This document discusses autoimmunity, including its definition as an inappropriate immune response against self cells/tissues due to self-tolerance failure. Various triggers are described, such as genetic factors like certain HLA alleles associated with diseases, environmental factors like molecular mimicry between pathogens and self-antigens, and non-genetic host factors including immunodeficiencies. Numerous autoimmune diseases are detailed along with their antibody targets and clinical features. Diagnosis involves clinical exams, labs to detect autoantibodies, and biopsies. Treatment focuses on reducing inflammation through steroids, blocking cytokines/integrins/B cells, or more extreme measures like immunosuppressants.

1. AUTOIMMUNITY
PRESENTER: KEAGAN KIRUGO
SUPERVISOR: DR.J.NYAGOL
GUIDELINES
•Definition
•Triggers
•Various antibodies and their
respective diseases
•Diagnosis of the autoimmune
diseases
•Treatment

2.  DEF
It is an inadequately controlled,
inappropriately targeted immune response
against host cells and tissue due to failure of
self-tolerance.

3. TRIGGERS
Classified into genetic,
environmental and non-genetic
host factors

4. Genetic predisposing factors
1. Presence of certain major histocompatibilty
II(MHC II) alleles: The following is a table
showing the human leucocyte antigens with
their respective disease association
HLA DISEASE
HLA DR2 Systemic lupus
erythematosus(SLE)
HLA DR3 Sjorgen’s syndrome,
myasthenia gravis, diabetes
mellitus type I(Type I DM)
HLA DR4 Rheumatoid arthritis, DM
type I, pemphigus vulgaris
HLA DRB1 Ulcerative colitis
HLA DR7 Crohn’s disease
HLA DQ4 Crohn’s disease

5.  2. Escape of autoreactive lymphocytes:
This is due to the negative selection
mechanism of eliminating immature
lymphocytes reacting to self antigens
strongly may be not be fully functional.
3. Lack of regulatory T lymphocytes (T-regs)

6. Environmental factors
 1.Crossreactive antigens: Presence of
epitopes within the pathogen that cross-react
with self antigen.
PATHOGEN TISSUE
CROSSREACTIVIT
Y
DISEASE
Streptococcus
pyogenes
Heart valves Rheumatic heart
disease
Campylobacter
jejuni,
Cytomegalovirus,
Influenza
Peripheral nerves Gullain-Barre
Syndrome

7. 2. Escape of sequestered antigens: Lymphoid
cells are not exposed to some of the self-antigens
during their maturation in the
thymus since these antigens are confined in
specialized tissue such as testes, brain or the
eye. Release of the sequestered antigens due
to trauma, surgery or infection may trigger an
autoimmune response.

8. 3.Chemical agents. For example hydralazine,
procainamide and isoniazid are associated with
increased antinuclear antibodies which are the
autoantibodies in systemic lupus
erythromatosus. The picture above shows the
clinical manifestation.

9. Non-genetic host factors
1. Immunodeficiency: Lack of appropriate
immune response required to clear a
pathogen may lead to perpetual host
immune system stimulation leading to
autoimmunity e.g. IBD
2. Hormonal influences: SLE is 10x higher in
females than males. Oestrogen triggers SLE
while androgens and progestins suppress the
immune response.

10. DISEASE TARGET ANTIBODY TO
Hashimoto’s thyroiditis Thyroid Thyroglobulin, thyroid
peroxidase
Pernicious anaemia Red cells Intrinsic factor
Addison’s disease Adrenal Adrenal cells
Premature onset
menopause
Ovary Steroid producing cells
Male infertility Sperms Spermatozoa
Insulin dependent
diabetes
Pancreas Pancreatic islet cells
Myasthenia gravis Muscle Muscle acetylcholine
receptor
Goodpasture’s
syndrome
Kidney, lung Renal and lung basement
membrane
Pemphigus Skin Desmosomes
Phacogenic uveitis Lens Lens protein

11. DISEASE TARGET ANTIBOBY TO
SLE Skin, joints, kidneys etc DNA, RNA,
nucleoproteins
Rheumatoid arthritis Joints IgG
Vitiligo Skin Melanocytes
Sjogren’s syndrome Secretory glands Duct tissue
Ulcerative colitis Colon Colon lipopolysaccharide
Idiopathic neutropenia Neutrophils Neutrophils
Primary biliary cirrhosis Liver Mitochondria

12. DIAGNOSIS
 A good history followed by a physical exam
 Routine laboratory test showing increases
erythrocyte sedimentation test or c-reactive protein
should be treated with a high index of suspicion
 This should be followed by specific serological assays
to detect autoantibodies. This is most appropriate
for systemic autoimmune diseases e.g. SLE
 Localised autoimmune disease are best diagnosed
by immunoflourescence of biopsy specimens

13. TREATMENT
Reducing inflammation is the mainstay of
treatment.
Drugs administered are
 Corticosteroids
 Blockers of:
-TNF
 integrins
 IL-1
 B cell depletion (anti-CD20)
In extreme cases, administer cyclosporine,
large doses of IgGs and do plasmaphoresis.
Supportive treatment where necessary: IV
fluids, analgesics, antipyretics

14. SLE
A systemic autoimmune disease
Epidemiology
Female: male 10:1
Peak ages is between 20 and 40 years
Clinical features
Malar rash, lymphadenopathy, arthralgias,
fever, fatigue and will often complain of
recurrent flu-like illness

15. With disease advancement
pleurisy, pericarditis, hair loss

16.  Laboratory diagnosis
Increased ESR and C-reactive protein
Evidence of kidney damage by red blood cells
and protein in urine
Presence of autoantibodies in serum especially
antinuclear antibody

17. REFERENCES
 2nd year immunology notes by Dr. Lyle
McKinnon given in 2012
 www.wikipedia.org//autoimmunity last
modified on 8th March 2013
 www.lupusinternational.comcopyright 2011
 Roitt Roitt’s Essential Immunology published
in 1995
 www.google.com//systemic lupus
erythromatosus

18. THANK YOU, SHUKRAN.