AUTOIMMUNITY. Prof. Emad A Koshak Professor and Consultant Internal Medicine, Allergy & Immunology King Abdulaziz University- Faculty of Medicine.
Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.
Prof. Emad A Koshak
Professor and Consultant
Internal Medicine, Allergy & Immunology
King Abdulaziz University- Faculty of Medicine
The immune system normally acquires self tolerance by clonal deletion of autoreactive T cells in the thymus before birth and by functional suppression of autoreactive T and B cells at later stages of development.
The word inflammation literally means "burning."
Inflammation occurs in response to a range of traumas from sunburn and wounds, to infection and auto-immune conditions. Whatever the cause, this process is basically the same....
Heat and redness result from dilation of the small blood vessels in the injured area and increased local blood flow.
Because blood vessels become more permeable
during inflammation, protein rich exudate escapes from blood plasma to the damaged tissue and causes swelling.
Pain is believed to result from such chemical substances as serotonin, specific cytokines or from tension of tissue over the inflamed area.
Autoimmune disorders are a diverse group of conditions, which occur due to abnormal stimulation and signaling within the immune system. "Self" versus "non-self" recognition is altered.
An autoimmune response occurs because, for some reason, helper T cells recognize a cell of the body (or self cell) as foreign, and mark it for destruction.
such as Guillain-Barré
Primary biliary cirrhosis
Autoimmune hemolytic anemia
Meisha, a lab/terrier/spaniel mix, was 3 years old when she was diagnosed with autoimmunue hemolytic anemia in January of 1992.
is an example of an autoimmune disorder in which Beta cells of the pancrease show destruction.
Type I (insulin -dependent) diabetes
(pancreatic beta-cell autoreactive T cells and autoantibodies)
Graves Disease is an autoimmune condition that strikes more women than men at a rate of 7:1. It affects the functioning of the thyroid and causes hyperthyroidism, but it can also affect the tissue surrounding the eyes.
Progressive systemic sclerosis
is an example of an autoimmune disorder in which skin cells show extensive dermal fibrosis.
This characteristic “butterfly” rash is made worse by exposure to sunlight.
Lupus is a potentially fatal autoimmune disease that strikes 1 in 2,000 Americans and 10 times as many women as men.
Among the most serious and disabling types of arthritis, 2.1 million Americans live with rheumatoid arthritis.
About one out of seven Americans exhibit some form of arthritis.
Many chronic inflammatory diseases have been shown to occur preferentially in individuals carrying certain variants of MHC (major histocompatibility complex) genes.
There are two classes of HLA antigens:
class I antigens (HLA A, B, Cw)
class II antigens (HLA DR [and DQ & DP])
22 different HLA A antigens
42 different B antigens
9 different Cw antigens
18 different DR antigens
Rheumatoid arthritis (RA) affects peripheral joints and may cause destruction of both cartilage and bone. The disease affects mainly individuals carrying the DR4 variant of MHC genes.
This fact can lead to better prognoses and in aiding efforts to change immune reactions that involve the DR4 variant while leaving other reactions intact.
Ankylosing spondylitis (Bechterew's Disease), a joint inflammation mainly affecting the spine, occurs only in individuals carrying a certain variant of MHC molecule (HLA-B27). Much evidence suggests that molecules derived from microorganisms interact with the B27molecule in causing the destructive immune reactions
Individuals with the DR2, DR3 variant of MHC genes are most susceptible to MS.
Some populations, such as Gypsies, Eskimos, and
Bantus, never get MS.
However, for susceptible populations, if one person in a family has MS, that person's first-degree relatives -- parents, children, and siblings -- have a one to three percent chance of getting the disease.
In MS, tumor necrosis factor-alpha (TNFa), interLeukin (IL)-2, and IL-6 lead to the activation of most peripheral T-Cells (mainly CD4 memory) by promoting a persistent intracellular calcium increase via two independent signaling pathways.
Family members with autoimmune diseases may inherit and share a set of abnormal genes, although they may develop different autoimmune diseases.
(APL), traditionally associated with rheumatic autoimmune diseases such as SLE (lupus anticoagulant)
APL has been identified as a "common thread" in families where at least one member suffers from an autoimmune disorder.
This necessitates a delicate balance, controlling the disorder while maintaining the body's ability to fight disease in general.
Drugs most commonly used are corticosteroid drugs.
Cyclosporin A (CsA) inhibits a signal transmission pathway in T lymphocyte cells.
1- Metabolic control:
a. Graves’ disease: antithyroid drugs, surgical, radiation
b. Hashimoto’s thyroiditis: Thyroxin.
c. Pernicious anemia: vitamin B12.
d. IDDM: insulin
2- Antiinfalamtory and cytotxic drugs:
Nonsteroidal antiinflamatory (NSAID)
Cytotoxic drugs: Cyclophosphamide, Azothioprine, Cyclosporin
Myasthenia gravis after anticholinesterase
4- Plasmapheresis or Plasma exchange:
GBS, SLE, Goodpasture’s
Hemolytic anemia, ITP
6- Intravenous Gammaglobulin therapy
7- Cytokines and inhibitors: anti-TNF
IVIG therapy is used in the treatment of various autoimmune diseases to reduce circulating immune complexes.
Another treatment approach is to manipulate immune system messenger molecules called cytokines.
Are low molecular mass proteins, secreted by lymphocytes, which activate other immune system cells to regulate:
examples: Interferons and InterLeukins
Some cytokines (for example, IL-8) are also chemotactic for specific cell types, and are called “chemokines”.
Tumor necrosis factor-a TNF-a: Released by macrophages, increases vascular permeability, adhesion molecule expression on blood vessel endothelium, increases MHC expression, platelet activation (clots keep infection from the blood, and direct products to the lymphatic system).
If the infection reaches the blood, TNF-a causes septic shock and death. Release into joints leads to Rheumatoid arthritis.
Use a chimeric monoclonal antibody against TNF-a, or a new drug, Etanercept, which is a recombinant protein with TNF receptor and the constant region of an antibody. Blocking TNF-a shows great promise as a new treatment for RA.