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

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)

Definitions Immunity: protection against infections Immune system: molecules, cells and tissues that mediate responses to foreign substances Antigens: substances recognized by the cells and molecules of the immune system and to which the system responds

The functional importance of the immune system

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 Microbes and hosts are engaged in an evolutionary struggle, each trying to overcome the other; many of the features of the immune system reflect the consequences of such evolution

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 The evolutionary struggle between microbes and hosts 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?

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

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

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

The concept of clonal selection Lymphocytes with highly specific and diverse antigen receptors develop prior to exposure to antigens

Active and passive immunity Active immunity: long-lasting protection (memory), multiple effector mechanisms activated, lag time Passive immunity: rapid protection, short duration

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

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

Classes of lymphocytes

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

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

Phases of adaptive immune responses Need for proliferation and differentiation results in delay (typically 4-7 days) in the adaptive immune response

Stages in the life history of lymphocytes Proliferation: expands number of antigen-specific cells Differentiation: converts lymphocytes into effective defenders

Naïve, effector and memory lymphocytes 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

Naïve, effector and memory lymphocytes 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 plasma cells

Naïve, effector and memory lymphocytes 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)