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Humoral Immunity

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  • Humoral Immunity

    Humoral Immunity

    1. To understand the basic structure of antibodies.
    2. To recognise the functions of antibodies and how different regions within the antibody molecule subserve these roles.
    3. To realise the essential differences of the primary and the secondary humoral immune response, and the requirement for immunological memory.
    4. To appreciate the way in which the immense diversity of antibody specificities is determined.
    Humoral Immunity
    This refers to immunity to infection conferred by proteins termed antibodies.
    Antibodies - What Are They?
    Basic Structure
    Antibodies (Immunoglobulins, abbreviated Ig) are proteins of molecular weight 150 - 900 kd. They are unique molecules, derived from the 'immunoglobulin supergene'. One end of the Ig binds to antigens (the Fab portion, so called because it is the fragment of the molecule which is antigen binding), and the other end which is crystallizable, and therefore called Fc, is responsible for effector functions:

    There are 5 classes ('isotypes') of Ig; IgM, IgG, IgA, IgD and IgE, plus 4 subtypes of IgG (IgG1-4), and 2 of IgA (IgA1, IgA2). Light chains exist in two classes, lambda and kappa. Each antibody molecule has either lambda or kappa light chains, not both. Igs are found in serum and in secretions from mucosal surfaces. They are produced and secreted by plasma cells which are found mainly within lymph nodes, and which do not circulate. Plasma cells are derived from B lymphocytes:

    As seen in the diagram, the immunoglobulin molecule consists of two light chains, each of approximate molecular weight 25,000, and two heavy chains, each of approximate molecular weight 50,000. IgA exists in monomeric and dimeric form, IgM in pentameric form, MW 900,000 kd. The links between monomers are made by a J chain. Additionally, IgA molecules receive a secretory component from the epithelial cells into which they pass. This is used to transport them through the cell and remains attached to the IgA molecule within secretions at the mucosal surface. The heavy and light chains consist of amino acid sequences. In the regions concerned with antigen binding, these regions are extremely variable, whereas in other regions of the molecule, they are relatively constant. Thus each heavy and each light chain possesses a variable and a constant region. The isotype of an Ig is determined by the constant region.
    L chains are separated from H chains by disulphide (S-S) links. Intrachain S-S links divide H and L chains into domains which are separately folded. Thus, an IgG molecule contains 3 H chain domains, written CH1, CH2 and CH3. Between CH1 and CH2, there are many cysteine and proline residues. This is known as the hinge region and confers flexibility to the Fab arms of the Ig molecule. This is used when antibody interacts with antigen.
    Antibodies - Where Are They Made?
    Antibodies are synthesised by lymphocytes. Lymphocytes may be T (= Thymus processed), or B (= bone marrow processed). Antibodies are made by B lymphocytes and exist in 2 forms - either membrane bound or secreted. B lymphocytes use membrane bound antibody to interact with antigens. A B cell makes antibodies all of the same specificity i.e. able to react with the same antigenic determinants, and its progeny (as a consequence of mitotic division) are referred to as a clone. The clone will continue making antibody of the same specificity. Simultaneously, there will be lots of other clones of different specificity. This is known as a polyclonal response. Antigens have determinants called epitopes. Epitopes are molecular shapes recognized by antibodies, which recognise 1 epitope rather than whole antigen. Antigens may be proteins, lipids or carbohydrates, and an antigen may consist of many different epitopes, and/or may have many repeated epitopes - see figure 2.
    B lymphocytes evolve into plasma cells under the influence of T cell released cytokines. Plasma cells secrete antibodies in greater amounts, but do not divide. They exist in lymphoid tissues, not blood. Other B cells circulate as memory cells.
    The Life Of The B Cell
    - (See Figure 3)
    B lymphocytes are formed within the bone marrow and undergo their development there. They have the following functions:
    • To interact with antigenic epitopes, using their immunoglobulin receptors.
    • To subsequently develop into plasma cells, secreting large amounts of specific antibody, or
    • To circulate as memory cells.
    • To present antigenic peptides to T cells, consequent upon interiorization and processing of the original antigen. (This will be explained later in the course).
    Antibodies - What Are Their Functions?
    Antibodies exist free in body fluids, e.g. serum, and membrane bound to B lymphocytes. Their function when membrane bound is to capture antigen for which they have specificity, after which the B lymphocytes will take the antigen into its cytoplasm for further processing. Free antibodies have the following functions:
    Agglutination of particulate matter, including bacteria and viruses. IgM is particularly suitable for this, as it is able to change its shape from a star form to a form resembling a crab.
    Opsonization i.e. coating of bacteria for which the antibody's Fab region has specificity (especially IgG). This facilitates subsequent phagocytosis by cells possessing an Fc receptor, e.g. neutrophil polymorphonuclear leucocytes ("polymorphs").
    Thus it can be seen that in opsonization and phagocytosis both the Fab and the Fc portions of the immunoglobulin molecule are involved.
    Neutralization of toxins released by bacteria e.g. tetanus toxin is neutralized when specific IgG antibody binds, thus preventing the toxin binding to motor end plates and causing persistent stimulation, manifest as sustained muscular contraction which is the hallmark of tetanic spasms. This applies particularly to IgG. In the case of viruses, antibodies can hinder their ability to attach to receptors on host cells. Here, only Fab is involved.
    Immobilization of bacteria. Antibodies against bacterial ciliae or flagellae will hinder their movement and ability to escape the attentions of phagocytic cells. Again, only Fab is involved.
    Complement activation (classical pathway) especially by the Fc region of IgM and IgG, leads eventually to death of bacteria by the terminal complement components which punch holes in the cell wall, leading to an osmotic death. Complement components also facilitate phagocytosis by cells possessing a receptor for C3b, e.g. polymorphs.
    Mucosal protection. This is provided mainly by IgA, and to a lesser degree, IgG. IgA acts chiefly by inhibiting pathogens from gaining attachment to mucosal surfaces. This is a Fab function.
    Expulsion as a consequence of Mast cell degranulation. As a consequence of antigen e.g. parasitic worms, binding to specific IgE attached to mast cells by their receptor for IgE Fc, there is release of mediators from the mast cell. This leads to contraction of smooth muscle, which can result in diarrhoea, and expulsion of parasites. Here we see involvement of both Fab v. Parasite antigen, and Fc anchoring the reacting participants. See figure 4.
    Precipitation of soluble antigens by immune complex formation. These consist of antigen linked to antibody. Depending on ratio of antigen to antibody, these can be of varying size. When fixed at one site, they can be removed by phagocytic cells. They may also circulate prior to localization and removal, and can fix complement. Here Fab and Fc are involved.
    Antibody dependent cell mediated cytotoxicity (ADCC). Antibodies bind to organisms via their Fab region. Large granular lymphocytes (Natural Killer cells - abbreviated NK cells), attach via Fc receptors, and kill these organisms not by phagocytosis but by release of toxic substances called perforins.
    Conferring immunity to the foetus by the transplantal passage of IgG. IgG is the only class (isotope) of immunoglobulin that can cross the placenta and enter the foetal circulation, where it confers immune protection. This is of great importance to the foetus in the first 3 months. The precise function of IgD is not known. It may serve as a maturation marker of B lymphocytes.
    Primary And Secondary Response
    When we are exposed to an antigen for the first time, there is a lag of several days before specific antibody becomes detectable. This antibody is IgM. After a short time, the antibody level declines. These are the main characteristics of the primary response. If at a later date we are re-exposed to the same antigen, there is a far more rapid appearance of antibody, and in greater amount. It is of IgG class and remains detectable for months or years. These are the features of the secondary response. If at the same time that we are re-exposed to an antigen, we are exposed to a different antigen for the first time, the properties of the specific response to this antigen are those of the primary response:

    Primary Response:
    • Slow in Onset
    • Low in Magnitude
    • Short Lived
    • IgM
    Secondary Response:
    • Rapid in Onset
    • High in Magnitude
    • Long Lived
    • IgG (Or IgA, or IgE)
    Thus we can see that the secondary response requires the phenomen known as class switching. This requires co-operation with T cells of various types, which release cocktails of substances called cytokines. These cytokines induce gene rearrangements culminating in class switching. Details of this will be given at other points in the course.
    This phenomenon is possible because the immune system possesses specific memory for antigens. It occurs because during the primary response, some B lymphocytes, in addition to those differentiating into antibody secreting plasma cells, become memory cells which are long lived.


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  • #2
    بارك الله فيك
    تحياتي لك
    :extra59: العلم نور :extra57:

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    • #3
      الله يعطيك العافية شرفني مرورك

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      • #4
        يعطيك الف عاافية..
        http://up1.m5zn.com/photo/2009/1/24/...36kx6u.jpg/jpg

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        • #5
          الله يعافيك شرفني مرورك

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          • #6
            جزاك اله خيراً...
            من الخطأ والظلمة ينبلج الصواب ونور الفجر,,

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            • #7
              يسلموو على المرور

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              • #8
                الله يعطيك ألف عافية أخي شواطي
                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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                • #9
                  يسلموووو على المرور

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                  • #10
                    يعطيك العاقية

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                    • #11
                      شكرا لك وسلمت الايادي

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                      • #12
                        ألف شكر ,,, الله يعطيك العافية

                        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


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