Pick an organ, any organ . . .

Autoimmunity can affect ANY organ/organ system in the human body

Autoimmune Uveitis Multiple Sclerosis

Sjogren’s Syndrome
Pemphigus

Rheumatic Fever Goodpasture’s Syndrome

Diabetes
Autoimmune Hepatitis
Addison’s Disease

Autoimmune Oophoritis Ulcerative Colitis

Rheumatoid Arthritis
Autoimmune hemolytic Anemi
 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.
 DEFINITION

Autoimmunity is a condition in which structural or

functional damage is produced by the action of
immunologically competent cells or antibodies against the
normal components of the body
AUTOIMMUNE DISEASES- FEATURES

An elevated level of immunoglobulins.

Demonstrable auto antibodies
Deposition of immunoglobulins or their derivatives at sites
of election, such as renal glomeruli.
Accumulation of lymphocytes and plasma cells at the sites
of the lesion.
Benefit from corticosteroid or other immunosuppressive
therapy
 The occurrence of more than one type of autoimmune
lesion in an individual.
A genetic predisposition towards autoimmunity.
Incidence higher among females.
Chronicity. Usually reversible.
MECHANISMS OF AUTOIMMUNITY
 Neoantigens
 Cross reacting antigen theory
 Molecular mimicry
 Polyclonal B cell activation
 Emergence of forbidden clones
 Enhanced helper T cells and decreased suppressor T cells
 Sequestrated antigens
 Defects in idiotype-antiidiotype network
 Spontaneous and induced autoimmunity
 NEOANTIGENS

 Cells or tissues undergoing antigenic alteration as a result of

physical, chemical or biological influences are neoantigens.
 Elicit an immune response.
• Physical agents : irradiation, photosensitivity, cold allergy.
• Chemicals: drugs causing contact dermatitis, drug induced
anemia, leukopenia and thrombocytopenia.
• Biological: viral infections, bacterial enzymes
• Mutation
 CROSS REACTING ANTIGEN THEORY
OF AUTOIMMUNISM

The similarity between some foreign and self antigens is the

basis of the theory
Organ specific antigens are present in several species.
Injection of heterologous organ specific antigens may induce
an immune response damaging particular organ or tissue in
the host.
Eg. Streptococcal M proteins and the heart muscle
share antigenic characteristics. The immune response
induced by repeated streptococcal infection can therefore
damage the heart.
 MOLECULAR MIMICRY

 Due to the presence of epitopes with identical peptide

sequences ( instead of similarities in cross reactions) in the
infecting microorganisms and self antigens
Eg. Mycobacterium tuberculosis and joint membrane
Coxsackie B and myocardium.
 POLYCLONAL B CELL ACTIVATION

 Certain stimuli nonspecifically turn on multiple B cell

clones producing multiple nonspecific antibodies.
 These antibodies are IgM in nature
Eg. Chemicals: 2-mercaptoethanol
bacterial products: PPD, lipoplysaccharide
enzymes : trypsin
antibiotics: nystatin
infections: mycoplasma, EB virus, F.malaria
 FORBIDDEN CLONES

 Breakdown of immunological homeostasis may lead to

cessation of tolerance and emergence of forbidden clones
of immunocompetent cells

ENHANCED HELPER T CELL AND

DECREASED SUPPRESSOR T CELL

 Defects in thymus, in stem cell development and

macrophage function are causes
 SEQUESTRATED ANTIGENS

 The self- antigens present in closed systems and not

accessible to the immune apparatus are called sequestrated
antigens.
Eg. Lens antigen of the eye, sperm antigens.

DEFECTS IN IDIOTYPE- ANTIIDIOTYPE NETWORK

 Genetic factors such a s defective Ir or Ig genes.

 In human autoimmune diseases and in animal models,
genetic factors influences development and fate of
autoimmune status.
 SPONTANEOUS AND INDUCED
AUTOIMMUNITY

 Spontaneous autoimmunity
Eg, insulin dependent DM in nonobese diabetic mouse,
and thyroiditis in the obese strain chicken.
 Induced autoimmunity
Eg. Experimenting thyroiditis with thyroid gland extract
CLASSIFICATION OF
AUTOIMMUNE DISEASES

BASED ON SITE OF INVOLVEMENT AND

NATURE OF LESIONS
 Hemocytolytic
 Localised( organ specific)
 Systemic (non organ specific)
 Transitory
 HEMOCYTOLYTIC AUTOIMMUNE
DISEASES

Autoimmune hemolytic anaemia

Autoimmune thromboctopenia
Autoimmune leucopenia
 AUTOIMMUNE HEMOLYTIC ANEMIA

 Autiantibodies produced against erythrocytes.

 Prematurely destroyed in spleen and liver
 Two groups:

COLD AUTOANTIBODIES WARM AUTOANTIBODIES

•complete agglutinating •incomplete nonagglutinating

•IgM class
•Agglutinate RBCs at 40C but
not 370C
•Seen in syphilis, atypical
pneumonia and blackwater
fever
•IgG class
•Coat RBCs in direct Coombs test
•Seen in patients taking drugs such
as sulphonamides, antibiotics.
 AUTOIMMUNE THROMBOCYTOPENIA

Autoantibodies directed against platelets

eg,. Idiopathic thrombocytopenic purpura
sedormid purpura
This condition is considered as an antibody mediated
hypersensitivity.
 AUTOIMMUNE LEUCOPENIA

 Nonagglutinating antileucocyte antibodies

demonstrated in the serum of patients with SLE and
rheumatoid arthritis.
HASHIMOTOS DISEASE
(LYMPHADENOID GOITRE)
• Enlargment of thyroid gland
• Symptoms of hypothyroidism
• Glandular structure is replaced by
lymphoid tissue
• Antibodies react with
thyroglobulin,microsomal antigen and
thyroid cell surface component
 THYROTOXICOSIS
(GRAVES DISEASE)

 Majority with antibody to thyroglobulin

 Combination of Long Acting Thyroid stimulator
with surface membrane of surface cells
stimulate excessive hormone secretion
 ADDISON’S DISEASE

 Lymphocytic infiltration of adrenal

glands and presence of circulating
antibodies directed against cells of Zona
glomerulosa
AUTOIMMUNE ORCHITIS

 Lymphocytic infiltration of testes and circulating

antibodies to sperms and germinal cells
 MYASTHENIA GRAVIS

  is an autoimmuneneuromuscular
disease leading to fluctuating muscle
weakness and fatiguability. It is
an autoimmune disorder, in which
weakness is caused by
circulating antibodies that
block acetylcholine receptors at the
post-synaptic neuromuscular junction,
[1] inhibiting the stimulative effect of

the neurotransmitter acetylcholine
MYASTHENIA GRAVIS

 Abnormal fatiguability of muscles due to malfunction of

myonueral junction
 Antibody prevents acetyl choline from combining with its
receptor and impairs muscular contraction
AUTOIMMUNE DISESES OF EYE

 Phacoanaphylaxis-auto Ab against lens protien

 Sympathetic ophthalmia
PERNICIOUS ANEMIA

 2 TYPES OF AUTO AB present

 One is directed against parietal cells of gastric mucosa-
cause Achlorydria,atrophic gastritis
 Second against intrinsic factor and prevents absorption
vit B12
AUTOIMMUNE DISEASES OF
NERVOUS SYSTEM

 Neuroparalytic accidents following rabies vaccination

represent injury to nervous system by immune response
against sheep nervous tissue in the vaccine which cross
reacts with human nervous tissue
 Idiopathic polyneuritis is an autoimmune response
against peripheral nervous tissue
 AUTOIMMUNE DISEASES OF
SKIN

 PEMPHIGUS VULGARIS –Ab to

intercellular cemnt substance
 BULLOUS PEMPHIGOID-Ab
against dermal epithelial
junction
 It includes conditions characterized by immune response
against a variety of self antigens and damage to several
organs and tissue systems
 SYSTEMIC LUPUS
ERYTHEMATOSUS

 Variety of antibodies directed against cell

nuclei,intracytoplasmic cell
constituents,immunoglobulins,thyroid and
other specific antigens
Clinical features
 Autoantibodies in SLE

 ANA (prevalence ~ 100%)

(prevalence 40-90%,
 anti – dsDNA

levels fluctuate with disease

activity)
 ENA (anti – Sm)
 antoantibodies against blood cells
 RHEUMATOID ARTHRITIS

 Symmetric polyarthritis with muscle wasting

and subcutaneous nodules
 Auto-immune disorder which results in
inflammation of the synovial lining of the joint
and cartilage destruction
 Presence of circulating Ab –Rheumatoid
factor(RF)
POLYARTERITIS NODOSA

 Necrotising angiitis involving medium sized

arteriess,ending fatally due to coronary
thrombosis,cerebral hemorrhage or git bleeding
 SJOGREN SYNDROME

 Triad of conjunctivitis
sicca,dryness of mouth,with or
without salivary gland
enlargement and rheumatoid
artheritis
TRANSITORY AUTOIMMUNITY

 It includes anemia,thrombocytopenia or nephritis that

follow certain infections or drug therapy
 Inf agent induces antigenic alteration in some self
antigens
 It causes tissue damage
 Disease is transient & undergoes spontaneous cure when
infection is controlled or drug withdrawn