Section 4 Autoimmune Diseases Section 4 Autoimmune Diseases

1. 1. Definition:Definition:

An immune reaction against “ self-An immune reaction against “ self-antigens” is the cause of certain antigens” is the cause of certain diseases in human. diseases in human.

2. 2. MechanismMechanism

(1) Alteration of self-proteins (modification of the molecule)

① Partial degradation of autoantigens.

② Complexing of self-antigens with drugs or micro-organisms.

(2) Hidden antigens exposure

(3) Cross-reactions (molecular mimicry)

① Antibodies to streptococcal antigens may react with constituents of cardiac muscle or connective tissue in rheumatic fever.

② Rabies vaccine may rise to encephalitis

(4) Breakdown of tolerance

① Bypass of helper T cell tolerance

② Imbalance of suppressor-helper T cell function

③ Geneic fators

④ Emergence of a sequestered antigen

⑤ Polyclonal lymphocyte activation

3. 3. ClassificationClassification

(1) Systemic autoimmune diseases

① Systemic lupus erythematosus (SLE)

a. Definition: It is the classic prototype of the multisystem disease of autoimmune origin.

Slide 7.23

Model for the pathogenesis of systemic lupus erythematosus. . (From Robbins Basic Pathology ,2003 ）

Slide 7.24

Lupus nephritis. There are two focal necrotizing lesions at 11 and 2 o’clock. (H&E stain.) (Dr. Helmut Rennke)

(From Robbins Basic Pathology ,2003 ）

Slide 7.25

Lupus nephritis, diffuse proliferative type. Note the marked increase in cellularity throughout the glomerulus. (H&E stain.) (Dr. Helmut Rennke) (From Robbins Basic Pathology ,2003 ）

Slide 7.26

Immunofluorescence micrograph stained with fluorescent anti-IgG from a patient with diffuse proliferative lupus nephritis. One complete glomerulus and part of

another one are seen. Note the mesangial and capillary wall deposits of IgG. (Dr. Helmut Rennke) (From Robbins Basic Pathology ,2003 ）

Slide 7.28

Lupus nephritis showing a glomerulus with several “wire loop” lesions representing extensive subendothelial deposits of immune complexes. (Periodic acid-Schiff [PAS] stain.) (Dr. Helmut Rennke)

(From Robbins Basic Pathology ,2003 ）

Slide 7.29

Systemic lupus erythematosus involving the skin. A, An H&E-stained section shows liquefactive degeneration of the basal layer of the epidermis and edema at the dermoepidermal junction. (Dr. Jag Bhawan) B, An immunofluorescence micrograph stained for IgG reveals deposits of immunoglobulin along the dermoepidermal junction. (Dr. Richard Sontheimer)

(From Robbins Basic Pathology ,2003 ）

Slide 7.30

Libman-Sacks endocarditis of the mitral valve in lupus erythematosus. The vegetations attached to the margin of the thickened valve leaflet are easily seen. (Dr. Fred Schoen)

(From Robbins Basic Pathology ,2003 ）

b. Characteristics(i) Immunologically, the disease involves a

bewildering array of auto-antibodies, particularly antinuclear antibodies (ANAs).

(ii) Anatomically, all sites of involment have in common vascular lesions with fibrinoid deposits.

(iii) Clinically, it is an unpredictable remitting, relapsing disease of acute or insidious in the body, but principally affects the skin, kidneys, serosal membranes, joints and heart

② Sjogren’s syndrome （口眼干燥综合征）

Definition: It is a clinicopathologic entity characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands.

Slide 7.31

Sjogren’s syndrome. A, Enlargement of the salivary gland. (Dr. Richard Sontheimer). B, The histologic view shows intense lymphocytic and plasma cell infiltration with ductal epithelial hyperplasia. (Dr. Dennis Burns) (From Robbins Basic Pathology ,2003 ）

③ Scleroderma(硬皮病）

④ Rheumatoid arthritis

⑤ Polymyositis （多发性肌炎）

⑥ Polyarteritis nodosa （结节性多动脉炎）

Slide 7.33

Note the extensive deposition of dense collagen in the dermis with virtual absence of appendages and thinning of epidermis. (Dr.

Trace Worrell) (From Robbins Basic Pathology ,2003 ）

Slide 7.34

The extensive subcutaneous fibrosis has virtually immobilized the fingers, creating a clawlike flexion deformity. Loss of blood supply has led to cutaneous ulcerations. (Dr. Richard Sontheimer)

(From Robbins Basic Pathology ,2003 ）

Slide 7.35

Note the rash affecting the eyelids. B, Dermatomyositis. The histologic appearance of muscle shows perifascicular inflammation and atrophy. C, Inclusion body myositis showing a vacuole within a myocyte. (Dr. Dennis Burns) (From Robbins Basic Pathology ,2003 ）

(2) Organ-specific diseases

①Hashimoto’s disease (chronic lymphocytic

thyroiditis)

② Graves’s disease

③ Goodpasture’s syndrome

④ Insulin-dependent diabetes mellitus

⑤ Primary billiary cirrhosis

⑥ Chronic ulcerative colitis

⑦ Malignant pernicious anaemia with

chronic atrophic gastritis

⑧ Chronic active hepatitis

⑨ Myasthenia gravis

Slide 26.8 Hyperthyroidism (Offered by Prof.Orr ）

Slide 26.11

Hyperthyroidism

Slide 26.9

Hashimoto’s thyroiditis (From Robbins Basic Pathology ,2003 ）