lecture 3- antibody structure

Question 1

___ is the secreted form of B-cell receptor

Answer 1

immunoglobulin (antibody)

Question 2

describe BASIC structure of an antibody

Answer 2

2 identical heavy chains & 2 identical light chains
- multiple disulfide bonds, both intra- and interchain
- antigen binding site made of 1 heavy chain and 1 light chain
- structure allows for flexibility and binding for a range of antigens

Question 3

describe antibody structure in deeper understanding

Answer 3

heavy chain = 1 constant region &1 variable region
light chain= 1 constant region & 1 variable region
- Fc region = (fragment crystallizable), first to be cloned and sequenced – only a heavy, constant chain
- Fab = (fragment antigen binding) — variable and constant heavy chain & variable and constant light chain
- Fc associated with a receptor – Fc determined what kind of isotype

Question 4

the membrane-bound form of the BCR co-resides with signaling molecules _____

Answer 4

IgB (beta) and Iga (alpha)
without them, can’t signal or be expressed on cell surface

Question 5

antigen contact by antibody is mediated through the ___ of the heavy and light chains

explain

Answer 5

hypervariable loops
- antigen contacted by six hypervariable loops- 3 in light and 3 in heavy chain – called complementary determining regions (CDR)
- most of the diversity between antibodies is in these regions

Question 6

the highest number of antigen-antibody contacts are usually with this CDR region

Answer 6

CDR3

Question 7

where are the CDR regions?

Answer 7

at very distal end of molecule in antigen-binding site
- 6

Question 8

Fab segement gives antibody ___ and Fc gives it ___

Answer 8

specificity
function

Question 9

conformational determinant

Answer 9

Certain antibody specificities only work on folded proteins, when denatured, the antibody would not work- epitope would fall apart
- Determinant lost by denaturation

Question 10

name the 5 isotypes of antibodies

Answer 10

IgM
IgA
IgD
IgG
IgE

Question 11

name the isotypes that multimerize

Answer 11

IgM- pentamerize when with J chain
IgA- dimerizes when with J chain

Question 12

which is the first antibody isotype expressed

Answer 12

IgM

Question 13

Which region of the antibody molecule is changed when the cell switches isotypes?

Answer 13

Fc

Question 14

define affinity

Answer 14

how tightly one molecule binds to another molecuel

Question 15

define avidity

Answer 15

affinity (x) how ever many interactions there are- the collective affinities through multimeric interactions (dimeric IgA has twice the avidity as monomeric IgA)

Question 16

Which antibody isotype has the greatest avidity?

Answer 16

IgM

Question 17

function of IgA

Answer 17

transport across mucosa, neutralization

Question 18

function of IgD

Answer 18

antigen receptor on naive B cells, sensitizes basophils

Question 19

function of IgE

Answer 19

immediate hypersensitivity, sensitizes mast cells

Question 20

function of IgG

Answer 20

neutralization, opsonization, complement activation, neonatal immunity (crosses placenta)

Question 21

function of IgM

Answer 21

antigen receptor on naive B cells, complement activation

Question 22

Consider the implications of deficiency in any of the isotypes.

Answer 22

• Would lose the most functions if lost IgG
• IgM is the first, needed to facilitate isotype switching
• Without IgA- impairs mucosal immunity

Question 23

monoclonal antibody generation

Answer 23

• need a source of antigen-specific B cells
• can grow an infinite number of these B cells in vitro- generate antibodies
• were originally developed in mouse cells
• humanized antibodies now without mouse proteins

Question 24

the generation of antibody diversity is due to:
(the first 2)

Answer 24

1- combinational diversity (at core of gene rearrangement)
. multiple germ line segments
. multiple heavy and light chains
2- junctional diversity
.

Question 25

there are about ___ variable gene segments in heavy chain

Answer 25

40

Question 26

describe rearrangement events in heavy chain

Answer 26

(starts with germline DNA)
1- D + J unite
2- V joins DJ
3- becomes attached to constant region

Question 27

describe rearrangement events in light chain

Answer 27

(starts with germline DNA)
1- V + J join
2- join with constant regions