Duhok Polytechnic University

Duhok Technical Institute

Department of Pharmacy

Autoimmune Disease

Name: Rasho Ali

Stage: 2nd Supervisor
Date: 11/11/2020 Dr. Rojan Ahmed
Introduction

Autoimmune disease
• Results from a failure of self-tolerance
• Immunological tolerance is specific unresponsiveness to an antigen
• All individuals are tolerant of their own (self) antigens
Autoimmunity
• is defined as an immune response against self antigens
• The principal factors in the development of autoimmunity are the inheritance of susceptibility
genes and environmental triggers, such as infections
• Most autoimmune diseases are polygenic and are asssociated wih multiple gene loci, the most
important of which are the MHC genes
• Infections may activate self-reactive lymphocytes, thereby triggering the development of
autoimmune diseases
Common Autoimmune Diseases

• Rheumatoid Arthritis
• Vitiligo Systemic Lupus
• Psoriasis Hyper and Hypo Thyroid
• Chrone's disease
• Multiple Sclerosis
• Ulcerative Colitis
• Pernicious and Celiac Disease
• hemolytic anemias
• Possible Autoimmune
• Diabetes Mellitus
Components
* Fibromyalgia
* Lyme's Disease
Effects of autoimmunity

• 1) Tissue destruction
Diabetes: CTLs destroy insulin-producing b-cells in pancreas
• 2) Antibodies block normal function
Myasthenia gravis: Ab binds acetylcholine receptors
• 3) Antibodies stimulate inappropriate function
Graves’ disease: Ab binds TSH receptor
Mimics thyroid-stimulating hormone
Activates unregulated thyroid hormone production
• 4) Antigen-antibody complexes affect function
Rheumatoid arthritis:
IgM specific for Fc portion of IgG
IgM-IgG complexes deposited in joints inflammation
Symptoms

The symptoms of autoimmune disease Vary depending on the disease as well as the person’s immune system.
Common symptoms include :
• Anxiety or depression
• Blood sugar Changes
• Digestive or gastrointestinal problems
• Dizziness
• Elevated fever and high body temperature
• Extreme sensitivity to cold in the hands and feet
• Fatigue
• Infertility
• Inflammation
• Irritability
• Low or high blood pressure
• Malaise
• Weakness and stiffness in muscles and joints
• Weight Changes
And depending on the type of Autoimmune disease :
• Destruction of an organ or tissue
• Increase in the size of an organ or tissue
Causes of autoimmunity

• 1) Release of sequestered Ag
• Smoking can trigger Good pasture's syndrome
• Alveolar basement membrane normally not exposed to
• immune system
• Smoking damages alveoli, exposes collagen
• Anti-collagen Ag damages lung and kidney
• Anti-sperm Ab produced in some men after vasectomy
• Injection of myelin basic protein (MBP) produces MS-like EAE
• in mice
• May be triggered by injury or infection

• 2) Immune stimulation

• Microbial infection stimulates APCs carrying self Ag

• High level of APCs with “second signal” breaks anergy

Mechanisms of autoimmunity

• Ag released from hidden location.

• Antigen generated by molecular changes.
• Molecular mimicry.
• Alteration in Ag processing.
• Infection.
• Genetic factors.
• Lymphocytes abnormalities.
• Failure of central tolerance.
• Overcome of peripheral tolerance.
• Polyclonal lymphocytes activation.
 Autoimmune diseases can be classified into 2 broad categories-
1. Organ-specific 2. Systemic
• 1. ORGAN-SPECIFIC AUTOIMMUNE DISEASES In this type, the immune response is directed
to a target antigen unique to a single organ or gland. The cells of the organ may be damaged directly
by humoural or cell- mediated effector mechanisms. Alternatively, the antibodies may overstimulate
or block the normal functions of the target organ. Eg- Hashimoto’s thyroiditis
Organ-specific Auto-immune diseases are mediated by-
• A. Direct Cellular Damage where lymphocytes or antibodies bind to cell- membrane antigens,
causing cellular lysis and/or an inflammatory response in the organ as a result of which the damaged
cellular structure is replaced by connective tissue (scar tissue) and the function of the organ declines.
Diseases caused by this are-
• HASHIMOTO’S THYROIDITIS
• AUTOIMMUNE ANEMIAS
• GOODPASTURE’S SYNDROME
• INSULIN-DEPENDENT DIABETES MELLITUS
• GRAVE’S DISEASE …..
HASHIMOTO’S THYROIDITIS

• Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which

the thyroid gland is gradually destroyed by a variety of cell and antibody mediated immune
processes due to production of auto-antibodies and sensitized Th1 cells for thyroid antigens. It
was the first disease to be recognized as an autoimmune disease and was discovered by Dr.
Hashimoto Hakaru
AUTOIMMUNE ANEMIAS

• An individual with this disease makes auto-antibody to RBC antigens, triggering complement-
mediated lysis or opsonization and phagocytosis of RBCs.
These are of 3 types-
• 1. Pernicious anemia
• 2. Autoimmune hemolytic anemia
• 3. Drug-induced hemolytic anemia

These are usually detected by Coomb’s test where RBCs are incubated with anti-human IgG
serum.
GOODPASTURE’S SYNDROME

• Here auto-antibodies specific for certain basement membrane antigens bind to the basement
membranes of kidney glomeruli and alveoli of lungs.
• Subsequent complement activation leads to cellular damage and an ensuing inflammatory
response. Death is ensued within several months of onset of symptoms.
GRAVE’S DISEASE

• Graves' disease is an autoimmune disease where the thyroid is overactive, producing an

excessive amount of thyroid hormones (a serious metabolic imbalance known as
hyperthyroidism and thyrotoxicosis. This is caused by autoantibodies (TSHR-Ab) that activate
the TSH-receptor (TSHR), thereby stimulating thyroid hormone synthesis and secretion, and
thyroid growth (causing a diffusely enlarged goiter. The resulting state of hyperthyroidism can
cause a dramatic constellation of neuropsychological and physical signs and symptoms.
SYSTEMIC AUTOIMMUNE DISEASES

• In this type, the immune response is not directed to a target antigen unique to a single organ or
gland, rather it is directed to any different organs, tissues, and cells of the body.
* Eg- Systemic lupus erythematosus
• SYSTEMIC LUPUS ERYTHEMATOSUS
Systemic lupus erythematous is a systemic autoimmune disease that can affect any part of the
body. Affected individuals produce auto-antibodies to a vast array of tissue antigens, such as
DNA,histones, RBCs,platelets, leukocytes etc often through excessive complement activation. The
treatment of SLE involves preventing flares and reducing their severity and duration when they
occur & treatment can include corticosteroids and anti- malarial drugs.
Treatment for autoimmunity

• Immunosuppression
(e.g., prednisone, cyclosporin A)
• Removal of thymus (some MG patients)
• Plasmapheresis (remove Ab-Ag complexes)
• T-cell vaccination (activate suppressing T cells??)
• Block MHC with similar peptide
• anti-CD4 monoclonal Ab
• anti-IL2R monoclonal Ab
Reference

• 1. Medline Plus : Autoimmune Disease

http://www.nlm.nih.gov/medlineplus/ency/article/000816.htm
• 2.National Institute of Allergy and Immune disorders : Lymes disease ,
http://www3.niaid.nih.gov/topics/lyme Disease / research / autoimmune.htm
• 3. Merck Manual Online : http://www.merck.com/mmhe/sec16/ch186/ch186a.html
• 4. Microbiology and Immunology online , University of So. Carolina School of Medicine
http://pathmicro.med.sc.edu/ghaffar/tolerance2000.htm
• 5. Environmental epidemiology and risk factors for Autoimmune disease Medscape :
http://www.medscape.com/viewarticle/449854
International Journal of Molecular Science : Effect of Xenoestrogens on T lymphocytes : Int .
J. Mol . Sci . 2003 , 4 , 45-61 http://www.mdpi.org/ijms/papers/i4020045.pdf
• 6. K. Spellman , Modulation of cytokine expression by traditional medicines : a review of herbal
immunomodulators , Alternative Medicine Review , June 2006 ; 11 ( 12 ) : 128-50

• 7. Alternative Therapies in Health and Medicine . 2009 Jul - Aug ; 15 ( 4 ) : 24-31 . Functional and
physiological effects of yoga in women with rheumatoid arthritis : a pilot study . Bosch PR ,
Traustadóttir T , Howard P , Matt KS Department of Physical Therapy , A.T. Still University , USA
Reference

• 8. Complement Ther Clin Pract . 2008 Aug ; 14 ( 3 ) : 176-84 . Epub 2008 May Esmonde L ,
Long AF.School of Healthcare , University of Leeds , Baines Wing , Leeds LS2 9UT , UK
• 9. Mult Scler . 2008 Sep ; 14 ( 8 ) : 1113-9 . Epub 2008 Jul 16.Schwarz S , Knorr C , Geiger
H , Flachenecker P. Central Institute of Mental Health , University of Heidelberg , J 5 ,
Mannheim 68159 , Germany
• 10. Natl Med J India . 2007 Sep - Oct ; 20 ( 5 ) : 236-9 . Zaman T , Agarwal S , Handa R. All
India Institute of Medical Sciences , New Delhi , 110029 , India
• 11. J Altern Complement Med . 2006 Oct ; 12 ( 8 ) : 817-32 . Arias AJ , Steinberg K , Banga A
, Trestman RL . Department of Psychiatry , University of Connecticut Medical School ,
Farmington , CT , USA . arias@psychiatry.uchc.edu 11.
http://www.wrongdiagnosis.com/a/ai/prevalence.htm#prevalence_intro