ABO/Rh - Multiple Myeloma

Question 1

Composition of Blood

Answer 1

Formed elements (red cells, white cells, platelets)

Plasma ( albumin, antibodies, complement, clotting factors, acute-phase proteins), etc

Question 2

Serum

Answer 2

Activate the clotting factors and pull out the clot = let with serum

Question 3

Blood Group Antigens

Answer 3

millions on each RBC of all different types

• terminal carbohydrate moieties on large glycoproteins and glycolipids on cell membrane
• core glycogen + terminal sugar

Question 4

Where are the major RBC antigens?

Answer 4

RBC, endothelial cells, platelets, and other cells

Question 5

Where is the Type A/B glycosyltransferase moiety in the genome?

Answer 5

Chromosome 9

Question 6

How does the glycosyltransferase moiety determine blood type?

Answer 6

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)

Question 7

Who has the H antigen on their cells?

Answer 7

almost everyone :)

Question 8

What are the potential genotypes of type A?

Answer 8

AA or AO

Question 9

What type of T antibodies are made against the A and B sugar moieties?

Answer 9

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

Question 10

Why are the natural Abs against A and B made?

Answer 10

Produced against glycolipid antigens expressed by intestinal microbes

These glycolipids cross-react with our A and B antigens

Question 11

What is the classification of the reaction if transfuse against wrong blood type?

Is it cytotoxic?

Answer 11

Type II Hypersensitivity Reaction

Severe - yes, it is cytotoxic

Question 12

What is the molecular presentation of Bombay-O?

Answer 12

No h –> H conversion

Therefore can never go on to add type A and B antigens

Question 13

What Abs and Antigens are present on Bombay-O cells?

How do they appear on routine typing?

Who can they receive blood from?

Answer 13

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

Question 14

Whole blood Transfusions

rules

Answer 14

Contains Abs as well as antigen, therefore donor/recipient needs to be IDENTICAL

Emergencies: O,Rh- RBC can be used as universal donor

Question 15

What type of transfusion can a type A person have?

Answer 15

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

Question 16

Erythrocyte Transfusion

Answer 16

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

Question 17

Plasma transfusion

Answer 17

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

Question 18

What happens in a transfusion rxn (mechanism)?

Answer 18

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

Question 19

What are the effects of complement lysis (result of transfusion)?

Answer 19

• 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

Question 20

Rh factor

Answer 20

• 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

Question 21

Which can cross the placenta: IgG or IgM?

Answer 21

IgG

Question 22

Rh Incompatibility Disease

Answer 22

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

Question 23

What is the treatment for Rh Incompatibility Disease?

Answer 23

• 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

Question 24

Anti ABO vs Anti Rh:

Anti ABO

Answer 24

abundant Ag,
IgM (T independent); 
Activate complement well;
Destroy RBC in blood stream;
Intravascular hemolysis

Question 25

Anti ABO vs Anti Rh: Anti ABO

Answer 25

``` Sparse Ag; IgG (protein); Does NOT activate complement well; Ab coated RBC destroyed by macrophage in liver and spleen; extravascular hemolysis ```

Question 26

IgM structure

Answer 26

Penta (5 Abs together)

Question 27

Agglutination of RBC

Answer 27

Can hold onto several RBCs at once to form a lattice structure (IgM) used for typing blood A/B/O)

Question 28

Can IgG be used to type blood?

Answer 28

No, too small to form lattice Recall IgG is related to Rh factor (protein)

Question 29

Direct Coomb's (DAT) Test

Answer 29

detects (directly) cell-bound Abs Against human constant region (Fc) --> can get agglutination of even IgGs

Question 30

Indirect Coomb's (IDAT) Test

Answer 30

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

Question 31

Multiple Myeloma

Answer 31

- 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

Question 32

What are key characteristics of multiple myleoma

Answer 32

"coin lesions" - wearing away of bone - most commonly lymphoid malignancy - 20,000 new cases/year in US - median age: 70

Question 33

What does the NORMAL Serum Electrophoresis look like?

Answer 33

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) ```

Question 34

Monoclonal Gammopathies (general details)

Answer 34

- 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"

Question 35

Monoclonal Gammopathies (what are the various types?)

Answer 35

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)

Question 36

What does the Multiple Myleoma Serum Electrophoresis look like?

Answer 36

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)

Question 37

What is the mech for immunosuppression in Multiple myleoma pts?

Answer 37

Pumping out tons of one type of Ab that normal Abs are repressed (get more bacterial/viral infections)

Question 38

How do you determine which isotype is elevated in Multiple Myleoma pts?

Answer 38

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