Lecture 11 - Autoimmunity In Hematology Flashcards
Positive protective immune response
- immunity
Negative protective immune response
- self tolerance
Defective positive immune response
- autoimmunity
- allergy
- negative defective immune response
- immunodeficiency
- infection - malignancy
Paroxysmal cold haemoglobinuria
- first described autoimmune disease
- something coats RBC and results in their lysis
- called “erythrocytes coating factors”
- ANA: antinuclear factors
Self/non self discrimination
- during development in primary lymphoid tissue
- T and B lymphocytes learn to discriminate between self and foreign antigens
Self tolerance two signal hypothesis
- in embryo: clonal deletion of T cell that bind to self molecules
- but also occurs later: need two signals: an antigen and a costimulatory signal
Stimulate CD28
- goes from anergy to activation and prloferation
Block B7
- goes from activation and proliferation to anergy
Autoimmunity
- precipitated by interaction of environment with genetic susceptibility: infection, drug
- transient responses can occur after inflammation but only persist if genetic susceptibility
Common features of autoimmune disease
- genetic predisposition
- female preponderance
- chronic fluctuating course
- lymphoid infiltrate in tissues
- presence of autoantibodies
- response to immunosuppression
Autoimmune hemolytic anemia
- antibodies to components of the erythrocyte membrane
- may be detected +/- complement -> hemolysis
- generally treatment is by immunosuppression
Type II cytotoxic reaction
Ab binds to RBC -> activation of complement pathway -> MAC complex punches whole in cell-> lysis
Immune thrombocytopenia
- decrease in platelet numbers -> petecchia
Causes of thrombocytopenia: isolated/incidental
- immune
- gestational
- occult liver disease
- myelodysplastic syndrome
- congenital
- HIV infection
- isolated, severe, symptomatic thrombocytopenia causes
- immune
- drug induced
Multisystem thrombocytopenia causes
- SLE
- Drug induced
- sepsis
- cancer
- liver disease
- lymphoma, leukemia
- antiphospholipid syndrome
- pregnancy
- PNH
- nutrient deficiency
Idiopathic thrombocytopenic purpura
- peripheral platelet destruction by antibodies
- antibodies bind to antigens on platelets, often GP IIb-IIIa
- removed particularly in spleen
- occurs in young women
- predisposed by viral infections: HIV, EBV
- often associated with other autoantibodies
Autoimmune thrombocytopenia
- decreased number of platelets, often large
- usually normal megakaryocytes in BM
- treatment only if
Antiphospholipid syndrome
- venous arterial and small vessel thrombosis
- pregnancy loss : 1st semester
- preerm delivery for patients with severe pre-ecclampsia or placental insufficiency
- migraine
- livedo reticularis
- cardiac/vascular disease
- thrombocytopenia
- heamolytic anaemia
- stroke, TIA
- chorea
- ulcers
- renal thrombotic microangiopathy
Heparin induced thrombocytopenia
- makes antibody to PF4
- associated with thrombosis, not bleeding
- occurs 5-10 days after exposure to heparin
- 50% reduction in platelet
- causes clotting in various tissues
