1 Antibody Structure and Function

Question 1

T-F–antigen receptors expressed by adaptive cells recognize a small diversity of antigens?

Answer 1

False–large diversity

Question 2

Does the innate or adaptive immune system use pattern recognition as the infection sensing system?

Answer 2

Innate–receptors are limited and have fixed specificities and recognize only a finite number of microbial products

Question 3

What molecules within B cell receptor complexes mediate antigen recognition and cell activation?

Answer 3

antibody molecules

Question 4

What component dictates the antigen specificity of the BCR?

Answer 4

membrane-bound forms of antibodies component –variable region is key to diversity

Question 5

Does engagement of one BCR complex by antigen lead to activation and the generation of antibodies?

Answer 5

No-multiple complexes engaging signal transduction along with other signals

Question 6

What is the antigen specificity of antibodies determined by in developing B cells?

Answer 6

Gene rearrangement

Question 7

What stage of B cell development rearrange genes encoding antibody components?

Answer 7

B cell progenitors– [more about this is later lecture]

Question 8

T-f–each B cell clone expresses an antibody with a unique antigen specificity?

Answer 8

True

Question 9

Are there a few different B cell clones produced or many? Why?

Answer 9

Millions

-produce antibodies specific to virtually any antigen

Question 10

coding sequences assembled by gene rearrangement make up what in the BCR complex?

Answer 10

antibody antigen binding sites

Question 11

T-F—antibodies recognize a variety of molecule as antigens?

Answer 11

True—proteins, nucleic acids, carbs, lipids

[NOTE: BROAD SPECIFICITY INCREASES ABILITY TO DETECT AND COMBAT MICROBIAL INFECTIONS]

Question 12

T-F—TCRs can recognize a variety of molecules as antigens?

Answer 12

False—only recognize peptide-MHC complexes as antigens

Question 13

Engagement of the BCR by antigen and activation of B cell leads to the production of what?

Answer 13

soluble antibodies

Question 14

What is the main role of B cells in immune response?

Answer 14

recognize and respond to antigen and produce soluble antibodies?

Question 15

What is the role of antibodies?

Answer 15

seek out and bind to antigens which initiates pathways to remove bound material

Question 16

T-F— costimulatory signals are not needed in B cell activation?

Answer 16

False

Question 17

Activated B cells proliferate and differentiate into?

Answer 17

antibody secreting cells

Question 18

How do soluble antibodies distribute throughout the body?

Answer 18

passage through bloodstream

Question 19

Antibodies are what shaped molecules?

Answer 19

Y

Question 20

What is the makeup of the main shape of the antibody?

Answer 20

2 identical heavy chains

2 identical light chains

Question 21

What holds the molecules together between anybody chains?

Answer 21

disulfide bonds

Question 22

What do covalently linked carbohydrate chains to heavy chains do?

Answer 22

maintain antibody structure and stability—can influence function of the molecule

Question 23

What are the 2 distinct functional domains of antibodies?

Answer 23

variable[Fab] and constant[Fc]

Question 24

How many variable regions are there in antibodies?

Answer 24

2

Question 25

amino acids in V regions are encoded by ?

Answer 25

randomly joined gene segments

Question 26

T-F--constant region formed by N termini of heavy chains?

Answer 26

False--C-termini

Question 27

What dictates the mulimerization state, anatomic localization and effector function?

Answer 27

Constant region

Question 28

What does Fab stand for?

Answer 28

fragment of antigen binding

Question 29

What does Fc stand for?

Answer 29

fragment crystallizable---form crystals when stored at cold temperatures

Question 30

T-F---at the gene level, V regions are encoded by portions of the heavy and light chain genes that are generated by gene rearrangement?

Answer 30

True

Question 31

T-F---within the V region, the C-termini of the heavy and light chains form a composite surface that mediates antigen binding?

Answer 31

False---it is the n-termini

Question 32

What are segments in V regions that are highly diverse in the A.A. content and mediate direct contact with antigens?

Answer 32

complementarity determining regions (CDRs)

Question 33

How can the antigen affinity of V regions be increased?

Answer 33

somatic mutation | affinity maturation

Question 34

What alters DNA sequences encoding V regions, resulting in AA changes within the antigen binding pocket?

Answer 34

somatic hypermutation

Question 35

What selects for B cell clones expressing antibodies with high affinity for antigen due to somatic hypermutation?

Answer 35

affinity maturation

Question 36

What does high affinity for antigen increase?

Answer 36

stability and duration of antigen-antibody interactions

Question 37

What do C regions dictate?

Answer 37

tissue distribution multimerization state antibody effector function

Question 38

How are human antibodies classified?

Answer 38

based on constant regions

Question 39

Where are IgM mostly found?

Answer 39

blood

Question 40

What is the most abundant Ig in body?

Answer 40

IgG-- distributes to blood and tissue

Question 41

Where is IgE mostly found?

Answer 41

little in blood mostly in tissues bound to mast cells

Question 42

Where is IgA mostly found?

Answer 42

some in blood, but mainly secreted across epithelial layers lining respiratory and digestive tracts

Question 43

What Ig is expressed by mature B cells, integrated into BCRs and secreted very little?

Answer 43

IgD

Question 44

What do naive B cells express?

Answer 44

IgM and IgD

Question 45

Antibody secreting cells express?

Answer 45

IgG, IgA or IgE

Question 46

Activated B cells with T cell help will do what to heavy chain?

Answer 46

will recombine DNA encoding the heavy chain

Question 47

T-F---generally, B cells that undergo class switching also undergo somatic hypermutation and affinity maturation

Answer 47

True

Question 48

What antibody is transferred across placenta?

Answer 48

IgG

Question 49

What Ig forms pentamer?

Answer 49

IgM

Question 50

What Ig forms dimers?

Answer 50

IgA

Question 51

Infants receive what Igs from mother?

Answer 51

IgA (breast) and IgG (placenta)

Question 52

What type of bonds holds together antibody dimers and pentamers? Where does the multimerization occurs?

Answer 52

- cysteine bonds with the J chain help | - occurs during transit through ER and Golgi

Question 53

What are the 5 pathways antibodies promote clearance of microbes?

Answer 53

- agglutination - neutralization - activation of complement cascades - Fc Receptor-mediated opsonophagocytosis - antibody-dependent cytotoxicity

Question 54

What traps microbes in a complex preventing cell-cell contact and colony formation/replication?

Answer 54

agglutination

Question 55

What blocks contacts with host molecules and cells impeding attachment or entry into cells?

Answer 55

agglutination

Question 56

Agglutinated materials are targets for what?

Answer 56

phagocytes

Question 57

What Ig is very effective for agglutination?

Answer 57

IgM--10 antigen sites per pentamer

Question 58

What does antibody neutralization do?

Answer 58

- block interactions with host cell receptors and eventual entry - prevent toxins from entering cells

Question 59

Neutralized material will eventually…?

Answer 59

be ingested by phagocytes

Question 60

Are monomers better for neutralization?

Answer 60

Yes

Question 61

Antibodies bound to surfaces can be recognized by what component of the complement system?

Answer 61

C1q

Question 62

Antibody-C1q interaction induce a conformation change in the C1 complex…what does this activate?

Answer 62

C1s and C1r proteases

Question 63

What does C1s generate?

Answer 63

C4b and C2a creating classical C3 convertase

Question 64

The C3 converses lead to what deposition?

Answer 64

C3b

Question 65

Deposition of C3b will drive formation of what?

Answer 65

- membrane attack complex--->cell lysis | - macrophage and neutrophil phagocytosis

Question 66

T-f---antibodies alone on the surface can be recognized by Fc receptors expressed on phagocytes?

Answer 66

True---multiple contacts will lead to phagocytosis

Question 67

Can monomeric or soluble antibodies activate cells via Fc receptors?

Answer 67

No

Question 68

T-f---infected cells often express microbial antigens on their surface?

Answer 68

True

Question 69

T-F---NK cells have Fc receptors that can recognize bound antibodies?

Answer 69

True---activation leads to cytotoxic function of NKs | [imporatant for virus or intracellular bacteria]

Question 70

What antibody is critical for early antibody responses and defense against extracellular microbes?

Answer 70

IgM

Question 71

Does IgM have a high or low affinity for antigen?

Answer 71

relatively low

Question 72

Surface bound IgM activates what>

Answer 72

complement pathway cascade

Question 73

Do IgG have a high or low affinity?

Answer 73

High----have a long half-life

Question 74

What are the main differences between IgG subtypes?

Answer 74

- hinge region - ability to fix complement - affinity for Fc receptors

Question 75

IgG3, IgG2, IgG4 and IgG1 is ordered in what order for ability to fix complement?

Answer 75

IgG3>IgG1>IgG2>IgG4

Question 76

IgG antibodies can engage 5 of 5 major B cell effector pathways?

Answer 76

false---4 of 5 - complement pathway - Fc mediated phagocytosis - neutralization - Ab dependent cytotoxicity

Question 77

Does IgA have high or low affinity?

Answer 77

generally high

Question 78

How does IgA chiefly function (main effector model)?

Answer 78

neutralization

Question 79

IgE has high or low affinity?

Answer 79

High

Question 80

T-F---IgE bind constitutively to IgE receptor expressed on mast cells

Answer 80

True---multiple IgE antigen contacts leads to activation