First Aid, Chapter 4 Laboratory Tests, Immune complexes, Complement Flashcards
What is the degree of complement activation by immunoglobulin in descending order?
IgM → IgG3 → IgG1 → IgG2.
How are immune complexes formed?
IgM or IgG antibodies specific for a soluble antigen bind to it, forming circulating immune complexes (ICs).
What happens if IgM or IgG binds to antigens on a normal host cell in a normal person?
If IgM or IgG binds to an antigen on a normal host cell, regulatory complement proteins, such as factor H and I, inactivate C3b to iC3b, thereby inhibiting IC formation. Thus, IC formation normally occurs only on foreign cells.
How are immune complexes eliminated?
C3b binds CR1 on RBCs, thus allowing transport of ICs to the liver and spleen, where they are eliminated by macrophages.
What equilibrium zone are large circulating immune complexes found at? Small immune complexes?
- Large circulating ICs are formed at the zone of equivalence (Figure 4-24).
- Small circulating ICs are formed at the zone of antigen or antibody excess. (see Figure 4-24).
Which immunoglobulins can activate the classical complement pathway?
IgM and IgG (subclass IgG1, IgG2, and IgG3) can activate the classical complement pathway.
How do immune complexes cause disease? How does measuring complement allow monitoring of disease burden in some diseases?
ICs that are not properly eliminated can cause inflammation, resulting in tissue injury. Excessive IC formation also results in complement consumption. Measuring, IC formation via complement consumption, allows for estimation of disease burden. Thus, C3 and C4 levels can be used to monitor disease activity (e.g., in SLE).
Where do circulating immune complexes deposit? What kind of inflammation does this cause and where?
Circulating ICs are deposited in vascular beds and complement, which leads to complement consumption and reduced levels of C3 and C4. This produces a neutrophilic inflammation, usually affecting small arteries, glomeruli, and synovial of joints, which results in clinical symptoms of vasculitis, nephritis, and arthritis.
What is the antigen involved in SLE?
DNA, nucleoproteins, and others
What is antigen involved in poststreptococcal glomerulonephritis?
Streptococcal cell wall antigen
What is the antigen involved in polyarteritis nodosa?
Hepatitis B virus surface antigen
What is the antigen involved in cryoglobinemia?
Hepatitis C virus or rheumatoid factor
What pathway does immune complex formation lead to the activation of? What coats the immune complex, and what does this allow for?
- IC formation leads to the activation of the classical complement pathway.
- C1q, C4b, and C3b coat the IC, maintain its solubility, and act as ligands for receptors on WBCs and RBCs.
What does conglutinin bind?
-Conglutinin: Binds iC3b, which can then be detected in an assay. Does not detect C3dg. iC3b is converted to C3dg within 1–8 hours of its generation.
What receptors does the Raji cell have? What detects Raji cells? What causes false positive?
Raji cell: Burkitt’s cell line with receptors for C1q, C3b, C3bi, and C3d. ICs bind to Raji cells, which are detected by antihuman IgG (IgA or M). False positive with warm reactive antilymphocyte Abs (e.g., SLE)
How does the C1q binding assay work? How do false positives occur?
C1q-binding assay: Radiolabeled C1q binds to circulating ICs and is then detected. False positives may occur with autoantibody to C1q, aggregated immunoglobulins, or heparin in test samples. C1q will also bind to polyanionic substances in serum, such as bacterial endotoxin or DNA, giving false positive results.
Type III hypersensitivity occurs with antigen or antibody excess?
Antigen excess results in the formation of small immune complexes that do not fix complement and are not cleared from circulation, leading to deposition in glomeruli, vessels, and joints.
