LECTURE

15
29.02.08

ADDISON DISEASE

1. Autoimmune disease of adrenal cortex

2. Cause by atrophy of adrenal cortex
3. Auto – Ab: anti – adrenal cortical Ab
4. Adrenal steroid hormone: metabolism of fat and protein
5. Most specific external clinical finding is hyper pigmentation of skin
6. Low blood pressure: reflect a decrease in cortisol level (hypotension –
faint in early morning)
7. Problems of regulating serum electrolyte levels resulting from loss of
adrenal hormone, aldosterone:
 Low sodium and chloride level
 Elevated level of potassium
8. Cellular auto – immunity responsible for the damage in human passive
transfer of lymphocytes from animals with auto – immune adrenalitis to
control animal produce the disease

DIABETES MELLITUS
1. Type – 1 – Juvenile – onset diabetes (in children)
 Insulin dependent diabetes mellitus
 Susceptible to developing ketoacidosis
 80% of patients have circulating Ab to Ag present in islet cells of
the pancreas
 Histological:
i. Chronic inflammatory infiltrate consisting mainly of T-
lymphocytes, within their pancreatic islets of langerhans
(Ag)
ii. Associated with islet cell antibodies
2. Type – 2 – adult onset diabetes (adult)
 Non insulin dependent diabetes mellitus
 No ketoacidosis
 Not associated with islets cell antibodies
 Have an increase frequency of occurrence in identical twins
 Can also cause by neoplasm of pancreas

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 Characteristics Type – 1 - diabetes Type – 2 – diabetes
Age of onset <25 years Later adult life
Nature of onset Abrupt Gradual
Metabolic features Washing of protein and
Obese
thin habitus
Insulin status Controlled with dietary
Require insulin therapy
modification
Insulin deficiency Partial. Given a tablet can
Complete enhance the production
of insulin

 In type 1 diabetes mellitus, insulin was give by intravascular not by oral

because it can damage the GIT
 However in type II diabetes mellitus, tablet was give by oral to stimulate
or enhance the production of insulin

RHEUMATID HEART DISEASE

1. Antibody against streptococcal Ag

2. This 3 are toxin that was produced by bacteria:
 Streptolysin O (ASO titer)
 DNAse B
 Streptokinase
3. Streptococci and human cardiac muscle share similar Ag or same
antigenecity (M protein)
4. Aschaff nodules (damaged area)
5. Ag in this case is exotoxin that produce by streptococcal bacteria
6. Toxin contains M protein. Ab against this. However, cardiac muscle also
contain M protein so it produce rheumatoid heart disease
7. Mononuclear cells involve in chronic reaction
8. Polymorphonuclear cells involve in acute reaction

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PERNICIOUS ANAEMIA

1. Auto immune disease of stomach

2. Anaemia: RBC precursor in bone marrow have large and blastic appearing
nuclei due to disturbance in the maturation of all the cells in body
resulting from deficiency of vitamin – B12
3. Plasma cell produce auto – Ab against both:
 Parietal cells
 Intrinsic factors
4. Auto – Ab decreasing the body ability to absorb vitamin B – 12
5. Parietal cells and chief cells are markedly decreased
6. Intestinal metaplasia: change in the cell types from gastric mucosa to
intestinal mucosa types
7. Laboratory diagnosis:
 History
 Haematologic studies: all cells are immature (RBC nucleated)
 Histology (biopsy from stomach)
 Indirect immuno-fluorescence technique (serum)
o Ab: patient serum (contain IgG) (anti – parietal cell Ab)
o Substrate (Ag): rodent stomach tissue section
o Positive test: Ab bind to parietal cells (after incubation for 30
minutes – incubate with Ab conjugate FITC)

GLUTEN (CELIAC DISEASE) (SENSITIVE ENTEROPATHY)

1. Autoimmune disease
 It limited to one target organ
 Anti – epithelial Abs can be demonstrated
2. The affected individuals have:
 Strong family history
Clinical finding – weight loss
Epithelial cell of GIT (vilus) sensitive to gandum (oat) – become
atrophy
3. Diagnosis:
 Biopsy (histological section) of the small intestine

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 o Atrophy of the villi
o Increase in the crypt depth
o Increased number of mitosis in the crypts
o Increased numbers of lymphocytes in inter – epithelial
 Endoscopy:
o Loss of villi and reduction or loss of mucosal folds
 Response to gluten – free diet followed by re – biopsy
o In this case gluten act as a antigen
 Humoral auto – immunity:
o Demonstration of Abs against:
 Gluten in the serum of patients
 Surface of epithelial cells
 Cell mediated immunity to gluten (T-lymphocytes):
o Peripheral blood lymphocytes proliferate in tissue culture in
response to gluten
o Gluten stimulates the production of migration inhibition factor
by peripheral blood lymphocytes
4. All mucosa will secrete IgA (local immunity)
 Secretory IgA = produce by mucosal surface
 Serum IgA = blood
 IgA is combination between two molecule of immunoglobulin by J
chain and produce secretory component
5. Mechanism: ingested gluten damages surface mucus:
 Immunologic mechanism:
o Injury occurs between 1-3 hours following oral administration
of gluten
o After 3 hours, villous atrophy with elongated crypts and
increase number of mitosis
o Lamina propria increased numbers of inflammatory cells
o Plasma cells (IgA and IgM) are increased in number
 Genetics
 Environmental factors:
o Similarity between gluten protein and EIB protein of adenovirus
o EIB protein virus and gluten share same antigenecity

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COMMON AUTOIMUNE DISEASE OF LIVER

1. Primary billiary cirrhosis (PBC)

 Laboratory diagnosis:
o Chemistry laboratory
 Elevated alkaline phosphatase, SGOT, SGPT
 Elevated cholesterol and bilirubin
o Serologic tests: detection of auto – Ab
 Anti – mitochondrial Ab (AMA)
 Anti – smooth muscle (SMA)
 Anti – microsomal Ab
 Anti – mitochondrial Ab (AMA)
o AMA substrate (Ag)
 Kidney of mouse or rat (indirect immunofluorescence)
• Stains the cytoplasm of kidney tubules
• Lack of staining in the nucleus
 Stomach of mouse or rat (indirect immunofluorescence)
• Stain the cytoplasm in the gastric parietal cells
o Ab that may confused with true mitochondrial Ab of primary
billiary cirrhosis
 Syphilis (anti – cardiolipin Ab)
 CAH (liver kidney microsomal Ab) – LKMA
 SLE (ANA) – anti nuclear Ab
2. Chronic active hepatitis (CAH)
 Auto – Ab in CAH
o SMA: smooth muscle Ab – most specific auto – Ab
o Microsomal Ab: not specific
o AMA: not specific
 SMA substrate (Ag) (indirect immuno fluorescence)
o Mouse kidney
o Mouse stomach
 Microsomal Ab (MA) (indirect immuno fluorescence)
o Mouse liver substrates
 Diffuse, finely granular staining of the cytoplasm
 No nuclear staining
o Mouse kidney

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  Staining is in the proximal convulated tubule
 No staining in distal convulated tubule or in the
ascending loops of Henle
 Mitochondrial Ab (indirect immuno fluorescence)
o Rat kidney substrate (Ag)
 Stain ascending loops of Henle and distal convulated
tubule strongly
 Proximal convulated tubule stain more weakly
o Rat liver substrate (Ag)
Mitochondrial Ab will give a more granular cytoplasmic

fluorescence than microsomal Ab on rat hepatocytes
3. Common Ab in auto – immune liver disease:
Ab Association
AMA Primary billiary cirrhosis
SMA Chronic active hepatitis

4. Acute: first line defense – polymorphonuclear cells

5. Chronic: mononuclear cells

SKIN DISORDERS (BULLOUS DISORDERS)

1. Pemphigus vulgaris
2. Pemphigoid:
 Bullous disease – blister
 Pemphigus vulgaris – blister was intra epidermal
 Pemphigoid – blister was sub epidermal
3. Pemphigus vulgaris
 Roof of the blister is very thin (only erosions or scabbed lesion on the
skin surface)
 Immunology: auto – Ab (pemphigus Ab) directed against intracellular
bridges (substances) of epidermis was found in serum
 Pemphigus Ab can be detected by:
o Direct immunofixation (skin biopsy). Cryostat section. The site
to detect Ab (IgG) is the edge of the lesions. Anti – IgG
conjugate with FITC (act as Ab) is used to detect the IgG (Ag)
staining pattern (intracellular space of epidermis)

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 o Indirect immunofixation (serological studies). Tissue (substrate,
Ag) in cryostat section.
• Guinea pig oesophagus
• Monkey oesophagus
i. Add diluted patient serum to float frozen tissue
section
ii. Incubate for 30 minutes at room temperature
iii. Wash 3X
iv. Add specific Ab (anti – IgG conjugate FITC) against
Ab (IgG, pemphigus Ab) in patient serum
v. Incubate 30 minutes at room temperature
vi. Wash 3X
vii. Mounting
viii. Observe under fluorescence microscope
ix. Run with patient sample quality control (negative and
positive control)
4. Bullous pemphigoid
 Pemphigoid (skin)
 Cicartecious pemphigoid (mucous membrane and skin)
5. Pemphigoid
 Lesions between the epidermis and dermis
 Auto – Ab directed against the dermal epidermal junction
 Blister: tense and do not rupture easily
 Roof of blister much thicker compose to whole epidermis
 Laboratory diagnosis
o Indirect immuno fluorescence (serological studies)
o Tissue (Ag): from monkey oesophagus
6. Cicatricial pemphigoid (benign mucous membrane pemphigoid)
 Blister not seen in mucous membrane but erosions – mucous
membrane lesions only no circulating Ab – cutaneous lesion present as
tense blister
 Circulating Ab to basement membrane were detected (IgG)
 Cicatricial pemphigoid IgA is found in addition to IgG
 Distinctive feature of disease is scarring of mucous membrane
particularly the conjunctiva (distinct from pemphigoid)
 Laboratory diagnosis:
o Direct immunofluorescence (skin biopsy) – 1 step

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o Indirect immunofluorescence (serological studies) – 2 step. The
tissue (Ag) obtained from monkey oesophagus

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