Human Immunology, Summary
Chapter 1, Properties and overview of immune responses
Immunology is the study of immune responses and of the cellular and molecular events that
occur after an organism encounters microbes and other foreign macromolecules.
The first disease that has been eradicated worldwide by vaccination is smallpox. AIDS and
COVID-19 however highlighted the significance of the immune system.
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 are
capable of reacting rapidly to invading
microbes.
The adaptive immune system recognizes
and reacts to a large number of microbial
and nonmicrobial substances, called
antigens. Pathogens that resist the innate
immune response, are eradicated by the
stronger and more specialized adaptive
immune responses.
The innate immune response to microbes provides early danger signals that stimulate
adaptive immune responses. Conversely, adaptive immune responses often work by
enhancing the protective mechanisms of innate immunity, making them more capable of
effectively combating microbes. Different mechanisms are used by the innate and adaptive
immune systems to prevent reactions against healthy host cells.
Innate immunity
The innate immune system responds almost immediately to microbes and injured cells, and
repeated exposures induce virtually identical innate immune responses. The receptors of
innate immunity are specific for structures that are common to groups of related microbes
and do not distinguish fine differences among microbes. The principal components of innate
immunity are
- Physical and chemical barriers, such as epithelia and antimicrobial chemicals
produced at epithelial surfaces
- Phagocytic cells (neutrophils, macrophages), dendritic cells (DCs), mast cells, natural
killer (NK cells), and other innate lymphoid cells
, - Blood proteins, including components of the complement system and other
mediators of inflammation.
The innate immune response combats microbes by two main strategies (1) by recruiting
phagocytes and other leukocytes that destroy the microbes, in the process called
inflammation; and (2) by blocking viral replication or killing virus-infected cells by
mechanisms distinct from inflammatory reactions.
Adaptive immunity
The adaptive immune response is mediated by cells called lymphocytes and their products.
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
The immune responses are specific for distinct antigens and often for a different portion of a
single complex protein or macromolecule. The parts of complex antigens that are specifically
recognized by lymphocytes are called determinants or epitopes.
Clones of lymphocytes with different specificities are
present in unimmunized individuals and are able to
recognize and respond to foreign antigens, this is called
clonal selection. Antigen-specific clones of lymphocytes
develop before and independent of exposure to
antigen. An introduced antigen binds to (selects) the
cells of the preexisting antigen-specific clone and
activates them, leading to an immune response specific
for that antigen. 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, or primary, immune response to that antigen. Immunologic memory
occurs because each exposure to an antigen generates long-lived memory cells specific for
the antigen.
There are two reasons why secondary responses are typically stronger than primary immune
responses: (1) 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 (2)
,memory cells react more rapidly and vigorously to antigen challenge than do naive
lymphocytes.
Memory enables the immune system to combat infections of prevalent and repeatedly
encountered microbes.
- Nonreactivity to self (self-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.
- Because of the ability of lymphocytes and other immune cells to circulate among
tissues, adaptive immunity is systemic
Even if an immune response is initiated at one site it can provide protection at distant sites.
This feature is, of course, essential for the success of vaccination.
- 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. This positive feedback is important to enable the small number
of lymphocytes that are specific for any microbe to generate the large response needed to
eradicate that infection. 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.
Overview of humoral and cell-mediated immunity
There are two types of adaptive immunity, called humoral immunity and cell-mediated
immunity, which are mediated 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. 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.
Microbes that are ingested but survive within phagocytes or viruses replicate in host cells
which are inaccessible to circulating antibodies and therefore need cell-mediated immunity.
, 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.
Transferring antibodies from an
immunized individual into an individual
who has not encountered the antigen is
called passive immunity. The recipient of
such a transfer becomes immune to the particular antigen without ever having been exposed
to or having responded to that antigen. The transfer of maternal antibodies through the
placenta to the fetus is an example of this.
Types of adaptive immunity
Initiation and
development of adaptive immune responses
