Immunopathology IV (Autoimmune dx)

Question 1

What are autoimmune dx❓

What are the 3 requirements to look out for before confirmatory diagnosis❓

Answer 1

1. Immunologic disorder characterized by immune rxns against self antigens

2.
Presence of an autoimmune rxn

Evidence that such reaction is not secondary to tissue damage

Absence of well-defined cause of the dx

Question 2

What are the theories of autoimmunity❓

Answer 2

1. Antigens normally inaccessible (lens, spermatozoa, myelin) may be exposed to released after injury and recognized as foreign
2. Abnormal T-cell function b/c most responses to Ag require T-cell activation
3. Molecular mimicry: similar antibodies against bacterial and self antigen
4. Polyclonal lymphocyte Activation: LPS can cause proliferation of B/T cells in the absence of Ag stimulation; progeny may become autoreactive

Question 3

List some examples of organ specific autoimmune dx

Answer 3

Type I DM- autoreactive T cells against beta cells of islets

Multiple sclerosis- autoantibodies against DNA, platelets, RBC

Good-pasture syndrome

Hasimoto’s dx

Autoimmune hemolytic anemia

Myasthenia gravis

Graves dx

Question 4

List some examples of systemic autoimmune dx

Answer 4

Systemic lupus erythematosus

Rheumatoid arthritis

Scleroderma (systemic sclerosis)

Question 5

Describe the epidemiology of Systemic Lupus Erythematosus

Answer 5

F, childbearing age:
1 in 700 women
F to male ratio- 9:1

F, child, after 65years
F to male ratio- 2:1

More common in African-American women- 1 in 245

Common in twenties and thirties

Question 6

Describe the pathogenesis of Systemic Lupus Erythematosus

Answer 6

🚫self-tolerance

Autoantibodies to nuclear and cytoplasmic components of cells

Autoantibodies to cell surface antigens

Injury to skin, joints, kidney and membranes

Results in immune-complex mediated glomerulonephritis

Question 7

1. List the 4 categories of ANAS are directed against nuclear antigens in Systemic Lupus Erythematosus
2. What patterns can be used to identify them by indirect immune florescence techniques❓

Answer 7

1.
Antibodies to DNA 
Antibodies to histone 
Antibodies to non-histone bound to RNA
Antibodies to nucleolar antigens 

2. 
Homogeneous/diffuse nuclear staining 
Rim/peripheral staining 
Speckled patterns
Nucleolar patterns

Question 8

1. The immunoflourescence test is sensitive but not specific for SLE, T/F❓
2. What would confirm your diagnosis of SLE❓

Answer 8

1. True
2. Antibodies to dsDNA
   Smith (SM) antigen

Question 9

Antiphospholipid antibodies are directed against blood elements and are present in 40-50% of lupus pt

True or false

Answer 9

True, directed against plasma proteins that complex w phospholipids

Question 10

What are the predispositing genetic, non-genetic and immunologic factors to SLE❓

Answer 10

1.
Genetic:
MHC genes
Non MHC genes

2. 
Non-genetic:
•Drugs: hydralazine, procainamide, D-penicillamine 
•Exposure to UV light 
•Sex hormones: F to M - 10:1

3. Derangement in T and B function

Question 11

What are the morphological changes characteristic of SLE in the vessels❓

Answer 11

Vessels:
•Acute necrotizing vasculitis of arterioles

• Fibrinoid necrosis of wall
• Narrowing of lumen

Question 12

What are the morphological changes characteristic of SLE in the kidney❓

Answer 12

5 patterns are observed:

Class 1:
Normal by light, electron and immunoflourescent microscopy (rare)

Class 2:
Mesangial lupus glomerulonephritis

Class 3:
Focal proliferative glomerulonephritis

Class 4:
Diffuse proliferative glomerulonephritis

Class 5:
Membrane glomerulonephritis

Question 13

What are the morphological changes characteristic of SLE in the skin❓

Answer 13

Erythema at facial butterfly area (bridge of nose and cheeks) 50% pt

Urticaria

Bullae

Maculopapular lesions

Ulceration

Histologically there is liquefactive degeneration of basal layer of epidermis

Dermis: 
Edema 
Perivascular mononuclear infiltration 
Vasculitis 
Fibrinoid necrosis

Question 14

What are the morphological changes characteristic of SLE in the joints❓

Answer 14

Non erosive synovitis

Exudation of neutrophils and fibrin into synovium

Question 15

What are the morphological changes characteristic of SLE in the CNS❓

Answer 15

Non-inflammatory occlusion of small blood vessels by intimal proliferation

Question 16

Serositis is a morphological change characteristic of SLE

True or false

Answer 16

True; pericarditis and other serosal cavity involvement

Question 17

What are the morphological changes characteristic of SLE in the CVS❓

Answer 17

Pericarditis 
Myocarditis 
Valvular stenosis/regurgitation 
Libman sacs endocarditis 
Coronary artery artherosclerosis

Question 18

What are the morphological changes characteristic of SLE in the spleen❓

Answer 18

Moderately enlarged
Capsular thickening
Follicular hyperplasia
Thick penicillary arteries w fibrosis (onion-skin lesion)

Question 19

What are the morphological changes characteristic of SLE in the lungs❓

Answer 19

Pleuritis
Pleural effusion
Edematous alveolar w destruction
Chronic interstitial fibrosis

Question 20

What are the morphological changes characteristic of SLE in other organs and tissues❓

Answer 20

Non specific portal triditis of liver

LE bodies in bone marrow

Reactive follicles in nodes filled w plasma cells

Anemia, thrombocytopenia

Hematuria, protenuria

RBC casts

Convulsions, psychosis

Question 21

How would you treat a case of SLE❓

What’s the prognosis❓

What is usually the cause of death❓

Answer 21

Steroids
Immunosuppressants

90% 5yrs
80% 10 yrs survival

Renal failure
Intercurrent infections
Coronary heart dx

Question 22

What is scleroderma❓

Epidemiology❓

Answer 22

Chronic autoimmune dx of connective tissue

150,000-500,000 Americans
Mostly females
30-50yrs onset

Question 23

What are the types of localized scleroderma❓

Answer 23

Morphea

Linea scleroderma

Juvenile scleroderma

CREST Variable:
Calcinosis 
Raynaud’s phenomenon
Esophageal dysfunction
Sclerodactyly 
Telengectasia