Role of HLA
Role in immune response Role in organ transplantation Role in predisposition to disease
A 20-year-old woman presented with complaints of fever for 2 weeks; pleuritic chest pain; and intermittent joint pain in her hands, feet, and knees. On examination, she was free of skin lesions. She had a pleural friction rub; a slightly swollen tender right knee; and enlarged axillary, cervical, and inguinal lymph nodes. A chest film showed a small right pleural effusion; joint films were normal except for a small amount of soft tissue swelling in the right knee. Hemoglobin was 10 g/dL, and urinalysis revealed 4+ proteinuria with white blood cells, red blood cells, and red cell casts in the urine sediment. A VDRL test was positive. A test for antitreponemal antibodies was negative. Blood urea nitrogen (BUN) and creatinine were slightly elevated, and moderate hypoalbuminemia and hypergammaglobulinemia were present. An ANA test was positive at a titer of 1:2560 and was reported as showing a speckled pattern. A dsDNA antibody determination by the Crithidia luciliae assay was positive at 1:320, and an extractable nuclear antigen (ENA) antibody determination was reported as RNP (U1-RNP) and Sm antibody present. A C4 level was less than 10 mg/dL (reference range 12-45 mg/dL) and a C3 level was less than 40 mg/dL (reference range 88-192 mg/dL). The patient was treated with prednisone, 60 mg/day. After 4 weeks, the urine protein was 2+, the sediment had cleared, and BUN and serum creatinine had returned toward normal. Diagnosis?
•Class I MHC molecules are expressed on....................................
all nucleated cells and platelets
•Class II MHC molecules are encoded in a region called....
•A number of autoimmune and other diseases are associated with the inheritance of ...........................
particular HLA alleles.
•a particular HLA produce diseases:
•the prevailing hypotheses implicate an auto-aggressive immune response due to an aberrant presentation of ...............................by particular HLA molecules.
self-mimicking-, or altered self-antigens
•Class I MHC= HLA-A, HLA-B, and HLA-C
molecules display peptides such as ----------------------antigens, that are located in the.............................
viral and tumor; cytoplasm
Biopsy kidney in renal failure. H&E stain.
Need special stain to confirm
B27 is associated with (diseases)
P A I R
DR 4 is associated with
RA, DM 1
•Disease with Antibody against a self-antigen” is called:
How these HLA genes produce autoimmunity?
•Defective tolerance or regulation.
•Abnormal display of self-antigens.
•Inflammation or an initial innate immune response.
•Polymorphisms in the gene for NOD2 are associated with................
Polymorphisms in a gene called PTPN22: encodes a protein tyrosine phosphatase, are associated with .......................
rheumatoid arthritis, type 1 diabetes
hidden self antigens are:
SPERMS, LENS MATERIALS
Mechanism of diseases is SLE-
mostly type III hypersensitivity
Biopsy skin rash in SLE will show (IF):
An immunofluorescence stained for IgG reveals linear deposits of
immunoglobulin along the dermal-epidermal junction.
Glomerulonephritis- Lupus nephritis is caused by.....
immune complex-mediated in the GBM (Type III)
Thrombosis ( DVT) in SLE is caused by
Anticardiolipin antibody: Antiphospholipid syndrome (APS) can occur in patients with SLE.
Diagnosis of the CT scan?
Thrombocytopenia in SLE is caused by
A 44-year-old woman has had tightening of the skin of her fingers for the past 2 years, making them difficult to bend. She has had increasing difficulty swallowing for the past 8 months. During the past winter, her fingers became cyanotic and painful on exposure to cold.
Likely Scleroderma or CREST
A 29-year-old woman has had increasing weakness over the past year and now has difficulty climbing a single flight of stairs. Her muscles are sore most of the time.
Polymyositis or dermatomyositis
A 22-year-old woman has been bothered by dryness in her mouth for the past 2 years. During this time, erythematous rashes have appeared on the skin of her face and upper neck. In the past 6 months, she has developed arthralgias.
Likely Sjögren syndrome
A 4-year-old boy has a history of recurrent sinopulmonary infections with Staphylococcus aureus and Streptococcus pneumoniae since age 17 months. He also developed an arthritis that diminished with intravenous immunoglobulin therapy.
B or T cell defect?
Type of amyloid in peripheral neuropathy
TTR or beta2- MG
A 2-year-old boy has had almost continuous infections since he was 6 months old. These infections have included otitis media, pneumonia, and impetigo. Organisms cultured include Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. He also has had diarrhea, with Giardia lamblia cysts identified in stool specimens.
B or T cell defect?
A 30-year-old woman gives birth at term to a normal-appearing infant girl. One hour after birth, the neonate exhibits tetany. On physical examination, she is at the 55th percentile for height and weight.
B or T cell defect?
Biopsy of ....................is diagnostic for Sjogren's syndrome.
1.CREST/Scleroderma- mechanism of pulmonary hypertension
subintimal fibrosis, vascular narrowing