12-immunopathology_part_2.pdf

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Dr. Samir Ayad 3

Etiology:

(1) Genetic factors: - familial incidence

- HLA-DR2 and DR3

(2) Immunological factors:

- deficiency of suppresor T-cells- hyperactive helper T-cells

- abnormal B-cells

(3) Drugs - induced (e.g. hydralazine, procainamide)

(4) Viral infection

(5) Sex hormones (exacerbations in pregnancy)



Dr. Samir Ayad 4

Mechanism:

(a) Autoimmune disease: antinuclear antibodies

(ANAs) against several nuclear antigens (DNA,

RNA, nucleoproteins) react with nuclei of

damaged cells (cannot penetrate intact cells)

(b) Formation of immune complexes and their

deposition in different tissues

(c) Activation of complement inflammatory lesions

(type III hypersensitivity

)



Dr. Samir Ayad 5

Antinuclear antibody test, homogenous pattern,fluorescence microscopy

Here is a positive ANA, homogenous or diffuse staining

reflecting antibodies to chromatin, histones, and double-stranded DNA.



Dr. Samir Ayad 6

Antinuclear antibody test, rim pattern, fluorescencemicroscopy

Sometimes when performing the ANA test, the cells

demonstrate particular patterns of staining rim or peripheralstaining, indicative of AB to double stranded DNA. This is theso-called "rim" pattern that is more characteristic of SLE.


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Antinuclear antibody test, nucleolar pattern, fluorescencemicroscopy

This is the so-called "nucleolar pattern" of staining in which

the bright fluorescence is seen within the nucleoli of the cells.This pattern is more suggestive of progressive systemicsclerosis.



Pathological changes:

(1) Blood vessels:(acute necrotizing vasculitis)

- acute vasculitis of small arteries and arteriolesdue to deposition of immune complexes

- necrosis & fibrinoid deposits within vessel wall

- later, fibrous thickening with luminal narrowing-perivascular lymphocytic infilterate

(2) Heart:

- pericarditis - myocarditis

- endocarditis (Libman-Sacks):

multiple, small, sterile, flat vegetations,

detachable embolization



Libman-Sacks endocarditis, gross

Here are flat, pale tan, spreading vegetations over the mitral

valve surface and even on the chordae tendineae. This patient

has SLE. Thus, these vegetations that can be on any valve or even on endocardial surfaces are consistent with Libman-

Sacks endocarditis. These vegetations appear in about 4% of

SLE patients.



(3) Kidneys: Normal (in few cases):

(i) Mesangial glomerulonephritis (10%):

increased cellularity of mesangial matrix

(ii) Focal proliferative glomerulonephritis (30%):

hypercellularity, but not all (focal) glomeruli, due to

proliferation of endothelial and mesangial cells. Presentwith hematuria, proteinuria, mild renal insufficiency.

(iii) Diffuse proliferative glomerulonephritis(45-50%):

Most serious, all glomeruli involved. Hematuria, proteinuria, hypertension, & renal insufficiency

(iv) Membranous glomerulonephritis (10%):

Thickening of capillary wall massive proteinuria



Rapidly progressive glomerulonephritis with crescents, microscopic

Seen here within the glomeruli are crescents composed of proliferating

epithelial cells. Crescentic glomerulonephritis is known as rapidly

progressive glomerulonephritis (RPGN) because this disease is very

progressive. There are several causes, and in this case is due to SLE.

Note in the lower left glomerulus that the capillary loops are markedly

thickened (the so-called "wire loop" lesion of lupus nephritis).



Lupus nephritis, kidney, microscopic

Here is a glomerulus with thickened pink capillary

loops, the so-called “wire loops", in a patient with

lupus nephritis. The surrounding renal tubules are

unremarkable.

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Lupus nephritis, electron micrograph

The thickened basement membrane (arrow) that

results from immune complex deposition in the

glomerular capillary loop is prominent in this electron

micrograph. The dark immune deposits are located

mainly in a subendothelial position.



(4) Skin:

- deposition of immune complexes along thedermo-epidermal junction

- activation of complement inflammation

skin rash

- erythema, maculopapular rash

- malar regions of the face and bridge of nose( butterfly rash, photosensitivity to UVR)



Vasculitis with marked inflammation, skin, patient with SLE,

microscopic

Here is a more severe inflammatory skin infiltrate in the upper

dermis of a patient with SLE in which the basal layer isundergoing vacuolization, and there is purpura with RBC's in

the upper dermis (which are the reason for the rash).



(5) Joints:

- arthritis (most common presenting symptom)

resembles rheumatoid arthritis but:

- involves large and small joints

- mild (rarely causes destruction of cartilage)

(6) C.N.S:

- vasculitis hemorrhages, ischemia, infarcts

(7) Lung:

- pleurisy with pleural effusion

- alveolitis and fibrosis



(8) Serosal cavities:

- Inflammation ( pleurisy, pericarditis, peritonitis)with serous effusion or fibrinous exudation inacute cases to fibrous opacification in chronic

cases.

(8) Spleen:

- enlarged slightly- capsule is thickened

- follicular hyperplasia


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Discoid lupus erythematosus



Dr. Samir Ayad 22

Discoid lupus erythematosus



Dr. Samir Ayad 23

Clinical features:

- females

- arthritis (larger joints)

- fever

- skin eruption (butterfly rash over face)

- hypertension

- hematuria, albuminuria, nephrotic syndrome

Di i



Dr. Samir Ayad 24

Diagnosis :

- antinuclear antibodies (ANAs) in the serum

- presence of LE cells (nuclear debris ingested by blood neutrophils)

Prognosis:- chronic course with repeated exacerbations and

remissions

- survival rate is 90% at 10 years (death mostly due

to renal failure)

LE ll ti i i



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LE cell preparation, microscopic

Here is the famous "LE cell" test which has value only in

demonstrating how the concept of autoantibodies work. The

pink blobs are denatured nuclei. Here are two, with one seen being phagocytozed in the center by a PMN.

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