Kuby Immunology, 7e: Chapter 1 Overview of the Immune System

A historical perspective of immunology What is immunity? Immunity is the state of protection against foreign pathogens or substances (antigens) Latin term immunis, meaning “exempt,” is the source of the English word immunity Observations of immunity go back over 2000 years Thucydides, an ancient historian, wrote in 430 bc of a plague in Athens where those who had recovered could safely nurse the currently ill

A historical perspective of immunology Can we generate immunity without inducing disease? YES…through vaccination Vaccination prepares the immune system to eradicate an infectious agent before it causes disease Widespread vaccine use has saved many lives Classic examples: rabies vaccine and eradication of smallpox

A historical perspective of immunology A portion of immunity involves both humoral and cellular components Humoral immunity combats pathogens via antibodies Antibodies are produced by B cells Antibodies can be transferred between individuals to provide passive immunity Cell-mediated immunity involves primarily T lymphocytes These can eradicate pathogens, clear infected self-cells, or aid other cells in inducing immunity

A historical perspective of immunology Clonal selection Individual B and T cells each have an individual specificity for a single antigen This is due to each cell having many copies of a receptor on their surface that only bind to one type of antigen When a B or T cell interacts with its specific antigen, it is selected and becomes activated Activation results in a proliferation, producing a large number of clones Each clone is reactive against the antigen that initially stimulated the original lymphocyte

Important concepts for understanding the mammalian immune response Pathogens fall into four major categories Immune responses are quickly tailored to the type of organism involved

Important concepts for understanding the mammalian immune response Immune responses rely on recognition molecules Germ-line encoded (pattern recognition receptors, PRRs) These bind to pathogen-associated molecular patterns (PAMPs)―generic molecules found on many different types of pathogens (e.g., peptidoglycan) Randomly generated (B and T cell receptors) These bind to very specific antigens, rather than generic molecules found on many pathogens

Important concepts for understanding the mammalian immune response Humoral and cell-mediated immunity relies on surface receptors (B and T cell receptors) These are randomly generated by DNA rearrangements in B and T cells Many of these are nonviable and are deleted during development

Important concepts for understanding the mammalian immune response Tolerance ensures that the immune system avoids destroying host tissue Many of the random rearrangements used to create B and T cell receptors could be anti-self Tolerance helps to keep these anti-self recognition molecules/cells from circulating in the bloodstream

Important concepts for understanding the mammalian immune response In response to pathogens, vertebrate immune systems use two interconnected systems Innate immunity Adaptive immunity

Important concepts for understanding the mammalian immune response Innate immune responses First line of defense Fast, but nonspecific Uses germ-line–encoded recognition molecules Also uses phagocytic cells

Important concepts for understanding the mammalian immune response Adaptive immune responses Humoral and cell-mediate responses Using B and T lymphocytes, respectively Slower to develop 5–6 days (or more) Use randomly generated antigen receptors Highly specific to individual antigen molecules

Important concepts for understanding the mammalian immune response Innate and adaptive immunity work cooperatively Activation of innate immune responses produces signal molecules (often cytokines) These signal molecules stimulate and direct adaptive immune responses

Important concepts for understanding the mammalian immune response Memory is the hallmark of adaptive immunity Primary response is initiated upon first exposure to an antigen Memory lymphocytes are left behind after antigen is cleared A second exposure to the same antigen re-stimulates memory lymphocytes Reactivation yields faster, more significant, better response Memory is NOT present in innate immunity

The good, bad, and ugly of the immune system Dysfunctions of immunity―two broad categories Overly active or misdirected immune responses Allergies/asthma Autoimmune disease (e.g., multiple sclerosis, Crohn’s disease) Immunodeficiency Primary (genetic) loss of immune function Secondary (acquired) loss of immune function Opportunistic infections (e.g., oral thrush) can occur in people with impaired immune responses

The good, bad, and ugly of the immune system Transplanted tissues A rare case where we want to AVOID an immune response (rejection) The body’s natural response to foreign tissue is to attack it and destroy it Cancer A situation where the dangerous cells we want to target are our own self cells Generally tolerated and hard to generate immunity against

Summary Immunity is a complex subject, broken down into many different layers and areas This is just a quick summary of the basics of the field―there’s MUCH more to come! Understanding how immunity works allows us to: Exploit it to prevent infections (vaccination) Exploit it to treat illness (shutting down autoimmune disease or ramping up anti-cancer responses) Provide safer organ and tissue transplants