Prof. Ibtesam Kamel Afifi Professor of Medical Microbiology & Immunology

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2 By Prof. Ibtesam Kamel Afifi Professor of Medical Microbiology & Immunology

3 Lecture objectives: At the end of the lecture you should be able to: Enumerate features that characterize acquired immune response Differentiate between active and passive immunity. Identify mechanisms of acquired immunity. Discuss stages of acquired immune response.

4 INNATE IMMUNITY Rapid responses to a broad range of microbes ACQUIRED IMMUNITY Slower responses to specific microbes External defenses Internal defenses Invading microbes (pathogens) Skin Mucous membranes Secretions Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes)

5 Generalized features of acquired (specific) immunity Discrimination between "self " and "non-self

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7 It is highly specific for the invading organism

8 Diversity: It can respond specifically to millions of antigens

9 Need previous exposure to pathogens Re-exposure is faster and stronger due to development of Memory for long time

10 Lecture objectives: At the end of the lecture you should be able to: Enumerate features that characterize acquired immune response Differentiate between active and passive immunity. Identify mechanisms of acquired immunity. Discuss stages of acquired immune response.

11 Active and passive immunity

12 Active acquired immunity: On exposure to foreign antigen or infective agent, the individual actively produces his own antibodies Immunity develops slowly, however it lasts for long time due to development of immunologic memory. It can be naturally acquired following clinical or subclinical infections, or artificially acquired following vaccination with live attenuated or killed infectious agents or their products e.g Diphtherial toxoid.

13 Passive acquired immunity ready made antibodies are transferred. This gives rapid protection, however immunity is short lasting. It can be naturally acquired e.g. antibodies are transferred from mother to fetus through the placenta (IgG) or in the breast milk (IgA) giving immunity to the infant for the first 6 months of life, or artificially acquired following injection of specific antibodies e.g. Diphtherial anti-toxins

14 Lecture objectives: At the end of the lecture you should be able to: Enumerate features that characterize acquired immune response Differentiate between active and passive immunity. Identify mechanisms of acquired immunity. Discuss stages of acquired immune response.

15 Mechanisms of acquired immunity The humoral (antibody mediated) immune response Against extra cellular Microbes and their toxins The cell mediated immune response intracellular pathogens e.g. virus, TB, Brucella,fungal, tumors Graft, Type IV hypersensitivity

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17 Lymphoid stem cell Bone marrow The humoral immune response The cell mediated immune response Thymus B cell T cell Blood, lymph, and lymphoid tissues (lymph nodes, spleen, and others)

18 Lecture objectives: At the end of the lecture you should be able to: Enumerate features that characterize acquired immune response Differentiate between active and passive immunity. Identify mechanisms of acquired immunity. Discuss stages of acquired immune response.

19 Stages of acquired immune response I. Antigen processing and presentation

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22 Other APCs are B-lymphocytes, dendritic cells and Langerhans cells of the skin

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24 Microbe Antigenpresenting cell II.Activation of Th cells: Antigen fragment IL-1 activate Th cell Class II MHC molecule T cell receptor Helper T cell

25 Activated specific Th cells undergo proliferation & secrete cytokines e.g INF-gamma &IL-2 which activate macrophage and NK cells increasing its killing effects against the antigens,4,5,6, IL- 2 and INF gamma (activated macrophage can kill target cells through release of TNF-α, nitric oxide and lytic enzymes) Macrophage &NK cells TNF, nitric oxide &lytic enzymes

26 Infected cell Antigen fragment Class I MHC molecule III.Activation of Tc cells: Tc cells are activated by 2 signals; antigen determinant presented to it on the surface of target cells in association with class I MHC molecule IL-2 Interleukin 2 by activated Th cells T cell receptor Cytotoxic T cell

27 The activated specific Tc undergo proliferation and secretes cytotoxins ( e.g. perforins and granzymes) to kill target cells e.g. graft cells, tumour cells or virus, bacterial or fungal infected cells (cell mediated immunity).

28 Antigen molecules B cells that differ in antigen specificity Antigen receptor IV. Activation of specific B- cells: Specific B-cell is activated by 2 signals ; IL-2, 4, 5 and 6 and antigen determinants of extracellular antigens e.g. bacteria or toxins Antibody molecules Clone of memory cells Clone of plasma cells

29 Clonal selection theory : each B- cell carry specific Ig receptor for one Ag,when this antigen enter the body,it selects the B-cell which carry Ig receptor specific to it,which is activated to produce humoral immune response against this particular antigen).this specific B-cell undergo proliferation and differentiation into plasma cells secreting specific antibodies to act against the inducing antigen. (humoral immunity).

30 Macrophage Bacterium Peptide antigen B cell Class II MHC molecule Clone of plasma cells Secreted antibody molecules TCR CD4 + Cytokines Endoplasmic reticulum of plasma cell Helper T cell Activated helper T cell Clone of memory B cells

31 V. Memory cells formation: Some activated Th, Tc and B-cells become memory cells that can respond to subsequent encounters with the same antigen.

32 VI. The usual outcome of the immune response is the elimination of the offending antigen, after that the response is down regulated by the Th regulatory cells.

33 Humoral immune response Cell-mediated immune response First exposure to antigen Intact antigens Antigens engulfed and displayed by dendritic cells Antigens displayed by infected cells Activate Activate Activate B cells Helper T cell Secreted cytokines activate Cytotoxic T cell Gives rise to Gives rise to Gives rise to Plasma cells Memory B cells Active and memory helper T cells Memory cytotoxic T cells Active cytotoxic T cells Secrete antibodies that defend against pathogens and toxins in extracellular fluid Defend against infected cells, cancer cells, and transplanted tissues

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