Lecture # 77
IMMUNITY - 3
Dr. Iram Sohail
Assistant Professor
Pathology
College Of Medicine
Majmaah University
OBJECTIVES
• Pathogenesis of important autoimmune
diseases
– SLE
– Rheumatoid arthritis
– Sjogren syndrome
SYSTEMIC LUPUS ERYTHEMATOSUS
(SLE)
• SLE is a multisystem autoimmune disease of
variable manifestations & behavior.
• It is a remitting & relapsing disease and may
involve almost each and every organ of body.
(skin, joints, heart, kidney)
• Associated with different types of antibodies
– Antinuclear antibodies (ANA)
– Anti phospholipid antibodies
• Combination of increased generation or defective
clearance of nuclear antigens released from
apoptotic cells
• Failure of T and B cells tolerance to these self-
antigens
• Failure of tolerance in CD4 + helper T cells and B
cells
• Peripheral blood cells of SLE releases IFN-alpha
• There are some genetic & non-genetic factors
involved in the pathogenesis of SLE.
Genetics factors
– Family members
– Monozygotic twins
– White people
– Class II HLA genes , HLA-DQ locus
– Deficiency of C1q
Non - Genetic factors
• Sun exposure (ultraviolet radiations)
• Drugs (procainamide, hydralazine)
• Sex hormones
Mechanism of tissue injury
• Autoantibodies & immune complexes cause
direct injury to tissues (glomeruli of kidney, red
blood cells, white blood cells, platelets).
• These autoantibodies and immune complexes
cannot penetrate intact cells, so these bind to
nuclei of damaged cells and form LE bodies
(hematoxylin bodies)
Morphology
• SLE is a multisystem, relapsing & remitting
disease.
Vessels
– Acute necrotizing vasculitis
Kidney
– Glomerulonephritis
Skin
– Butterfly rash (degeneration of basal layer of
epidermis, edema at dermoepidermal junction)
Joint
– Swelling & mononuclear infiltration of synovial
membrane
CNS
– Infarctions, Vasculitis, thrombosis
Spleen
– Enlargement, onion skin lesions
lungs
– Pleuritis
Heart
– Libman-Sacks endocarditis
– pericarditis
RHEUMATOID ARTHRITIS
• Rheumatoid arthritis is a systemic, chronic
inflammatory disease mainly affecting the joints,
but skin, heart, blood vessels and muscle can
involve.
• More common in young women.
• In severe disease, RA factor increased in blood.
Pathogenesis
Morphology
• Systemic arthritis especially involving small
joints of hands, feet, ankle, elbow.
• Histologically, chronic synovitis
• Rheumatoid subcutaneous nodules
• Fibrinoid necrosis with a rim of macrophages
SJOGREN SYNDROME
• Sjogren syndrome is an inflammatory disease
characterized by
– Keratoconjectivitis (dry eyes)
– Xerostomia (dry mouth)
Etiology & pathogenesis
• It is an autoimmune disease, causing
destruction of salivary and lacrimal glands.
• It is caused by anti-SS-A and anti-SS-B
antibodies.
• Loss of tolerance in CD4+T –cells
• Genetics can also play a role.
Morphology
• Lacrimal glands, salivary gland and glands of
nasopharynx, upper airway and vagina involved
• Infiltration of T- Lymphocytes & plasma cells to
these glands with associated destruction.
• Destruction of these glands lead to dry mouth,
dry eyes and dry nose.
Clinical features
• More common in females, aged (35 – 45)
• About 60% patients have associated
rheumatoid arthritis.
• Dry mouth (xerostomia)
• Dry eyes (keratoconjuctivitis)
• Dry nose