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

• 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)

Why the great interest in Immunology?

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

– Antigens are useful models for studying immune responses to microbes

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?

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”.

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

Innate and adaptive immunity

The two features that best distinguish adaptive and innate immunity are specificity and memory

Properties of adaptive immune responses

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

Development of specificity and diversity precedes exposure to antigens

The concept of clonal selection

Active and passive immunity

Active immunity: long-lasting protection (memory), multiple effector mechanisms activated, lag time

Passive immunity: rapid protection, short duration

Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th edition, 2011

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

Congenital immunodeficiency diseases are often caused by blocks at different stages of lymphocyte maturation

Development of B and T lymphocytes

Classes of lymphocytes

Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th edition, 2011 c Elsevier

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

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

Types of adaptive immunity

Need for proliferation and differentiation results in delay (typically 4-7 days) in effective adaptive immunity

Phases of adaptive immune responses

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

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

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)

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)