Antibodies & Immunoglobulins

Question 1

Regions of antibody

Answer 1

Fab

• Fragment, antigen binding
• determines idiotype (unique Ag-binding pocket/ only 1 antigenic specificity expressed per B cell)

Fc (Four Cs)

• Constant
• Carboxy terminal
• Complement binding
• Carbohydrate side chains (macrophage binding)
• Determines isotype (IgM, IgD…)

Question 2

Which is dependent on the type of antigen:

- generation of antibody diversity or generation of antibody specificity?

Answer 2

Generation of antibody specificity

Question 3

What is generation of antibody diversity?

Answer 3

Antigen independent

• Random recombination of VJ (light chain) or V(D)J (heavy chain) genes
• Random addition of nucleotides to DNA (by TdT terminal deoxynucleotidyl transferase)
• Random combination of heavy chains with light chains

Question 4

TdT (terminal deoxynucleotidyl transferase) is used as a marker for early stage T cell & B cell development in which disease?

Answer 4

Acute lymphoblastic leukemia

Question 5

What is generation of antibody specificity?

Answer 5

Antigen dependent

• Somatic hypermutation & affinity maturation (variable region)
• Isotype switching (constant region)

Question 6

Functions of antibodies

Answer 6

OPSONIZATION
Antibody promotes phagocytosis

NEUTRALIZATION
Antibody prevents bacterial adherence

COMPLEMENT ACTIVATION
Antibody activates complement → enhancing opsonization & lysis

Question 7

Somatic hypermutation & affinity maturation & isotype switching are antibody specificity or diversity?

Answer 7

Antibody specificity

Question 8

Random recombination of VJ (light chain) or V(D)J (heavy chain) genes
& random addition of nucleotides to DNA (by TdT terminal deoxynucleotidyl transferase) is part of antibody specificity or diversity?

Answer 8

Antibody diversity

Question 9

Which immunoglobulins do mature, naïve B cells express prior to activation?

Answer 9

IgM

IgD

Question 10

Which immunoglobulin is the main antibody in 2° (delayed) response to an antigen?

Answer 10

IgG

Question 11

Which immunoglobulin is the most abundant isotype in serum?

Answer 11

IgG

Question 12

IgG function

Answer 12

Fixes complement

Passive immunity in infants (crosses placenta)

Opsonizes bacteria

Neutralizes bacterial toxins & viruses

Question 13

Which immunoglobulin is most produced antibody overall?

Answer 13

IgA

Question 14

Which immunoglobulin has the lowest serum concentration?

Answer 14

IgA

Question 15

Which immunoglobulin is released into secretions (tears, saliva, mucus) & breast milk?

Answer 15

IgA

Question 16

IgA function

Answer 16

Prevents attachment of bacteria & virus to mucous membranes

Protects against gut infections (eg by Peyer patches against Giardia)

Protects Fc portion from luminal proteases (picks up secretory component from epithelial cells)

Question 17

How does IgA cross epithelial cells?

Answer 17

Transcytosis

(receptor-mediated uptake of a ligand on one side of the cell →
vesicular transport across the cell →
exocytosis of the vesicle contents on the opposite side. ‘trans: across/ through’)

Question 18

Which antibodies can fix complement?

Answer 18

IgM

IgG

Question 19

Which is the only antibody that can cross placenta?

Answer 19

IgG

Question 20

Which antibody has highest avidity?

Answer 20

IgM

Monomer on B cell → pentamer with J chain when secreted → ↑binding to antigen while humoral response evolves

Question 21

Antibody deficiency in babies whose mothers who don’t breastfeed them?

Which infections are common?

Treatment?

Answer 21

IgA

↑GI infections / diarrhea

Fortify milk/feed with IgA

Question 22

IgE function

Answer 22

Binds mast cells & basophils

Cross-links when exposed to allergen
→ immediate type I hypersensitivity
→ release of inflammatory mediators (histamine)

Activates eosinophils
worm immunity against helminths (ascaries, strongyloides, hookworms, trichinella)

Question 23

Which type of autoimmune hemolytic anemia is IgG associated with?

Answer 23

WARM autoimmune hemolytic anemia

(Warm: anti-RBC autoantibodies trigger extravascular hemolysis at body temp or higher. direct antiglobulin test is +ive at 37° C)

*cold hemolytic anemia is < 37° C (cold agglutinin disease)

Question 24

What are isotypes?

Answer 24

Differences in heavy chains
(IgG vs IgA vs IgE vs IgD vs IgM)

Different Fc region

Question 25

What are allotypes?

Answer 25

Allelic variation resulting in subtle differences in a single amino acid on the same antibody

Difference in species

Question 26

What are idiotypes?

Answer 26

Differences that happen between two of the same type of antibody in the same person within the variable region

Each idiotype recognizes a different part or different type of antigen

Question 27

What is meant by allelic exclusion?

Why is it important?

Answer 27

Expression of heavy chain gene product of either the maternal or paternal chromosome, but not both
-BCR is the product of a chromosomal rearrangement: only one allele is expressed and the other is shut down

(All of the B cell receptors on a given B cell are identical)

Ensures clonal specificity - each B cell produces only a single, unique receptor

Question 28

What is clonal specificity?

Answer 28

Each B cell produces only a single, unique receptor

Question 29

Which cytokine leads to the proliferation and expansion of immature T and B cell progenitors?

Answer 29

IL-7