Exam 2 Lecture 12: Antibody Function

Question 1

Form and function of IgM

Answer 1

Primary response
Second highest concentration in blood
Secreted as pentamer, 10 antigen binding sites, strong binding
Activates classical complement cascade
Bulky, difficult to get out of blood and to infection or placent

Question 2

Which antibodies provide defense in the blood

Answer 2

circulating: IgM (pentameric), IgG, IgA
Protect against blood borne infections and septicemia

Question 3

Which antibodies provide mucosal immunity

Answer 3

Dimeric IgA, pentameric IgM
Includes GI, eyes, nose, throat, lung, urinary tract, genital tract, mammary glands
Antibodies produced in MALT
Transported to mucosal lumen by polymeric Ig receptor (plgR)

Question 4

Polymeric Immunoglobulin receptor

Answer 4

aka plgR or Poly-IgR
Chaperone
Binds IgA or IgM and transports across epithelium (MALT) to mucosal lumen
Leaves secratory piece of receptor behind to retain antibody in mucosa and degraded (one time trip)

Question 5

Transcytosis

Answer 5

Receptor mediated transport of a macromolecule from one side of a cell to the other
ex. Poly-IgR

Question 6

Form and function of IgA

Answer 6

Dimeric (4 binding sites)
Mucosa

Question 7

Form and function of IgG

Answer 7

Highest concentration in blood
Monomeric (2 binding sites)
High affinity
Able to enter tissues
4 subclasses distinguished by: length of hinge region, number disulfide bonds, conformational flexibility
Transported out of blood vessels by FcRn

Question 8

Function of FcRn

Answer 8

Chaperone
Transports IgG out of blood vessel through endothelial cells
Prevents IgG lysomal degradation

Question 9

Form and function of IgE

Answer 9

Monomeric
Defends against parasites, causes allergies
Binds to FcεRI and functions as cell-surface receptor
Made in very small amounts
Non soluble
FcεRI on mast cells, eosinphils, basophils “pre-loaded” with IgE
Direct parasite killing

Question 10

FcεRI

Answer 10

IgE binds to FcεRI > FcεRI on APCs (?) lead to internalization and antigen presentation
FcεRI cross-linking lead to activation, degranulation, histamine release by: mast cells, basophils, eosinophils
Histamine release: sneeze, cough, vomit, diarrhea, smooth muscle contractions

Question 11

Which antibodies can be passively transferred

Answer 11

IgG reaches fetal circulation during pregnancy
Dimeric IgA transferred to infants through breastmilk

Question 12

Form and function of IgD

Answer 12

Monomeric
Very low serum levels
Co-expressed with IgM on mature B cells
Function unknown

Question 13

Regions of an antibody

Answer 13

Fab:
Fragment antibody binding
“the arms”

Fc:
Fragment Crystallizable region
“the stem”

Question 14

Fab Region

Answer 14

Made of paired heavy and light chain, contains variable region
Determines specificity
Allows to bind
3 hypervariable regions of each chain that bind with antigen directly: CDR1. CDR2, CDR3

Question 15

Fc Region

Answer 15

Made of all heavy chain and only constant region
Important for effector function/biological activity

Question 16

How are antibodies transported from where they are produced to where they are needed

Question 17

How do antibodies (adaptive response) collaborate with the Innate response through complement activation and Fc receptor binding

Question 18

How do antibodies inhibit viral and bacterial infection

Answer 18

IgA: high affinity neutralizing antibodies (NAbs)
NAbs or BNAbs block viral and bacterial infections
NAbs block viral entry and prevent bacterial surface adherence

Question 19

How do antibodies neutralize toxin and venom

Answer 19

Performed by IgA and IgG
Some vaccines (diphtheria, tetanus) elicit antibodies that neutralize toxins rather than pathogens
Anti-venom products are antibodies that bind to venom proteins to neutralize them as form of passive transfer

Question 20

What do Fc receptors bind

Answer 20

IgE binds FCε
IgA binds FCα
IgG binds FCγ

Question 21

Fcγ receptors: where are they expressed and what are their functions

Answer 21

Expressed on neutrophils, granulocytes, macrophages, DCs, NK cells
FcγRI: high affinity, pathogen uptake & degradation
RII & RIII: lower affinity, binds cross-linked IgG, activating or inhibiting forms
RIII: expressed by NKs, responsible for ADCC (antibody-dependent cell-mediated cytotoxicity)

Question 22

What are some unusual antibody types in different species and how might they serve as useful therapeutic tools

Answer 22

Camelid:
heavy chain only Abs adapted to become nanobodies
Only one binding site
Nb’s can be used to bind cytokines, drugs, nanoparticles, viruses etc.
Used for COVID

Bovine:
Very long CDR3 Abs
Very long variable domain, folds into ball & stalk structure
Ball highly variable and binds antigen
Could provide better protection against some diseases like HIV

Question 23

How can antibodies activate complement cascade

Answer 23

Pentameric IgM > classical
2 or more IgG
Immune complexes cleared via CR1 (complement receptor 2) mediated binding