Defense Mechanisms of the Body
679
Nonspecifi
c Immune Defenses
I. External barriers to infection are the skin, the linings of the
respiratory, gastrointestinal, and genitourinary tracts, the
cilia of these linings, and antimicrobial chemicals in glandular
secretions.
II. Infl ammation, the local response to injury or infection,
includes vasodilation, increased vascular permeability to
protein, phagocyte chemotaxis, destruction of the invader via
phagocytosis or extracellular killing, and tissue repair.
a. The mediators controlling these processes, summarized
in Table 18–4, are either released from cells in the area or
generated extracellularly from plasma proteins.
b. The main cells that function as phagocytes are the
neutrophils, monocytes, macrophages, and dendritic cells.
These cells also secrete many infl
ammatory mediators.
c. One group of infl ammatory mediators—the complement
family of plasma proteins activated during nonspecifi c
infl ammation by the alternate complement pathway—not
only stimulates many of the steps of infl ammation but
mediates extracellular killing via the membrane attack
complex.
d. The fi nal response to infection or tissue damage is tissue
repair.
III. Interferon stimulates the production of intracellular proteins
that nonspecifi cally inhibit viral replication.
Specifi
c Immune Defenses
I. Lymphocytes mediate specifi c immune responses.
II. Specifi c immune responses occur in three stages.
a. A lymphocyte programmed to recognize a specifi c antigen
encounters it and binds to it via plasma membrane receptors
specifi c for the antigen.
b. The lymphocyte undergoes activation—a cycle of cell
divisions and differentiation.
c. The multiple active lymphocytes produced in this manner
launch an attack all over the body against the specifi c
antigens that stimulated their production.
III. The lymphoid organs are categorized as primary (bone marrow
and thymus) or secondary (lymph nodes, spleen, tonsils, and
lymphocyte collections in the linings of the body’s tracts).
a. The primary lymphoid organs are the sites of maturation
of lymphocytes that will then be carried to the secondary
lymphoid organs, which are the major sites of lymphocyte
cell division and specifi c immune responses.
b. Lymphocytes undergo a continuous recirculation among
the secondary lymphoid organs, lymph, blood, and all the
body’s organs and tissues.
IV. The three broad populations of lymphocytes are B, T, and NK
cells.
a. B cells mature in the bone marrow and are carried to the
secondary lymphoid organs, where additional B cells arise
by cell division.
b. T cells leave the bone marrow in an immature state, are
carried to the thymus, and undergo maturation there.
These cells then travel to the secondary lymphoid organs
and new T cells arise from them by cell division.
c. NK cells originate in the bone marrow.
V. B cells and T cells have different functions.
a. B cells, upon activation, differentiate into plasma cells,
which secrete antibodies. Antibody-mediated responses
constitute the major defense against bacteria, viruses, and
toxins in the extracellular fl
uid.
b. Cytotoxic T cells directly attack and kill virus-infected cells
and cancer cells, without the participation of antibodies.
c. Helper T cells stimulate B cells and cytotoxic T cells via
the cytokines they secrete. With few exceptions, this help is
essential for activation of the B cells and cytotoxic T cells.
VI. B-cell plasma-membrane receptors are copies of the specifi c
antibody (immunoglobulin) that the cell is capable of producing.
a. Any given B cell or clone of B cells produces antibodies
that have a unique antigen binding site.
b. Antibodies are composed of four interlocking polypeptide
chains; the variable regions of the antibodies are the sites
that bind antigen.
VII. T-cell surface plasma-membrane receptors are not
immunoglobulins, but they do have specifi c antigen binding
sites that differ from one T-cell clone to another.
a. The T-cell receptor binds antigen only when the antigen
is complexed to one of the body’s own plasma membrane
MHC proteins.
b. Class I MHC proteins are found on all nucleated cells of
the body, whereas class II MHC proteins are found only
on macrophages, B cells, and dendritic cells. Cytotoxic T
cells require antigen to be complexed to class I proteins,
whereas helper T cells require class II proteins.
VIII. Antigen presentation is required for T cell activation.
a. Only macrophages, B cells, and dendritic cells function
as antigen-presenting cells (APCs) for helper T cells.
The antigen is internalized by the APC and hydrolyzed
to peptide fragments, which are complexed with class
II MHC proteins. This complex is then shuttled to
the plasma membrane of the APC, which also delivers
a nonspecifi c costimulus to the T cell and secretes
interleukin 1 (IL-1) and tumor necrosis factor (TNF).
b. A virus-infected cell or cancer cell can function as an
APC for cytotoxic T cells. The viral antigen or cancer-
associated antigen is synthesized by the cell itself and
hydrolyzed to peptide fragments, which are complexed to
class I MHC proteins. The complex is then shuttled to the
plasma membrane of the cell.
IX. NK cells have the same targets as cytotoxic T cells, but they
are not antigen-specifi c; most of their mechanisms of target
identifi cation are not understood.
X. Immune tolerance is the result of clonal deletion and clonal
inactivation.
XI. In antibody-mediated responses, the membrane receptors
of a B cell bind antigen, and at the same time a helper T cell
also binds antigen in association with a class II MHC protein
on a macrophage or other APC.
a. The helper T cell, activated by the antigen, by a
nonantigenic protein costimulus, and by IL-1 and TNF
secreted by the APC, secretes IL-2, which then causes the
helper T cell to proliferate into a clone of cells that secrete
additional cytokines.
b. These cytokines then stimulate the antigen-bound B cell
to proliferate and differentiate into plasma cells, which
secrete antibodies. Some of the activated B cells become
memory cells, which are responsible for active immunity.
c. There are fi ve major classes of secreted antibodies: IgG,
IgM, IgA, IgD, and IgE. The fi rst two are the major
antibodies against bacterial and viral infection.
d. The secreted antibodies are carried throughout the body
by the blood and combine with antigen. The antigen-
antibody complex enhances the infl
ammatory
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