Lecture 7: Serum Proteins Flashcards
What are the 2 major types of proteins in the blood and where are they synthesized?
- Albumin - liver
- Globulins are also synthesized in the liver except for Igs and complement
Light chains that are not bound to heavy chains are called?
Free light chains
Free light chains in urine are called?
Bence Jones proteins
What are the most common to least common serum Ig?
IgG > IgA > IgM > IgD > IgE
What is bad about cross-reactivity?
With polyclonal antibodies, there is a high chance of finding imposters a.k.a false positives
What are the structures of the different types of immunoglobins?
IgG = monomer
IgA = monomer in serum, dimer in secretions
IgM = pentamer
IgD = monomer
IgE = monomer
What are the functions of IgG?
- Activates the classical pathway of the complement system
- Binds and neutralizes viruses and toxins
- Ab-dependent cell-mediated cytotoxicity (ADCC) & intracellular Ab-mediated proteolysis
- Type 1 and 2 hypersensitivity reactions
IgG participate predominantly in which immune response?
Secondary
What are the structural differences between IgG subclasses?
Number of disulfide bonds and length of hinge region
Which IgG subclass fixes complement (most to least)?
IgG3 > IgG1 > IgG2
IgG4 does not fix complement
Which IgG subclass binds to Fc receptor (strongest to weakest)?
IgG1 = IgG3 > IgG4 > IgG2
Which IgG subclass crosses the placenta?
IgG1, IgG3 and IgG4
IgG2 does not cross placenta well
List the IgG subclasses from most to least in quantity.
IgG1 > IgG2 > IgG3 > IgG4
What are the half-lives of the IgG subclasses?
IgG1, IgG2 and IgG4 = 21 days
IgG3 = 7 days
Give 4 clinical situations of when IgG increases.
- Acute and chronic infections
- Inflammation
- Autoimmune disease
- Liver disease
Give 4 clinical situations of when IgG decreases.
- Secondary IgG hypogammaglobulinemia
a. Malignancies: lymphoproliferative disease can occupy and suppress normal bone marrow development of stem cells
b. Renal failure
c. Drugs - Abnormal loss (ex. nephrotic syndrome)
- Selective Ig deficiencies
- Combined failure of Ab and cell-mediated immunity
What is the function of IgA?
Prevents colonization by pathogens
Give 4 clinical situations of when IgA increases.
- Chronic infection
- Cirrhosis of liver
- Autoimmune disease
- Wiskott-Aldrich syndrome
Give 4 clinical situations of when IgA decreases.
- Secondary Ig deficiency ex. malignancies
- Heriditary ataxia telangicctasia
- Malabsorption syndromes
- Lymphoid aplasia
What is the function of IgM?
- 1st Ig made by B cells in fetus
- Agglutination
- B cell surface Ig that functions as a receptor for Ags on B cells
Give 4 clinical situations of when IgM increases.
- Primary biliary cirrhosis
- Viral infections
- Intrauterine infections
- In newborns, > 0.2 g/L is indicator of utero stimulation of the immune system
Give 4 clinical situations of when IgM decreases.
- Malignancy
- Selective Ig deficiency
- Primary immune deficiency
- Abnormal loss
What is the function of IgD?
Ag receptor on B cells that have not been exposed to Ag which can activate basophils and mast cells to produce antimicrobial factors
Does not bind complement
When does IgD increase?
- Chronic infections
- IgD myelomas
What is the function of IgE? How does it work?
- Binds to allergens and triggers histamine release from mast cells and basophils
- Protect against parasitic worms
Eosinophils have F꜀ receptors for IgE
Binding of eosinophils to IgE-coated helminths kills these parasites
Does not bind complement
Give 4 clinical situations of when IgE increases.
- Eczema
- Allergies
- Asthma
- Anaphylactic shock
Give 2 clinical situations of when IgE decreases.
- Congenital agammaglobulinemia
- Hypogammaglobulinemia due to faulty metabolism or synthesis of Ig
What is the pathophysiology of monoclonal diseases?
- Malignancies of plasma cells/B-lymphocytes
- Disorders of monoclonal protein structure
- Apparently benign, premalignant conditions
What are the signs/symptoms of multiple myeloma (MM)?
- Bone pain and fractures
- Spinal cord compression
- Anemia and bleeding
- Infections
- Renal failure
- Hypercalcemia
What is the pathophysiology of multiple myeloma?
- In MM cells, genes for Ig production have mutated resulting in abnormal aa sequence & protein structure
- Ab function lost & 3D structure abnormal
What is the pathophysiology of monoclonal proteins (MCP)?
- Bind to each other/tissues
- Can cause hyperviscosity syndrome
- Can bind to blood clotting factors which result in higher bleeding tendency and more blood clotting
- Can bind to nerves and hormones causing pain
- Can rsult in bone disease
What is the pathophysiology of plasmocytomas?
Can compress/displace nerves
What kind of damage does MM do to the body?
CRAB
C - Calcium
R - Renal dysfunction
A - Anemia
B - Bone lesion
What is the diagnostic criteria for MM?
All 3 must be met
1. Serum/urinary monoclonal band or abnormal lambda:kappa
2. > 10% are clonal plasma cells in bone marrow/plasmacytoma
3. End organ damage related to abnormal plasma cell function
What is the diagnostic criteria for Benign Monoclonal Gammapathy (MGUS)?
- Low-risk progression to MM (< 5%)
a. MCP < 15 g/L
b. IgG heavy chain
c. Normal kappa:lambda - Increased-risk (60%)
a. MCP > 15 g/L
b. IgA/IgM heavy chains
c. Abnormal kappa:lambda ratio
What is the diagnostic criteria for Waldenstrom’s Macroglobulinemia?
- Plasma cell disorder associated with monoclonal increase in IgM which increased blood viscosity
- Anemia and infections
What are the tests associated with immunoglobulin interpretation? What are the abnormal results?
- Total protein, albumin
- MM cytokines inhibit liver production of albumin so albumin is decreased - Calcium
- May be increased - Creatinine
- If there is renal dysfunction, might be elevated - Immunoglobulins
- Electrophoresis including immunofixation
- To find out the type of monoclonal protein - Bone marrow biopsy
- >10% are plasma cells is indicator of multiple myeloma - CDC
- Low RBC
What lab test can be used to determine the prognosis of myeloma?
Beta-2-microglobulin
What are the pre-analytical issues for immunoglobulin and FLC testing? Give at least 2.
- Patient preparation ex. fasting, hydration
- Sample collection ex. sitting/recumbent
- Sample transport and handling ex. centrifuge within 2 hrs
- Sample stability
What are the analytical issues for immunoglobulin and FLC testing?
- Method ex. Immunoassay, electrophoresis, MS
- Assay challenges such as INTERFERENCE
- Result description ex. measurement uncertainty
- Analytical specificity & sensitivity
What are the post-analytical issues for immunoglobulin and FLC testing?
- Result interpretation
- Reference intervals
- Significant change is a cloudy term
- Appropriate utilization & reflexive testing
