B13. Natural Autoimmunity B14. Organ Specific Autoimmune Diseases

Question 1

Natural Autoimmunity

Answer 1

• Only one thing important in veterinary - it may develop into an autoimmune disease.
• It is used to protect us form our own immune system (other immunity is to protect our own integrity)
• Central immune system will not attack self or foreign atg under normal circumstances - autoimmunity is an active protection of essential phylogenetically conserved molecules. This system is always present and should not be harmful.
• E.g. DNA, albumin, heat shock proteins, myoglobulin, enzymes of energy production, transferrin etc.

Question 2

There are 2 immune response systems

Answer 2

• External/peripheral: destruction of foreign atg and protection of integrity.
• Internal/central: maintenance of homeostasis, atg selection (harmful, harmless) and reaction to common tags (bacterial/self DNA).

Question 3

CIS

Answer 3

• reaction is based on gamma delta low reaction receptors.
• affinity is enough to bind to the atg but it will not lead to structural changes or activation of B cells with cell division
• the affinity for the receptors will not change —> low level affinity IgM can be produced
• the regulation can be default or become sensitive to Th cytokines —> in those cases they will start to detect the conserved molecules - the basis of autoimmune disease.

Question 4

Organ Specific Autoimmune Diseases

Answer 4

• Autoimmune diseases are of unknown or not clear aetiology. They are inflammatory, and degenerative due to their direction to self atg.
• Normally the body is tolerant to self-antigens during the development of the immune system as a foetus, and later in life by other mechanisms. But degranulation of the immune response may be initiated by cross- reactivity with microbial antigens, polyclonal activation of lymphocytes induced by tumours or infection, or a genetic predisposition caused by lack of toleration to specific antigens.
• Autoimmune reactions result from the presence of autoantibodies. Activated T cells and hypersensitivity reactions.

Question 5

Auto reactive cells

Answer 5

• B and T cells. If no reaction, the immune system is tolerating the atg.
o Central / peripheral
o Deletion, anergy
o Ignorance
o Cytokine regulation
• If the immune system recognise to the self atg, an auto immune reaction takes place
• It can be physiological (faulty MHCI) or pathological (auto immune diseases).

Question 6

Dysfunctions of auto-tolerance:

Answer 6

Genetic factors
• Cytokine genes
o TNF↑: arthritis, vasculitis
o TNF↓, IFNγ↑: SLE o IL-2, -7, -10↑: Colitis
o IL3↑: demyelinisation
• Apoptotic genes
• Hormones (females more susceptible - 9:1 for Graves, estrogen: SLE↑) External factors
• Physical and chemical injuries, infections o Exposure of hidden atgs
• Cross reactions
o Yersinia →TSH receptor →Graves-Basedow
o Streptococcus →myosin →myocarditis
o Plasmodium, mycobacteria → heat shock proteins
• Polyclonal cell activation
o B cell proliferation: Gamma herpesv, retrov
o T cell proliferation: Superantigens, over 10% of Th

Question 7

Organ Specific Autoimmune Diseases Mechanisms

Answer 7

• T cells
o Perforine, granzyme, apoptosis (TNF)
o Both Th and Tc cytokines

• B cells and atb 
o Complement activation 
o Opsonization 
o Immune complexes (Type III) 
o Enzyme activation (pemphygus, protease) o Interference 
o TSH receptor (Graves) 
o Acetylcholine receptor block 
o (myasthenia gravis)

Question 8

Organ specific:

Answer 8

• Thyroid:
o Graves-Basedow hyperthyreosis (TSH activation)
o Hashimoto’s disease (hypothyreosis, anti thyroid hormone)
• Eye
o Equine recurrent uveitis (Leptospira, Borrelia)
o Vogt-Koyanagi-Harada (dogs, anti-melanin, iris, retina, hair, skin depigmentation)
• Nervous system
o Sclerosis multiplex (myelin protein)
o Myasthenia gravis (acetylcholine receptor block)
• Blood: Haemolytic anaemia, Thrombocytopenia, Arteritis
• Skin:
o Psoriasis
o Pemphygus (endogenous atg + ab, Eosinoph↑)
-Vulgaris (epidermis)
-Foliaceaus (whole body, bellow upper ayer of epithelium)
-Bullosus (bellow epidermis)
• Kidneys: Addison disease (adrenal cortex)
• Gastrointestinal: colitis ulcerosa, ulcers in oral cavity, Chrone’s
• Urogenital tract