autoimmune diseases related to hematology Flashcards
(48 cards)
a consequence of long standing gastritis leading to atrophy of all the cells of the stomach (secretory).
Pernicious Anaemia
Autoimmune gastritis (AIG) is an organ-specific inflammatory
disorder leading
gastric atrophy & pernicious anemia.
Pathogenesis of AIG: caused by () with specificity for the () of the parietal cell proton pump () located in parietal cells of gastric mucosa. Gastric T cell recognition of the peptide epitopes results in secretion of ()
CD4+ T cells
beta sub-unit
(H+ /K+ ATPase)
TH1 cytokines.
Inflammation of gastric mucosa results in loss of parietal cell function 4 points
1- hydrochloric acid & intrinsic factor secretion;
2- iron deficiency,
3- vitamin B12 deficiency (some casespernicious anaemia);
4- gastric atrophy.
Pernicious Anaemia (PA) AutoimmuneFeatures
1- Anti–parietal cell antibodies
2- Anti–intrinsic factor antibodies
Anti–parietal cell antibodies
react with gastric parietal cells and are present in >90% of patients
major antigen for α-Parietal cell Abs
The acid-producing enzyme H+/K+-ATPase (92-kDa protein) present on the luminal membrane of parietal cells
occur in the serum, saliva, and gastric juice of 50-75% of patients with PA.
Anti–intrinsic factor antibodies
Pernicious Anemia is more common in individuals with
other autoimmune disease, especially polyglandular autoimmune syndromes, (e.g., Hashimoto’s thyroiditis, Graves’ disease, vitiligo, diabetes mellitus & Addison’s Disease).
acquired disorder characterized by isolated thrombocytopenia due to pathogenic anti-platelet antibodies
Immune Thrombocytopenia (ITP)
Acute ITP
usually self-limited occurring 1-3 weeks after a viral infection (e.g., nonspecific upper respiratory or gastrointestinal tract, rubella or chickenpox). Abrupt onset of bruising petechiae &/or epistaxis in previously healthy children is characteristic.
Chronic ITP
↑ incidence in females. Presenting symptoms include mucocutaneous bleeding, with menorrhagia, recurrent epistaxis & easy bruising.
mainly due to IgG autoantibodies which bind to platelets and megakaryocytes (MKs), targeting very abundant surface Ags such as glycoprotein (GP) αIIbβ3 (GPIIb/IIIa) and GPIb−IX.
Itp
Platelets with bound autoantibodies are subsequently recognized by () -> enhanced Ab-mediated platelet phagocytosis & removal from circulation ()
phagocytes bearing FcγRs
by reticuloendothelial cells (mainly in spleen).
Direct lysis of platelets by () has been detected along with an ↑ () cytokines & ↓ (_)
cytotoxic T lymphocytes (CTLs)
TH1/TH17
Tregs
Autoantibody binding to MKs & CTLs can lead to
deficiency in platelet release.
Many drugs can induce acute thrombocytopenia including
analgesics, antibiotics & sedatives.
Platelets: Common mechanism involves Ig binding () by their Fab (Ag-binding) region. () bind the Fc portion of the Ig. This may result in (_)
a platelet membrane Ag or Ag-drug combination
M⍬ Fc receptors
platelet removal & thrombocytopenia
Heparin-Induced Thrombocytopenia is mediated
by FcγRIIa
IgG autoantibodies that recognize PF4 in complex with heparin
FcRIIa.
Ig Fc domains within the immune complex bind to the platelet receptor FcγRIIa, and activate platelets leading to
platelet aggregation (thrombosis) & clearance
Rare disorder characterized by premature RBC destruction and anemia caused by autoantibodies that bind the RBC surface with or without complement activation
Autoimmune Hemolytic Anemia (AIHA)
the severity of Autoimmune Hemolytic Anemia (AIHA) depends on:
Characteristics of AutoAb (titer, ability to react at 37oC, ability to activate complement, and specificity & affinity for the autoAg).
Ag characteristics (density on RBCs, immunogenicity)
Patient related factors (age, B.M. compensation ability, M⍬ functionality, complement function/regulation)
erythrocytes are destroyed in the blood vessel itself
Intravascular Hemolysis
