ABO/Rh Multiple Myeloma - Schein 4/7/16 Flashcards
[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
vs
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
plasma
- 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
glycosyltransferase
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]
vs.
RBC transfusion [consider donor antigens only]
vs.
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 :(
tx
- 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
vs
anti-Rh
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
IgG
IgA
antibodies!
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
