ABO/Rh Multiple Myeloma - Schein 4/7/16 Flashcards Preview

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Flashcards in ABO/Rh Multiple Myeloma - Schein 4/7/16 Deck (22):

[unrelated material - need to know!]


cytokines in Th1 and Th2 devpt

Th1 : IL2, IFNgamma → activates macrophages

Th2 : IL4, IL10 → help B cells produce antibody


[unrelated material - need to know!]


tuberculoid leprosy


lepromatous leprosy


tuberculoid leprosy

characterized by relatively good control of the M. leprae by Th1 activation of infected macrophages → granuloma formation, local infl


lepromatous leprosy

Th2 response → antibody response

  • ineffective against intracellular pathogen


composition of the blood

formed elements

  • RBCs (erythrocytes)
  • WBCs (leukocytes)
  • platelets


  • albumin
  • antibodies
  • complement
  • clotting factors
  • acute phase proteins
  • etc


*plasma - (clot formed when activating clotting factors) = SERUM!


blood group antigens

terminal carbohydrate moieties on large glycoprotein/glycolipids on cell membranes

  • core glycan + terminal sugar
  • approx 2M on each RBC membrane



chr9 : glycosylase gene (3 alleles(

adds terminal sugars onto core carb that's already on blood cells

  • + GalNAC = type A
  • + galactose = type B
  • + nothing = type O


in general:

h antigen + fucosyl [fucosyltransfersase] → H antigen + terminal sugar [glycosyltransferase] → ABO blood

  • sets you up with the RBC antigen (H, A, B, AB) specific for your blood type (O, A, B, AB)


antibodies against blood antigens

"natural antibodies"


blood antigens are glycolipids (sugar moieties)

  • T-indep antibodies are produced
  • usually IgM subtype (do not type-switch)
  • preformed and "opposite" to the blood type that you have...WHY/HOW?
    • antibodies produced against glycolipids expressed by gut bacteria!

bc antibodies against other blood types exist...

  • transfusion of wrong blood type → severe rxn (Type II hypersensitivity)


special case:

Bombay O!

typically: h → H → A/B/O

in Bombay O, no h → H conversion takes place [no fucosyltransferase]

  • people appear to be type O on blood test, but with important diff in antibody production...
  • make anti-A, anti-B, and also anti-H antibodies → react with normal O blood! (nothing else does)
    • recog'd by agglutination of type O with anti-H


blood transfusion rules

whether transfusion rxn occurs depends on...

  • what you transfuse
  • volume transfused
  • whether transfusion occuring is routine or emergent
    • O- RBCs ONLY  can used in emergency situations (antigen-less)

don't want cross-rxn between antigens/antibodies, so need to consider:

  • recipient RBC antigens [ex. A]
  • recipient plasma antibodies [ex. anti-B]
  • what blood type doesn't contain antigen/antibodies that would cross-react


what to consider in diff types of blood transfusions (whole vs. RBC vs. plasma)

whole blood transfusion [consider donor antigens&antibodies]


RBC transfusion [consider donor antigens only]


plasma transfusion [consider donor antibodies only]


transfusion reaction


primary rxn

mop up rxn

2 additional rxns

anti-ABO antibodies coat the RBCs they recognize as foreign


primary rxn : intravascular hemolysis via complement rxn [type II rxn]

  • anti-ABO antigens are IgM → excellent at activating complement

to a lesser degree : RBCs opsonized with antibody and/or complement can be phagocytosed by macrophages in liver/spleen 


cytokines released in large quantities → CYTOKINE STORM, activation of whole immune system

possible disseminated intravascular coagulation (DIC)

  • localized clotting in circulation
    • cuts off organ blood supply
    • sequesters clotting factor supply → bleed out even with DIC in effect 



Rh factor


  • what is it
  • antibodies?

non-glycosylated RBC cell surface protein 

  • many genes, of which one is medically important: Rh0D gene (15% of the pop has a deletion, making them Rh-)


BODY WILL NOT MAKE NATURAL ANTIBODIES TO IT! → will make IgG antibodies on exposure [IgG because protein]

  • IgG can cross placental barrier (IgM cannot...)
    • explains why mom/child situation can arise with Rh mismatch, but not with ABO mismatch!
  • IgG does not activate complement well, but does opsonize RBCs for phagocytosis in spleen


Rh Incompatibility Disease

important in the fetus...

  • erythroblastosis fetalis
  • hemolytic disease of the newborn
  • hydrops fetalis


Rh- moms can be sensitized by blood that enters their circ during birth of an Rh+ child

  • moms have immune response, which is retriggered by the next Rh+ child in utero
  • mom's now-extant IgG can cross the placental barrier → fetal hemolysis :(


  • blood type parents
  • give rhogam (anti-Rh antibodies during 3rd trimester, within 72 hours of birth) → suppresses mom from making anti-Rh antibodies!
    • kill fetal cells that get into mom's circ BEFORE they can trigger an immune response!
    • Ab feedback → presence of anti-Rh will suppress MOM'S synthesis of anti-Rh through her own immune response
  • cytokines interrupt antigen-specific B cells from becoming plasma cells
  • ABO incompatibility can also have a "protective" effect → kill baby's cells that enter mom's circ before she becomes sensitized to the Rh and starts pumping out the antibodies!


compare and contrast:





anti-ABO - IgM

  • have abundant Ag to bind to
  • activate complement well
  • destroy RBC in bloodstream, primarily by complement rxn
    • intravascular hemolysis

anti-Rh - IgG

  • have ltd Ag to bind to
  • don't activate complement well
  • destroy antibody-opsonized RBC in liver and spleen via macrophage phagocytosis
    • extravascular hemolysis


other minor blood groups

similar to Rh...

  • require exposure for antibody response (not natural; not preformed)
  • trigger IgG production
  • make up low proportion of proteins on RBCs
  • hemolytic disease of newborn is possible...but not likely at all







IgM - pentamers

  • easy for them to agglutinate RBCs (can hold on to several at once, binding the antigens which are all over the place) → form lattice

IgG - monomer

  • small, don't agglutinate well (and have sparse antigen to hang on to...and RBCs have a net neg charge which makes them tricky to get close together anyway) → need fixes to get around these barriers


IgMs are big enough to bridge zone of repulsion, but IgGs are not → use solutes that neutralize RBC charge and/or increase cell crowding with IgG!


IgA - dimer




Coombs' Test

(Antiglobulin Test)


two forms: direct and indirect

direct Coombs' test

  • detects cell-bound antibodies
  • positive: indicative of some kind of autoimmune hemolytic rxn

patient RBC + Coombs' reagent( rabbit anti-humanIgG)

indirect Coombs' test

  • detects anti-Rh (aka anti-D) IgG in plasma
  • positive: detects sensitization of Rh- mom to current/future Rh+ kid

patient plasma + donor RBC [or RBC with whatever you want to check reactivity with] + Coombs reagent


multiple myeloma

malignancy of antibody-producing plasma cells

  • most common lymphoid malignancy (20k new cases annually, median age 70)


multiple bc by time of detection, there are usually multiple foci - many clumps of tumor cells

myeloma bc tumors form in bone marrow (where most normal plasma cells are) → erodes bone via stimulation of osteoclasts



osteoclasts often activated → coin lesions

immunosuppression : despite pumping out extra antibodies, overproduction of one might be leading to underproduction of another isotype → can't mount approp immune response → recurrent infections




serum electrophoresis



blood protein profile

  • peaks for albumin, alpha1, alpha2, beta, GAMMA (contains antibodies aka gamma-globulins)
  • myeloma = "gammopathy" bc antibodies are in the gamma section

narrow peak : 1 or small number of proteins

broad peak : large number of proteins within that group


why is multiple myeloma aka monoclonal gammopathy?

monoclonal : plasma cell tumors with uncontrolled prolif of one cell type → overproducing one isotype of antibody

  • secreted antibody aka paraprotein or M protein

gammopathy : antibodies aka gamma-globulins are found within the gamma peak in serum electrophoresis


monoclonal gammopathies

  • multiple myeloma [own flashcard]
  • Waldenstrom's macroglobulinemia


  • less mature B cells → secretes IgM
  • big molecules! → viscous blood
  • less bone marrow involvement

heavy chain disease

  • only heavy chain secreted

light chain disease

  • only light chain secreted
  • light chains in urine = Bence-Jones proteins


serum electrophoresis results in multiple myeloma

will see a large increase in gamma region!

aka "M spike" = myeloma spike


monoclonal : will see a realtively thin gamma peak (bc one type that's being overprolif'd)

polyclonal : will see a broader peak


how do you figure out which Ig is elevated in multiple myeloma???

immunofixation : separate proteins, add anti-Ig antibodies

  • see which antibodies bind!
  • multiple myelomas should have 1 light chain (kappa, lambda) and 1 heavy chain (G, M, A) being overrepresented