Disorders of immunity-II

Autoimmune disorders

Dr. Mehzabin Ahmed

 AUTOIMMUNE DISORDERS

 Immune reaction against self antigens

 Auto antibodies are produced against ones own
(self) tissues
 Autoimmunity can involve a single organ or
multiple systems
Examples of single organ or cell type autoimmunity
Hashimoto's thyroiditis

Graves disease

Autoimmune hemolytic anemia

Autoimmune atrophic gastritis of Pernicious anemia

Autoimmune thrombocytopenia

Autoimmune orchitis

Insulin-dependent diabetes mellitus

Myaesthenia gravis

Goodpasture syndrome
 Examples of systemic/ multi organ
involvement

 Systemic lupus erythematosus,

 Rheumatoid arthritis,

 Sjogren syndrome,

 Reiter syndrome.
 Immunological tolerance
A state of incapability of developing an immune response
to a specific antigen
 Self-tolerance refers to lack of responsiveness to self
antigens (an individual's own antigens).
 Autoreactive T cells are thus controlled by the body's own
mechanisms.
 Failure of these mechanisms results in autoimmunity
 Factors influencing autoimmunity
Genetic:
 Familial clustering of several human autoimmune
diseases is seen e.g. SLE, autoimmune thyroiditis.
 Several autoimmune diseases are linked to HLA, class
II antigens.
 
Microbial Agents:
 Cross reaction of the microbial epitopes with self -
antigens.
 Tissue necrosis causes up-regulation of the T cell
activation.
 Super antigens can activate a large pool of T and B cells,
some of these may be autoreactive.
 Systemic Lupus Erythematosus
 Autoimmune disorder,
 Acute or insidious in onset

 Becomes a chronic remitting, relapsing disease

 Lesions mainly in skin, joints, kidney, and serosal

membranes.
 Autoantibodies directed against nuclear antigens like
DNA, histones, nucleolar and non-histones bound to RNA.
 Factors influencing SLE

Genetic:
 Genetic predisposition is linked to HLA - DQ.

Environmental:
 Drugs - hydrallazine, procainamide, D-pencillamine UV
light.
 Hormones : Females> male in reproductive years.

Immunological:
 Helper T cell induced production of IgG against self
antigens.
 Lesions in SLE
 Kidney: Glomerulonephritis- deposition of DNA and
then the anti-DNA antibody.
 Skin: Butterfly pattern of malar rash. Also seen on trunks
and limbs and increase on exposure to light.
 Joints: Non-erosive synovitis and little deformity

 CNS: Non-inflammatory occlusion of small vessels

because of damage by antibodies.
 Heart: Endocarditis

 Spleen, Lungs, liver, may be involved.

 Sjogren Syndrome: Sicca Syndrome
 Can occur singly or in association with other
autoimmune disorders like, Rheumatoid arthritis, SLE,
thyroiditis.
 It is characterized by
dry conjunctiva - keratoconjunctivitis sicca
dry mouth - xerostomia.
 Autoimmune destruction of lacrimal and salivary
glands.
 HLA - B, DR, DQ.
 Causes

• Immunological

• Environmental: Virus: Ebstein Barr Virus (EBV)

HIV- I and HTLV - 1
 Lesions
• Salivary glands:
Dry mouth → dysphagia & loss of taste sensation.
Cracks and fissures- at the angles of the mouth.

2. Lacrimal glands:
Dry eyes → blurring of vision,
Burning sensation & itching
Thick secretions in the conjunctival sac.
Enlargement of the
Parotid gland
 Systemic Sclerosis - Scleroderma

Excessive fibrosis throughout the body.

Two categories:
1) Diffuse - widespread, rapid, viscera involved early.
2) Localized - limited area, viscera involved later.

Causes:
1) Immunological: abnormal activation of immune system.
2) Vascular abnormalities: Intimal fibrosis
 Clinical features of
Females > males - 3:1.
Skin : diffuse, sclerotic atrophy
Alimentary: Progressive atrophy & fibrosis rubber hose
inflexibility,
Esophageal dysmotility
Musculoskeletal - Synovial inflammation and fibrosis
Kidneys - Intimal thickening causing hypertension
Lungs - Fibrosis, pulmonary hypertension
Heart - Fibrosis of myocardium, pericarditis
CREST syndrome - limited sclerosis
Calcinosis, Raynaud phenomenon, Esophageal
dysmotility, Sclerodactyly, Telangiectasia
early
gangrenous
necrosis from
vasospasm
with the
Raynaud
phenomenon
 Tightening of the
skin over the
fingers- making
them appear claw
like

Tight shiny skin

Cheilosis at the
angles of the mouth
is due to riboflavin
deficiency due to
malabsorption
 Inflammatory Myopathies
3 distinct disorders are seen
Dermatomyositis

Polymyositis

Inclusion body myositis

Causes :

Immunological: CD 8 + T cells, MCH – I, Anti nuclear

antibodies are found
 Dermatomyositis
Skin as well as the muscles are involved.
Children or adults
Skin - Lilac rash of upper eyelids with periorbital edema
Grotton lesion - Knuckles, elbows, knees have red patches.
Muscles:
Weakness of proximal muscles first,thus fine
movements are affected last.
Bilateral symmetry
Slow onset
Dysphagia can occur
Heart and lungs can be involved
 Polymyositis
Adults

No skin involvement

Proximal muscle involvement

Heart and lung can be involved

 Inclusion Body myositis

Adults over 50 years

Distal muscle involvement

Extensors of knee, flexor of wrist and fingers

Asymmetrical involvement
 Rheumatoid Arthritis
Chronic systemic inflammatory disorders of joints.

Synovitis causes destruction of articular cartilage

Factors involved in pathogenesis:

Genetic susceptibility: Association with HLA - DR

Microbial agents: EBV, Borrelia, myoplasma

Autoimmunity: EBV and collagen type 2- crossing over of

immune response , eg. joint cartilage.
 Clinical features of RA
General symptoms of malaise, fatigue, pain
Involvement of small joints of hands and feet
Joints - Swelling, pain, early morning stiffness
Deformities occur because of destruction of tendons,
ligaments and joint capsules.
Loss of range of movements and decreased stability
 Ulnar deviation of the wrist
Destruction of articular cartilage by the
inflammatory pannus

Boutonniere & the swan neck deformity

 Myaesthenia Gravis

Immune mediated loss of acetylcholine receptors.

Most commonly seen in women when it arises before 40

years. But after 40 years both sexes are equally affected.

Pathogenesis:
Anti - acetylcholine receptors antibodies

Thymic hyperplasia is seen in 65%

Thymoma in 15%
Clinical features of Myaesthenia Gravis

Weakness begins in
extra ocular muscles

Drooping of eyelids &

double vision
(diplopia).