Immunology

Autoimmunity
 Introduction

Immunological reaction to self antigen

Classified as
Organ specific diseases
Systemic diseases
 Mechanisms of Tissue Injury
in Autoimmune Diseases
Three mechanism
 Cell lysis and release of inflammatory
mediators
 Immune complex diseases
 T cell mediated damage
 Cell lysis by autoantibodies

Autoantibodies with cell surface antigen

Addison’s diseases (Anti adrenal cell)

Bind to cell surface receptor

Myasthenia gravis (acetylcholine reseptor)

 Diabetes mellitus

 Graves diseases
 Immune complex deposition

 Systemic autoimmune diseases

 Systemic Lupus erythematosus

 haemolytic anaemia, leukopenia,

thrombocytopenia
 DNA- anti DNA containing Complex
 Immune complex deposition

 Rheumatoid arthritis


 T cell mediated damage

 T cell leads to tissue destruction

 Cytotoxicity by C8+ Cell

 Cytokinins

 Recuitment and activation of macrophages

 Apoptosis by T cell protein

 T cell mediated damage

 T cell leads to tissue destruction

 Cytotoxicity by C8+ Cell

 Cytokinins
 Aetiopathogenesis of
Autoimmune Diseases
Exposure of sequestered antigens

Hidden antigen

Against lens protein

Heart muscle antigen

 Aetiopathogenesis of
Autoimmune Diseases
Altered self antigen

Rabbit with bovine serum albumin

Viral and bacterial infection

Mycoplasma pneumonia

Drugs such as methyl dopa, Procainamide

 Aetiopathogenesis of
Autoimmune Diseases
Altered self antigen

Rabbit with bovine serum albumin

Viral and bacterial infection

Mycoplasma pneumonia

Drugs such as methyl dopa, Procainamide

 Aetiopathogenesis of
Autoimmune Diseases
Molecular mimicry

Foreign antigen resembles self antigen

Encephalitis due to Rabies vaccines

Streptococcal antigen
 Aetiopathogenesis of
Autoimmune Diseases
Idiotype – Anti-idiotype network

Foreign antigen resembles self antigen

Encephalitis due to Rabies vaccines

Streptococcal antigen
 Aetiopathogenesis of
Autoimmune Diseases
Abnormal expression of MHC antigen

MHC factor

Neural and endocrine antigen

Induced by virus
 Aetiopathogenesis of
Autoimmune Diseases
Genetic and other factors

Parentral
 Organ Specific Autoimmune
Diseases
Disease mediated by direct cellular damage
1. Hashimoto’s Thyroidits
Middle aged women

Autoantibodies for TDTH for Thyroid antigen

 Organ Specific Autoimmune
Diseases
Disease mediated by direct cellular damage
1. Hashimoto’s Thyroidits
 Middle aged women

 Autoantibodies for TDTH for Thyroid antigen

 Intense infliteration of lymphocytes, macrophages, and

plasma cell
 Inflammation causes goiter
 Organ Specific Autoimmune
Diseases
Disease mediated by direct cellular damage
1. Hashimoto’s Thyroidits

Middle aged women

Autoantibodies for TDTH for Thyroid antigen

Intense infliteration of lymphocytes, macrophages, and

plasma cell
Inflammation causes goiter
 Organ Specific Autoimmune
Diseases
Disease mediated by direct cellular damage
1. Hashimoto’s Thyroidits

Middle aged women

Autoantibodies for TDTH for Thyroid antigen

Intense infliteration of lymphocytes, macrophages, and

plasma cell
Inflammation causes goiter
 Organ Specific Autoimmune
Diseases
A 39-year-old woman presented with a large, painless swelling
in her neck. The enlargement had been a gradual process over
2 years. She complained of dry scaly skin, and cold hands but
felt generally well. On examination, her thyroid was
diffusively enlarged and had a rubbery consistency. There were
no signs of thyrotoxicosis or of thyroid failure.

Thyroid function tests:; T3 was 1.2nmol/l (NR 0.8-2.4), T4

was 12nmol/l (NR 9-23) and TSH was 6.3mU/l (NR
0.4-5mU/l). However, her serum contained high titre
antibodies to thyroid peroxidase (1/64000; 4000iu/ml).
 Organ Specific Autoimmune
Diseases
Autoimmune Anaemia
Pernicious anaemia or auto immune haemolytic
anaemia
Autoantibody binds to intestinal proteins intrinsic
factor
Intrinsic factor binds to vitamin B12
Require for haematopoiesis
Mature RBC decreases
 Organ Specific Autoimmune
Diseases
Autoimmune Anaemia
Pernicious anaemia or auto immune haemolytic
anaemia
Autoantibody binds to intestinal proteins intrinsic
factor
Intrinsic factor binds to vitamin B12
Require for haematopoiesis
Mature RBC decreases
Organ Specific Autoimmune
Diseases
 Organ Specific Autoimmune
Diseases
During a checkup for hypertension, a 65-year-old female reports
about 2 months of tiredness, feeling faint from "getting up too
fast", and "memory problems".
History

On review of symptoms, she reports difficulty concentrating,

fatigue, feeling faint when she stands quickly, and vague
gastrointestinal discomfort with some decrease in appetite.

She denies any history of previous trauma, diplopia, dysphagia,

vertigo, vision loss, loss of consciousness, back pain, or
symptoms of bowel or bladder dysfunction.
 Organ Specific Autoimmune
Diseases
Her family history is negative for neurologic, psychiatric, and
autoimmune diseases. Her medications include an
antihypertensive as well as an occasional anti-inflammatory drug
for episodic headache. Social history reveals a single woman who
smokes about one-half pack of cigarettes per day, drinks alcohol
only socially, and denies illicit drug use.
 Organ Specific Autoimmune
Diseases
Labs:
WBC: 4.5 x109/L Differential:
RBC: 2.50 x 1012/L Lymphocyte % 36.0
B12: <50 pg/mL (Low)
Folate: 10.3 ng/mL (Normal)
Total bilirubin 2.5 mg/dL (High)
*AST: 35 U/mL (Normal)
*ALT: 30 U/mL (Normal)
 Organ Specific Autoimmune
Diseases
Goodposture’s diseases
Antibody specific to basement membrane
Kindey and lung
Direct killing through activation of complement cells
Cell lysis
 Organ Specific Autoimmune
Diseases
Miss FN, 21-years old woman, treated for pulmonary tuberculosis
in 2000, was admitted to the nephrology ward in 2001 for
advanced oligo-anuric ARF, hypertension, macroscopic hematuria
and proteinuria. The patient did not present with symptoms or
signs of pulmonary hemorrhage on admission. Laboratory
investigations revealed normochromic normocytic anemia with
Hgb (60 g/L). Anti-nuclear antibodies and antiDNA were
negative, pANCA was positive, anti-GBM antibodies were
positive. Renal biopsy revealed crescentic glomerulonephritis in
100% of the glomeruli, and linear IgG deposits were confirmed
along the GBM by IF. IAH was suggested by the presence of
siderophages with BAL
 Organ Specific Autoimmune
Diseases
Insulin Dependent Diabetes Mellitus
 Autoimmune attack on pancreas
 Attack against Beta cell
 Destroy Beta cells- decreases the production of
insulin - increases level of blood glucose
 Diseases mediated by
stimulating antibodies
Antibodies acts as agonist
 Bind to hormone receptor
 Overproduction of hormone
 Diseases mediated by
stimulating antibodies
Graves Diseases
 Diseases mediated by
stimulating antibodies
Antibodies acts as agonist
 Bind to hormone receptor
 Overproduction of hormone
 Diseases mediated by
Blocking antibodies
Antibodies acts as antagonist
 Bind to hormone receptor
 underproduction of hormone
 Diseases mediated by
Blocking antibodies
Myasthenia Gravis
 Diseases mediated by
Blocking antibodies
Myasthenia Gravis
A healthy male, age 61, presents to the ophthalmologist
in September 2006 with a complaint of double vision.
He is employed full-time in a physically demanding job
and is in good physical condition. He denies use of any
medications except 81 mg aspirin daily.
 Diseases mediated by
Blocking antibodies
Symptoms included:
Muscle weakness over whole body,
increasing with use
Drooping eyelid on right side
Sagging face on right side
Lack of facial expression on right side
Weakness of the hand muscle
Extreme tiredness in daytime
Sleep disturbance at night
Equilibrium/Balance problems
 Diseases mediated by
Blocking antibodies
Myasthenia Gravis

Labs:
Tensilon test was positive but electromyography was
inconclusive.
His serum contained antibodies to thyroid microsomes
(positive at 1/1600) and to acetylcholine receptors
 Systemic autoimmune
diseases
 Generalized defect in immune regulation
Systematic Lupus Erythematosus
 20-40 Yrs Women
 Fever, weakness, lesions, Kidney dysfunction
 Autoantibodies against DNA, histone, Platelet,
leucocytes
 Destroy by cell lysis
 Destroy by complex formation
 Systemic autoimmune
diseases
 Generalized defect in immune regulation
Systematic Lupus Erythematosus
 20-40 Yrs Women
 Fever, weakness, lesions, Kidney dysfunction
 Autoantibodies against DNA, histone, Platelet,
leucocytes
 Destroy by cell lysis
 Destroy by complex formation
 Systemic autoimmune
diseases
Multiple Sclerosis
 Affecting CNS
 T cell causes immflamtory lessions in nerve fibres
 Activated T cell inflitrate brain tissue and destroy
myelin
 Systemic autoimmune
diseases
Rheumatoid Arthritis
 40-60 yrs old women
 Systemic autoimmune
diseases
Rheumatoid Arthritis
 Affecting CNS
 T cell causes immflamtory lessions in nerve fibres
 Activated T cell inflitrate brain tissue and destroy
myelin
 Systemic autoimmune
diseases
Rheumatoid Arthritis
36 year old male with history of Psoriasis since age 12
and Psoriatic Arthritis. Takes Indocin 50 mg twice daily.
He complains of swollen, painful heel, nail changes, left
low back pain that wakes him from sleep and is better
with exercise. 1-2 hours of morning stiffness. Psoriasis
over elbows and knees bothers him. Physical exam
reveals nails thickened, yellow, onycholysis. Left 3rd
and 4th toes swollen, left knee 2+ swollen, warm
Achilles tendon swollen and warm, very tender to
touch, plantar fascia regions tender bilaterally, gait
abnormal.
 Systemic autoimmune
diseases
Labs:
RF 120 IU (elevated)
ANA 1:80, homogenous
CCP Ab 212
ESR 55 (elevated)
CRP 3.6 mg/dL (elevated)
LFT's 1.5 times upper limits of normal
Creatinine 1.6
Cholesterol 190
HDL 43
LDL 110
TG's 200fascia regions tender bilaterally, gait abnormal.