Autoimmune diseases

Autoimmunity

• An inappropriate response of the immune system

against self-components termed autoimmunity.

• Self reactive lymphocytes – clonal anergy, clonal

suppression; a breakdown in this regulation can lead to
activation of self reactive clones of T & B cells,
generating humoral or cell mediated responses.
Two categories of autoimmune diseases

1. Organ specific autoimmune diseases

2. Systemic autoimmune diseases

 Organ specific autoimmune diseases

1. Hashimoto’s thyroiditis
• Middle aged women susceptible
• Auto Abs & sensitized Th1 cells specific for thyroid Ags.
• DTH response, infiltration of thyroid gland by immune
cells.
• Abs are formed to no. of thyroid proteins: thyroglobulin
& thyroid peroxidase , involved in iodine uptake; leads
to decreased production of thyroid hormone.
• Hypothyroidism causes goiter or visible enlargement of
thyroid gland.
 2. Autoimmune anemias
i) Pernicious anemia
• Caused by auto Abs to intrinsic factor involved in vit. B 12
absorption
• Vit.B 12 required for proper hematopoiesis,its absence RBCs
decreased in no.,anemia
• Treatment: vit.B12 injection

ii) Autoimmune hemolytic anemia

• Auto Abs to RBC Ags.
• Complement mediated lysis or Ab mediated opsonization &
phagocytosis of RBCs.
• Coomb’s test: RBCs + anti human IgG antiserum.

iii) Drug induced autoimmune anemia

• Penicillin or anti hypersensitive agent methyldopa interact with
RBCs, cell become antigenic.
Coomb’s test
 3.GOODPASTURE’S SYNDROME
• Damage to glomerular & alveolar basement membrane –
kidney damage, pulmonary hemmorrhage.

• Auto-Abs specific for certain basement-membrane

antigens bind to the basement membranes of the kidney
glomeruli and the alveoli of the lungs.

• Cellular damage, Inflammatory response, complement

activation, build up of complement split products.

• Death after several months of symptoms.

Deposits of IgG & C3b along basement membrane of a kidney
biopsy from patient with Good pasture's syndrome.
 4.Insulin dependent Diabetes Mellitus(IDDM)

• Autoimmune attack on pancreas: islets of Langerhans,

beta cells.
• Decreased production of insulin, increased level of blood
glucose.
• CTLs infiltration & activation of macrophages (insulitis)
→ cytokine release: IFN-gamma, TNF-alpha, IL1→auto
Abs → DTH response→ Ab + complement lysis/ADCC.
• Keto acidosis, increased urine production,
atherosclerotic vascular lesions, gangrene, renal failure,
blindness, death if untreated.
• Treatment : insulin injections.
 5.Grave’s disease

• TSH (pituitary gland)→receptor on thyroid cells→

adenylate cyclase stimulation →thyroxin (T4) & tri-
idothyronin (T4) synthesis.

• In Grave’s disease, auto Abs bind to TSH receptor,

mimic TSH, over stimulates thyroid.

• These auto Abs are called Long Acting Thyroid

Stimulating Abs (LATS).
 6.Myasthenia Gravis

• Blocking Abs :bind to Ach receptors,

complement mediated lysis of the cell,
weakening of skeletal muscles

• Drooping eyelids, inability to retract corners of

mouth gives appearance of snarling.

• Impairment in eating, problem with movement.

 Systemic autoimmune diseases
1. Systemic lupus erythematosus (SLE)
• Occurs in 20-40 yrs age women, female:male patient ratio 10:1
• Fever, weakness, arthritis, skin rashes, kidney dysfunction
• Auto Abs against DNA, histones, RBCs, platelets, leukocytes,
clotting factors.
• Abs to RBCs & platelets : complement mediated lysis, hemolytic
anemia & thrombocytopenia.
• Immune complexes deposits along the walls of blood vessels : type
III hypersensitivity reactions – complement split products,
membrane attack complex formed.
• Elevated serum levels of complement spilt products C3a & C5a,
neutrophil aggregation & attachment to vascular endothelium, no.
of circulating neutrophils decreases (neutropenia) & various
occlusions of small blood vessels develops (vasculitis) – tissue
damage.
• Treatment: antinuclear antibodies.
 2.Multiple sclerosis (MS)

• Attacks central nervous system.

• Numbness in limbs, paralysis, loss of vision.
• Patient’s age ranges between 20-40 yrs.
• Auto reactive T cells that forms inflammatory lesions
along myelin sheath of nerve fibres.
• CSF contain activated T lymphocytes which infiltrate
brain tissues, inflammatory lesions, destroys myelin,
numerous neurological dysfunction.
• Most prevalent in females.
• May be related to some viral infections.
 3.Rheumatid arthritis

• Attacks joints.
• Women from 40-60 yrs old.
• Chronic inflammation of joints, hematologic,
cardiovascular, respiratory system also may affected.
• Auto Abs called rheumatoid factors, reactive with
determinants in Fc region of IgG.
• IgG-IgM complexes deposits in joints → complement
cascade → type III hypersensitivity reactions →
inflammation of joints.
 Treatment of autoimmune diseases
• Immunosuppressive drugs e.g. corticosteroids, azathioprine &
cyclophosphamide : slows proliferation of lymphocytes, by
depressing immune response; autoimmune diseases can be treated.
But risk of cancer or infection.
• Cyclosporin A/FK 506 (immunosuppressive drugs): blocks signal
transduction mediated by T cell receptors.
• Removal of thymus (Myasthenia Gravis)
• Plasmapheresis
• T cell (specific for given auto Ag) vaccination.
• mAb to Ag activated T helper cells
• Oral Ags can induce tolerance (immunological unresponsiveness)
• Administration of synthetic blocking peptides that compete with auto
Ag for binding to MHC molecule.
HLA & Diseases