specialized proteins that exhibit a broad range of antibiotic activity against bacterial,fungi and viruses.As compared to neutrophils monocytes take a little longer to reach a site of infection but once they arrive,they arrive in large number and destroy microbes.On their arrival at a site of infection monocytes enlarge and differentiate into wandering macropahges which clean up cellular debris,following the infection Eosinophils are believed to release enzymes such as histaminase that combats the effects of Histamine is allergic reactions.Eosinophils are most effective against parasitic worms a high high eosinophil count often indicates prarsitic infection.Basophils are also involved in inflammatory and allergic reactions.They develop into mast cells which liberate chemicals like Histamine,Heparin and Serotonin.These substances intensify inflammatory reactions and are involved in hypersnsitivity or allergic reactions.

Leucocytes(W.B.C)Immune system|Immunity.

Posted by Mumtaz khan Saturday, 25 February 2012 0 comments

W.B.C. Anatomy And types:
       Unlike R.B.C.s leucocytes of W.B.C. have a well defined nucleus and do not contain hemoglobin.The two major groups of W.B.C.s are granular W.B.C.s and Agranular W.B.C.s.,

Types of WBCs
Granular Leucocytes:-
      Also called as granulocytes showing lobed nuclei and conspicuous granules in the cytolasm.These are of three types viz.,Neutrophils,Eosinophils and Basophils.These name reflect the types of granules seen when using hematology stain Giemsa stain or Leishman's stain.But the most preferred stain is Wright's stain which include both acidic Eosin and Basic dye.The nuclei of Neutrophils may have 2-6 lobes connected by very thin strands as the cells age the extent of nuclear lobulation increases.Because the older Neutrophils appear to have many differently shaped nuclei they are often called as polymorphonuclear leucocyte or simply polymorphs.The younger neutrophils are often called as bands because their nucleus id rod shaped.The cytoplasm of neutrophils shows fine lilac colored granules.The nucleus of an Eosinophils usually has two lobes connected by a thin or thick strand.The granules in the cytoplasm are large and they stain reddish orange.The nucleus of a basophils is irregular often in the form of letter 'S'.The granules in their cytoplasm are variable in size and stain bluish black.

Agranular Luecocytes:-
       Also called Agranulocytes whereby no cytoplasmic granules can be seen.The two kinds of Agranulocytes or Lymphocytes and Monocytes.The nuclei of Lymphocytes are darkly stained,roundish showing slightly indented shape.The cytoplasm stains sky blue.The nuclei of monocytes are kidney shaped and the cytoplasm has blurred appearance.Some of them reside in a particular tissue and are referred as fixed macrophages.E.g., macrophages are wandering or free macrophages which roam and gather at sites of infection or inflamation.Just like RBCs have surface(Major Histo Compatibility antigen)(these are contains for each person).

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Abzymes Are Monoclonal Antibodies that Catalyze Reactions

Posted by Mumtaz khan Wednesday, 22 February 2012 1 comments

                The binding of an antibody to its antigen is similar in many ways to the binding involves weak,non covalent interactions and exhibits high affinity.What distinguishes an antibody-antigen interaction is that the antibody does not alter the antigen,whereas the enzyme catalyzes a chemical change in its substrate.However,like enzymes,antibodies of appropriate specificity can stabilize the transition state of a bound substrate,thus reducing the activation energy for chemical modification of the substrate.
               The similarities between antigen-antibody interactions and enzymes-substrate interactions raised the question of whether some antibodies could behave like enzymes and catalyze chemical reactions.To investigate this possibility,a hapten-carrier complex was synthesized in which the hapten structurally resembled the transition state of an ester undergoing hydrolysis.Spleen cells from mice immunized with this transition state analogue were fused with myeloma cells to generate monoclonal antihapten monoclonal antibodies.When these monoclonal antibodies were incubated with an ester substrate,some of them accelarated hydrolysis by about 1000-fold;that is,they acted like the enzyme that normally catalyzes the substrate's hydrolysis.This catalytic activity of these antibodies was highly specific;that is,they hydrolized only esters whose transition-state structure closely resembled the transition state analogous used as hapten in the immunizing in reference to their dual role as antibody and enzyme.
              A central goal of catalytic antibody research is the derivation of a battery of abzymes that cut peptide bonds at specific sites.Such abzymes would be invaluable tools in the structural and functional analysis of proteins.Additionally,it may be possible to generate abzymes with the ability to dissolve blood clots or to cleave viral glyco[roteins at specific sites,thus blocking viral infectivity.Unfortunately,catalytic antibodies that cleave the peptide bonds of proteins have been exceedingly difficult to derive.Much of the research currently being pursued in this field is devoted to the solution of this important but difficult problem.

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Monoclonal Antibodies Have Important Clinical Uses:
                Monoclonal antibodies are proving to be very useful as diagnostic,imaging,and therapeutic reagents in clinical medicine.Initially,monoclonal antibodies were primarily as in vitro diagnostic reagents.Among the many monoclonal antibody diagnostic reagents now available are products for detecting pregnancy,diagnosing numerous pathogenic microorganisms,measuring the blood levels of various drugs,matching histo compatibility antigens, and detecting antigens shed by certain tumors.
                Radiolabeled monoclonal antibodies can also be used in vivo for detecting or locating tumor antigens,permitting earlier diagnosis of some primary or metastatic tumors in patients.For example,monoclonal antibody to breast-cancer cells is labeled with iodine-131 and introduced into the blood to detect the spread of tumor to regional lymph nodes.This monoclonal imaging technique can reveal breast-cancer metastates that would be undetected by other,less sensitive scanning techniques.
Immunotoxins composed of tumor-specific monoclonal antibodies coupled to lethal toxins are potentially valuable therapuetic reagents.The toxins used in preparing immunotoxins include ricin,shigella toxin,and diphtheria toxin,all that s single molecule has been shown to kill a cell.Each of these toxins consists of two types of functionally distinct polypeptide comonents,an inhibitory(toxin)chain and one or more binding chains,which interact with receptors on cell surfaces;without the binding polypeptide(s) the toxin cannot get into cells and therefore is harmless.An immunotoxin is prepared by replacing the binding polypeptide(s) with a monoclonal antibody that is monoclonal antibody that is specific for a particular tumor cell.In theory,the attached monoclonal antibody will deliver the toxin chain sppecifically to tumor cells,where it will cause death by inhibiting protein synthesis.The initial clinical  responses to such immunotoxins in patients with leukemia,lymphoma,and some other types of cancer have shown promise,and research to develop and demonstrate their safety and effectiveness is underway.

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Monoclonal Antibodies,Immune system,Immuity,Immunology.

Posted by Mumtaz khan Saturday, 18 February 2012 1 comments

 Monoclonal Antibody Production:
            As we have studied earlier,most antigens offer epitopes and therefore induce proliferation and differentiation of a variety of B-cell clones,each derived from a B cell that recognizes a particular epitope.The resulting serum antibodies are heterogeneous,comprising a mixture of antibodies,each specific for one epitope.Such a polyclonal antibody response facilitates the localization,phagocytes,and complement-mediated lysis of antigen;it thus has clear advantages for the organism in vivo.Unfortunately,the antibody heterogenecity that increases immune protection in vivo often reduces the efficacy of an antiserum for various in vitro uses.For most research,diagnostic, and therapeutic purposes, monoclonal antibodies,derived from a single clone and thus specific for a single epitope,are preferable.

            Direct biochemical purification of a monoclonal antibody from a polyclonal antibody preparation is not feasible. In 1975,Georges Kohler and Cesar Milstein devised  a method for preparing monoclonal antibody,which quickly became one of immunology's key technologies.By fusing a normal activated,antibody-producing B cell with a myeloma cell(a cancerous plasma cell),they were able to generate a hybrid cell,called a hybridoma,that possessed the immortal growth properties of the myeloma cell and secreted the antibody produced by the B cell.The resulting clones of hybridoma cells,which secrete large quantities of monoclonal antibody,can be cultured indefinitely.The development of techniques for producing monoclonal antibodies,gave immonologists a powerful and versatile research tool.The significance of the work by kohler and Milstein was acknowledged when each was awarded a nobel Prize.

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Antibodies Are Heterodimers,Immune system,Immunity.

Posted by Mumtaz khan Friday, 17 February 2012 0 comments

Basic structure of antibodies: Antibodies are Heterodimers                Antibody molecules have a common structure of four peptide chains.This structure of two identical light(L)chains, polypeptides of about 25,000 molecular weight,and two identical heavy(H)chains,larger polypeptides of molecular weight 50,000 or more.Like the antibody molecules they constitute,h and L chains are also called immunoglobulins.Each light chain is bound to a heavy chain by a disulfide bond,and by such noncovalent interactions as salt linkages,hydrogen bonds,and hydrophobic bonds,to form a heterodimer(H-L)chain combinations to each other to form the basic four-chain(H-L)(H-L)antibody structure,a dimer of dimers.As we shall see,the exact number and precise positions of these interchain disulfide
 bonds differs among antibody classes and subclasses.

     The first 110 or so amino acids of the amino-terminal region of a light or heavy chain varies greatly among antibodies of different specificity.These segments of highly variable sequence are called V regions.All the differences in specificity displayed by different antibodies can be traced to differences in the amino acid sequences of V regions.In fact,most of the differences among antibodies fall within areas of the V regions called complementary-determining regions(CDRs),and it is these CDRs on both light and heavy chains,that constitute the antigen-binding site of the antibody molecule.By contrast,within the same antibody class,far fewer differences are seen when one compares sequences throughout the rest of the molecule.The regions of relatively constant sequence beyond the variable regions have been dubbed C regions.Antibodies are glycoproteins;with few exceptions,the sites of attachment for carbohydrates are restricted to the constant region.We do not completely understand the role played by glycosylation of antibodies,but it is probably increases the solubility of the molecules.Inappropriate glycosylation,or its absence,affects the rate at which antibodies are cleared from the serum,and decreases the efficiency of distraction between antibody and the complement system and between antibodies and Fc receptors.

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Basic Structure of Antibodies,Immune system,Immunity.

Posted by Mumtaz khan Wednesday, 15 February 2012 1 comments

Basic Structure of Antibodies:
            Blood can be separated in a centrifuge into a fluid and a cellular fraction contains red blood cells,leukocytes,and platelets.Plasma contains all soluble small molecules and macromolecules of blood,including fibrin and other proteins required for the formation of blood clots.If the blood or plasma is allowed to clot,the fluid phase that remains is called serum.It has been known since the turn of century that antibodies reside in the serum.The first evidence that antibodies were contained in particular serum protein fractions came from a classic experiment by A.Tiselius and E.A.Kabat,in 1939.

         They immunized rabbits with the protein ovalbumin(the albumin of egg white)and then divided the immunized rabbits serum intoo two aliquots.Electrophoresis of one serum aliquot revealed four peaks corresponding to albumin and alpha,beta,and gamma globulins.The other serum aliquot was reacted with ovalbumin,and the precipitate that formed was removed;the remaining serum proteins,which did not react with the antigen,were then electrophoressed.A comparison of the electrophoretic profiles of these two serum aliquots revealed that there was a significant drop in the gamma-globbulin peak in the aliquot that had been reacted with antigen.Thus,the gamma-globulin fraction was identified as containing serum antibodies,which were called immunoglobulins,to distinguish them from any other proteins that might be contained in the gamma-globulin fraction.We now know that although immunoglobulin G(IgG),the main class of antibody molecules are found in the gamma-globulin fraction,significant amounts of it and other important classes of antibody molecules are found in the alpha and the beta fractions of serum.

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Immune benefits of breat milk:

Antibodies of secretory IgA:- Bind to microbes in baby's digestive tract and thereby prevent their attachment to the walls of the gut and their subsequent passage into body's tissues.

B-12 binding factor:- Reduces amount of vitamin B-12,which bacteria need in order to grow.

Bifidus factor:- Promotes growth of Lactobacillus bifidus,,a harmless bacterium,in baby's gut.Growth of such nonpathogenic bacteria helps to crowd out dangerous varieties.

Fatty acids:- Disrupt membranes surrounding certain viruses and destroy them.

Fibronectin:- Increase antimicrobial activity of macrophages;helps to repair tissues that have been damaged by immune reactions in baby's gut.

Hormones and growth factors:- Stimulate baby's digestive tract to mature more quickly.Once the initially "leaky" membranes lining the gut mature,infants become less vulnerable to microorganisms.

Interferon:- Enhances antimicrobial activity of immune cells.

Lactoferrin:- Binds to iron,a mineral many bacteria need to survive.By reducing the available amount of iron,lactoferrin thwarts growth of pathogenic bacteria.

Lysozyme:- Kills bacteria by disrupting their cell walls.

Mucins:- Adhere to bacteria and viruses,thus keeping such microorganisms from attaching to mucosal surfaces.

Oligosaccharides:- Bind to microorganisms and bar them from attaching to mucosal surfaces.

SOURCE:Adapted from J.Newman,1995,How breast milk protects newborns,Sci.Am.273(6):76.

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Immunoglobulin D(IgD):
IgD was first discovered when a patient developed a multiple myeloma protein failed to react with anti-isotype antisera against the then-known isotypes:IgA,IgM,and IgG.When rabbits were immunized with this myeloma protein,the resulting antisera were used used to identify the same class of antibody at low levels in normal human serum.
The new class,called IgD,has a serum concentration of 30 mu d/ml and constitute about 0.2% of the total immunoglobulin in serum.IgD,together with IgM,is the major membrane-bound immunoglobulin expressed by mature B cells,and its role in the physiology of B cells is under investigation.No biological effector function has been identified for IgD.

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Immunoglobulin E(IgE),Immunology,Immune system,Immunity.

Posted by Mumtaz khan Tuesday, 14 February 2012 0 comments

Immunoglobulin E(IgE):
           The potent biological activity of IgE allowed it to be identified in serum despite its extremely low average serum concentration.IgE antibodies mediate the immediate hypersensitivity reactions that are responsible for symptoms of hay fever,asthma,hives,and anaphylactic shock.The presence of a serum component responsible for allergic reactions was first demonstrated in 1921 by K.Prausnitz and H.Kustner,who injected serum from an allergic person intra-dermally into a nonallergic individual.When the appropriate antigen was later injected at the same site,a wheal and flare reaction(analogous to hives)developed there.This reaction,called the P-K reaction(named for its originators,prausnitz and kustner),was the basis for the fiorst biological assay for IgE activity.

a) Cross-linkage by a single allergen and b) Cross-linkage by a single IgG antibody to two allergen molecules.
          Actual identification of IgE was accomplished  by K.prausnitz and T.Ishizaka in 1966.They obtained serum from an allergic individual and immunized rabbits with it to prepare anti-isotype antiserum.The rabbits antiserum was then allowed to react with each class of human antibody known at that time(i.e.,IgG,IgA,IgM,IgD).In this way,each of known anti-isotype antibodies was precipitated and removed from the rabbit anti-serum.What remained was an anti-isotype antibody specific for an unidentified class of antibody.This antibody turned out to completely block the P-K reaction.the new antibody was called IgE(in reference to the E antigen of ragweed pollen,which is a potent inducer of this class of antibody).
         IgE binds to Fc receptors on the membranes of blood basophils and tissue mast cells.Cross-linkage of receptor-bound IgE molecules by antigen(allergen)induces basophils and mast cells to translocate their granules to the plasma membrane and release their contents to the extracellular environment, aprocess known as degranulation.As a result,a variety of pharmacologically active mediators are released and give rise to allergic manifestations.Localized mast-cell degranulation induced by IgE also may release for antiparasitic defense.

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Immunoglobulin(IgA),Immunology,Immune system,Immunity.

Posted by Mumtaz khan Monday, 13 February 2012 0 comments

Immunoglobulin A (IgA):
            Although IgA constitutes only 10%-15% of the total immunoglobulin in serum,it is the predominant immunoglobulin class in external secretions such as breast milk,saliva,tears,and mucus of the bronchial,genitourinary,and digestive tracts.In serum,IgA exists primarily as a monomer,but polymeric forms(dimers,trimers,and some tetramers)are sometimes seen,all containing a J-chain polypeptide.The IgA of external secretions,called secretory IgA,consists of a dimer or a tetramer,a J-chain polypeptide,and a polypeptide chain called secretory component.As is explained below,secretory component is derived from the receptors that is responsible for transporting polymeric IgA across cell membranes.The J-chain polypeptide in IgA is identical to that found in pentameric IgM and serves a similar function in facilitating the polymerization of both serum IgA and secretory IgA.The secretory component is a 70,000-MW polypeptide produced by epithelial cells of mucous membranes.It also consists of five immunoglobulin-like domains that bind to the Fc region domains of the IgA dimer.This interaction is stabilized by a sulfide bond between the fifth domain of the secretory component and one of the chains of the dimeric IgA.

           The daily production of secretory IgA is greater than that of any other immunoglobulin class.IgA-secreting plasma cells are concentrated along mucous membrane surfaces.Along the jejunum of the small intestine,for example,there are so many IgA secreting plasma cells- a number that surpasses the total plasma cells population of the bone marrow,lymph and spleen combined ! Every day,a human secretes from 5 g to 15 g of secretory IgA into mucous secretions.
           The plasma cells that produce IgA preferentially migrate to sub epithelial tissue,where the secreted IgA binds tightly to receptor for polymeric immunoglobulin molecules.This poly-Ig-receptor is expressed on the basolateral surface of most mucosal epithelia(e.g.,the lining of digestive,respiratory,and genital tracts)and on glandular epithelia in the mammary,salivary,and lacrimal glands.After polymeric IgA binds to the poly-Ig receptor,the receptor-IgA complex is transported across the epithelial barrier to the lumen.Transport of the receptor-IgA complex involves receptor-mediated endocytosis into coated pits and directed transport of the vesicle across the epithelial cell to the luminal membrane,where the vesicle fuses with the plasma membrane.The poly-ig receptor is then cleaved enzymatically from the membrane and becomes the secretory component,which is bound to and released together with polymeric IgA into the mucous secretions.The secretory component masks sites susceptible to protease cleavage in the hinge region of secretory IgA,allowing the polymeric moleculs exist longer in the protease-rich mucosal environment than would be possible otherwise.Pentameric IgM is also transported into mucous secretions than does IgA.The poly-Ig receptor interact with the J- chain of both polymeric IgA and IgM antibodies.
         Secretory IgA serves an important effector function at mucous membrane surfaces,which are the main entry sites for most pathogenic organisms.Because it is polymeric,secretory IgA can cross-link large antigens with multiple epitopes.Binding of secretory IgA to bacterial and viral surface antigens prevents attachment of the pathogens to the mucosal cells,thus inhibiting viral infection and bacterial colonization.Complexes of secretory IgA and antigens are easily entrapped in mucus and then eliminated by the ciliated epithelial cells of respiratory tract or by peristalsis of the gut.Secretory IgA has been shown to provide an important line of defense against bacteria such as Salmonella,Vibrio cholerae,and Neisseria gonorrhoeae and viruses such as polio,influenza,and reovirus.
         Brast milk contains secretory IgA and many other molecules that help protect the newborn against infection during the first month of life.Because the immune system of infants is not fully functional,breast-feeding plays an important role in maintaining the health of newborns.

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Immunoglobulin M(IgM),Immunology,Immunity,Immune system

Posted by Mumtaz khan Friday, 10 February 2012 0 comments

Immunoglobulin M (IgM):      
    IgM accounts for 5%-10% of the total serum immunoglobulin,with an average serum concentration of 1.5 mg/ml.Monomeric IgM,with a molecular weight of 180,000, is expressed as membrane-bound antibody on B cells.IgM is secreted by plasma cells as a pentamer in which five monomer units are held together by disulfide bonds that link their domains.The five monomer subunits are arranged with their Fc regions in the center of the pentamer and the ten antigen-binding sites on the periphery of the molecule.Each pentamer contains an additional Fc-linked polypeptide called the J (joining)chain,which is disulfide-bonded to the carboxyl-terminal cysteine residue of two of the ten chains.The J chain appears to be required for polymerization of the monomers to form pentameric Igm;it is added just before secretion of the pentamer.
IgM is the first immunoglobulin class produced in a primary response to an antigen,and it is also the first immunoglobulin to be synthesised by the neonate.because of its pentameric structure with 10 antigen-binding sites,serum IgM has a higher valency than the other isotypes.An IgM molecule can bind 10 small hapten molecules;however,because of steric hindrance,only 5 or fewer molecules of larger antigens can be bound simultaneously.Because of its high valency,pentameric IgM is more efficient than other isotypes in binding antigens with many repeating epitopes such as viral particles and red blood cells(RBCs).For example,when RBCs are incubated with specific antibody,they clump together into large aggregates in a process called agglutination.It takes 100 to 1000 times more molecules of IgG than IgM to achievethe same level of agglutination.A similar phenomenon occurs with viral particles:less igM is required to neutralize viral infectivity.IgM is alsoefficient than IgG at activating complement.Complement activation requires two Fc regions in close proximity,and the pentameric structure of a single molecule of IgM fulfills this requirement.
         Because of its large size,IgM does not diffuse well and therefore is found in very low concentrations in the intercellular tissue fluids.The presence of J chain allows IgM  to bind to receptors on secretory cells,which transport it across epithelial linings to enter external secretions that bathe mucosal surfaces.Although IgA is the major isotype found in tese secretions,IgM plays an important accessory role as a secretory immunoglobulin.

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Antibody Classes and Biological Activities,Immunoglobulin(IgG)

Posted by Mumtaz khan Wednesday, 8 February 2012 0 comments

          The various immunoglobulin isotypes and classes have been mentioned briefly already.Each class is distinguished by unique amino acid sequences in heavy-chain constant region that confer class-specific structural and functional properties .In this section,the structure and effector functions of each class are described in more detail.

Immunoglobulin G (IgG):
IgG,the most abundant class in serum,constitutes about 80% of the total serum immunoglobulin.The IgG molecule consists of two heavy chains and two light chains.There are four human IgG subclasses,distinguished by differences in heavy-chain sequence and numbered according to their decreasing average serum concentrations:IgG1,IgG2,IgG3,and IgG4.

The amino acid sequence that distinguish the four IgG subclasses are encoded by different germ-line genes,whose DNA sequences are 90%-95% homologous.The structural characteristics that distinguish these subclasses from one another are the size of the hinge region and the number and position of the interchain disulfide bonds between the heavy chains.The subtle amino acid differences between subclasses of IgG affect the biological activity of the molecule:
* IgG1,IgG3,and IgG4 readily cross the placenta and play an important role in protecting the developing fetus.
* IgG3 is the most effective complement at all.
* IgG1 and IgG3 bind with high affinity to Fc receptors on phagocytic cells and thus mediate opsonization.IgG4 has an intermediate affinity for Fc receptors,and IgG2 has an extremely low affinity.

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Immunoglobulin Fine structure|Immunology,Immune system,Immunity

Posted by Mumtaz khan Tuesday, 7 February 2012 0 comments

           The structure of the immunoglobulin molecule is determined by the primary,secondary,tertiary, and quaternary organization of the protein.
The primary structure,the amino acid sequence,accounts for the variable and constant regions of the heavy and light chains.The secondary structure is formed by folding of the extended polypeptide chain back and forth upon itself into an antiparallel beta pleated sheet.

The chains are then folded into tertiary structure of compact globular domains by continuations of the polypeptide chain that lie outside the beta pleated.Finally,the globular domains of adjacent heavy and light polypeptide chains interact in the quaternary structure,forming functional domains that enable the molecule to specifically bind antigen and,at the same time,perform a number of biological effector functions.

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Hematopoiesis|Formation of blood cells|Immune system.

Posted by Mumtaz khan Monday, 6 February 2012 0 comments


        All blood cells arise from a type of cell called the hematopoietic stem cell(HSC).Stem cells are cells that can differentiate into other cell type;they are self renewing-thy maintain their population level by cell division.In humans,hematopoeisis,the formation and development of red and white blood cells,begins in the embryonic yolk sac during the first weeks of development.Here,yolk sac stem cells differentiate into primitive erythroid cells that contain embryonic hemoglobin.In the third month of gestation, hematopoietic stem cells migrate from the yolk sac to the fetal liver and then to the spleen;these two organs have major roles in hematopoiesis from third to the seventh months of gestation.After that,the differentiation of HSCs in the bone marrow becomes the major factor in hematopoiesis,and by birth there is little or no hematopoiesis in the liver and spleen.
       It is remarkable that every functionally specialized,mature blood cell is derived from the same type of stem cell.In contrast to a uni-potent cell,which differentiates into a single cell type,a hematopoeitic stem cell is multipotent,or pluripotent,able to differentiate in various ways and thereby generate erythrocytes,granulocytes,monocytes,mast cells,lymphocytes,and megakaryocytes.These stem cells are few,normally fewer than one HSC per 5 X 100000 cells in the bone marrow.
      The study of hematopoietic stem cells is difficult bot because of their scarcity and because they are hard to grow in vitro.As a result,little is known about how their proliferation for self-renewal,hematopoietic stem cells are maintained at stable levels throughout adult life;however,when there is an increased demand for hematopoiesis,HSCs display an enormous proliferative capacity.This can be demonstrated in mice whose hematopoietic systems have ben completely destroyed by a lethal dose of x-rays.Such irradiated mice will die within 10 days unless they are infused with normal bone-marrow cells from a syngeneic(genetically identical) mouse.
        Early in hematopoiesis, a multipotent stem cell differentiates along one of two pathways,giving rise to either a common lymphoid progenitor cell or common myeloid progenitor cell.The types and amounts growth factors in the microenvironment of a particular stem cell or progenitor cell control its differentiation.During the development of the lymphoid and myeloid lineages,stem cells differentiate into progenitors cells,which have lost the capacity for self-renewal and are committed to a particular cell lineage.Common lymphoid progenitor cells give rise to B,T,and NK(natural killer)cells and some dendritic cells.Myeloid stem cells generate progenitors of red blood cells(erythrocytes),many of the various white blood cells(neutophils,eosinophils,basophils,monocytes,mast cells,dendritic cells.),platelets.Progenitors commitment depends on the acquisition of responsiveness to particular growth factors and cytokines.when the appropriate factors and cytokines are present,progenitor cells proliferate and differentiate into corresponding cell type,either a mature erythrocyte,a particular type of leukocyte,or a platelet-generating cell(the megakaryocyte).Red and white blood cells pass into bone-marrow channels,from which they enter the circulation.
        In bone marrow,hematopoietic cells grow and mature on a meshwork of stromal cells,endothelial cells,fibroblasts,and macrophages.Stromal cells influence the differentiation of hematopoietic stem cells by providing a hematopoietic-including micro-environment (HIM) consisting of a cellular matrix and factors are soluble agents that arrive at their target cells by diffusion,others are membrane-bound molecules on the surface of stromal cells that require cell-to-cell contact between the responding cells and the stromal cells.During infection,hematopoiesis is stimulated by the production of hematopoietic growth factors by activated macrophages and T cells.

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