Week 1 - Tuesday Flashcards
What is the alternate pathway of complement fixation?
Alternate Pathway: activated by cell wall components from certain bacteria and yeasts, endotoxin, and aggregated IgA. Does not require antibody, C1, C4, or C2
Which of the following is NOT a feature of a B-lymphocyte cell?
A) Expresses CD4 receptors
B) Mediates humoral immunity
C) Recognizes antigen
D) Induced by antigen presenting cells
E) Produced in the bone marrow
B cells do not express CD4 receptors (a marker of helper T-cells).
B-cells are produced in the bone marrow. They can independently recognize some antigens, but are also induced by APCs (antigen presenting cells).
Deficiency of which complement factors predisposes to Neisseria bacteremia?
Deficiency of the terminal pathway (C5, C6, C7, and C8) predisposes to Neisseria infections
What is the classic pathway of complement fixation?
Classic Pathway: the binding of proenzyme C1 to an Ag-Ab complex triggers a sequential reaction resulting in cell lysis
The immunoglobulins IgG and IgM can activate the classic pathway of the complement system
Mannose-binding lectin pathway: mannitose-binding lectin replaces C1q; does not need the presence of antibodies to be activated
During injury to a blood vessel, which protein binds to platelet glycoprotein Ib?
A) von Willebrand factor
B) GpIIb/IIIa
C) Hyaluronic acid
D) Keratan sulfate
E) Glycoprotein Ia
**A) von Willebrand factor **
Injury to a blood vessel exposes subendothelial collagen and von Willebrand factor Platelets adhere to the von Willebrand factor via GpIb.
Endothelial injury → collagen exposed → platelets adhere to vWF in the subendothelium (adhesion)
vWF (synthesized in megakaryocytes and endothelial cells) binds GpIb on the platelet →adhesion
There is also a brief arteriolar vasoconstriction mediated by the local factorendothelin.
What role does fibrinogen play in platelet aggregation?
Aggregation is mediated by fibrinogen, which binds GpIIb/IIIa on adjacent platelets
Name three functions of the complement cascade.
C3b and IgG are the two primary opsonins in bacterial defense
C1, C2, C3, C4 are key for viral neutralization
C3a, C4a, and C5a promote anaphylactic activity, such as degranulation of mast cells
C5a is a potent chemoattractant: recruits neutrophils and other inflammatory cells
C5b, C6, C7, C8, and C9 form the membrane attack complex (MAC) which results in cell lysis. (Note: deficiency in these factors leads to Neisseria bacteremia)
What tissue type phagocytozes aged and defective red blood cells and is the site of B lymphocyte formation?
Myeloid tissues also phagocytize aged and defective red blood cells (as do the spleen and liver) and are the sites of B lymphocyte formation.
What role does ADP play in platelet activation?
Role of ADP in platelet activation: ADP binds receptors on platelet surface, causing insertion of GpIIb/IIIa (fibrinogen receptor) → allows aggregation of platelets
Antiplatelet agents ticlopidine and clopidogrel block ADP receptors and thus inhibit expression of GpIIb/IIIa
Deficiency of which complement factor leads to severe, recurrent pyogenic sinus and respiratory tract infections?
Lack of C3 or any other activator proteins can predispose to severe, recurrent pyogenic sinus and respiratory tract infections
What is the myeloid to erythroid ratio?
The myeloid to erythroid ratio (M:E) is the ratio of myeloid precursor cells (immature white blood cell) to erythrocyte precursor cells (immature erythrocytes). Useful in diagnosis of blood dyscrasias. Normal: 3:1 to 5:1.
Clinical Correlate: After severe hemorrhage the body should stimulate erythropoiesis to compensate for blood loss → the M:E ratio will be decreased.
Clinical Correlate: In cases of aplastic anemia (bone marrow failure), the bone marrow is unresponsive to EPO → inappropriately high M:E ratio.
Which factors prevents complement activation on self-cells?
Decay accelerating factor (DAF, also known as CD55) inhibits the assembly of C3 convertases; DAF and C1 esterase inhibitor both prevent inappropriate complement activation
Mutations of C1 esterase inhibitor can lead to hereditary angioedema and HUS(hemolytic uremic syndrome)
Deficiency of DAF → complement-mediated lysis of RBCs → paroxysmal nocturnal hemoglobinuria (PNH)
Name 4 components of the granules in basophils.
Basophil granules contain:
Bilobed nucleus. Intracellular granules stain well with basic dyes, hence “basophilic”
Heparin
Histamine → key role in mediating allergic reactions
Leukotrienes and cytokines are synthesized on demand
Name 3 components of granules in neutrophils.
Neutrophil granules contain myeloperoxidase, lactoferrin, hydrolytic enzymes
Most common WBC, highly motile
2-5 nucleus lobes; can become hypersegmented in vitamin B12 or folate deficiency
Phagocytic, but also has granules
Phagocytosed molecules/cells are exposed to respiratory burst: NADPH oxidase produces superoxide, which is converted to H2O2. H2O2 is then converted to OCl- by MPO.
What are the four major components of the dense granules found in platelets?
Binding of platelets also activates them to release their granules which contain key molecules: ADP, Ca2+, and serotonin. Thromboxane A2 (TXA A2) is generated by thromboxane synthase.
TXA2 activates more platelets (↑ aggregation)
ADP increases glycoprotein IIb/IIIa’s binding of fibrinogen → plug is strengthened
Serotonin enhances overall platelet procoagulability; mechanisms still being elucidated.
