Lecture 9

Question 1

What are two functions of antibodies?

Answer 1

Bind specifically to pathogens
Recruit other cells to destroy the pathogens

Question 2

What is the structure of a B Cell Receptor (BCR)

Answer 2

Y shape, two heavy chains and two light chains joined by disulfide bonds so that each heavy chain is linked to a light chain, and the two heavy chains are linked together

Question 3

What is avidity?

Answer 3

total strength of interaction

Question 4

What is affinity?

Answer 4

Strength of interaction between single antigen-binding site and its antigen

Question 5

What is the difference between the membrane and secreted form of BCRs?

Answer 5

portion of carboxyl terminus of heavy chain C region is hydrophobic on BCR, hydrophilic to allow secretion on antibody

Question 6

What is the Ig domain?

Answer 6

similar but not identical sequence of 110aa, 2 on light, 4 on heavy

Question 7

How many isotypes of constant region of antibody are there?

Answer 7

5: IgM, IgD, IgG, IgA, IgE

Question 8

What is the purpose of IgM?

Answer 8

first responder

Question 9

What is the purpose of IgD

Answer 9

Naive B cells, mostly surface

Question 10

What is the purpose of IgG

Answer 10

Most abundant, long-term protection

Question 11

What is the purpose of IgE

Answer 11

Allergy

Question 12

What is the purpose of IgA

Answer 12

Mucosal site, breastmilk

Question 13

What does the Fc region do?

Answer 13

can bind to C1q complement protein and initiate classical complement cascade, which recruits/activates phagocytes to engulf and destroy pathogens

Question 14

What do Fcγ receptors do?

Answer 14

expressed on surface of macrophages, neutrophils bind Fc portions of antibodies, facilitating phagocytosis of pathogens coated with antibodies

Question 15

How does IgE interact with mast cells?

Answer 15

Fc region of IgE binds to Fcε receptor on mast cells, basophils, activated eosinophils, triggering the release of inflammatory mediators in response to antigens

Question 16

What is the first class of Ig secreted after B cells are activated? What form is it secreted as?

Answer 16

IgM, secreted as a pentamer

Question 17

How does the shape of IgM help it?

Answer 17

Increases avidity for antigens before its affinity is increased through affinity maturation and hypermutation

Question 18

How does having multiple binding sites help an antibody?

Answer 18

dissociation rates will be slower due to improvement in overall binding strength

Question 19

Where is IgA found? In what form?

Answer 19

mucosal surface, gut, respiratory, and breastmilk
Dimer in mucosal surface, monomer in plasma

Question 20

In what form does IgA get transported through the epithelial cell?

Answer 20

dimer

Question 21

How can antibodies get delivered to places they could not reach without active transport? Examples?

Answer 21

Fc portion can deliver! poly Ig receptor or neonatal Fc receptor (FcRn)
ex: IgG from mother into fetal blood

Question 22

How do hypervariable regions form the antigen-binding site?

Answer 22

Location in the Gene sequence: small, specific sections in variable (V) domain

Loop structures in protein: hypervariable regions form loops extending outward from
β strands of Ig domain

Formation of the binding pocket: loops fold into compact domain, creating unique surface

Proximity: hypervariable loops from both chains come together at the tip of each arm

Question 23

What are hypervariable regions also called?

Answer 23

complementarity-determining regions (CDRs)

Question 24

Describe pocket binding

Answer 24

antibody has a deep pocket where a small molecule (hapten) fits snugly

Question 25

Describe groove binding

Answer 25

antibody forms a long groove where a peptide or small protein fragment can bind

Question 26

Describe extended surface binding

Answer 26

antigen and antibody fit together over a large, flat area

Question 27

Describe protruding surface binding

Answer 27

some antibodies have long loops that stick out and interact with deep pockets in the antigen

Question 28

What is a linear epitope?

Answer 28

continuous sequence of amino acids, antibody recognizes this sequence even if the protein is denatured

Question 29

What is a conformational epitope?

Answer 29

discontinuous, formed by amino acids that are far apart in the linear sequence but come together in folded structure, antibody binds only when protein is properly folded

Question 30

What determines antibody binding vs release?

Answer 30

affinity (for single binding and single epitope), avidity (total binding strength when multiple binding sites), conformational fit and stabilizing noncovalent interactions, pH/salt/temperature, competition

Question 31

What must happen to an antigen for it to be directly recognized by TCRs?

Answer 31

protein must be unfolded, processed into peptide fragments, presented by an MHC

Question 32

What is the antigen-binding portion of the T-cell receptor?

Answer 32

αβ heterodimer

Question 33

How do TCRs respond with only one antigen binding site?

Answer 33

TCRs are never secreted, αβ T cells respond to short, continuous amino acid sequences

Question 34

MHC Class I molecules

Answer 34

made of 2 polypeptide chains, only α spans membrane peptide-binding groove binds ~8-10aa long expressed on all nucleated cells presents intracellular antigens processed by proteasome

Question 35

MHC Class II Molecules

Answer 35

made of α and β polypeptide chains, both span membrane peptide-binding groove open ended ~13-25aa long expressed on antigen-presenting cells (APCs) like dendritic, macrophage, B presents extracellular antigens degraded in endosomes/lysosomes

Question 36

How do CD4 and CD8 work together?

Answer 36

act as co-receptors that bind to invariant sites on MHC molecules to stabilize TCR-MHC complex, improving T cell activation

Question 37

What cells are able to activate naive CD8 T cells? Why?

Answer 37

professional APCs (like dendritic) because they provide costimulatory signals (CD80/CD86)