Flashcards in Diseases of Immune System- Nelson Deck (37):
Using just a few sentences, define autoimmune disease and state the key underlying immune defect.
Autoimmune disease = immune-mediated inflammatory diseases in which tissues and cell injury are due to immune reactions to self-antigens. Can be mediated by:
**Autoimmunity → LOSS of self tolerance
State the two key factors that combined together lead to autoimmune disease
-inheritance of susceptibility genes
In what ways can infections cause autoimmunity?
-may up-regulate expression of co-stimulators on APCS
-Molecular mimicry = antigens might have same amino acid sequences as self antigens
-Some viruses- polyclonal B-cell activation
-Tissue injury (from infection) can release antigens and also structurally alter self antigens so that they activate T-cells
Does presence of autoantibodies always indicate an autoimmune disease?
the phenomenon of unresponsiveness to an individual's own antigens
Describe the pathological mechanism for Systemic Lupus Erythematosis
-production of anti-nuclear antibodies (ANAs)
-Antibodies to double stranded DNA
-Antibodies to Smith (Sm) antigen
-Systemic lesions caused my immune complex deposition (type III hypersensitivities)
-may also have auto abs to proteins complexed with phospholipids
State the potential complication of the presence of anti-phospholipid antibodies in SLE
***Complications of a hypercoaguable state
-venous and arterial thrombosis
What are the pathological features seen SLE involving the skin?
-Erythema in light exposed areas
-Typically immune complex deposition at the dermoepidermal junction
What are the pathological features seen SLE involving the kidney?
-lupus nephritis due to immune complex deposition in the glomeruli
-Variety of patterns of glomerular injury are seen
What are the pathological features seen in SLE involving the joints?
Non-erosive, non-deforming small joint inolvement
What are the pathological features seen in SLE involving the cardiovascular system?
Non bacterial verrucous endocarditis
Accelerated coronary atherosclerosis in long term disease
What does SOAP BRAIN MD stand for?
Systemic lupus erythematosis!
P=photosensitivity, pulmonary fibrosis
I=immunologic (anti-Sm, anti-dsDNA)
In Rheumatoid arthritis what are the auto-antibodies directed against?
Citrullinated peptides (CCPs)
What is the pathogenesis for rheumatoid arthritis?
-Activation of CD4+ T cells and B cells
-Forms pannus (mass of inflammed synovium)
-Pannus grows over the joint cartilage -- inflammatory destruction of the joint
What is Sjogren syndrome?
Chronic disease = dry eyes and dry mouth resulting form immunologically mediated destruction of the lacrimal glands and salivary glands
-Can be primary or secondary
What is the auto antibody directed against in Sjogren syndrome?
Antibodies to ribonucleoproteins SS-A and SS-B (not specific)
What is CREST syndrome?
Develops from Limited scleroderma
R- Raynaud's phenomenon
E- esophagel dysmotility
What is the difference between diffuse and limited scleroderma?
Diffuse- widespread involvement of the skin at onset, early visceral involvement
Limited- skin involvement limited to fingers, forearms and face. May develop CREST syndrome
What is the pathogenesis of Systemic sclerosis?
(aka as scleroderma)
-widespread damage to small blood vessels and progressive interstitial and perivascular fibrosis of skin and multiple organs
What are the autoantibodies to in systemic sclerosis?
Scl-70 (DNA topo I)
What are the antibodies directed to in CREST syndrome?
Pathogenesis of dermatomyositis and polymositis?
Damage to small blood vessels and capillaries in the skeletal muscles
Antibodies in dermatomyositis/polymyositis?
Anti-Jo1 = directed against histidyl t-RNA synthetase
Difference between dermatomyositis and polymyositis?
Dermatmyositis has skin involvement, polymyositis does NOT.
Describe the difference between primary and secondary immunodeficiencies. In what patient population does one typically encounter primary immunodeficiencies
Primary = congenital, genetically determined → manifest in infancy (6 months)
Secondary = due to complications of cancer, infection, malnutrition, immunosuppression, irradiation or chemotherapy
Isolated IgA deficiency
failure of B cells to differentiate into IgA producing plasma cells
serums and secretory IgA decreased
weakend mucosal defesenses
T-cell deficiency due to failure of development of the third and fourth pharyngeal pouches
Hyper IgM syndrome
Pts able to make IgM but are deficient in their ability to make IgG, IgA, and IgE anbitodies
-defect in class switching
Severe Combined Immunodeficiency
profound defects in both humoral and cell mediated immunity (death in one year without hematopoietic cell transplant)
X-linked lymphoproliferative syndrome
inability to eliminate EBV leading to severe and sometime fatal infectious mononucleosis
State which type of infection patients without a spleen are at risk for and why.
Asplenia → loss of splenic macrophages can lead to increased risk of bacterial infection with encapsulated organisms
List the three ways that one could suspect a patient has an immunodeficiency.
Presents with an opportunistic infections from a “signature organism”
Presents with repeated infections
State the laboratory tests you would order to assess B-cell function, T-cell function, phagocytic function, and complement.
B-cell function → immunoglobulin levels
Phagocytic function → CB, peripheral smear, genetic tests, specific tests of neutrophil function
Complement → total serum complement
What is chediak-higashi syndrome?
Gene → defective fusion of phagosomes and lysosomes in phagocytes, resulting in defective phagocyte function and susceptibility to infections
autosomal recessive disorder, recurrent pyogenic infections, partial oculocutaneous albinism, progressive neurologic abnormalities, and mild coagulation defects
How do you make the diagnosis of chediak-higashi syndrome?
Diagnosis can be made w/ peripheral smear for pathognomonic giant cytoplasmic granule in leukocytes
X-linked recessive disorder
Progressive deletion of B and T cells
Marked vulnerability to recurrent infection