[W5] Intro to Antibodies

Question 1

What are the two arms of the immune system?

Answer 1

Innate (natural) and adaptive immunity

Question 2

What are the two types of adaptive immune responses?

Answer 2

Humoral (B cells, antibodies) and cell-mediated (T cells)

Question 3

What is an antigen?

Answer 3

Any substance that binds specifically to an antibody or T cell receptor

Question 4

What is an epitope (antigenic determinant)?

Answer 4

The small, specific part of an antigen that interacts with an antibody or TCR

Question 5

What is another name for an antibody?

Answer 5

Immunoglobulin (Ig)

Question 6

What happens when an antibody binds to an antigen?

Answer 6

It facilitates antigen clearance or destruction

Question 7

In which serum fraction are most antibodies found?

Answer 7

Gamma globulin fraction

Question 8

What are the main components of an IgG antibody?

Answer 8

2 light chains (~25 kDa) and 2 heavy chains (~55 kDa)

Question 9

What is the molecular weight of IgG?

Answer 9

~160 kDa

Question 10

What are the functional regions of IgG?

Answer 10

Two Fab arms (antigen-binding) and one Fc region (effector function)

Question 11

How many antigen-binding sites does IgG have?

Answer 11

Two

Question 12

What does papain digestion yield?

Answer 12

Two Fab fragments and one Fc fragment

Question 13

What does pepsin digestion yield?

Answer 13

One F(ab’)₂ fragment (retains cross-linking ability)

Question 14

How many Ig domains are in IgG?

Answer 14

12 (4 from light chains, 8 from heavy chains)

Question 15

What structural motif do Ig domains share?

Answer 15

Conserved beta-barrel fold

Question 16

Name other members of the Ig superfamily.

Answer 16

• TCRs
• MHC molecules
• Fc receptors
• Integrins

Question 17

Where does antigen bind on an antibody?

Answer 17

At the tip of the Fab arm, in the hypervariable regions

Question 18

What are the CDRs?

Answer 18

Complementarity-Determining Regions — 3 on VH and 3 on VL

Question 19

How big is the antigen-binding cleft?

Answer 19

~2 × 1 × 0.5 nm — fits ~6 amino acids or sugars

Question 20

Name the four non-covalent forces in Ab-Ag binding.

Answer 20

• Ionic
• Hydrogen bonds
• Hydrophobic interactions
• Van der Waals forces

Question 21

Are these binding interactions reversible?

Answer 21

Yes — individually weak, collectively strong

Question 22

What is affinity in immunology?

Answer 22

Strength of binding between one antibody site and one epitope

Question 23

What is avidity?

Answer 23

Overall strength of multivalent Ab-Ag interactions

Question 24

What does Ka represent?

Answer 24

Association constant; higher Ka = stronger binding

Question 25

What is an immunogen?

Answer 25

A substance that can elicit an immune response

Question 26

What is an antigen?

Answer 26

A substance that can bind to an antibody (may not be immunogenic)

Question 27

What is a hapten?

Answer 27

A small molecule that binds antibodies but cannot elicit a response unless conjugated to a carrier

Question 28

How can a non-immunogenic hapten be made immunogenic?

Answer 28

By conjugating it to a carrier protein (e.g. DNP + ovalbumin)

Question 29

What does the carrier provide in hapten-carrier conjugates?

Answer 29

T cell epitopes, enabling full immune activation

Question 30

What is a linear epitope?

Answer 30

A continuous stretch of amino acids — survives denaturation

Question 31

What is a conformational epitope?

Answer 31

Non-contiguous residues brought together by folding — lost upon denaturation

Question 32

What kind of antibodies are produced during an immune response?

Answer 32

Multiple antibodies targeting different epitopes (polyclonal response)

Question 33

What’s the benefit of multiple antibodies binding an antigen?

Answer 33

Increased avidity and more effective clearance

Question 34

How many different antibody specificities can humans produce?

Answer 34

Around 10⁸

Question 35

Can each antibody be encoded by a separate gene?

Answer 35

No — the genome only has ~30,000 genes

Question 36

What explains antibody diversity?

Answer 36

Gene rearrangement — multiple segments recombine to form variable regions

Question 37

What is multiple myeloma?

Answer 37

A B cell cancer that produces excess homogeneous antibodies or light chains

Question 38

What are Bence-Jones proteins?

Answer 38

Light chains secreted in urine by myeloma patients — used to study antibody structure

Question 39

Who sequenced light and heavy chains?

Answer 39

Hilchman (light, 1965), Edelman (heavy, 1969)

Question 40

What did Wu & Kabat variability plots reveal?

Answer 40

Regions of high variability (CDRs) in antibody variable domains