inflamation process

1. INFLAMMATION:-
1.What is Inflammation ?
Inflammation is a response triggered by damage to living tissues.
The inflammatory response is a defense mechanism that evolved in
higher organisms to protect them from infection and injury.
Its purpose is to localize and eliminate the injurious agent and to remove
damaged tissue components so that the body can begin to heal.
The response consists of changes in blood flow, an increase in
permeability of blood vessels, and the migration of fluid, proteins, and
white blood cells (leukocytes) from the circulation to the site of tissue
damage.
An inflammatory response that lasts only a few days is called acute
inflammation, while a response of longer duration is referred to as
chronic inflammation.
Causes:-
The factors that can stimulate inflammation include microorganisms,
physical agents, chemicals, inappropriate immunological responses, and
tissue death.
Infectious agents such as viruses and bacteria are some of the most
common stimuli of inflammation. Viruses give rise to inflammation by
entering and destroying cells of the body; bacteria release substances
called endotoxins that can initiate inflammation.
Physical trauma, burns, radiation injury, and frostbite can damage
tissues and also bring about inflammation, as can corrosive chemicals
such as acids, alkalis, and oxidizing agents.
As , malfunctioning immunological responses can incite an
inappropriate and damaging inflammatory response. Inflammation can
also result when tissues die from a lack of oxygen or nutrients, a
situation that often is caused by loss of blood flow to the area.

2. Signs
The four cardinal signs of inflammation—redness
(Latin rubor), heat (calor), swelling (tumor), and pain (dolor)—were
described in the 1st century AD by the Roman medical writer Aulus
Cornelius Celsus.
Redness is caused by the dilation of small blood vessels in the area of
injury.
Heat results from increased blood flow through the area and is
experienced only in peripheral parts of the body such as the skin.
Fever is brought about by chemical mediators of inflammation and
contributes to the rise in temperature at the injury.
Swelling, called edema, is caused primarily by the accumulation of fluid
outside the blood vessels.
The pain associated with inflammation results in part from the distortion
of tissues caused by edema, and it also is induced by certain chemical
mediators of inflammation, such as bradykinin, serotonin, and
the prostaglandins.
A fifth consequence of inflammation is the loss of function of the inflamed
area, a feature noted by German pathologist Rudolf Virchow in the 19th
century. Loss of function may result from pain that inhibits mobility or
from severe swelling that prevents movement in the area.
Chemical mediators of inflammation
Although injury starts the inflammatory response, chemical factors
released upon this stimulation bring about the vascular and cellular
changes outlined above. The chemicals originate primarily from
blood plasma, white blood cells (basophils, neutrophils, monocytes, and
macrophages), platelets, mast cells, endothelial cells lining the blood
vessels, and damaged tissue cells.
One of the best-known chemical mediators released from cells during
inflammation is histamine, which triggers vasodilation and increases
vascular permeability. Stored in granules of circulating basophils and mast
cells, histamine is released immediately when these cells are injured.

3. Other substances involved in increasing vascular permeability are
lysosomal compounds, which are released from neutrophils, and certain
small proteins in the complement system, namely C3a and C5a.
Many cytokines secreted by cells involved in inflammation also have
vasoactive and chemotactic properties.
The prostaglandins are a group of fatty acids produced by many types of
cells. Some prostaglandins increase the effects of other substances that
promote vascular permeability. Others affect the aggregation of platelets,
which is part of the clotting process. Prostaglandins are associated with
the pain and fever of inflammation. Prostaglandins are synthesized from
arachidonic acid, as are the leukotrienes, another group of chemical
mediators that have vasoactive properties.
The plasma contains four interrelated systems of proteins—complement,
the kinins, coagulation factors, and the fibrinolytic system—that generate
various mediators of inflammation.
Activated complement proteins serve as chemotactic factors for
neutrophils, increase vascular permeability, and stimulate the release of
histamine from mast cells. They also adhere to the surface of bacteria,
making them easier targets for phagocytes.
The kinin system, which is activated by coagulation factor XII, produces
substances that increase vascular permeability. The most important of the
kinins is bradykinin, which is responsible for much of the pain and itching
experienced with inflammation.
The coagulation system converts the plasma protein fibrinogen into fibrin,
which is a major component of the fluid exudate. The fibrinolytic system
contributes to inflammation primarily through the formation of plasmin,
which breaks down fibrin into products that affect vascular permeability.
Process:-
In response to any harmful or foreign molecule, inflammation generally starts
within few minutes by activation of immune system . Innate system comprises
immune cells that include lymphocytes, dendritic cells (DC’s), neutrophils,
macrophages and mast cells that play significant functions in inflammatory
reactions.

4. 1. Firstly, the pathogens get adhere to particular receptors i.e. G-protein
attached receptors ,Pattern realization receptors and Chemokine
receptors .
2. The fabrication of the inflammatory cytokines including IL-1, IL-6,
chemokines and TNF is initiated by these receptors. These inducers
quickly change the vascular endothelial permissibility and releases
antibodies, complement factors and neutrophils in the site of septicity.
[The inflammatory cytokines increases the excretion of coagulation factors and
C-reactive protein by means of the liver cell. They invoke brain endothelium
and smooth the secretion of prostaglandins. They are important for the key
symptoms of pain and fever via their detrimental effects on CNS (central
nervous system) . Alternatively the viral contamination follows one kind of
signaling pathway via producing different type of cytokines known as type1
interferons (IFN’s). Furthermore, parasitic infections and allergens invoke the
assembly of other inflammatory cytokines IL-13, IL-5, and histamine where the
rest of the pathway is nearly the same .
Inflammation is a complex biochemical mechanism which leads to the
stimulation of infectious agents and promotes injury. It causes tissue damage
and pain monitored through treatment .Chemical agents are secreted by
immune cells like cytokines, chemokine and reactive oxygen species at injury
site to eliminate pathogens. A major constituent of inflammatory process is
arachidonic acid which is a by product of fast acting cell membrane.
Arachidonic acid is transformed into prostaglandins and thromboxane enzyme
by cyclooxygenase (COX).]
3. Neutrophil:-
1. Leukocyte margination and endothelial adhesion:-
Neutrophils begin to attach strongly to the endothelium by using carbohydrate
ligands to show symptoms of inflammation. Endothelial cells in their
stimulated form are responsible for the production of surface bonded and
soluble particles. They produce a strong adhesion between neutrophils and
endothelium.

5. 2.Migration across the endothelium, known as transmigration, via
the process of diapedesis:
Chemokine gradients stimulate the adhered leukocytes to move
between adjacent endothelial cells. The endothelial cells retract and the
leukocytes pass through the basement membrane into the surrounding
tissue .(Neutrophils leave the bloodstream and travels across endothelium . )
3.Movement of leukocytes within the tissue via chemotaxis:
Leukocytes reaching the tissue interstitium bind to extracellular
matrix proteins via expressed integrins and CD44 to prevent them from
leaving the site. A variety of molecules behave as chemoattractants, for
example, C3a or C5, and cause the leukocytes to move along a
chemotactic gradient towards the source of inflammation.
Production of particular cells like cell adhesion molecules (CAMs), their
activators and chemical stimulus is responsible for the neutrophils emigration .
4.Phagocytosis:-
Extravasated neutrophils in the cellular phase come into contact with
microbes at the inflamed tissue. Phagocytes express cell-surface
endocytic pattern recognition receptors (PRRs) that have affinity and
efficacy against non-specific microbe-associated molecular
patterns (PAMPs).
Most PAMPs that bind to endocytic PRRs and initiate phagocytosis .
Upon endocytic PRR binding, that endocytoses the plasma membrane
containing the PRR-PAMP complex, and the microbe.
pathways have been implicated to traffic the endocytosed phagosome
to intracellular lysosomes, where fusion of the phagosome and the
lysosome produces a phagolysosome. The reactive oxygen
species, superoxides and hypochlorite bleach within the
phagolysosomes then kill microbes inside the phagocyte.
Phagocytic efficacy can be enhanced by opsonization. Plasma derived
complement C3b and antibodies that exude into the inflamed tissue
during the vascular phase bind to and coat the microbial antigens. As
well as endocytic PRRs, phagocytes also express opsonin receptors Fc
receptor and complement receptor 1 (CR1), which bind to antibodies

6. and C3b, respectively. The co-stimulation of endocytic PRR and opsonin
receptor increases the efficacy of the phagocytic process, enhancing
the lysosomal elimination of the infective agent.
Molecular or cellular actions of infectious response tend to increase blood
movement, capillary damage, leukocytes access and the creation of chemical
agents . Stimulation of these chemical agents initiates the formation of
inflammatory cytokines including TNF, IL-1, chemokines and IL-6 that causes
tissue damage.
5.Due to phagocytic activity of cells, migratory neutrophils are eventually
removed from inflammatory site through apoptosis and produce anti-
inflammatory cytokines .