2. • Basically means immunity to self antigens.
• A condition that occurs when the immune system
mistakenly attacks and destroys healthy body tissue.
•Most important steps in production of autoimmune
disease: activation of self reactive CD4+T cells i.e failure
of immune tolerance . So… Most are antibody
mediated.
4. GENETIC FACTORS :-
• (+) genetic
predisposition
• Strong association with
HLA specificities,
especially class- II
genes.
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5. Examples:-
• Class I MHC-related :-
- ankylosing spondylitis & Reiter’s
syndrome.
- more common in men.
• Class II MHC-related :-
- RA , Grave’s disease & SLE.
- more common in women.
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6. HORMONAL FACTORSHORMONAL FACTORS
• Approximately 90% occur in women
• Estrogen can alter the B-cell repertoire and enhance
formation of antibody to DNA
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8. ENVIRONMENTAL FACTORSENVIRONMENTAL FACTORS
• Exposure to an environmental agent can
trigger a cross-reacting immune response
against some component of normal tissue.
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10. • Defects in clonal deletion mechanismsDefects in clonal deletion mechanisms
• Polyclonal lymphocyte activationPolyclonal lymphocyte activation
• Molecular mimicryMolecular mimicry
• Release of sequestered antigensRelease of sequestered antigens
• Co-stimulatorsCo-stimulators
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AUTOIMMUNITY:MECHANISM:-AUTOIMMUNITY:MECHANISM:-
11. Defects in clonal deletion mechanismsDefects in clonal deletion mechanisms
• Thymic defects that lead to proliferation of self-reactive T cells.
• Failure of central tolerance.
• Examples:-
-Diabetes,
-Multiple Sclerosis,
-Thyrotoxicosis &
-Myasthenia Gravis.
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13. Diabetes
Disease in which
the body does
not produce or
properly use
insulin
“ T cell” Disease
T cells attack and
destroy
pancreatic beta
cells
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14. Multiple Sclerosis
MS patients can have autoantibodies and/or self reactive T
cells which are responsible for the demyelination
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18. Polyclonal lymphocyte activation
Examples:-
• Microorganism-derived mitogens stimulate
lymphocytes
-Microbial products (e.g. LPS) act as
superantigens activate a large pool of T and B
cells.
. S.L.E
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20. Molecular mimicryMolecular mimicry
• Microbial antigens with similar structure to self-
antigens activate auto-reactive T cells.
• Cross-reactivity-induced immune response.
• Example: M protein of S. pyogenes and myosin of
cardiac muscle.
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22. Release of sequestered antigensRelease of sequestered antigens
• Immunologically privileged sites (brain, ant. eye
chamber, ovary, placenta, testis, pregnant uterus)
not exposed to immune system
• Damage release of antigens elicit immune
response
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23. • Release of sequestered
Ag.
• Smoking can trigger
Goodpasture’s
syndrome.
• Alveolar basement
membrane normally
not exposed to immune
system.
Lungs of a patient
with Goodpasture’s
Goodpasture’s
syndrome
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24. AUTOIMMUNITY: MechanismsAUTOIMMUNITY: Mechanisms
Defects in the regulation of THDefects in the regulation of TH11 andand
THTH22 cellscells
• Impaired T suppressor cellImpaired T suppressor cell
immunoregulationimmunoregulation
25. Pick an organ, any organ . . .
Autoimmunity can affect ANY organ/organ system in the human body
Pemphigus
Multiple Sclerosis
Sjogren’s Syndrome
Rheumatic Fever
Autoimmune Hepatitis
Ulcerative Colitis
Goodpasture’s Syndrome
Diabetes
Autoimmune Uveitis
Autoimmune hemolytic Anemia
Addison’s Disease
Rheumatoid Arthritis
Autoimmune Oophoritis
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30. Immune Regulation
A defect in any arm of the immune system can trigger autoimmunity
Complement
T cells B cells
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31. Complement Deficiencies
• Deficiencies in the
classical complement
pathway renders pts
more likely to
develop immune
complex diseases
– SLE
– RA
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32. Symptoms :-
• Initial diagnosis may be missed in patients as
diseases present with general symptoms.
– Fever, muscle ache, fatigue, joint pain
• Disease specific manifests:-
– SLE – rash
– Sjogren’s – dry mouth, dry eyes
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33. • General tests:-
– C Reactive Protein .
– Autoantibody titers (anti
DNA, anti phospholipids,
etc) .
– Presence of Rheumatoid Factor.
• Disease specific tests :
– Neurological exam – MS.
– Fasting glucose – Diabetes.
Diagnosis:-
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The concept that a single gene mutation leads to a single autoimmune disease is the EXCEPTION not the RULE
Because of this autoimmune diseases are generally classified as complex diseases as there is not a single “pinpoint-able” gene. …
Exception 2 rule is e.g:-autoimmune lymphoproliferative syndrome(ALPS)…single gene is FAS ,FASL ….lead 2 failure of apoptotic death of self reative T or B cells.
Complex Disease and Genetics:-There have been numerous disease associated genes or disease “susceptibility” genes linked to autoimmunity e.g:- ankylosing spondylitis…..genes B27
Somatostatin (also known as growth hormone-inhibiting hormone (GHIH) or somatotropin release-inhibiting factor (SRIF)) orsomatotropin release-inhibiting hormon
Somatostatin is secreted in several locations in the digestive system:
stomach
intestine
delta cells of the pancreas[7]
Brain:-
Somatostatin is produced by neuroendocrine neurons of the periventricular nucleus of the hypothalamusAnterior pituitary
In the anterior pituitary gland, the effects of somatostatin are:
Inhibit the release of growth hormone (GH)[8] (thus opposing the effects of Growth Hormone-Releasing Hormone (GHRH))
Inhibit the release of thyroid-stimulating hormone (TSH)[9]
Systemic lupus erythematosus :- often abbreviated to SLE or lupus, is a systemic autoimmune disease (orautoimmune connective tissue disease) that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage.[1] It is a Type III hypersensitivity reaction caused by antibody-immune complex formation.
SLE most often harms the heart, joints, skin, lungs, blood vessels, liver, kidneys, and nervous system. The course of the disease is unpredictable, with periods of illness (called flares) alternating with remissions. The disease occurs nine times more often in women than in men, especially in women in child-bearing years ages 15 to 35, and is also more common in those of non-European descent.[2][3][4]
SLE is treatable using immunosuppression, mainly with cyclophosphamide, corticosteroids and other immunosuppressants; there is currently no cure. SLE can be fatal, although with recent medical advances, fatalities are becoming increasingly rare
Scleroderma is a chronic systemic autoimmune disease (primarily of the skin) characterized by fibrosis (or hardening), vascular alterations, and autoantibodies.
Vitiligo :- is a condition that causes depigmentation of sections of skin. It occurs when melanocytes, the cells responsible for skin pigmentation, die or are unable to function. The cause of vitiligo is unknown, but research suggests that it may arise from autoimmune, genetic,oxidative stress, neural, or viral causes.
Plasmapheresis (from the Greek —plasma, something molded, and —aphairesis, taking away) is the removal, treatment, and return of (components of) blood plasma from blood circulation.
