بسم الل ه الرحمن الرحيم

1. بسم الله الرحمن الرحيم

2. Acquired (Adaptive) Immunity Dr / Tamer El Mokadem

3. 1) Innate immunity (Natural or Non specific) 2) Acquired immunity (Adaptive or Specific) Cell-mediated immunity Humoral immunity

4. Aquired (specific) immunity * The acquired immune response is morespecialized than innate immune response * The acquired immune response involves a combination of two mechanisms : 1) Humoral immune response 2) cell mediated immune response * They interact with one another to destroy foreign body (microorganisms, infected cells, tumor cells)

5. 1) Humoral immune response: - Antibodies are produced by B-lymphocytes - These have the ability to recognize and bind specifically to antigen that induced their formation 2) The cell mediated immune response (CMI): -It is mediated by certain type of T-lymphocytes - T-lymphocytes recognize foreign material by means of surface receptors - T-lymphocytes attack and destroy foreign material directly or through release of soluble mediators i.e. cytokines

6. Characters Of Acquired Immunity 1) Highly specific for the invading organism 2) Differentiate between “self and “non self” Ag The response only occurs to “non self” molecules 3) Diversity: - It can respond to millions of different antigens - Lymphoctes population consists of many different clones (one cell and its progny) - Each clone express an antigen receptor and responds only to one antigenic epitope

7. Mechanism Of Acquired Immunity * Recognition of the antigen by specific lymphocytes * Activation of these specific lymphocytes * Proliferation and differentiation into effector cells; -The effector cells eliminate the antigen -Return of homeostasis and development of memory cells * Memory cells evoke a more rapid and long response on re-exposure to same antigen

8. Cells of Immune System bone marrow Stem cells differentiate into Lymphoid series Myeloid series B-lymphocytes T-lymphocytes NK monocyte-macrophage dendritic cells eosinophils mast cell

9. B lymphocytes • B lymphocytes (30%)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 • develop into plasma cells, secreting large amounts of specific antibody, or • To circulate as memory B cells • To present antigenic peptides to T cells, consequent upon interalization and processing of the original antigen

10. B-lymphocytes in bon marrow * The lymphoid stem cells differentiate into B cells * B-cells precursors mature, differentiate into immunocomptent B-cells with a single antigen specificity * Immature B-cells that express high affinity receptors for self antigens, die or fail to mature i.e negative selection or clonal deletion * This process induces central self tolerance and reduces autoimmune diseases

11. B-lympocytes * Immature B cells express receptors on the surface(IgM) * Mature B cells express IgM, IgD molecules on surfaces * IgM and IgD molecules serve as receptors for antigens * Memory B-cells express IgG or IgA or IgE on the surface * B-cells bear receptors for Fc portion of IgG and a receptor for C3 component of the complement • They express an array of molecules on their surfaces that are important in B-cells interactions with other cells such as MHC II, B7 and CD40

12. T- Lmphocytes T-lmphocytes (60-80%)migrate from bon marrow to enter thymus 1) In the outer cortex of thymus: - T-lymphocytes acquire specific receptors (TCRs) - This receptor commit lymphocyte to a single antigen specificty - Responding by proliferation and production of a clone of cells (clonal selection) - They differentiate to express CD3, both CD4 and CD8 coreceptors (double positive cells)

13. T-Lmphocytes 2) In the medulla of thymus: - TCRs recognize MHC molecules, loaded with self-peptides (p-MHC) - TCRs capable of binding with low affinity to p-MHC will receive positive selection signals to divide and establish clones - TCRs that bind too strongly to p-MHC undergo (negative selection) - This selection process will eliminate the potentially most harmful self reactive T-cells (central self tolerance)

14. T-Lmphocytes Immature T-cells express both CD4 and CD8 (DP) As they mature * T-cell with TCRs that have affinity to bind to MHC class II will become helper T-cells with CD4 molecule only * T-cell with TCRs that have affinity to bind with MHC class I will become cytotoxic T-cells with CD8 molecule only

15. T-Lmphocytes Mature positively selected T-cells are MHC restricted * CD4 T-cells are MHC II restricted and only recognize specific foreign peptide only when they are presented in association with specific MHC II molecules * CD8 T-cells are MHC I restricted and recognize specific foreign peptidees only when they are presented in association with specific MHC I molecules

16. T-cell surface markers These are molecules that by witch we can identify T-cells and divide them to subsets They are required to for interactions between T-cells and APC and for antigen recognition These are TCRs, CD3, CD4, CD8, CD2, CD28,and CD40L on activated T-cells

17. T cell Receptor (TCR) Composed of two polypeptide chains(/ ) or (/)(5%). Each chain has a constant region and a variable region simiolar to Fab portion of Antibodies The TCR only recognizes specific peptide/MHC complexes expressed on the surfaces of cells TCR complex is composed of TCR + CD3 complex which is involved in cell signalling for T cell activation. CD4,CD8 as Coreceptor CD28 as costimulatory mplecule Cd40L on activated T cells

18. T cell subpopulations • 1- CD4 T Cell ( T helper) (TH) • 2- CD8 T Cell (T cytotoxic)(TC)(CTL)

19. CD4 T Cell ( T helper) (TH) • 65% of T lymphocytes • Present in Blood ,tonsils, Thymic medulla • The main orchestrators of the immune system as they activate all other immune cells • Secrete cytokines • 2 subsets of naive TH0 <<<TH1 , TH2 based on the secreted cytokines & functions

20. TH 1 • IL-12 & IFN-  induce NaiveTH0<<< TH1 • Secrete cytokines <<< IL2, IFN-  , TNF-β • Involved in Cell mediated immunity (CMI)

21. TH 2 • IL-4 induce Naive TH0<<<TH2 • TH2 secrete cytokines <<< IL-4, IL-5, IL-6, IL-10, IL-13 • Involved in B cell activaion & differentiation & antibody production

22. Regulatory T cell (T reg) • 5-10 % of CD4 T cell • Express CD25 on its surface • CD25 <<<α chain of IL-2 receptor • Regulate & inhibit the immune response after activation • Secrete IL-10, TGF-β

23. Thanks