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Antibodies

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  • Antibodies

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    Antibodies


    antibody structure

    ::Antibodies are plasma glycoproteins , also known as gamma globulins becasue of their electrophoretic mobility & immunoglobulins (Ig) because of their role in immunity::

    :: All the antibodies have the same molecular structure::

    :: In basic Immunoglobulins there are two identical heavy chains & two identical light chain linked togther by intermolecular disulified bonds::

    ::each chain contains variable region & constant regions::

    ::Each light chain is attached to one heavy chain & the two heavy chains are attached to each other, all by disulfide bonds::

    :: A light chain is made up of one V & one C domain & heavy chain have one V & three or foure C domains ::

    :: Each domain folds into a characteristics three-dimensional shape which is called immunoglobulin (Ig) domain ::

    :: Each variable region of heavy chain (called VH) or of the light chain (called VL) contains three hypervariable regions, or CDRs ::

    :: Ig Domains are present in many others proteins in the immune system, & of these proteins are involved in sensings signals from enviroment & from other cells. all these proteins are said to be members of Ig superfamily::

    :: Regions of the antibody molecules are often named based on the properties of prolytic fragments of immanoglobulins::

    :: the fragment of antibody that contains a whole light chain (with its signal V &C domain) attached to the V & first C domains of heavy chains contains the protien of antibody required fro antigen recognition & is therefore called Fab (fragment antigen binding)::

    :: The remaining heavy chain C domains make up the Fc region, with Fc referring to fragment crystalline (so named because this fragments tend to crystallize in solution) ::

    :: In each Ig molecule, there are two identicl Fab regions that bind antigen & one Fc region that is responsible for the most of the biological activity & effector function of the antibodies::

    :: If the enzyme papin is used to cleave IgG, two major typees of gragments are obtained ::
    1- one fragment binds antigen & is referred to as Fab
    2- other fragment knowns as Fc dose not bind antigen but activites a molecular pathway known as complement & has various bilogic effector functions, such a the ability to bind receptor found on macrophages & various other cells::

    :: If pepsin is used, the two Fab fragments remain linked but Fc fragment is digested to small fragments & effector functions are lost::

    :: Because Fab & Fc regions of most antibodies molecules is a flexiable portion called hinge region::

    :: the hinge region allows the two-antigen binding Fab regions of each antibody molecules to move, enabling them to stimultaneously bind antigen epitopes that are seperated by varying distance::

    ::so as we said before the Ig basic structure composed of two identical heavy chains & two identical light chains::

    :: There are five differet classes of human chain
    ==1== Ig M
    ==2== Ig D
    ==3== Ig G
    ==4== Ig E
    ==5== Ig A

    :: Light chain are divided into two types
    ==1== Kappa
    ==2== lambda

    :: Both types of light chain are found in all five class of immunoglobulin, but any one antibody contaninsonly one type of light chain, in other words each types of light chain any may complex with any type of heavy chain in an antibody moelcules::

    :: The IgG class can be divided into four subclasses::

    :: Antibodies that contain different heavy chain are said to belongs to different isotypes or classes & are named according to their heavy chain regardless of the light chain class
    Antibodies: are immunoglobulins that react specifically with the antigen that stimulated their production.
    - Makes 20% of the plasma protein & detected by electrophoresis, in the "gamma globulin" fraction of the serum. (different from plasma in lacking the protein fibrinogen)
    - Antibodies that arise in response to a single complex antigen (bacterial protein with multiple epitopes) are heterogeneous in chemical structure & specificity because they are formed by several different clones of B cells, each expressing an immunoglobulin capable of binding to a different epitope on the antigen.
    - Antibodies can occur as soluble proteins in the circulation of be displayed on the surface of B cells.
    - The primary function of all antibodies is to bind antigen; this can result in the inactivation of a pathogen.
    - Antibodies can also activate complement & initiate a lytic reaction that destroys the cell to which the antibody is bound.
     Note:
    - After electrophoresis of serum, the immunoglobulin region in patients with a B-cell malignancy was often a band covering a very narrow range of electrophoretic mobility; because in this disease a single clone of B cells may proliferate & these cells secrete a multiple homogenous immunoglobulin that accumulates in the serum at relatively high concentration. "monoclonal antibodies"
    - Monoclonal antibodies, homogenous antibodies from a single clone of B cells, can be prepared in virtually unlimited quantities.
     Monoclonal antibodies:
    - Monoclonal antibodies are homogenous immunoglobulins.
    - Monoclonal antibodies produced using Hybridoma technology.
    - The aim is produce immortalized cells that only secrete immunoglobulin directed against antigen used in immunization.
    - It's important to be sure that myeloma cells that have not fused with immunized B cells do not survive.
    1. Immunize with antigen of choice. Remove spleen when the mouse is making an antibody response.
    2. Fuse with the immune spleen cells with a myeloma tumor cells.
    3. The cells are cultured in a selective medium. Only fused cells survives & after several days. Cells are diluted so that one cell is plated per well.
    4. Cells are grown in individual culture plate wells & culture supernatants from wells containing hybrid cells are screened for presence of desired antibody by Elisa.
    5. This clone (Hybridoma) is an immortal produced or the desired monoclonal antibody.
     Antibody Structure:
    - In the basic immunoglobulin (Ig) molecule, there are two heavy & two light chains linked together by intermolecular disulfide bonds.
    - There are five different classes of human heavy chain, these are:
    1. µ  IgM
    2. δ  IgD
    3. γ  IgG
    4. α  IgA
    - light chain are divided into two types κ & λ [both types of light chain are found in all five classes of immunoglobulin, but any one antibody contains only one type of light chain]
    - Any one IgG molecules consists of identical H chains & identical L chains organized into the Y-shaped structure. [human IgG molecules can be subdivided into IgG1-IgG4]
    - The basic immunoglobulin contains molecular parts with distinctive functions:
    • If the enzyme papain is used to cleave IgG, two major types of fragment are obtained. One fragment binds antigen & is referred to as Fab (fragment antigen-binding), the other fragment, known as Fc (fragment antigen-binding), dose not bind antigen but activates a molecular pathway known as complement & has various biologic effector functions, such as ability to bind to receptor found on macrophages & various other cells.
    • If the proteolytic enzyme pepsin is used, the two Fab fragments remain linked (F(ab')2) but the Fc fragment is digested to small fragments & the effector functions are lost.
    - The L & H chains can be differentiated into regions that are highly variable in sequence (VL & VH) & regions that are essentially constant (CL & CH).
    - The C region carry out the biologic effector functions, such as the ability to bind complement proteins, & the V regions bind antigens.
    - The variable regions are critical for the ability to respond to a vast number of different antigen structures.
    - The Igs are composed of folded, repeating segments called domains.
    - An L chain consists of one variable domain & one constant domain, & an H chain consists of one variable & three or more constant domains.
    - Each domain is 110 amino acid residues long & is connected to other domain by short segment of more extended polypeptide chain.
    - Other molecules of the immune system have similar folded polypeptide domains, giving rise to the term immunoglobulin supergene family.
     IgM:
    - The predominant antibody early in an immune response.
    - It has a pentameric structure, composed of five H2L2 units (each similar to an IgG), held together by a joining (H) chain.
    - It has 10 potential antigen-binding sites & because of this it is the most efficient antibody at agglutinating bacteria & activating complement.
     IgD:
    - IgD is chiefly found on the surface of B cells as receptor molecules & is involved in cell activation.
     IgG:
    - The most prevalent antibody molecule in serum.
    - It also survives intact in the serum for longest time, & is able to cross the placenta to allow maternal protection of the newborn.
    - There are four subclasses of human IgG (IgG1-IgG4).
    - IgG2 is generally the antibody subclass found to predominate in response to against polysaccharide antigens of encapsulated bacteria.
     IgE:
    - Binding of antigen to IgE coupled to an Fc receptor on mast cells & basophile triggers an allergic reaction by the activation of the mast cell & release mediators such as histamine.
    - IgE originally evolved to protect against parasitic infections.
     IgA:
    - The main immunoglobulin in secretions such as saliva, milk & tears & it is heavily represented in the mucosal epithelia of the respiratory, genital, & intestinal tracts.
    - The IgA found in secretions (sIgA) consists of two molecules of IgA, a joining (J) chain, & one molecule of secretory component.
    - The secretory component appears to protect the molecules from proteolytic attack & to facilitate its transfer across epithelial cells into secretions
    :extra59: العلم نور :extra57:

  • #2
    يسلموووووووووووووووووووو

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    • #3
      شكراً جزيلاً الله يوفقك :sm188:
      تواضع تكن كالنجم لاح لناظر على صفحات الماء وهو رفيع

      و لا تك كالدخان يعلو بنفسه على طبقات الجو و هو وضيع


      http://up1.m5zn.com/photo/2009/2/10/...okezwv.gif/gif

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      • #4
        شكرا لك يا نور على المشاركات المتميزة و جزاكي الله كل خير
        تحياتي اليك
        عيادة الدكتور أحمد بكور لطب الأطفال
        أهم مواضيع عيادة الدكتور أحمد بكور لطب الأطفال

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        • #5
          المشاركة الأصلية بواسطة الشواطي مشاهدة المشاركة
          يسلموووووووووووووووووووو
          الله يسلمك تحياتي لك
          :extra59: العلم نور :extra57:

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          • #6
            المشاركة الأصلية بواسطة Berooo مشاهدة المشاركة
            شكراً جزيلاً الله يوفقك :sm188:
            شكرا لكي على مرورك عزيزتي نور الموضوع بوجودك تحياتي لكي
            :extra59: العلم نور :extra57:

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            • #7
              الله يعطيك العافية وعقبال مواضيع جديدة ان شاء الله...
              http://www.up07.com/up8/uploads/e2c116f840.jpg

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              • #8
                المشاركة الأصلية بواسطة أحمد مهدي بكور مشاهدة المشاركة
                شكرا لك يا نور على المشاركات المتميزة و جزاكي الله كل خير
                تحياتي اليك
                شكرا لك دكتور أحمد على تشجيعي الدائم وهذا من بعض ما عندكم دكتور
                تحياتي لك
                :extra59: العلم نور :extra57:

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                • #9
                  المشاركة الأصلية بواسطة الزعـessamـيم مشاهدة المشاركة
                  الله يعطيك العافية وعقبال مواضيع جديدة ان شاء الله...
                  الله يعافيك وأشكرك على مرورك ومشاركتك
                  :extra59: العلم نور :extra57:

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                  • #10
                    شـــــــــــــــــTHANXـــــــــــــــكرا

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                    • #11
                      بارك الله فيك يااختي




                      وجزاك الله خيرا

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                      • #12
                        شكرا اختي نور
                        *- الإرادة ... والأمل .. قوتان إذا فلحت فى صهرهما ..... لصنعت المستحيل ... !!!

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                        • #13
                          موضوع رائع يا نور الله يعطيك العافية و ألف شكر ’’’ يثبت الموضوع لمدة


                          قال رسول الله صلى الله عليه وسلم :

                          من سلك طريقاً يلتمس فيه علماً .. سهل الله له به طريقاً
                          إلى
                          الجنه

                          لا خير في كاتم علم

                          يا حي يا قيوم برحمتك أستغيث أصلح لي شأني كله و لا تكلني إلى نفسي طرفة عين


                          مع أطيب التمنيات
                          CAESAR22

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                          • #14
                            مشكورررررررررررررة نور الف شكر
                            *- الإرادة ... والأمل .. قوتان إذا فلحت فى صهرهما ..... لصنعت المستحيل ... !!!

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                            • #15
                              شكرا جزيلا على الموضوع الرائع مع تحياتى
                              د. محمد

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