Properties and Functions of Antibodies

Question 1

How do the two regions of an antibody relate to its function?

Answer 1

1. variable Fab region defines Ag specificity
2. constant Fc region defines function

Question 2

Why does an antibody have two Ag binding sites?

Answer 2

permits cross linking (forming immune complexes)
improves neutralisation and controls innate cell activation

is required to bind to and activate FcγR and FcαR
distinguishes Ab that are bound to pathogen/infected cell from free antibody

Question 3

Why can the Fc region change?

Answer 3

allows different effector functions

swapping constant Fc regions changes Ab function without changing specificity for Ag

Question 4

What is a difference in function between a membrane Ab and a secreted Ab?

Answer 4

secreted Ab = effector functions
membrane = cell surface Ag receptor

Question 5

How are IgM and IgD produced and what is their function?

Answer 5

only isotypes that can be produced simultaneously by a B cell
they are the first isotypes produced
are produced by differential RNA splicing

IgD = secreted in small quantities, function unknown
IgM = first response Ab

Question 6

What is Class/Isotype switching?

Answer 6

mechanism by which B cells start producing IgG. IgA, or IgE
irreversible change in DNA, once switched you cannot go back
can only produce one isotype at a time

Question 7

What cells control class switching?

Answer 7

Th cells
tell B cells which isotype to produce

Question 8

State the different antibody classes and their properties.

Answer 8

IgM = great complement fixer, first antibody made

IgA = resistant to stomach acid, protects mucosal surfaces

IgG = helps NK cell kill, can cross placenta

IgE = defends against parasites, causes allergies

Question 9

How does IgM make up for its lower affinity?

Answer 9

IgM forms pentamers via J chain

compensates for lower affinity (as they are produced prior to affinity maturation)
v good at binding repeating epitopes
v efficient at activating complement

(J chain is different from J gene segement)

Question 10

How is IgA adapted to mucosal surfaces?

Answer 10

forms a dimer via J chain which facilitates transport across intestinal epithelium
resistant to low pH and digestive enzymes
keeps pathogens away from epithelium by clumping them together for expulsion with faeces
Weak ADCC function and complement activation - avoids collateral damage in gut

Question 11

What is an FcR?

Answer 11

Fc Receptors
present on innate cells such as macrophages which bind to Fc region of Ab
gives specificity of adaptive immunity to innate immune cells
innate cell expression of FcR defines which Ab isotypes they work in partnership with and so defines effector function

Question 12

Different Ab isotypes bind different FcR. What are they?

Answer 12

FcγR - binds IgG (gamma binds G)
FcαR – binds IgA (alpha binds A)
FcεR – binds IgE (epsilon binds E)

Question 13

What is opsonisation and what antibodies induce it?

Answer 13

an immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes

opsonisers: IgG, IgA, (IgM via complement)
non-opsoniser: IgE

Question 14

How does IgE make innate cells into memory cells?

Answer 14

FcεR has high affinity for IgE
binds monomeric IgE (doesnt require Ag cross linking)
receptors become loaded w IgE
gives the mast cell an Ag-specific receptor

Question 15

How does somatic hypermutation select for B cell producing Ab w highest affinity for Ag?

Answer 15

after somatic hypermutation, B cell was tested to see if it can still bind its Ag:
1. loses ability to bind Ag - B cell dies
2. binds Ag with lower affinity - B cell survives but is outcompeted
3. binds Ag w higher affinity - B cell outcompetes those w lower affinity

Question 16

Define affinity maturation.

Answer 16

the overall process by which activated B cells increase their Ab’s affinity for Ag

Somatic hypermutation (100,000x greater mutation rate in V D J genes) occurs to slightly modify Ag binding region

Question 17

How is affinity maturation controlled so that self-reactive Ab’s are not created?

Answer 17

B cells require T cell permission to undergo affinity maturation and to survive thereafter

after affinity maturation a B cell must present the Ag it recognises to a T cell
- if T cell recognises the Ag, B cell is still microbe specific and is
allowed to survive
- if T cell no longer recognises the Ag then affinity maturation has likely changed the B cells specificity for Ag. B cell is no longer useful or is potentially self reactive so is deleted

Question 18

Membrane vs secreted Ab production?

Answer 18

Differential RNA splicing for transmembrane Ig vs secreted Ig gives them different carboxylate termini

Question 19

IgE specialisation?

Answer 19

FcR has high IgE affinity
Main antibody for linking with innate cells
FcR binds monomeric IgE (doesn’t require cross linking)
Gives mast cells Ag specific receptor
Aids in killing helminths
Doesn’t opsonise

Question 20

How do Clonal expansion, isotype switching and affinity maturation for together?

Answer 20

B cells activated and migrate to germinal centre
B cell proliferation
Somatic mutation, affinity maturation and isotype switching occur
Exit of high affinity antibody secreting cells and memory cells

Question 21

Difference in antibodies in primary and secondary response?

Answer 21

Increased number of Ag specific B cells present
B cells usually class switched to IgG,A, or E
Ab produce by B cells has higher Ag affinity

Question 22

What are the antibody isotypes?

Answer 22

IgA
IgD
IgE
IgG
IgM

= MAGED 🦑
So true 🐮

Question 23

Why does IgA have higher affinity?

Answer 23

Peyer’s patch (gut immune centres) B cells have higher rates of somatic hypermutation

Question 24

Components of mucosal immunity?

Answer 24

Gentler approach
Tight junctions prevent epithelium penetration
Mucus layer prevents microbes reaching epithelium
Anti microbial peptides in mucus layer damage microbes that get too close
IgA gentler activity

Passive approach allows living with commensals