genetic and environmental factors, are still poorly understood.
Some, like rheumatoid arthritis, are mainly autoimmune in
nature, but all appear to be associated with positive feedback
increases in the production of cytokines and other inﬂ
Yet another example of excessive inﬂ
ammation in a non-
infectious state is the development of atherosclerotic plaques
in blood vessels (Chapter 12). It is likely that, in response to
endothelial cell dysfunction, the vessel wall releases inﬂ
matory cytokines (IL-1, for example) that promote all stages
of atherosclerosis—excessive clotting, chemotaxis of various
leukocytes (as well as smooth muscle cells), and so on. The
endothelial-cell dysfunction is caused by initially subtle ves-
sel wall injury by lipoproteins and other factors, including ele-
vated blood pressure and homocysteine (Chapter 12).
In summary, the various mediators of inﬂ
immunity are a double-edged sword: In usual amounts they
are essential for normal resistance, but in excessive amounts
they can cause illness.
This completes the section on immunology.
presents a summary of immune mechanisms in the form of a
miniglossary of cells and chemical mediators involved in immune
responses. All of the material in this table has been covered in
Some Possible Causes
of Autoimmune Attack
1. There may be failure of clonal deletion in the thymus or of
clonal inactivation in the periphery. This is particularly true
for “sequestered antigens,” such as certain proteins that are
unavailable to the immune system during critical early-life
2. Normal body proteins may be altered by combination with
drugs or environmental chemicals. This leads to an attack on
the cells bearing the now “foreign” protein.
3. In immune attacks on virus-infected bodily cells, so many
cells may be destroyed that disease results.
4. Genetic mutations in the body’s cells may yield new proteins
that serve as antigens.
5. The body may encounter microbes whose antigens are so
close in structure to certain of the body’s own proteins that
the antibodies or cytotoxic T cells produced against these
microbial antigens also attack cells bearing the self proteins.
6. Proteins normally never encountered by lymphocytes may
become exposed as a result of some other disease.
A Miniglossary of Cells and Chemical Mediators Involved in Immune Functions
Macrophages whose killing ability has been enhanced by cytokines, particularly IL-2 and interferon-gamma.
Antigen-presenting cells (APC)
Cells that present antigen, complexed with MHC proteins, on their surface to T cells.
Lymphocytes that, upon activation, proliferate and differentiate into antibody-secreting plasma cells; provide major defense
against bacteria, viruses in the extracellular ﬂ uid, and toxins; and can function as antigen-presenting cells to helper T cells.
Cytotoxic T cells
The class of T lymphocytes that, upon activation by speciﬁ c antigen, directly attack the cells bearing that type of
antigen; are major killers of virus-infected cells and cancer cells; and bind antigen associated with class I MHC proteins.
Leukocytes involved in destruction of parasites and in immediate hypersensitivity responses.
Helper T cells
The class of T cells that, via secreted cytokines, play a stimulatory role in the activation of B cells and cytotoxic T cells;
also can activate NK cells and macrophages; and bind antigen associated with class II MHC proteins.
The type of leukocyte responsible for speciﬁ c immune defenses; categorized mainly as B cells, T cells, and NK cells.
Cell type that (1) functions as a phagocyte, (2) processes and presents antigen to helper T cells, and (3) secretes cytokines
involved in inﬂ ammation, activation of lymphocytes, and the systemic acute phase response to infection or injury.
Dendritic (macrophage-like) cells
Several cell types that exert functions similar to those of macrophages.
Tissue cells that bind IgE and release inﬂ ammatory mediators in response to parasites and immediate hypersensitivity reactions.
B cells and cytotoxic T cells that differentiate during an initial immune response and respond rapidly during a subsequent
exposure to the same antigen.
A type of leukocyte; leaves the bloodstream and is transformed into a macrophage; has functions similar to those of macrophages.
Natural killer (NK) cells
Class of lymphocytes that bind to cells bearing foreign antigens without speciﬁ c recognition and kill them
directly; major targets are virus-infected cells and cancer cells; participate in antibody-dependent cellular cytotoxicity (ADCC).
Leukocytes that function as phagocytes and also release chemicals involved in inﬂ
Cells that differentiate from activated B lymphocytes and secrete antibodies.
Lymphocytes derived from precursors that differentiated in the thymus; see cytotoxic T cells and helper T cells.