leukotrienes. Assistance from
environ- mental cues (released clotting factors, kininogens, and
complement) is critical to the preparation of vascular beds to allow
cellular influx.As a class, they are small polypeptides
synthesized by a wide variety of cell types, all of which
Pathological Consequences of the
Inflammatory Response
The initiation of the pro inflammatory responses is extremely
potent to limit the spread of microorganisms; however, full clearance
of the infectious agent typically requires adaptive immune
components.The opsonins act as molecular
beacons, allowing interaction with receptors on
macrophages, monocytes, and neutrophils to enhance
phagocytosis and elevate mechanisms of targeted organism
destruction.Recognition can occur directly
through mannose receptors, scavenger receptors, or Tolllike receptors (TLRs), receptors that detect common
pathogenic motifs (pathogen-associated molecular patterns;
PAMPs).Proteolytic
Pathogen Recognition and Cytokine
Signaling
Phagocytes bear several unique receptors that recognize
microbial components, bind bacterial carbohydrates, and
induce phagocytosis.Clotting and formation of a fibrin matrix impede the movement
of microorganisms in the local area; generation of breakdown
products in the cascading events also attracts and activates
incoming leukocytes.Overall, complement and its
related components exert multiple biological functions that
are critical components of inflammation, including activation
and regulation of both innate and adaptive immune
functions (Fig.Plasma serine proteases, normally present
as inactive molecules, are activated; some of these function to
produce kinins to mediate firbrinolytic events, vascular
permeability, and sensation of pain.Activation of complement
enzymes results in sub- sequent cleavage of proteins to
yield specific polypeptide fragments with short-lived
enzymatic functions related to inflammation.Depending
on prior exposure or positive vaccination status, there may also
be an abundance of specific antibodies reactive to antigenic
features present in destructive pathogens.In these enzymatic cascades, complement components bind
directly to pathogens via the recognition of bacterial sugars
and lipids.Similar to the events described here, the
deposition of complement on the invading pathogen leads to
a cascade of enzymatic reactions, culminating in pore
channel assembly on the organism surface.In addition, internal protein
complexes, such as the inflammasome, further the response
to the recognition event via internal processing of inactive
forms of proinflammatory molecules to produce mature and
active mediators.Activation of local response is followed by activity of the
lymphatics to functionally drain fluids, cells, and debris to nearby
lymph nodes, where phagocytic antigen presenting cells -show?Antibody entry to the area offers multiple functions, the
most critical of which resides within the end of the antibody
molecule that can recognize unique shapes and forms, with a
specific and unique binding site for foreign substances.Antibody recognition of multiple regions on the
microorganism can result in a latticework structure, a precipitate,
which promotes organism clearance.Two other pathways of complement activation, the
alternate pathway and the lectin pathway, function to allow
direct lysis of microorganisms in the absence of antibodies.Activation and Directed Migration
of Leukocytes
One of the most prevalent by-products of the complement
enzymatic cascade is the production of molecules with the
ability to call in and activate leukocytes.Proteolytic degradation of
complement components releases leukocyte chemotactic
factors referred to as anaphylatoxins.Dilated local blood vessels, capillaries,
and small venules/arterioles subsequently allow fluid (edema)
to accumulate in the damaged area.In effect, antibodies recognize toxins and
deleterious factors; recognition results in the inhibition and
neutralization of their toxic properties.35
An intracellular vesicle, referred to as the complosome,
has a strong impact on cell processes and metabolism, perhaps
exerting influence on how the host cell adjusts to the presence
of intracellular pathogens.In addition to the
PAMP molecules described here, a unique subset of
danger-associated molecular patterns (DAMPs), can trigger
similar responses.However, there is also a great need for systemic
communication that can mediate responses across great
distances to direct cells and organs located distant from the
site of tissue damage.If the breach in the
mechanical barrier is deep enough, damaged blood vessels also
directly flood the local area with leukocytes, red blood cells
(RBCs), and platelets.Simply
coating the agent with antibodies targets it for attack by
serum enzymes that comprise the complement cascade (Fig.The complement components
may be circulating in the blood, may be expressed on cell
surfaces, and may even be found as intracellular-residing
proteins.Synthesis of this structure culminates in
a pore channel, called a membrane attack complex (MAC),
which causes osmotic lysis of the pathogen or infected cell.Indeed, we will see in later
chapters that the direct interaction of cells that initiate the
proinflammatory response with incoming lymphocytes
triggers adaptive cell activity.Cell-to-cell contact gives the
advantage of directly delivering cytokines and mediators,
allowing functional lymphocyte development in the
immediate area to target productive immune function.Chemokines assist in leukocyte migration into
tissue (diapedesis).Fig. 2.2). 2.3).