Untitled - D Ank Unlimited

acute graft-vs.-host reaction 12 acute inflammatory response
This liver section from a patient with graft-vs.-host disease demonstrates
the cholestatic changes that evolve from hepatocellular ballooning to cholangiolar
cholestasis with bile microliths, signifying prolonged disease.
acute graft-vs.-host reaction
The immunopathogenesis of acute graft-vs.-host disease
(GVHD) consists of recognition, recruitment, and effector
phases. Epithelia of the skin, gastrointestinal tract, small
intrahepatic biliary ducts, and lymphoid system constitute
primary targets of acute GVHD. GVHD development
may differ in severity based on relative antigenic differences
between donor and host and the reactivity of donor
lymphocytes against non-human leukocyte antigens (HLAs)
of recipient tissues. The incidence and severity of GVHD
have been ascribed also to HLA-B alleles (i.e., increased
GVHD incidence is associated with HLA-B8 and HLA-
B35). Epithelial tissues serving as targets of GVHD include
keratinocytes, erythrocytes, and bile ducts that may express
Ia antigens following exposure to endogenous interferon
produced by T lymphocytes. When Ia antigens are
expressed on nonlymphoid cells, they may become antigenpresenting
cells for autologous antigens and aid perpetuation
of autoimmunity. Cytotoxic T lymphocytes mediate
acute GVHD. While most immunohistological investigations
have implicated CD8 + (cytotoxic/suppressor) lymphocytes,
others have identified CD4 + (T helper lymphocytes)
in human GVHD, whereas natural killer (NK) cells have
been revealed as effectors of murine but not human GVHD.
Following interaction between effector and target cells,
cytotoxic granules from cytotoxic T or NK cells are distributed
over the target cell membrane, leading to perforininduced
large pores across the membrane and nuclear lysis
by deoxyribonuclease. Infection, rather than failure of the
primary target organ (other than gastrointestinal bleeding),
is the major cause of mortality in acute GVHD. Within
the first few months post-transplant, all recipients demonstrate
diminished immunoglobulin synthesis, decreased
T helper lymphocytes, and increased T suppressor cells.
Acute GVHD patients manifest an impaired ability to
combat viral infections and demonstrate an increased risk
of cytomegalovirus (CMV) infection, especially CMV
interstitial pneumonia. GVHD may also reactivate other
viral diseases such as herpes simplex. Immunodeficiency
in the form of acquired B cell lymphoproliferative disorder
(BCLD) represents another serious complication of bone
marrow transplantation. Bone marrow transplant patients
treated with pan-T cell monoclonal antibody or those in
which T lymphocytes have been depleted account for most
cases of BCLD, which is associated with severe GVHD. All
transformed B cells in cases of BCLD have manifested the
Epstein–Barr viral genome.
acute humoral rejection
A type of acute graft rejection in which antibodies are
produced against allogeneic antigens in the graft, leading to
vascular inflammation and neutrophil infiltration. Referred
to also as delayed graft rejection or delayed vascular rejection.
Characterized by C4d “staining” by immunofluorescence
of peritubular capillaries in renal allotransplants
undergoing acute humoral rejection.
acute inflammation
A reaction of sudden onset marked by the classic symptoms
of pain, heat, redness, swelling, and loss of function. Also
observed are dilation of arterioles, capillaries, and venules
with increased permeability and blood flow; exudation of
fluids, including plasma proteins; and migration of leukocytes
into the inflammatory site. Inflammation is a localized
protective response induced by injury or destruction of
tissues. It is designed to destroy, dilute, or wall off both the
offending agent and the injured tissue.
acute inflammatory response
An early defense mechanism to contain an infection and
prevent its spread from the initial focus. When microbes
multiply in host tissues, two principal defense mechanisms
mounted against them are antibodies and leukocytes. The
three major events in acute inflammation are (1) dilation of
capillaries to increase blood flow, (2) changes in the microvasculature
structure leading to escape of plasma proteins
and leukocytes from the circulation, and (3) leukocyte
emigration from the capillaries and accumulation at the
site of injury. Widening of interendothelial cell junctions of
venules or injury of endothelial cells facilitates the escape
of plasma proteins from the vessels. Neutrophils attached to
the endothelium through adhesion molecules escape microvasculature
and are attracted to sites of injury by chemotactic
agents. This process is followed by phagocytosis of
microorganisms that may lead to their intracellular destruction.
Activated leukocytes may produce toxic metabolites
and proteases that injure endothelium and tissues when they
are released. Activation of the third complement component
(C3) is also a critical step in inflammation. Multiple chemical
mediators of inflammation derived from plasma cells
have been described. Mediators and plasma proteins such as
complement are present as precursors in intracellular granules,
such as histamine and mast cells. These substances
are secreted following activation. Other mediators such as
prostaglandins may be synthesized following stimulation.
These mediators are quickly activated by enzymes or other
substances such as antioxidants. A chemical mediator may
also cause a target cell to release a secondary mediator
with similar or opposing action. Besides histamine, other
preformed chemical mediators in cells include serotonin
and lysosomal enzymes. Those that are newly synthesized
include prostaglandins, leukotrienes, platelet-activating
factors, cytokines, and nitric oxide. Chemical mediators
in plasma include complement fragments C3a, C5a, and
the C5b–g sequence. Three plasma-derived factors—
kinins, complement, and clotting factors—are involved in