Lecture 4 and 5 Immunology Antigens and Antibody By Dr. Dalia Galal Hamouda

1. Lecture 4 and 5 Immunology Antigens and AntibodyBy Dr. Dalia GalalHamouda

2. 1- Antigens • Antigen:any substance that stimulate the specific immune response (antibody or a T-cell ) and binds specifically to them • Epitope, or, Antigenic determinants,are the portions of antigen molecules that interact with paratopes (combining sites) of antibody or T cell.

3. Types of antigen 1- Immunogen: • Substance that stimulate the specific immune response (production of antibody and T cell) without help from APCs. • Usually has a high molecular weight. • Such as proteins, lipoproteins, polysaccharides, some nucleic acids 2. Hapten: • Substance that cannot stimulate an immune response but can bind to antibodies or T cells • Low molecular weight molecule • It can be immunogenic by conjugation to a carrier.

4. 3- AllergenAn allergen is a substance that causes the allergic reaction. The reaction may result after exposure through ingestion, inhalation, injection or contact with skin. 4- AutoantigensAn autoantigen is a normal protein (and sometimes DNA or RNA) that is recognized by the immune system of patients suffering from a specific autoimmune disease. 5- SuperantigensThey are secreted proteins (exotoxins) that stimulate T lymphocyte strongly and simultaneously bind to class II MHC molecules. Examples are staphylococcal products that involved in toxic shock syndrome in humans

5. Antigens can be classified according to their origins 1. Exogenous antigens are antigens that have entered the body from the outside, for example by inhalation, ingestion, or injection. By endocytosis or phagocytosis, these antigens are taken into the antigen-presenting cells (APCs) and processed into fragments. 2. Endogenous antigens Endogenous antigens are antigens that have been generated within the cell for example viral or intracellular bacterial infection

6. The immunogenicity of a substance is affected by a number of characteristics: 1. Foreignness: • The substance should present in configuration that is unfamiliar to the organism. • As the antigen is recognized as non-self by an individual’s immune system, the more antigenic it is. 2. Molecular weight: • The antigen molecule must have a high molecular weight. • As the molecule is large, the more antigenic it is.

7. 3. Structural stability: Structural stability is essential characteristic; structurally instable molecules are poor antigens, eg. Gelatin. 4. Structural complexity: As the antigen is more complex, it becomes more antigenic for example, complex proteins are better antigens than large repeating polymers such as lipids, carbohydrates, and nucleic acid, which are relatively poor antigens. 5. Route of administration: In general, intravenous (in to the vein) and intraperitoneal(into the peritoneal cavity) routes offer a stronger stimulus than subcutaneous (beneath the skin) or intramuscular (in to the muscle) routes.

8. 2- Antibody Antibodies (immunoglobulin)are serum proteins stimulated in response to a foreign antigen that is capable of reacting specifically with that antigen. • Antibodies structure: • 2 identical Light Chains (identical) and 2 identical Heavy Chains • Each Light Chain bind To Heavy Chain By Disulfide (H-L) • Light Chain consists of variable (VL) and constant region (CL) • Heavy Chain consists of variable (VH) and constant region (CH)

9. All variable regions are functioned in Antigen binding while all the constant regions are functioned in Biological activity • Hinge Region: This is the region at which the arms of the antibody molecule forms a Y. It is called the hinge region because there is some flexibility in the molecule at this point.

10. Digestion With Papain enzyme in hinge region,produces • 3 Fragments • 2 identical Fab and 1 Fc • Called Fab because this Fragment is Antigen Binding • Called Fc because this Fragment Crystallize In Cold Storage and perform with biological functions • Digestion with Pepsin enzyme produces • F(ab`)2 , it is divalent, its function is antigen binding but it does not mediate the biological functions of antibodies • No Fc, it is digested into small peptides by pepsin Enzymatic Digestion Of Antibodies

11. The B-cells produce antibodies. • Therefore, the B-cells activate the antibody-mediated immunity which is also called Humoral immunity. • Antibodies have 3 main function: 1) Agglutination of particles which include bacteria and virus. 2) Opsonisation or coating of bacteria which enables phagocytosis 3) Neutralisation of toxins released by bacteria, For e.g., Tetanus toxin

12. Other functions for antibodies

13. Five major immunoglobulin (Ig) classes exist; which are called: • IgG • IgA • IgM • IgD • IgE, These five classes are due to with different heavy chains of the antibody such as: • Gamma (γ) chain for IgG • Alpha (α) chain for IgA • Mu (μ) chain for IgM • Delta(δ ) chain for IgD • Epsilon(Є) chain for IgE

14. IgG: • Is the predominant immunoglobulin in normal serum, accounting for about 85% of the total immunoglobulin • Is the only immunoglobulin to be transferred from mother to fetus, through the placenta, a fact that explains its role in the etiology of hemolytic disease of the new born (HDN) • Is the smallest antibody which has a MW of 150,000 • Is capable of binding complement - Is predominantly produced during the secondary immune response.

15. IgM: • Accounts for about 10% of the immunoglobulin pool, with a concentration of about 1.0 g/l in normal serum. • Is structurally composed of five basic subunit (pentameric), and has the largest MW of 900,000. Because of its large size IgM cannot pass the placental barrier to the fetus • Is complement binding • Is the predominant antibody produced in a primary immune response

16. IgA: • Ig A with a MW of 160,000 constitutes 10 to 15 % of the total circulatory immunoglobulin pool. • Is the predominant immunoglobulin in secretions such as, tears, saliva, colostrum, breast milk, and intestinal secretions. - Does not fix complement and is not transported across the human placenta

17. IgD It is a monomer, which constitutes less than 1% of the total immunoglobulin pool. It is very susceptible to proteolysis It is primarily a cell membrane immunoglobulin found on the surface of B-lymphocytes in association with IgM.

18. IgE • IgE is a monomer, which founds, in minute quantity, 0.004%, in the blood plasma of parasitized individuals. • It is of major importance because it mediate some types of hypersensitivity (allergic) reactions and responsible for the immunity to invading parasites. • The IgE molecule is unique in that it binds strongly to a receptor on mast cells and basophiles. It causes the release of histamines and heparin from these cells

19. The End