ABO/Rh - Multiple Myeloma Flashcards
Composition of Blood
Formed elements (red cells, white cells, platelets)
Plasma ( albumin, antibodies, complement, clotting factors, acute-phase proteins), etc
Serum
Activate the clotting factors and pull out the clot = let with serum
Blood Group Antigens
millions on each RBC of all different types
- terminal carbohydrate moieties on large glycoproteins and glycolipids on cell membrane
- core glycogen + terminal sugar
Where are the major RBC antigens?
RBC, endothelial cells, platelets, and other cells
Where is the Type A/B glycosyltransferase moiety in the genome?
Chromosome 9
How does the glycosyltransferase moiety determine blood type?
Adds terminal sugars to a core carbohydrate + H
A allele: adds terminal N-acetylgalactosamine
B allele: adds terminal galactose
O allele: no activity (only H antigen)
Who has the H antigen on their cells?
almost everyone :)
What are the potential genotypes of type A?
AA or AO
What type of T antibodies are made against the A and B sugar moieties?
Mostly IgM (some IgG)
T-independent (no helper T cells needed)
Thus, T-independent Abs are usually of IgM subtype (do not usually class switch)
Preformed Natural Abs
Why are the natural Abs against A and B made?
Produced against glycolipid antigens expressed by intestinal microbes
These glycolipids cross-react with our A and B antigens
What is the classification of the reaction if transfuse against wrong blood type?
Is it cytotoxic?
Type II Hypersensitivity Reaction
Severe - yes, it is cytotoxic
What is the molecular presentation of Bombay-O?
No h –> H conversion
Therefore can never go on to add type A and B antigens
What Abs and Antigens are present on Bombay-O cells?
How do they appear on routine typing?
Who can they receive blood from?
Lack both A and B antigens. SO LOOK LIKE “O”
Antibodies: anti-A, anti-B, AND anti-H
***CAUTION: will react to blood of bc of anti-H, thus can only get transfusion from other Bombay-O
Whole blood Transfusions
rules
Contains Abs as well as antigen, therefore donor/recipient needs to be IDENTICAL
Emergencies: O,Rh- RBC can be used as universal donor
What type of transfusion can a type A person have?
Note: antigen on red cells = A; Ab in plasma: anti-B
Compatible donor plasma lacks anti-A = A and AB
Compatible donor red cells lack B antigen = A and O
Thus only whole blood donor = A
Erythrocyte Transfusion
Packed RBC: donor red cells must lack antigens which bind to recipient abs
A (has anti-B), so donor cells must lack B = compatible donors A and O
B (same as A but invert A/B)
AB can get from A, B, AB, and O
O can only get from O
Plasma transfusion
donor cells must lack Abs which bind to recipients red cells
A: donor plasma must lack anti-A, so compatible donors are A and AB
AB: donors must lack Anti-A and Anti-B (so compatible=AB)
O: compatible with A, B, AB, O
What happens in a transfusion rxn (mechanism)?
1) IgM coat RBCs and activate compliment –> complement lysis (IgM with many antigens on RBC)
2) Intravascular lysis (can lead to jaundice) –>
macrophages in liver & spleen phagocytose Ab and complement coated RBC
What are the effects of complement lysis (result of transfusion)?
- Hb liberated in amts toxic to the kidney
- Cytokines released in large qtys
-DIC (disseminated intravascular coagulation) possible: lots of clotting factor released –> localized clotting in circulation; cut off blood supply to organs;
bc clotting factor used up –> bleed out even with DIC
Rh factor
- Surface Protein (so major Ab are IgG)
- nonglycosylated
- CAN cross placenta
- do not activate complement well
Fxn: opsonize RBCs and facilitate phagocytosis in the spleen
Which can cross the placenta: IgG or IgM?
IgG
Rh Incompatibility Disease
Medically important in fetus (esp second fetus: 1) Rh- moms sensitized by Rh+ fetus, 2) subsequent Rh+ babies: hemolysis by maternal Abs that cross placenta)
Rh- mom with a Rh+ fetus. Mom makes Abs agains Rh that attack fetus blood
What is the treatment for Rh Incompatibility Disease?
- Type the parents
- Anti-Rh_0_D Abs ruding 3rd trimester w/in 72 hrs of 1st birth
RHOGAM IMMUNE GLOBULIN:
destroy fetal RBCs before initiate immune response
-Ab fb repress own synthesis (Ab-mediated immune response)
-Cytokines interrupt antigen specific B cells, turning into plasma cells
-ABO incompatibility can have a partial protective effet
Anti ABO vs Anti Rh:
Anti ABO
abundant Ag, IgM (T independent); Activate complement well; Destroy RBC in blood stream; Intravascular hemolysis
Anti ABO vs Anti Rh:
Anti ABO
Sparse Ag; IgG (protein); Does NOT activate complement well; Ab coated RBC destroyed by macrophage in liver and spleen; extravascular hemolysis
IgM structure
Penta (5 Abs together)
Agglutination of RBC
Can hold onto several RBCs at once to form a lattice structure (IgM)
used for typing blood A/B/O)
Can IgG be used to type blood?
No, too small to form lattice
Recall IgG is related to Rh factor (protein)
Direct Coomb’s (DAT) Test
detects (directly) cell-bound Abs
Against human constant region (Fc) –> can get agglutination of even IgGs
Indirect Coomb’s (IDAT) Test
Detects anti-red-cell IgG in plasma
(Ie: testing mother’s serum to check babies)
if not agglutination, means you don’t have the antigen/RBCs
Multiple Myeloma
- malignancy of Ab-producing plasma cells
- 1 type of Ab usually not directed toward any type of specific Antigen
- “multiple” bc by time detected, multiple foci of tumor cells are present.
- “myeloma” bc tumors form in the bone marrow, that is where most normal plasma cells reside
What are key characteristics of multiple myleoma
“coin lesions” - wearing away of bone
- most commonly lymphoid malignancy
- 20,000 new cases/year in US
- median age: 70
What does the NORMAL Serum Electrophoresis look like?
Anode (L) to cathode (R)
Albumin: tall, thin alpha1; alpha 2; beta; gamma: long and thin (that's where most of the Abs lie = in the gamma band)
Monoclonal Gammopathies (general details)
- plasma cell tumors
- monoclonal - begin with a single cell
- all cells of tumor secrete Ab of same isotope
- the secreted Ab: paraprotein, M protein
“Monoclonal Gammopathies”: bc “gamma globulins lie there”
Monoclonal Gammopathies (what are the various types?)
MM: many clumps of tumor cells in bone marrow –> erodes bone via stimulation of osteoclasts; secretes IgG (60%) or IgA (25%) or IgE (rarely)
Waldenstorm’s macroglobulinemia: less mature B cell, secretes IgM; viscous blood; less bone marrow involement
Heavy-chain disease: only heavy chain secreted from B cells
Light-chain disease: only light chain secreted secreted from B cells
Light chains in urine are Bence-Jones Proteins (due to MM)
What does the Multiple Myleoma Serum Electrophoresis look like?
Increased gamma protein!
Anode (L) to cathode (R)
Albumin: tall, thin alpha1; alpha 2; beta; gamma: thin and ELEVATED (M (for myeloma) spike)
NB: serum electrophoresis does not show which isotype is elevated –> need further testing (myeloma electrophoresis)
What is the mech for immunosuppression in Multiple myleoma pts?
Pumping out tons of one type of Ab that normal Abs are repressed (get more bacterial/viral infections)
How do you determine which isotype is elevated in Multiple Myleoma pts?
Immunofixation:
- separate proteins on cellulose acetate strips;
- flood a strip with Abs to a specific human isotype (eg: sheep Ab specific for human alpha chains, binds only IgA)
- if Ab binds to plasma protein on strip, a ppt forms
In Multiple Myleoma , a single type of light chain and single type of heavy chain should be elevated
