Experiment modelling of Auto-immune diseases

Published by Pratik Umesh Parikh
Master of Pharmacy (Pharmaceutical Biotechnology)

1. Experimental
models of auto-
immune diseases
PRATIK UMESH PARIKH
F. Y. M. PHARMACY
(PHARMACEUTICAL BIOTECHNOLOGY)
ROLL NO.: 08
SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH, KOPARGAON

2. Contents :
❖Tolerance and Autoimmunity
❖Needs of experimental models
❖Selection of appropriate animal model
❖Types of experimental models
❖Spontaneous Models
❖Induced models
❖Reference
SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH, KOPARGAON

3. Tolerance & Auto-immunity :
Tolerance: Unresponsiveness of immune system towards specific tissue, cells or
substances.
Self tolerance is shown against self antigens and cells.
Autoimmunity: If self tolerance mechanisms fail and our immune system acts against
our own body, it is known as autoimmunity. It can be organ specific or systemic
Examples of autoimmune diseases:
❖Doganspecific: Hashimoto's thyroiditis, Diabetes type I, Myasthenia gravis
❖Systemic:Systemic lupus erythematous (SLE)
SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH, KOPARGAON

4. Need for animal models :
We need something which can provide with similar or at least analogous results like
humans.
All mammals have developed with their own complex, distinct functions. But all mammals
share a significant amount of similarity
➢Human diseases can be seen in animals too. Mechanisms are 90% similar.
➢Animal model is a nonhuman species used in research for various purposes. Induced
and spontaneous pathological mechanisms can be studied in them.
SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH, KOPARGAON

5. Selection of appropriate animal model :
1.Relevance: Must be similar to humans. Disease must occur spontaneously or
after induction
2.Easy to handle: Size definitely matters. Easy to control and fit in animal
centresbut large enough to perform experiments
3.Well characterized genetically
4.Rapid reproduction: Obtain more models with lowest genetic variation
5.Life span : Must be alive for long enough to study the effects.
SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH, KOPARGAON

6. Animals model in Auto-immunity :
Significant amount of immunology studied right now has been developed using animal
models.
They have helped us to understand the pathogenesis of the disease and also try
potential treatment strategies.
Animals used generally include-mice, rabbits, guinea pigs, Horses and also primates.
Most commonly used animal model is the mouse Musmusculus. It has a huge impact in
understanding many human diseases and. Gene similarity 99%
Types of Animal models in autoimmunity:
1.Spontaneous models
2.Induced models
SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH, KOPARGAON

7. Spontaneous experimental models :
Some animals develop autoimmunity spontaneously.
Show similar symptoms as human.
Some models are discussed:
1) Obese strain(OS) of chicken:
Autoantibodies against thyroid antigens are seen in serum. This leads to destruction of thyroid gland.
This disease in OS is similar to Hashimoto's disease in humans. Many similarities between both
diseases.
-Developed both humoraland cell mediated reaction
SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH, KOPARGAON

8. 2) Non Obese Diabetic(NOD) Mouse
Used to study type diabetes (Insulin Dependent Diabetes Mellitus IDDM)
Primarily develops insulitis-Infiltration of Pancreatic islets by leucocytes. Thus less or no insulin is
produced
Diabetes can be transferred from NOD to non-diabetic recipient by transferring T cells
Experiment: To understand the importance of T cells in IDDM, some experiments were
performed using NO
SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH, KOPARGAON

9. SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH, KOPARGAON
Healthy NOD mice
Immune system
destroyed by X rays
Inject bone marrow
from normal mice
NOD does not
develop diabetes
Normal mice
Immune system
destroyed by X rays
Inject bone marrow
from normal mice
Diabetes develops
in healthy mouse
T cells transfer diabetes from diseased to healthy mice

10. Normal vsdiabetic pancreas
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• NZB spontaneously develops autoimmune haemolyticanaemiajust like humans.
It develops autoantibodies against nuclear proteins, DNA, erythrocytes and T lymphocytes.
It is also a well known model for SLE (Systemic Lupus Erythematous)
F1 hybrid of NZB (NZB/W)
Hybrid between NZB and New Zealand White mouse.
Develops autoantibodies against kidney antigens
Immune complexes gets deposited in kidney causing glomerulonephritis.
3) New Zealand Black (NZB) mouse

12. Induced Animal models :
SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH, KOPARGAON
Not all animals develop autoimmune disease simultaneously. In some cases it must be induced.
Question: Chediak-Higashi syndrome (Enlarged granules in leukocytes)
1) Rabbit model
Rabbits were induced with acetylcholine receptors from electric eel.
Developed muscular weakness like myasthenia gravis.
Rabbit made Abagainst eel acetylcholine receptors. Cross reaction with self acetylcholine receptors
occurred.
No neurotransmission, muscular weakness.

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14. Used to study multiple sclerosis in humans (MS)
Best studied model in autoimmunity.
Can be induced in many strains of mice and rats by injecting myelin basic protein (MBP) or proteolipid
antigen (PLP).
Cellular infiltration resulting in demyelination and paralysis.
SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH, KOPARGAON
2) Experimental autoimmune encephalomyelitis (EAE) :

15. Lesions formed in humans and mice are same.
Mouse EAE model, helped to test treatment strategies for humans.
Normal Nerve Can be induced in many experimental animals
Induction can be done by using type 2 collagen molecules
Autoimmune response against collagen is induced causing inflammation in several joints.
This is similar to Rheumatoid arthritis in humans.
SANJIVANI COLLEGE OF PHARMACEUTICAL EDUCATION & RESEARCH, KOPARGAON
2) Experimental autoimmune encephalomyelitis (EAE) :

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17. Reference :
1.Abbas, A. K., Lichtman, A. H., & Pillai, S. (2014). Cellular and molecular immunology E-book.
Elsevier Health Sciences, BE
2.Punt, J., Stranford, S. A., Jones, P. P., & Owen, J. A. (2019). Kubyimmunology.8E
3.Held, J. R. (1983). Appropriate animal models. Annals of the New York Academy of Sciences.
4.Burkhardt, H., & Kalden, J. R. (1997). Animal models of autoimmune diseases. Rheumatology
international, 17(3), 91-99.
5.GangalS. and SontakkeS. (2013) Textbook of Basic and Clinical Immunology. University Press,
India.
6.RoittI., BrostoffJ. and Male D. (1993) Immunology Sixth edition Mosby & Co. London.
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