Antibodies, Antigens & Interactions Flashcards

1
Q

describe basic immunoglobulin structure

A

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

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2
Q

3 major mechanisms for generation of antibody diversity

A

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)

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3
Q

define allelic exclusion; why is this a good thing?

A

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

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4
Q

describe receptor editing

A

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

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5
Q

T-B-NK+ SCID - cause, effects

A

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

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6
Q

X-linked agammaglobulinemia - cause, effects

A

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.

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7
Q

define isotype

A
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
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8
Q

define allotype

A

allelic differences in H chains

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9
Q

define idiotype

A

antigenic determinants on the V regions

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

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10
Q

IgM - structure, fxn

A

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

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11
Q

IgG - structure, fxn

A

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

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12
Q

IgA - structure, fxn

A

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

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13
Q

IgE - structure, fxn

A

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

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14
Q

IgD - structure, fxn

A

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

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15
Q

describe heavy chain formation

A

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

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16
Q

why is junctional diversity so useful for generating antibody diversity?

A

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

17
Q

define idiotope

A

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

18
Q

protein Ags are always…

A

T-dependent Ags

19
Q

polysaccharide and lipid Ags can be…

A

both T-dependent or T-independent Ags

usually multiple epitopes can cross-link BCRs

20
Q

how do superantigens work?

A

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

21
Q

compare/contrast affinity and avidity

A

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

22
Q

describe hapten/carrier effect

A

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

23
Q

Yervoy (ipilimumab) - MOA

A

Ab
blocks CTLA-4
prolongs immune response