Antigens and Immunoglobulins PDF

Antigens and Immunoglobulins LECTURE (4) Antigen & immunoglobulin 1  Antigens and Immunoglobulins  Substance recognized by immune system which may be: Simple or complex....

Antigens and Immunoglobulins LECTURE (4) Antigen & immunoglobulin 1  Antigens and Immunoglobulins  Substance recognized by immune system which may be: Simple or complex. Carbohydrate, lipid, protein, nucleic acid, phospholipids. Any biological Ag. Peptide Ag presented on MHC.  Smallest part on Ag which bind with BCR & T cell receptors.  Large Ag with epitopes capable of binding with immune receptor & inducing immune response. (Notice that: not all antigens are immunogens)  Small Ag with epitopes capable of binding with immune receptor & without inducing immune response.  BUT can produce immune response only when conjugated with large carrier molecule (as a protein) → immune response against epitopes of hapten & carrier. Haptens → ‫صغري مش هيحفز جهاز املناعة‬ Carrier → ‫الكبري اللي هيشيل ال هابنت‬ ‫وخيليه متشاف من املناعة‬  Self Ag (MHC) normally not stimulate immune system. 2  Antigens and Immunoglobulins  Proteins > 10 KDs are more immunogenic  Complex proteins with numerous, diverse epitopes are more to induce an immune response than are simple peptides that contain only one or few epitopes.  Epitopes must be “seen by” and be accessibile to the immune system. Good immunogens Poor immunogens Not immunogenic  Activate B cells without help from T cell.  Requires T cell help for B cell activation.  E.g.: polysaccharides (Pneumococcal  E.g.: proteins (microbial proteins & non- polysaccharide, LPS). self or altered-self proteins). 3  Antigens and Immunoglobulins  Glycoproteins which mediate humoral immunity.  Ag stimulation of B cells with help of T helper cytokines  B cell proliferate  Differentiate into plasma cell which secrete antibodies  Enter circulation  site of infection.  Mature B cell express membrane bound antibodies (BCR).  Expressed on B cell surface (IgM & IgD) as  In plasma & mucosa & interstitial BCR for Ag. fluids of tissues.  If bind with Ag, initiate B cell response. 4  Antigens and Immunoglobulins  1 variable domain  1 variable domain (VL) Connect heavy chain with light (VH)  1 constant domain (CL). chain & heavy chain with heavy  3 or 4 constant chain. domains (CH).  Each variable domain (VL or VH) contains 3 hypervariable regions called complementary determining repeats (CDR). 5  Antigens and Immunoglobulins  Contain whole light +  Contain remaining of both  Flexible region. VH + CH1 heavy chains C domain.  Lies between Fab & Fc  2 in number  1 in number  Give mobility to both  Ag recognition and  Tend to crystallize in solution Fab to accommodate binding  Effector & biological different Ag. function. 6  Antigens and Immunoglobulins  Immunoglobulins →divided into five different classes → according to the difference in structure in constant domains of heavy chain: 1) Gamma heavy chains → IgG 2) Alpha heavy chains → IgA 3) Mu heavy chains → IgM 4) Epsilon heavy chains → IgE 5) Delta heavy chains → IgD  Different classes and subclasses of antibodies perform different effector functions.  There are two types of light chains, called κ (kappa) and λ (lambda).  An antibody has either two κ or two λ light chains.  Heavy chain class (isotype) switching: The switch from one Ig isotype to another. After activation of B lymphocytes, a specific clone of B cells proliferate and differentiate into progeny that secrete antibodies; some of the progeny secrete IgM, and other progeny produce antibodies of different isotypes Monomer 1gA1, 2 α1 or α2 3.5 Mucosal immunity dimer, tri - δ Traces None B cell receptor Parasite - ε 0.05 Monomer Allergy Opsoniz. 1gG1-4 γ (1,2,3,4) 13.5 Monomer Comp. ADCC B cell rec. - μ 1.5 Pentamer Comp. 7  Antigens and Immunoglobulins  Monoclonal antibodies: Identical monospecific antibodies produced by one type of immune cell that are all clones of a single parent cell.  Polyclonal antibodies: Ab obtained from blood of immunized host.  Steps: 1. A mouse is immunized with the antigen. 2. B cells are isolated from the spleen of the mouse. 3. B cells (Antibody-producing cell) are then fused with myeloma cells (malignant cell) in vitro by using a fusion agent as poly- ethylene glycol, a virus. 4. The cell fusion forms an antibody-producing cell “hybridoma”. 5. Hybrids (fused cells) are selected for growth in special culture media. The B cells that fuse with another B cell or do not fuse at all die because they do not have the capacity to divide indefinitely. Only hybridomas between B cells and myeloma cells survive. 6. Hybridomas, secrete a large amount of mAbs. 8  Antigens and Immunoglobulins  Used to define clusters of differentiation (CD markers) on lymphocytes.  The diagnosis of many infectious and systemic diseases relies on the detection of specific antigens or antibodies in the circulation or tissues by use of mAbs.  Tumor-specific monoclonal antibodies are used for detection of tumors by imaging techniques.  A number of mAbs are used therapeutically today: Anti-CD3 for immunosuppression and prevention of graft rejection  A pregnant woman in the first trimester aged 27 years suffered from pink continous maculopapular rash and posterior auricular lymphadenopathy.  The tests for Measles IgG was positive with negative Cytomegalo virus IgM and positive rubella IgM. Give a diagnosis for this case and what is expected to happen to the fetus? 9