Immunology summary
Chapter 1: Properties and Overview of Immune Responses
The cells and molecules responsible for immunity constitute the immune system, and their collective
and coordinated response to the introduction of foreign substances is called the immune response.
The physiologic function of the immune system is defense against infectious microbes; even noninfectious
foreign substances and products of damaged cells can elicit immune responses. Mechanisms that
normally protect individuals from infection and eliminate foreign substances also are capable of causing
tissue injury and disease in some situations. A more inclusive definition of the immune response is a
reaction to microbes as well as to molecules that are recognized as foreign, regardless of the physiologic
or pathologic consequence of such a reaction. Under some situations, even self molecules can elicit
immune responses (autoimmune responses). Immunology is the study of immune responses in this
broader sense and of the cellular and molecular events that occur after an organism encounters
microbes and other foreign macromolecules. Historically, the first clear example of this manipulation,
was Edward Jenner’s successful vaccination against smallpox. Jenner, noticed that milkmaids who had
recovered from cowpox never contracted the more serious smallpox. On the basis of this observation, he
injected the material from a cowpox pustule into the arm of an 8-year-old boy. When this boy was later
intentionally inoculated with smallpox, the disease did not develop. Jenner’s landmark treatise on
vaccination was published in 1798. It led to the widespread acceptance of this method for inducing
immunity to infectious diseases, and vaccination remains the most effective method for preventing
infections. Advances in cell culture techniques, immunochemistry, recombinant DNA methodology, x-ray
crystallography, and creation of genetically altered animals (transgenic and knockout mice) have
changed immunology.
INNATE AND ADAPTIVE IMMUNITY
Defense against microbes is mediated by sequential and
coordinated responses that are called innate and adaptive
immunity. Innate immunity (natural immunity or native
immunity) is essential for defending against microbes in
the first few hours or days after infection, before adaptive
immune responses have developed. Innate immunity is
mediated by mechanisms that are in place even before an
infection occurs and that facilitate rapid responses to
invading microbes. In contrast to innate immunity, there are other immune responses that are
stimulated by exposure to infectious agents and increase in magnitude and defensive capabilities with
each successive exposure to a particular microbe. Because this form of immunity develops as a response
to infection and adapts to the infection, it is called adaptive immunity (specific immunity or acquired
immunity). The adaptive immune system recognizes and reacts to a large number of microbial and
nonmicrobial substances, called antigens. Although many pathogens have evolved to resist the innate
immune response, adaptive immune responses, being stronger and more specialized, are capable of
eradicating even these infections. Adaptive immune responses often work by enhancing the protective
mechanisms of innate immunity, making them more capable of effectively combating microbes. Every
individual’s immune system is able to recognize, respond to, and eliminate many foreign (non-self)
antigens but does not usually react against that individual’s own (self) antigens and tissues.
,Different mechanisms are used by the innate and adaptive immune systems to prevent reactions against
healthy self cells. Because of the ability of lymphocytes and other immune cells to circulate among
tissues, immunity is systemic, meaning that even if an immune response is initiated in one site it can
provide protection at distant sites. This feature is essential for the success of vaccination - a vaccine
administered in the subcutaneous or muscle tissue of the arm can protect from infections in any tissue.
Immune responses are regulated by a system of positive feedback loops that amplify the reaction and by
control mechanisms that prevent inappropriate or pathologic reactions. When lymphocytes are
activated, they trigger mechanisms that further increase the magnitude of the response. Many control
mechanisms become active during immune responses, which prevent excessive activation of
lymphocytes that could cause collateral damage to normal tissues, and also prevent responses against
self antigens. Mechanisms for defending the host against microbes are present in all multicellular
organisms. The antigen receptors on early immunological cells are proteins with limited variability that
are capable of recognizing many antigens but are distinct from the highly variable antibodies and T cell
receptors that appeared later in evolution. The more specialized defense mechanisms that constitute
adaptive immunity are found in vertebrates only. Most of the components of the adaptive immune
system, including lymphocytes with highly diverse antigen receptors, antibodies, and specialized
lymphoid tissues, evolved coordinately within a short time in jawed vertebrates approximately 360
million years ago.
Innate Adaptive
Characteristics
Specificity For molecules shared by groups of related For microbial and nonmicrobial
microbes and molecules produced by antigens
damaged host cells
Diversity Limited; recognition molecules encoded by Very large; receptor genes are
inherited (germline) genes formed by somatic recombination of
gene segments in lymphocytes
Memory None or limited Yes
Nonreactivity to self Yes Yes
Components
Cellular and chemical Skin, mucosal epithelia; antimicrobial Lymphocytes in epithelia; antibodies
barriers molecules secreted at epithelial surfaces
Blood proteins Complement, various lectins and agglutinins Antibodies
Cells Phagocytes (macrophages, neutrophils), Lymphocytes
dendritic cells, natural killer cells, mast cells,
innate lymphoid cells
INNATE IMMUNITY: THE EARLY DEFENSE
The innate immune system responds almost immediately to microbes and injured cells, and repeated
exposures invoke virtually identical innate immune responses. The receptors of innate immunity are
specific for structures that are common to groups of related microbes. The principal components of
innate immunity are (1) physical and chemical barriers, such as epithelia and antimicrobial chemicals
produced at epithelial surfaces; (2) phagocytic cells (neutrophils, macrophages), dendritic cells (DCs),
mast cells, natural killer (NK cells) and other innate lymphoid cells; and (3) blood proteins, including
components of the complement system and other mediators of inflammation. Many innate immune
cells, such as macrophages, dendritic cells, and mast cells, are always present in most tissues, where they
function as sentinels to keep watch for invading microbes. The innate immune response combats
microbes by two main reactions - by recruiting phagocytes and other leukocytes that destroy the
,microbes, in the process called inflammation, and by blocking viral replication or killing virus-infected
cells without a need for an inflammatory reaction.
ADAPTIVE IMMUNITY
The adaptive immune response is mediated by cells called lymphocytes and their products. Lymphocytes
express highly diverse receptors that are capable of recognizing a vast number of antigens. There are two
major populations of lymphocytes, called B lymphocytes and T lymphocytes, which mediate different
types of adaptive immune responses.
Cardinal Features of Adaptive Immune Responses
Specificity and diversity
Immune responses are specific for distinct antigens and often for different portions of a single complex
protein, polysaccharide, or other macromolecule. The parts of complex antigens that are specifically
recognized by lymphocytes are called determinants or epitopes. Individual lymphocytes express
membrane receptors that can distinguish subtle differences in structure between distinct epitopes.
Clones of lymphocytes with different specificities are present in unimmunized individuals and are able to
recognize and respond to foreign antigens. This fundamental concept is called clonal selection. Antigen-
specific clones of lymphocytes develop before and independent of exposure to antigen. An introduced
antigen binds to the cells of the pre-existing antigen-specific clone and activates them. As a result, the
cells specific for the antigen proliferate to generate
thousands of progeny with the same specificity, a process
called clonal expansion. The total number of antigenic
specificities of the lymphocytes in an individual, called the
lymphocyte repertoire, is extremely large. This ability of the
lymphocyte repertoire to recognize a very large number of
antigens, called diversity, is the result of variability in the
structures of the antigen-binding sites of lymphocyte
receptors for antigens. In other words, there are many
different clones of lymphocytes and each clone has a unique
antigen receptor and therefore a singular antigen specificity,
contributing to a total repertoire that is extremely diverse.
Memory
Responses to second and subsequent exposures to the same antigen, called secondary immune
responses, are usually more rapid, greater in magnitude, and often qualitatively different from the first
immune response to that antigen. Immunologic memory occurs because each exposure to an antigen
generates long-lived memory cells specific for the antigen. Memory cells accumulate and become more
numerous than the naive lymphocytes specific for the antigen that exist at the time of initial antigen
exposure, and memory cells react more rapidly and
vigorously to antigen challenge than do naive lymphocytes.
Memory enables the immune system to mount heightened
responses to persistent or recurring exposure to the same
antigen and thus to combat infections by microbes that are
prevalent in the environment and are encountered
repeatedly.
, Nonreactivity to self (self tolerance)
One of the most remarkable properties of every normal individual’s immune system is its ability to
recognize, respond to, and eliminate many foreign (non-self) antigens while not reacting harmfully to
that individual’s own (self) antigens. Immunologic unresponsiveness is also called tolerance. Tolerance to
self antigens, or self-tolerance, is maintained by several mechanisms. These include eliminating
lymphocytes that express receptors specific for some self antigens, inactivating self-reactive
lymphocytes, or suppressing these cells by the actions of other (regulatory) cells. Abnormalities in the
induction or maintenance of self-tolerance lead to immune responses against self (autologous) antigens,
which may result in disorders called autoimmune diseases.
Overview of Humoral and Cell-Mediated Immunity
There are two types of adaptive immunity, called humoral immunity and cell-mediated immunity, which
are induced by different types of lymphocytes and function to eliminate different types of microbes.
Humoral immunity is mediated by molecules in the blood and mucosal secretions, called antibodies,
which are produced by B lymphocytes. Antibodies recognize microbial antigens, neutralize the infectivity
of the microbes, and target microbes for elimination
by phagocytes and the complement system.
Humoral immunity is the principal defense
mechanism against microbes and their toxins
located outside cells because secreted antibodies
can bind to these microbes and toxins, neutralize
them, and assist in their elimination. Cell-mediated
immunity, also called cellular immunity, is
mediated by T lymphocytes. Many microbes are
ingested by but survive within phagocytes, and
some microbes, notably viruses, infect and replicate
in various host cells. Defense against such infections
is a function of cell-mediated immunity, which promotes the destruction of microbes inside phagocytes
and the killing of infected cells to eliminate reservoirs of infection. Protective immunity against a microbe
may be provided either by the host’s response to the microbe or by the transfer of antibodies that defend
against the microbe. The form of immunity that is induced by exposure to a foreign antigen is called
active immunity because the immunized individual plays an active role in responding to the antigen.
Individuals and lymphocytes that have not encountered a particular antigen are said to be naive,
implying that they are immunologically inexperienced. Individuals who have responded to a microbial
antigen and are protected from subsequent exposures to that microbe are said to be immune. Immunity
can also be conferred on an individual by transferring antibodies from an immunized individual into an
individual who has not encountered the antigen. This form of immunity is called passive immunity.
Passive immunization against potentially
lethal toxins by the administration of
antibodies from immunized animals or
people is a lifesaving treatment for rabies
infection and snake bites. Patients with some
genetic immunodeficiency diseases are
passively immunized by transfer of pooled
antibodies from healthy donors. The
definition of antigens includes molecules that
bind to specific lymphocyte receptors,
