•What is inflammation?
•What are the cardinal signs?
•What are the vascular changes in Acute Inflammation?
•What are the cellular changes in Acute Inflammation?
INFLAMMATION
• It is a complex reaction to injurious agents such as
microbes and damaged, usually necrotic, cells that
consist of
– Vascular responses,
– Migration and activation of leukocytes and
– Systemic reactions
‘the reaction of a tissue and it’s microcirculation to injury’
TISSUE INJURY
•
•
•
•
•
Physical
Chemical
Biological
Ischaemia
Neoplasm
Inflammation and repair are
fundamentally protective
but may be
potentially harmful
TYPES
•Acute Inflammation : of short duration, edema
and leukocyte emigration esp. Neutrophils
•Chronic Inflammation : of longer duration,
Lymphocytes, Macrophages, Blood vessel
proliferation, Fibrosis and Tissue necrosis
COMPONENTS
• Fluid & Plasma proteins
• Cells
– Circulating : N, L, M, E, B
– Connective tissue : Mast cells, Fibroblasts, Macrophages
• Extracellular matrix
– Structural : Collagen, Elastin
– Adh Glycoproteins : Fibronectin, Laminin, Tenascin etc
– Proteoglycans
SIGNS
•
•
•
•
Rubor (redness)
Tumor (swelling)
Calor (heat)
Dolor (pain)
-Cornelius Celsus
• Functio laesa (loss of function)
- Rudolf Virchow
Ilya Mechnikov
( Elie Metchnikoff ) and the
Phagocyte Cells
• In 1882, the Russian scientist Ilya Mechnikov was working
in Messina, Italy, studying the larvae of the sea star. When
he inserted a thorn into a larva, something weird
happened. Mechnikov noticed strange cells gathering at
the point of insertion. The cells surrounded the thorn,
eating any foreign substances that entered through the
ruptured skin. Mechnikov was thrilled. He decided to name
these new cells phagocytes from the Greek words
meaning "devouring cells."
Paul Ehrlich and the
Side-chain Theory
•
•
•
At the end of the nineteenth century, the German scientist Paul Ehrlich
developed the "side-chain theory" to explain immunity and how antibodies
were formed. Although we now know that some of his ideas were incorrect,
this theory allowed him to accomplish important work and provided the
groundwork for later researchers in this field.
Ehrlich argued that all cells have a wide variety of special receptors that he
called side-chains. He thought that these receptors worked like gatekeepers
or locks for the cell. Each receptor/side-chain had a unique structure, and
only substances matching this structure were allowed to enter the cell.
The side-chain receptors’ primary function was to absorb nutrients for the
cell. Unfortunately, the receptors also allowed many toxic substances to
enter. According to Ehrlich, the body defended itself against these toxins in
the following way: When a cell was attacked by a toxin, it started to produce
excess side-chains matching the toxin. These excess side-chains then were
released, flooding the body and neutralizing free toxins by attaching to
them. The toxin was wiped out and remaining healthy cells protected.
Historical Commentary
Nature Immunology 9, 705 - 712 (2008)
doi:10.1038/ni0708-705
Immunology's foundation: the 100-year
anniversary of the Nobel Prize to Paul Ehrlich
and Elie Metchnikoff
Stefan H E Kaufmann
Abstract
One hundred years ago the birth of immunology was made official by the Nobel
Prize award to Elie Metchnikoff and Paul Ehrlich. Metchnikoff discovered
phagocytosis by macrophages and microphages as a critical host-defense
mechanism and thus is considered the father of cellular innate immunity.
Ehrlich described the side-chain theory of antibody formation and the
mechanisms of how antibodies neutralize toxins and induce bacterial lysis with
the help of complement and thus is considered one of the fathers of humoral
adaptive immunity. Despite many discordant discussions in the initial phase
after these discoveries, innate and adaptive responses are now known to be
complementary partners in producing robust immunity.
ACUTE INFLAMMATION
• Changes in vascular caliber
• Changes in vascular structure
• Emigration of leukocytes,
accumulation at site of injury and
their activation
Changes in Vascular Flow and Calibre
Vasodilatation and increased blood flow
First involves arterioles
Increased Vascular
permeability
Leads to escape of protein rich fluid into the
extravascular tissue
Endothelial changes lead to increased
permeability
The series of events are:
• Vasodilation: leads to greater blood flow to the area of
inflammation, resulting in redness and heat.
• Vascular permeability: endothelial cells become "leaky"
from either direct endothelial cell injury or via chemical
mediators.
• Exudation: fluid, proteins, red blood cells, and white blood
cells escape from the intravascular space
• Vascular stasis: slowing of the blood in the bloodstream
• An exudate is an inflammatory extravascular fluid
that has a high protein concentration, cellular
debris, and a specific gravity above 1.020
• A transudate is a fluid with low protein content (most
of which is albumin) and a specific gravity of less
than 1.012
Pus, a purulent exudate, is an inflammatory exudate
rich in leukocytes (mostly neutrophils), the debris of
dead cells and, in many cases, microbes.