inflammation by wasif

16th December 2011

INFLAMMATION

By

M. Wasif ZafarBpd01093-095

5th C

Inflammation:

Definition:

Inflammation is a protective response intended to remove injurious stimuli as well as the necrotic cells and tissues resulting from original insert.

ADVANTAGES:

It causes destruction of microbes.

Causes detoxification of toxins.

Clears infections.

Helps in healing process.

Causes repair of damaged tissues.

DIS-ADVANTAGES:

Life threatening anaphylactic reactions to insects bites, drugs and other chronic

diseases like Rheumatoid arthritis, Atherosclerosis etc.

Inflammation of peritoneum leads to firous bands that causes obstruction of

intestines.

Pericardial inflammation causes the formation of dense pericardium that

impairs cardiac functions.

PROCESS OF INFLAMMATION:

Inflammatory stimulus

Chemical mediators

Inflammatory response (until

injurious stimulus is removed)

When the inflammatory stimulus is removed these

mediators are then dissipated, catabolized or

removed.

PLAYERS OF INFLAMMATION:

CIRCULATING CELLS

CIRCULATING PROTEINS

VASCULAR WALL CELLS

EXTRA CELLULAR MATRIX

The inflammatory responses have many players. They include


1. CIRCULATING CELLS:

Bone marrow derived polymorph nuclear leukocytes e.g., Basophils, Esinophils and Neutrophils.

Lymphocytes

Monocytes

Platelets.


2. CIRCULATING PROTEINS:

Clotting factors

Kininogens

Complement proteins


3. VASCULAR WALL CELLS:

Connective tissue cells

Smooth muscle cells

Epithelial cells


4. EXTRA CELLULAR MATRIX:

Fibrous structural proteins e.g., Elastin & Fibrinogen

Gel-forming proteoglycans

Adhesive glycoprotein e.g., Fibronectin, that are cell-ECM and ECM-ECM connectors.

TYPES OF INFLAMMATION:

Acute inflammation

Chronic inflammation

Acute Inflammation

“Inflammation, usually of sudden onset, marked by the classical signs in which vascular and exudative processes pre-dominate.”

Acute inflammation begins within seconds to minutes following the injury of tissues. The damage may be purely physical, or it may involve the activation of an immune response.

Events in Acute Inflammation

Increased blood flow

Increased permeability

Migration of neutrophils

Increased Blood Flow and Edema

The first two of the above effects are readily visible within a few minutes following a scratch that does not break the skin. At first, the scratch is visible as a pale red line. Then the surrounding few millimeters of tissue on both sides of the scratch becomes red as blood flow increases locally. Finally, the area swells as additional fluid accumulates in the interstitial spaces of the region, a condition known as edema. The increased permeability of the capillaries occurs because the endothelial cells separate from one another at their edges.

Cell Adhesion Molecules

The first step is the binding of the neutrophils to the endothelium of the blood vessels. The binding is due to molecules, called cell adhesion molecules (CAMs), found on the surfaces of neutrophils and on endothelial cells in injured tissue.

The binding occurs in two steps.

In the first, adhesion molecules called selectins lightly bind the neutrophil to the endothelium, so that it begins rolling along the surface.

In a second step, a much tighter binding occurs through the interaction of ICAMs on the endothelial cells with integrins on the neutrophil.

The figure below describing the recruitment of neutrophils.

Chemotaxis

Once outside the blood vessel, a neutrophil is guided towards an infection by various diffusing chemotactic factors. Examples include the chemokines and the complement peptide C5a, which is released when the complement system is activated either via specific immunity or innate immunity.

Eosinophils

In some circumstances eosinophils rather than neutrophils predominate in acute inflammation. This tends to occur with parasitic worms, against which neutrophils have little success, or with a response involving the antibody IgE. Eosinophils release several proteins, such as major basic protein, which are often effective against parasites. Eosinophils also release several regulatory molecules that increase endothelial permeability.

Inflammatory Paracrines

What causes the characteristic sequence of events in acute inflammation?

Various cells at the site of tissue damage or of a specific immune response release regulatory molecules that act locally as paracrines.

Macrophages and lymphocytes are important sources of inflammatory paracrines; macrophages release IL-1 and TNF-alpha, which have powerful widespread effects.

Also important are mast cells, which are found throughout the body, especially under epithelia. Mast cells are filled with large vesicles containing histamine and other inflammatory paracrines (They also release PG D2, several LTs and TNF-alpha, described below). Factors associated with tissue damage can trigger the exocytosis. But sometimes it is a specific immune response that triggers the release of the inflammatory paracrines.

Inflammatory Paracrines

Also, various arachidonic acid derivatives are important. Both prostaglandins (notably PG D2) and leukotrienes (LT) can be important, depending on the tissue.

Complement peptides, C3a and C5a

Various other molecules including nitric oxide, certain platelet products, kinins, and serotonin, etc

CHRONIC INFLAMMATION:

Chronic inflammation is the inflammation with prolonged duration usually from weeks to months and sometimes to years in which active inflammation, tissue injury and healing process proceed simultaneously.

DISTINGUISHING FEATURES:

Infiltration of mono-nuclear cells like lymphocytes,

macrophages and plasma cells.

Destruction of tissue by inflammatory cells.

Proliferation of new vessels leading to repair (angiogenesis & fibrosis).

ORIGIN AND PROCESS:

Chronic inflammation arises from acute inflammation. This transition takes place if the acute responses cannot be resolved either because of the persistence e.g., of injurious stimuli or by interference of the normal healing process e.g., peptic ulcer.

Some types of injuries engender responses with chronic inflammation initially e.g., viral infections.

SETTINGS LEADING TO CHRONIC INFLAMMATION:

Viral infections

Persistent microbial infections

Prolonged exposure to potentially toxic materials

Autoimmune diseases

CHRONIC INFLAMMATORY CELLS & MEDIATORS:

1) MACROPHAGES

2) LYMPHOCYTES

3) ESINOPHILS

4) MAST CELLS


1) MACROPHAGES:

Macrophages are white blood cells within tissues, produced by the division of monocytes.

A majority of macrophages are stationed at strategic points where microbial invasion or accumulation of dust is likely to occur. Each type of macrophage, determined by its location, has a specific name:

In liver Kupffer cells

Spleen and lymph nodes Sinus histocytes

Nervous system Microglial cells

Lungs Alveolar macrophages


FUNCTIONS OF MACROPHAGES:

Filter the particulate matter

Kill microbesAlert immune system of the

body.

Their life is 1-2 days.


ACTIVATION SIGNALS:

Cytokines produced by T-lymphocytes

Bacterial endotoxins

Different mediators produced during acute inflammation

Extra cellular matrix proteins e.g., Fibrinogen

When macrophages become activated they produce different type of biologically active substances that either cause one of• Cell injury • Fibrosis.


Cell injury causing substances:

Acid and neutral proteases

Complement proteins C1 to C5

Coagulating factors V & VШ

Amino acids metabolites

Cytokines

Tumor necrosis factor


Fibrosis causing substances:

Growth factors

Fibrogenic cytokines

Angiogenesis factors

Regeneration and remodeling factors


2) LYMPHOCYTES:

Both T- & B-lymphocytes are involved in chronic inflammation. Their migration is brought about by specific adhesion molecules and cytokines. The T-lymphocytes work in reciprocal with B-lymphocytes in chronic inflammation. The already activated macrophages release TNF & IL1 and activate the inactive lymphocytes which then produce different antibodies that cause destruction of antigens at the inflammatory site.


3) ESINOPHILS:

They are usually found in parasitic infections and IgE mediated allergic reactions. Their migration is brought about by adhesion molecules produced by leukocytes and epithelial cells. Esinophils specific granules contain Major Basic Proteins which is highly cationic &toxic for parasites.


4) MAST CELLS:

Mast cells are tissue cells which are like basophils in shape. They are present in bone marrow and around blood vessels and do not enter the blood. They are specifically armed with IgE antibodies against certain antigens. When these antigens are encountered, they release histamines and amino acid metabolites. They cause initial vascular changes in acute inflammation and also cause anaphylactic reactions.

TYPES OF CHRONIC INFLAMMATION:

AGRANULOMATOUS

GRANULOMATOUS


1) GRANULOMATOUS INFLAMMATION:

Characterized by aggregates of activated macrophages that assume a squamous cell like epithelloid appearance.

GRANULOMA is defined as aggregates of macrophages formed due persistant response of T-lymphocytes to particular antigens.

This has a granular cheesy appearance called as caseous necrosis.


Examples are:

Bacterial: Tuberculosis , Leprosy, Syphilis gumma etc.

Parasitic: Schistosomiasis

Fungal: Histoplasma capsulatum, Blastomycosis.

Inorganic metals / Dust: Silicosis

Foreign bodies: Suture, Vascular graft.

Unknown: Sarcodiosis.


2) AGRANULOMATOUS:

Granuloma is not formed,

Inflammation is characterized by all features of chronic inflammation.

Examples:

Chronic viral infections e.g., Hepatitis

Chronic autoimmune diseases e.g., Rheumatoid arthritis and Ulcerative colitis

Chronic chemical intoxication e.g., Chronic alcoholic liver disease

Allergic reactions e.g., Bronchial asthma

inflammation by wasif

Education

players of inflammation

chronic inflammation

process of inflammation

types of inflammation

various cells

endothelial cells

mast cells

necrotic cells