Antibodies, Antigens & Interactions

Question 1

describe basic immunoglobulin structure

Answer 1

2 heavy chains (mu, delta, gamma, epsilon, or alpha) and 2 light chains (kappa or lambda)
chains held together by disulfide bonds
constant region: Fc
antigen binding region: Fab

Question 2

3 major mechanisms for generation of antibody diversity

Answer 2

primary: multiple germ-line genes and junctional diversity (addition of nucelotides [P/templated or N/non-templated] during process of D-J or V-D/J joining; catalyzed by TdT [terminal deoxyribonucleotidyl transferase])
secondary: somatic hypermutation (point mutations occurring in fully assembled V-J or V-D-J regions during an immune response)

Question 3

define allelic exclusion; why is this a good thing?

Answer 3

rearranged heavy chain or light chain genes come from only one chromosome (maternal or paternal)
“Bobby dress-up”
expression of both alleles would render the B cell multispecific -> not as useful

Question 4

describe receptor editing

Answer 4

non-productive light chain gene rearrangement can be rescued by further gene rearrangement
ex. 5’ Vk gene segment can recombine with an unused 3’ Jk gene segment and replace nonproductive Jk gene segment
can happen up to 5 times (?) for kappa light chain

Question 5

T-B-NK+ SCID - cause, effects

Answer 5

null mutations in RAG1 and/or RAG2
autosomal recessive
account for 3-4% of SCID cases
decreased IgG, WBCs, and B cells
neither lymphocyte pool matures into effector cells (no receptors, no fxn!)
typically severe, life-threatening opportunistic infxns in early infancy

Question 6

X-linked agammaglobulinemia - cause, effects

Answer 6

also Bruton’s agammaglobulinemia
Bruton tyrosine kinase (Btk) normally delivers signal from pre-BCR for survival of cell -> mutation destroys this fxn
recurrent infxns - haemophilus influenzae, streptococcus pneumoniae, staphylococcus aureus, enteroviruses, giardia, etc.

Question 7

define isotype

Answer 7

determined by C region of H chain, defines class and subclass
each isotype has its own gene
differ in size, charge, aa sequence and carb content

Question 8

define allotype

Answer 8

allelic differences in H chains

Question 9

define idiotype

Answer 9

antigenic determinants on the V regions

we all may see an antigen, but we respond with slightly different V region determinants

Question 10

IgM - structure, fxn

Answer 10

pentamer; 10 Ag-binding sites
first antibody produced in primary Ag response
efficient binding of multiple repeating epitopes and C’
J piece: Fc linked polypeptide disulfide-bonded to 2 of the 10 mu chains; binds to secretory cells -> mucosa
5-10% of total serum Igs

Question 11

IgG - structure, fxn

Answer 11

singular “Y” Ab
predominant Ab of secondary immune response
4 subclasses: IgG1, IgG2, IgG3, and IgG4
IgG3 - efficient activator of C’
IgG1/3 bind w/ high affinity to Fc receptors on phagocytic cells (opsonization)
FcR CD markers are all multiples of 16! (CD16, CD32, CD64)
80% of total serum Igs

Question 12

IgA - structure, fxn

Answer 12

secretory (dimer) or serum (80% monomeric)
constituent of secondary immune response
polypeptide produced by epithelial cells of mucous membranes binds to Fc domain of IgA dimer -> allows secretion
IgA plasma cells concentrated along mucous membrane surfaces

Question 13

IgE - structure, fxn

Answer 13

singular “Y” antibody
binds to basophils and mast cells by Fc receptor with very high affinity
primarily fight helminths (worms)

Question 14

IgD - structure, fxn

Answer 14

singular “Y” antibody
no known fxn in serum
monomeric form present as Ag-specific receptor on mature B cells
only monofxnal Ab

Question 15

describe heavy chain formation

Answer 15

1) D+J -> (Rag-1/Rag-2) -> D/J
2) LV +D/J -> (Rag-1/Rag-2) -> LVDJ
3) VDJ + Cm/Cd (make IgM and IgD, respectively)
RSSs (recombination signal sequences) flanking V, D, and J segments aid process

Question 16

why is junctional diversity so useful for generating antibody diversity?

Answer 16

leads to further diversity in the third hypervariable region (idiotype)
provides the largest contribution to the diversity of Ag receptors

Question 17

define idiotope

Answer 17

hypervariable regions or complementarity determining regions (CDRs) create an interaction site that is complementary in shape, charge, and hydrophobicity to the epitope it binds
6 CDRs per Ab/TCR

Question 18

protein Ags are always…

Answer 18

T-dependent Ags

Question 19

polysaccharide and lipid Ags can be…

Answer 19

both T-dependent or T-independent Ags

usually multiple epitopes can cross-link BCRs

Question 20

how do superantigens work?

Answer 20

directly bind MHC-II and Vb of TCR
not within binding site!!!
activate up to 25% of circulating T cells

Question 21

compare/contrast affinity and avidity

Answer 21

both refer to Ab/Ag binding

affinity: strength of interaction btw univalent Ag and univalent Ab
avidity: strength of interaction btw multivalent Ag and multivalent Ab (IgG or IgM); dependent on affinities of individual Ab binding sites

Question 22

describe hapten/carrier effect

Answer 22

drugs are poor stimulators of immune responses due to simple structure and low molecular weight, but can form multivalent hapten/carrier complexes (hapten: drug, carrier: non-immunogenic protein)
penicillins and other beta-lactams do this

Question 23

Yervoy (ipilimumab) - MOA

Answer 23

Ab
blocks CTLA-4
prolongs immune response