*abai - Immunoglobulins

Front 1

Where does papin and pepsin cleave immunoglobulins?

Back 1

Papin - above the hinge (producing 3 pieces, 2 Fabs and Fc)

Pepsin - below the hinge (producing the connected Fab and a Fc - like a cup of "Pepsi")

Front 2

What are the number of constant domains in each Ig?

Back 2

IgM, IgE have 4 the other have 3

Front 3

Where does omalizumab bind?

Back 3

bind CH3 domain on IgE

Front 4

Which CDR is most variable?

Back 4

CDR3 of the heavy chain

Front 5

Which Ig is first produced after birth?

Back 5

IgM

Front 6

Which Ig reaches adult levels first?

Back 6

IgM

Front 7

Which Ig is first made after antigen stimulation?

Back 7

IgM

Front 8

Which Ig crosses the placenta?

Back 8

IgG

uses the neonatal Fc receptor (FcRn)

Front 9

Which Ig is produced in the highest quantity per day?

Back 9

IgA

Takes several years to get to the adult level (~7 years)

Front 10

Which Ig is highest in the plasma?

Back 10

IgG

Front 11

What is rheumatoid factor (RF) and what does it bind?

Back 11

Usually an IgM that binds the Fc portion of IgG

Front 12

What is the order (highest to lowest) of Ig in the adult serum?

Back 12

IgG, IgA, IgM, IgE
(GAME)

Front 13

What is the half-life of Ig (highest to lowest)?

Back 13

IgG (23 days), IgA (6 days), IgM (5 days), IgE (2 days)

Note - IgG3 is 8 days

Front 14

What cytokines are associated with class switching to IgE?

Back 14

IL4, IL13

Front 15

What cytokines are associated with class switching to IgA?

Back 15

IL5, TGFBeta

Front 16

What cytokines are associated with class switching to IgG?

Back 16

IFNy (IgG1-3)
IL4, IL13 (IgG4)

Front 17

Which Ig fix complement?

Back 17

IgM > IgG3/1 > IgG2

Front 18

Which produces more diversity - combinatorial diversity or junctional?

Back 18

combinatorial diversity = VDJ recombination

junctional diversity = non-template nucleotide additions at junctions and causes more diversity

Front 19

How does somatic hypermutation occur?

Back 19

Occurs in the germinal centers

AID converts C --> U
UNG clips out Us and repairs

Leads to affinity maturation

Only occurs in B cells

Front 20

Define receptor editing?

Back 20

In immature B cells, changes in the Ig when they are self reactive.

Salvage technique for self reactive Ig

Front 21

Which Fc receptor is associated with mast cell degranulation?

Back 21

FcεRI

Front 22

Which Fc gamma receptor has the highest affinity?

Back 22

FcyRI - major receptor for phagocytosis

Front 23

Which Fc gamma receptor is associated with ADCC?

Back 23

FcyR3a (CD16)

Front 24

Which Fc gamma receptor is associated with feed back inhibition of B lymphocytes?

Back 24

FcyR2b (CD32)

Front 25

Nephelometry:
Is it qualitative or quantitative?
Antigen excess/Zone of Equivalence/Antibody Excess?
How does it work?

Back 25

Quantitative
Zone of equivalence

Serum is added to solution with antibodies
Automated photon source calculates turbidity.

Used for IgG, IgA, IgM, C3, C4

Front 26

RID:

Qualitative/quantitative?
Antigen excess/Zone of Equivalence/Antibody Excess?
How does it work?

Back 26

Quantitative
Zone of equivalence

Diffusion on a gel with diameter relating to the amount of antigen/antibody (measured against standard curve)

Front 27

Laurel rocket:

Qualitative/quantitative?
Antigen excess/Zone of Equivalence/Antibody Excess?
How does it work?

Back 27

Quantitative and qualitative
Zone of equivalence

Voltage is applied to gel plate with sample, height of precipitin line = amount

Front 28

Double immunodiffusion:

Qualitative/quantitative?
Antigen excess/Zone of Equivalence/Antibody Excess?
How does it work?

Back 28

Quantitative
Zone of Equivalence

Antigen in wall of cell, serum in nearby cell, precipitin line determines amount

negative controls should not form a line.

Front 29

ELISA:

Qualitative/quantitative?
Antigen excess/Zone of Equivalence/Antibody Excess?
How does it work?

Back 29

Quantitative
Antigen or Ab excess

Bound protein in plate identified by labeled antibody, quantified by luminescence

Front 30

Western blot:

Qualitative/quantitative?
Antigen excess/Zone of Equivalence/Antibody Excess?
How does it work?

Back 30

Qualitative
Antibody excess

Protein run on gel, secondary blotted with antibody (immunoassay)

Front 31

How do you do an ELISpot?

Back 31

Cells stimulated to produce cytokine, cytokines are bound by capture antibody --> identified by labeled antibody, quantified by luminescence (ELISA like)

Front 32

What is the difference between RAST vs ImmunoCAP/FEIA?

Back 32

RAST = qualitative, inconsistent, solid phase assay that uses radiolabeled detection

ImmunoCAP = quantitative, consistent (cannot compare different platforms), sandwich ELISA

Front 33

What are the beneficial uses of Ig replacement?

Back 33

PID
Graves ophthalmopathy
ITP
CIDP
Guillain barre
Multifocal neuropathy
Kawasaki's Disease
CMV pneumonitis

Front 34

How is Ig isolated?

Back 34

Cold ethanol fractionation

Front 35

Name Ig purification methods?

Back 35

Nanofiltration - pepsin, low pH, ultracentrifugation
Stabilization - albumin, glycine, proline, PEG, D-mannitol, D-sorbitol, sucrose, glucose, maltose
Viral inactivation - solvents, detergents, low pH, caprylate precipitation
Physical - pasteurization, nanofiltration, column chromatography

Front 36

What dose of IVIG, SQIG, immunomodulatory are most common

Back 36

IV: 400-600mg/kg/3-4 weeks
Immuno: 2g/kg/1-2 weeks
SQ: 100mg/kg/week

Front 37

What are the mechanisms of action of IVIG?

Back 37

1) Block FcyR3a (CD16) - blocks ADCC
2) Block FcyR2b (CD32) - inhibits Ab production
3) Block Fc receptors on phagocytes
4) Neutralize pathogens/toxins/etc
5) Inhibit cytokine production
6) Inhibit complement uptake and deposition on target tissues (eg, C' scavenging)
7) Inhibits FAS-mediated apoptosis on keratinocytes in toxic epidermal necrolysis

Front 38

What stabilizer in IVIG has been associated with acute renal failure?

Back 38

Sucrose

Front 39

What risk factors are associated with acute renal failure from Ig?

Back 39

1) Diabetes
2) Baseline renal disease
3) Old age
4) Dehydration
5) Paraproteinemia (eg, Waldenstrom's/etc)
6) Sucrose (as stabilizer)
7) Those receiving immunomodulatory doses

Front 40

What are cryoglobulins?

Back 40

Ig's that precipitate in cold, leading to MPGN and palpable purpura

Front 41

What are the types of cryoglobulins?

Back 41

Type 1: Monoclonal Ig
- Associated with multiple myeloma, Waldenstrom's macroglobulinemia
Type 2: Monoclonal Ab and polyclonal Ag (mixed)
- Usually IgM, associated with HepC
Type 3: Monoclonal Ab, polyclonal Ag (mixed)
-A/w SLE, autoimmunity, HepC
Labs: Decreased complement, +RF, +/- Hep C
*>80% mixed cryo a/w HepC
In GN, 50% have cryo
Also a/w arthritis, neuropathy

Front 42

What are risk factors for aseptic meningitis from Ig?

Back 42

1) Large doses
2) Rapid infusions
3) Patients with autoimmune disorders or inflammatory disorders
4) History of migraines
5) Contaminated Ig

Front 43

Rare adverse effects of Ig?

Back 43

Thrombosis (esp if preexisting autoimmunity or if using lyophilized product)
Serum sickness-like (IgG anti-IgA) reaction
False glucose readings

Front 44

Rules for live vaccines in patients on Ig?

Back 44

Vaccines may have decreased immunogenicity when given before or shortly thereafter

Front 45

What has less systemic reactions: SQIG or IVIG?

Back 45

SQIG