autoimmunity - metropolis india...autoimmunity •basically means immunity to self •a condition...
TRANSCRIPT
![Page 1: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/1.jpg)
AUTOIMMUNITY
DR SANDEEP WARGHADE
![Page 2: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/2.jpg)
Autoimmunity
• Basically means immunity to self
• A condition that occurs when the immune system mistakenly attacks and destroys own healthy body tissue.
![Page 3: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/3.jpg)
Autoimmunity Origins
Horror autotoxicus:
Literally, the horror of
self-toxicity.
A term coined by the
German immunologist
Paul Ehrlich (1854-
1915) to describe the
body's innate
aversion to
immunological self-
destruction.
![Page 4: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/4.jpg)
The “Immunology Definition”
Failure of immune
tolerance
![Page 5: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/5.jpg)
![Page 6: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/6.jpg)
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
![Page 7: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/7.jpg)
Autoimmunity Classification
Can be classified into clusters that are either
organ-specific or systemic
![Page 8: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/8.jpg)
Examples of Organ Specific
Lungs of a
patient with
Goodpasture’s
Vitiligo Hashimoto’s disease
(thyroiditis)
![Page 9: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/9.jpg)
Examples of Systemic Autoimmunity
Sjogren’s Syndrome
![Page 10: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/10.jpg)
Causes of Autoimmunity
![Page 11: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/11.jpg)
Genes and Autoimmunity
• 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
![Page 12: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/12.jpg)
Exceptions to the Rule – Simple
Genetic Autoimmune Illnesses
Disease Gene Mechanism
APS-1 (Autoimmune polyglandular
syndrome type 1)
AIRE Decreased expression of
self-antigens in the thymus,
resulting is a defect in
negative selection
IPEX (Immunodysregulation,
polyendocrinopathy, enteropathy,
X-linked)
FOXP3 Decreased generation of
Tregs
ALPS (autoimmune lymphoproliferative
syndrome )
FAS, FASL Failure of apoptotic death of
self reactive T or B cells
![Page 13: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/13.jpg)
Complex Disease and Genetics There have been numerous disease associated genes or
disease “susceptibility” genes linked to autoimmunity
![Page 14: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/14.jpg)
Environment
• Pathogens, drugs, hormones, and toxins
are just a few ways that the environment
can trigger autoimmunity
![Page 15: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/15.jpg)
Pathogens
![Page 16: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/16.jpg)
Rheumatic
fever is a
classic
example of
molecular
mimicry
![Page 17: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/17.jpg)
Drugs and Toxins
• Drugs – Examples: Procainamide
– Drug induced lupus
• Toxins – Examples: Toxic Oil Syndrome
– Occurred in Spain in 1981 after people ate contaminated olive oil.
– People developed unique illness marked by lung disease, eosinophilia, and excessive IgE
![Page 18: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/18.jpg)
Hormones
• Females are much more likely to develop autoimmune illness
• Rise in hormones associated with pregnancy may even cause abortion of the fetus
• Endometriosis and preeclampsia are both thought to be autoimmune in nature
Hypothesis: estrogen response elements (EREs) in several genes
![Page 19: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/19.jpg)
Estrogens and Autoimmunity
![Page 20: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/20.jpg)
Nature Immunology 2, 777 - 780 (2001)
Sex
differences in
autoimmunity
![Page 21: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/21.jpg)
Autoimmune diseases in India
• Accurate estimates for all diseases not available
• For celiac disease, rheumatoid arthritis, autoimmune hepatitis: rates compare to the western world
• Autoimmune skin disorders: Higher in India
• Chopra A. J Assoc Physicians India 2001;49:240-6
• Kumar KA. Indian J Derm Venerol Lep 2008;74:349-51
• Gupta R et al. W J Gastroenterol 2009;28:6028-33.
• Udayakumar N. Minerva Gastroenterol Diet 2008;54:229-30
![Page 22: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/22.jpg)
Immune Regulation
A defect in any arm of the immune system can trigger autoimmunity
Complement
T cells B cells
![Page 23: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/23.jpg)
Complement Deficiencies
• CD59 or CD55 – – Paroxysmal nocturnal
hemoglobinuria
– autoimmune hemolytic anemia
– autoimmune thrombocytopenia
– lupus lymphopenia
• Deficiencies in the classical complement pathway renders pts more likely to develop immune complex diseases – SLE
– RA
![Page 24: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/24.jpg)
The Complement See-Saw
• The complement system is a mediator in both the
pathogenesis and prevention of immune complex
diseases
• It has a protective effect when functioning in
moderation against pathogens; at the same time,
the inflammation promoted by complement
activation can result in cellular damage when not
kept in check.
![Page 25: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/25.jpg)
B or T? That is the question?
Autoimmunity is hard to classify as strictly a
B cell or T cell mediated disease as
multiple arms of the immune system are
involved
![Page 26: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/26.jpg)
Diagnosis of Autoimmune
Diseases Methods
Solid-phase
– Immunofluoroscence
– ELISA
– Western Blot
Liquid-phase
– Immunoprecipitation
– Radioimmunoassay
– Flow cytometry
![Page 27: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/27.jpg)
![Page 28: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/28.jpg)
Treatment
The key to treating
autoimmunity is
immunomodulation
![Page 29: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/29.jpg)
Treatment Options
• Anti-inflammatory drugs • NSAIDS, Corticosteroids
• Immunosuppressant drugs • Methotrexate
• Radiation
• Plamapheresis
• Cell Blocking Reagents • aCD20 (Rituxan)
• aCD3 (Teplizumab)
• Cytokine Blocking Reagents • TNF (Humira, Enbrel)
![Page 30: AUTOIMMUNITY - Metropolis India...Autoimmunity •Basically means immunity to self •A condition that occurs when the immune system mistakenly attacks and destroys own healthy body](https://reader033.vdocuments.site/reader033/viewer/2022042003/5e6eac82d454bd4c6d5c73d3/html5/thumbnails/30.jpg)
THANK YOU