294
UNIT IV
Infection, Inflammation, and Immunity
nodes, peritoneum, central nervous system (
i.e.,
microglial
cells), and other areas. Macrophages are activated during the
innate immune response where they engulf and break down
complex antigens into peptide fragments. These fragments can
then be associated with MHC-II molecules for presentation to
cells of the “cell-mediated” response so that self–nonself rec-
ognition and activation of the immune response can occur.
DCs are also responsible for presenting processed anti-
gen to activated T lymphocytes. The starlike structure of the
DCs provides an extensive surface area rich in MHC-II mol-
ecules and other non-HLA molecules important for initiation
of adaptive immunity. DCs are found throughout the body in
tissues where antigen enters the body and in the peripheral
lymphoid tissues. Both DCs and macrophages are capable of
“specialization” depending upon their location in the body.
For example, Langerhans cells are specialized DCs in the
skin, whereas follicular DCs are found in the lymph nodes.
Langerhans cells transport antigens found on the skin to
nearby lymph nodes for destruction. They are also involved
in the development of cell-mediated immune reactions such
as allergic type IV contact dermatitis. Finally, DCs are found
in the mucosal lining of the bowel and have been implicated
in the development of inflammatory bowel diseases such as
Crohn disease and ulcerative colitis, where they present anti-
gens to the B and T lymphocytes through the production of
proinflammatory cytokines.
22
B Lymphocytes and Humoral
Immunity
The humoral immune response is mediated by antibodies,
which are produced by the B lymphocytes. The primary func-
tions of the B lymphocytes are the elimination of extracellular
microbes and toxins and subsequent “memory” for a height-
ened response during future encounters. Humoral immunity is
more important than cellular immunity in defending against
microbes with capsules rich in polysaccharides and lipid tox-
ins because only the B lymphocytes are capable of responding
to and producing antibodies specific for many types of these
molecules. The T cells, which are the mediators of cellular
immunity, respond primarily to surface protein antigens.
B lymphocytes are produced in the bone borrow and
are classified according to the MHC-II proteins, Ig, and
HLA genes are inherited as a unit, called a
haplotype
,
because the class I and II MHC genes are closely linked on
one chromosome. Since each person inherits one chromo-
some from each parent, each person has two HLA haplotypes.
Tissue typing in forensics and organ transplantation involves
the identification of these haplotypes. In organ or tissue
transplantation, the closer the matching of HLA types, the
greater is the probability of identical antigens and the lower
the chance of rejection. However, not all people that develop
organ rejection after transplantation develop anti-HLA anti-
bodies. Non-HLA target antigens exist including the MHC
class I chain-related antigens A (MICA).
28
These antigens
are expressed on epithelial cells, monocytes, fibroblasts, and
endothelial cells. Therefore, donor-specific antibodies are not
detected prior to organ tissue typing prior to transplantation
because they are not expressed on the leukocytes tested.
28
Antigen-Presenting Cells
During the adaptive immune response, activation of a T lym-
phocyte requires the recognition of a foreign peptide (anti-
gen) bound to a self-MHC molecule. This process requires
that stimulatory signals be delivered simultaneously to the
T lymphocyte by another specialized cell known as an
antigen- presenting cell (APC)
. Therefore, APCs play a key
role in bridging the innate and adaptive immune systems
through cytokine-driven up-regulation of MHC-II molecules.
Cells that function as APCs must be able to express both
classes of MHC molecules and include DCs, monocytes,
macrophages, and B lymphocytes residing in lymphoid fol-
licles. Under certain conditions, endothelial cells are also able
to function as APCs. APCs have been shown to play a key role
in the development of autoimmune diseases and atherosclero-
sis. Activated T lymphocytes appear to be proatherogenic, and
in experimental models, APC and T-cell deficiency have been
associated with up to an 80% reduction in atherosclerosis.
29
Macrophages function as a principal APC. They are key
cells of the mononuclear phagocytic system and engulf and
digest microbes and other foreign substances that gain access
to the body. Since macrophages arise from monocytes in the
blood, they can move freely throughout the body to the appro-
priate site of action. Tissue macrophages are scattered in con-
nective tissue or clustered in organs such as the lung (
i.e.,
alve-
olar macrophages), liver (
i.e.,
Kupffer cells), spleen, lymph
TABLE 13.3 PROPERTIES OF CLASS I AND II MHC MOLECULES
PROPERTIES
HLA ANTIGENS
DISTRIBUTION
FUNCTIONS
Class I MHC HLA-A, HLA-B, HLA-C Virtually all nucleated cells
Present processed antigen to cytotoxic CD8
+
T
cells; restrict cytolysis to virus-infected cells,
tumor cells, and transplanted cells
Class II MHC HLA-DR, HLA-DP,
HLA-DQ
Immune cells, antigen-
presenting cells, B cells,
and macrophages
Present processed antigenic fragments to CD4
+
T cells; necessary for effective interaction
among immune cells
HLA, human leukocyte antigen; MHC, major histocompatibility complex.
