Autoimmunity

HBMLS IV
Prof E Gomo
 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.
The “Immunology Definition”

Failure of immune
tolerance
 Mechanisms Breaching Self Tolerance

• Disruption of self or tissue barrier

• Infection of antigen presenting cell

• Binding of pathogen to self antigen

• Molecular mimicry

• Superantigen
 Autoimmunity vs Autoimmune Disease

• Autoimmunity: reactivity of Immune System

vs self
– May be normal and non-destructive
– Characterised by auto-antibodies and autoreactive
cells
• Autoimmune disease: damage or destruction
to (including dysfunction) self tissue as a
result of autoimmunity
Autoimmunity Vs. Autoimmune Disease

Autoimmunity Autoimmune disease

• Existence of harm- • Dependent on
less self-reactive genetic, pathogen
lymphocytes and and hormonal
antibodies factors
• Potentially reversible • Features of severe
• Incidence higher in tissue damage
older age • Clinical symptoms
• Significance unclear, • Protracted course
possibly physiological but usually fatal
• Familial clustering
 Aetiology of Autoimmunity
• Genetic predisposition
• Damage to
Immunologically privileged
sites
• Exposure to infectious
antigens
• Hormonal influences

Janeway’s Immunobiology 9th Edition

Genetic Predisposition
 Genetics and Autoimmune Disease

• Multiple genes determine susceptibility to AD

• No particular gene is necessary or sufficient
for disease expression
• MHC and multiple non-MHC genes are
involved
• Genetic alleles increasing susceptibility are
relatively frequent in the general population
 Genetic Predisposition

• Rheumatoid arthritis is associated with

HLA-DR4
• Thyroditis with HLA-DR5
• Multiple sclerosis with HLA-DR2
• SLE with HLA-DR2/DR3
• Type I diabetes with HLADR3/DR4
• Ankylosing spondylitis with HLA-B27
Damage to Immunologically Privileged Sites
Damage to Immunologically Privileged Sites

Janeway’s Immunobiology 9th Edition

Exposure to Infectious Antigens

An immune response to these

antigens will result
in immune attack against
self antigens (molecular
mimicry)
 Molecular Mimicry
Definition:
Antigens of infectious agent mimic a host
antigen and trigger self-reactive T-cell
clones to attack host tissues
OR
lead to production of auto-antibodies
Examples:
• Rheumatic fever due to group A streptococcus
• SLE due to Epstein-Barr virus cross reactive with
nuclear Sm antigen
Pathogens in AID
Autoantibodies
Diseases Mediated by Auto-Ab
Against Cell- Surface Receptors

Janeway’s Immunobiology 9th Edition

Myasthenia Gravis
 Other Factors
• Hormonal influences play a role e.g. SLE
affects women 10 times more than men
• Overproduction and/or dysregulation of
cytokines
• Disturbances of apoptosis
• Adjuvant effect of microorganisms
• Pre-existing defects in the target organ
• Direct stimulation of autoreactive cells by
foreign antigen
 Immune Dysregulation
A defect in any arm of the immune system can trigger
autoimmunity

Complement

T cells B cells
 Complement and AID

• CD59 or CD55 –
– Paroxysmal nocturnal haemoglobinuria
– autoimmune hemolytic anemia
– autoimmune thrombocytopenia

• Deficiencies in the classical complement

pathway predisposes to immune complex
diseases
– Systemic Lupus Erythematosis
– Rheumatoid Arthritis
Sex and Autoimmunity

Nature Immunology 2, 777 - 780 (2001)

Autoimmune Disease
Some Common AIDs

Janeway’s Immunobiology 9th Edition

 Organ-specific And Non Organ- Specific Autoimmune
Diseases

Organ-specific Non organ- specific

(systemic)
• Autoimmune attack vs. • Widespread self-anti-gens
self-antigens of given are targets for autoimmune
organ attack
• It results in a damage of • Damage affects such
organ structure and structures as blood
function vessels, cell nuclei etc.
• Treatment is focused on • Treatment is aimed to
the replacement of organ inhibit excessive activation
function of the immune system
Mechanisms of Tissue damage
Auto-Ab Mediated Damage

Janeway’s Immunobiology 9th Edition

Autoimmune
Haemolytic
Anaemias

Janeway’s Immunobiology 9th Edition

Grave’s Disease

Janeway’s Immunobiology 9th Edition

Myasthenia
Gravis

Janeway’s Immunobiology 9th Edition

Goodpasture’s Syndrome

Janeway’s Immunobiology 9th Edition

SLE

Janeway’s Immunobiology 9th Edition

T Cell Mediated Damage

Janeway’s Immunobiology 9th Edition

Diabetes

Janeway’s Immunobiology 9th Edition

Multiple Sclerosis

Janeway’s Immunobiology 9th Edition

Rheumatoid Arthritis

Janeway’s Immunobiology 9th Edition

 Diagnosis
• History: characteristic symptoms
• Classical physical findings and signs
• Laboratory:
– General: CBC, ↑ESR, ↑CRP, Complement, ↑IgG
– Specific auto-antibodies
– Hormonal assay
– Radiological
– ? HLA
 Treatment
• Immunomodulation
– This necessitates a delicate balance, controlling the disorder while maintaining the
body's ability to fight disease in general.
• Drugs
– Corticosteroids : prednisolone
– Immunosuppressants: Cyclosporin A - inhibits a signal transmission pathway in T
lymphocyte cells.

• Metabolic control:
– Graves’ disease: antithyroid drugs, surgical, radiation
– Hashimoto’s thyroiditis: Thyroxin.
– Pernicious anemia : vitamin B12
– IDDM: insulin

• Anti-infalamtory and cytotxic drugs:

– Nonsteroidal antiinflamatory (NSAID)
– Corticosteroids
– Cytotoxic drugs: Cyclophosphamide, Azothioprine
 Treatment

– Thymectomy: Myasthenia gravis after

anticholinesterase

– Plasmapheresis or Plasma exchange: SLE

– Spleenectomy: Hemolytic anemia

– Intravenous Gammaglobulin therapy

– Cytokines and inhibitors: anti-TNF

Summary

Janeway’s Immunobiology 9th Edition

Thank You