1. GENERAL IMMUNOLOGY PHT 324 Dr. Rasheeda Hamid Abdalla Assistant Professor E-mail rasheedahamed12@hotmail.com

2. Objectives Antigens Immunoglobulins Immunoglobulins genes 2

3. Immunogen: A substance that induces a specific immune response  Antigen (Ag): A substance that can bound by an antibody,or whose peptide fragment can be recognized by a Tcell receptor via major histocompatability complex (MHC) molecules presentation

4. Epitope or antigenic determinant: that portion of an antigen that combines with the products of a specific immune response Paratope: “The site in the variable (V) domain of an antibody or T-cell receptor that binds to an epitope on an antigen.

5.  Antibodies recognize and react with antigenic determinants or epitopes. Figure 17.3

6. Haptens Are not immunogenic because they cannot bind to MHC proteins, and therefore are unable to activate helper T cells Thus all immunogens are antigens but not all antigens are immunogens Almost all antigens are immunogens,the term “antigen” is commonly employed as a single term to encompass both immunogen and antigen

7. Figure 17.4

8. Foreignness ((recognized as nonself by the body). Molecular size Chemical composition and heterogeneity Degradability

9.  Exogenous (external) Exogenous antigens are antigens that have entered the body from the outside, for example by inhalation, ingestion or injection  Endogenous (internal) Endogenous antigens are generated within normal cells as a result of normal cell metabolism, or because of viral or intracellular bacterial infection

10. Exogenous: -presented by Antigen Presenting Cells (APC’s). -These are macrophages, B-cells, and some dendritic cells Endogenous: -typically peptides derived from any protein; an infected cell displays “not-self” proteins and is, thus, an “altered self cell”

11. Exogenous: these antigens are presented in MHC-II; they are seen by T-cells with a TCR and an associated protein called CD4 Endogenous: these antigens are presented by MHC-I; they are seen by T-cells with a TCR and an associated protein called CD8

12. Chemical Nature of Immunogens  Proteins  Polysaccharides  Nucleic Acids  Lipids ◦ Some glycolipids and phosopholipids can be immunogenic for T cells and illicit a cell mediated immune response

13.  An antibody (Ab), also known an immunoglobulin (Ig), is a large shaped protein produced mainly by plasma cells that is used by the immune system to identify and neutralize pathogens such as bacteria and viruses.  The antibody recognizes a unique molecule of the harmful agent, called an antigen, via the variable region.

14. Figure 17.5a-c

15.  Antibodies have many functions including  Neutralization of toxins  Activation of complement which result in improved  Opsonization,and lysis of invading microoganisms

16.  IgG - Gamma ( γ ) heavy chains  IgM - Mu (µ) heavy chains  IgA - Alpha ( α ) heavy chains  IgD - Delta ( δ ) heavy chains  IgE - Epsilon ( ε ) heavy chains  Each has unique structural and functional characteristics

17. IgGIgDIgEIgAIgM

18.  Five classes of Ab ◦ IgM  First Ab to respond to infection  5 – 13% of Ab in circulation  Structure: pentamer  Five monomer units joined together at the constant region  Found on the surface of B lymphocytes as a monomer  Only Ab that can be formed by the fetus

19. ◦ IgG  Dominant Ab in circulation  80 – 85% Ab in circulation  Structure = monomer  Only Ab that can cross the placenta  The antibody of memory !!!!!

20. IgA  Found in secretions  10 - 13 % of Ab in circulation  Structure: Monomer in serum  Dimer in secretions  Breast milk, mucus, tears and saliva

21. ◦ IgD  <1% of total Ab in circulation  Structure = monomer  Maturation of antibody response ◦ IgE  Barely detectable in circulation  Structure = monomer  Active in allergic reaction

22.  Have a common structure with four polypeptide chains.  The heavy chain is chromosome no.14 & they are called isotypes.  Light chain are 2 types:- K (60% more chr.2) λ(30% less chr.22)  The disulphide bonds joining the antibody heavy chains are located in a flexible region of the heavy chain known as the hinge region.

23. light chains An antibody molecule is composed of two identical Ig heavy chains (H) and two identical light chains (L), each with a variable region (V) & constant region (C).

25.  One of the important feature of the vertebrate immune system is its ability to respond to an apparently limitless array of foreign antigens.  As immunoglobulin (Ig) sequence data accumulated, virtually every antibody molecule studied was found to contain a unique amino acid sequence in its variable region but only one of a limited number of invariant sequences in its constant region.

26.  The genetic basis for this combination of constancy and tremendous variation in a single protein molecule lies in the organization of the immunoglobulin genes.  An Ab combining site is made up of one V L and one V H.  The specificity of any combining site is determined by its amino acid sequence.  There exist at least 10 6 unique combining sites.

27.  Three families of Ig genes exist in mammals, one encoding HEAVY chains, another KAPPA chains, and the third LAMBDA chains.  Each of these clusters contains one or more constant region genes and a number of variable region gene segments.

28.  The formation of a complete variable region of a light or heavy chain requires the joining of two or three separate genetic elements by a process of GENE REARRANGEMENT; a separate DNA rearrangement in the heavy-chain complex is required for subsequent CLASSSWITCHING.  Both germ-line and somatic events contribute to antibody diversity, including COMBINATORIAL JOINING, SOMATIC MUTATION and COMBINATORIAL ASSOCIATION.

29.  Germ-Line Model  Somatic-Variation Model  Two-Gene Model

30.  When the B-cell is maturing in the bone marrow.(the stem cell helps to make B-cell mature)  Maternal is expressed and paternal is silence.  Conclusion:-1 B- cell will only expressed immunoglobulin that have gene coming from father or mother.

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