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U N I T 4
Infection and Immunity
Autoimmune Disease
Autoimmune diseases represent a group of disorders
that are caused by a breakdown in the ability of the
immune system to differentiate between self- and
nonself-antigens. They can affect almost any cell or tis-
sue in the body. Some autoimmune disorders, such as
Hashimoto thyroiditis, are tissue specific, whereas oth-
ers, such as SLE, affect multiple organs and systems.
Chart 16-1 lists some of the common autoimmune dis-
eases. Many of these disorders are discussed elsewhere
in this book.
ImmunologicTolerance
To function properly, the immune system must be able
to differentiate foreign antigens from self-antigens
in a process called
self-tolerance.
1–3
It is the HLAs
encoded by MHC genes that serve as recognition
markers of self and nonself for the immune system
(see Chapter 15). To elicit an immune response, an
antigen must first be processed by an antigen-pre-
senting cell (APC), such as a macrophage, which then
presents the antigenic determinants along with an
MHC II molecule to a CD4
+
helper T cell. The dual
recognition of the MHC–antigen complex by the
T-cell receptor (TCR) of the CD4
+
helper T cell acts
like a security check. Similar recognition checks occur
between CD8
+
cytotoxic T cells and the MHC I–antigen
complex of tissue cells that have been targeted for
elimination. A number of chemical messengers
(e.g., interleukins) and costimulatory signals are essen-
tial to the activation of immune responses and the
preservation of self-tolerance.
Several mechanisms have been postulated to explain
the tolerant state, including central tolerance and
peripheral tolerance.
1,2,20–23
Central tolerance
refers to
the elimination of self-reactive T cells and B cells in the
central lymphoid organs (i.e., the thymus for T cells
and the bone marrow for B cells).
Peripheral tolerance
derives from the deletion or inactivation of autoreactive
T cells or B cells that escaped elimination in the central
lymphoid organs.
Anergy
represents the state of immu-
nologic tolerance to specific antigens. It may take the
form of diminished immediate hypersensitivity, delayed-
type hypersensitivity, or both.
■■
Destruction of the cells or tissues of the graft
can result from direct action of the recipient’s
cytotoxicT cells, fromT-cell–generated cytokines
and a delayed hypersensitivity reaction, or
from antibodies generated against antigens in
the graft.
■■
Hyperacute rejection occurs almost immediately
after transplantation and is caused by existing
recipient antibodies to graft antigens that
initiate a type III, Arthus-type hypersensitivity
reaction in the blood vessels of the graft. Acute
rejection occurs within the first few weeks or
months after transplantation and occurs when
graft tissue or blood vessels are damaged
by alloreactiveT cells or antibodies. Chronic
rejection occurs over a prolonged period
and is caused byT-cell–generated cytokines
that damage blood vessels, causing ischemic
damage to graft tissue.
■■
Graft-versus-host disease (GVHD), which
occurs most often following bone marrow
transplantation, develops when immunologically
competent cells or precursors are transplanted
into recipients who are immunologically
compromised. Three basic requirements
are necessary for GVHD to develop: (1) the
transplant must have a functional cellular
immune component, (2) the recipient tissue
must bear antigens foreign to the donor
tissue, and (3) recipient immunity must be
compromised to the point that it cannot destroy
the transplanted cells.
CHART 16-1
Probable Autoimmune Disease*
Systemic
Mixed connective tissue disease
Polymyositis-dermatomyositis
Rheumatoid arthritis
Scleroderma
Sjögren syndrome
Systemic lupus erythematosus
Blood
Autoimmune hemolytic anemia
Autoimmune neutropenia and lymphopenia
Idiopathic thrombocytopenic purpura
Other Organs
Acute idiopathic polyneuritis
Atrophic gastritis and pernicious anemia
Autoimmune adrenalitis
Goodpasture syndrome
Hashimoto thyroiditis
Type 1 diabetes mellitus
Myasthenia gravis
Premature gonadal (ovarian) failure
Primary biliary cirrhosis
Sympathetic ophthalmia
Temporal arteritis
Thyrotoxicosis (Graves disease)
Crohn disease, ulcerative colitis
*Examples are not inclusive.
SUMMARY CONCEPTS
(continued)
