Lecture outline

1. Lecture outline • The nomenclature of Immunology • Types of immunity (innate and adaptive; active and passive; humoral and cell-mediated) • Features of immune responses • The major cells of the immune system

2. Why the great interest in Immunology? • Basic science: understanding a complex biological system • Impact on many aspects of human disease • Immunization is the ONLY approach for eradicating a disease • New therapies based on biology • Potential for major role in emerging therapies (gene therapy, stem cell therapy)

3. The functional importance of the immune system

4. The central questions • How does the immune system respond to different infections? • Different types of microbes are eliminated by different effector mechanisms, which are designed to best combat each type of microbe • Antigens are useful models for studying immune responses to microbes

5. The central questions • How does the immune system respond to different infections? • Antigens are useful models for studying immune responses to microbes • Different types of microbes are eliminated by different effector mechanisms, which are designed to best combat each type of microbe • Why does the immune system not respond to self antigens? • What are the pathogenic mechanisms and clinico-pathologic consequences of abnormalities in the immune system?

6. Definitions • Immunity: protection against infections • Sensitivity: detectable reaction to exposure to previously encountered substance (antigen) • In clinical practice, it is not possible to measure protective immunity by challenging with infectious agents. Immunity is inferred from reactions to microbial antigens; individuals who show such reactions are said to be “sensitized”.

7. Innate and adaptive immunity Innate immunity: always present (ready to attack); many pathogenic microbes have evolved to resist innate immunity Adaptive immunity: stimulated by exposure to microbe; more potent

8. Properties of adaptive immune responses The two features that best distinguish adaptive and innate immunity are specificityand memory

9. Primary and secondary immune responses illustrate specificity and memory in adaptive immunity

10. The concept of clonal selection Development of specificity and diversity precedes exposure to antigens

11. Active and passive immunity Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th edition, 2011 Active immunity: long-lasting protection (memory), multiple effector mechanisms activated, lag time Passive immunity: rapid protection, short duration

12. Cells of the immune system • Lymphocytes • Mediators of adaptive immune responses; only cells with specific receptors for antigens • Antigen-presenting cells (APCs) • Specialized to capture, concentrate, and display antigens for recognition by lymphocytes • Dendritic cells; macrophages, B cells; follicular dendritic cells • Effector cells • Function to eliminate microbes; include lymphocytes, granulocytes (neutrophils, eosinophils), macrophages

13. Development of B and T lymphocytes Congenital immunodeficiency diseases are often caused by blocks at different stages of lymphocyte maturation

14. Classes of lymphocytes c Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th edition, 2011 Elsevier

15. The CD Nomenclature • Structurally defined leukocyte surface molecule that is expressed on cells of a particular lineage (“differentiation”) and recognized by a group (“cluster”) of cell-specific antibodies is called a member of a cluster of differentiation (CD) • CD molecules (CD antigens, CD markers) are: • Used to classify leukocytes into functionally distinct subpopulations, e.g. helper T cells are CD4+CD8-, CTLs are CD8+CD4- • Often involved in leukocyte functions • Antibodies against various CD molecules are used to: • Identify and isolate leukocyte subpopulations • Study functions of leukocytes • Eliminate particular cell populations

16. Types of adaptive immunity Different types of immune responses are mediated by different classes of lymphocytes and defend against different types of microbes

17. Phases of adaptive immune responses Need for proliferation and differentiation results in delay (typically 4-7 days) in effective adaptive immunity

18. Phases of lymphocyte activation Proliferation keeps pace with replicating microbes (e.g. 1 B cell --> 4,000 Ab-secreting cells --> ~1012 antibody molecules/hour) Differentiation: converts lymphocytes into effective defenders

19. Stages of lymphocyte activation • Naïve lymphocytes • Mature lymphocytes that have not previously encountered antigen; function -- antigen recognition • Preferential migration to peripheral lymphoid organs (lymph nodes), the sites where antigens are concentrated and immune responses start

20. Stages of lymphocyte activation • Naïve lymphocytes • Mature lymphocytes that have not previously encountered antigen; function -- antigen recognition • Preferential migration to peripheral lymphoid organs (lymph nodes), the sites where antigens are concentrated and immune responses start • Effector lymphocytes • Activated lymphocytes capable of performing the functions required to eliminate microbes (‘effector functions”) • Effector T lymphocytes: cytokine secretion (helper cells), killing of infected cells (CTLs) • B lymphocytes: antibody-secreting cells (e.g. plasma cells)

21. Stages of lymphocyte activation • Naïve lymphocytes • Mature lymphocytes that have not previously encountered antigen; function -- antigen recognition • Preferential migration to peripheral lymphoid organs (lymph nodes), the sites where antigens are concentrated and immune responses start • Effector lymphocytes • Activated lymphocytes capable of performing the functions required to eliminate microbes (‘effector functions”) • Effector T lymphocytes: cytokine secretion (helper cells), killing of infected cells (CTLs) • B lymphocytes: antibody-secreting cells (e.g. plasma cells) • Memory lymphocytes • Long-lived, functionally silent cells; mount rapid responses to antigen challenge (secondary responses)