lecture 1- antibody effector functions

Question 1

Fc receptor on naive B cells called ___ prevents involvement of naive B cells in secondary responses when there’s a pre-existing antibody response against the pathogen

Answer 1

FcyRIIB1

Question 2

1- primary response: if naive B cells binds pathogen, this causes…
2- secondary: if naive B cells binds pathogen coated with specific antibody…
3- if memory B cell binds pathogen…

Answer 2

1- naive B cell activated- production of low affinity IgM antibodies
2- negative signal given to naive B cell to prevent activation- no production of low affinity IgM
3- memory B cell activated and becomes antibody-producing plasma cell - production of high affinity IgG

Question 3

describe what happens with Rh- mothers and Rh+ babies

Answer 3

first pregnancy: incompatibility, primary immune response- IgM and low-affinity IgG, fetal erythrocytes only have minor destruction because initial antibody response is not high affinity and not high affinity IgG

second pregnancy: if mom not treated and has another Rh+ baby, secondary immune response- high-affinity IgG –> massive destruction of erythrocytes –> anemic baby

• if mother is treated and infused with anti-Rh IgG : primary immune response is inhibited by presence of RhD-specific IgG –> fetal erythrocytes not destroyed –> healthy baby

Question 4

many antibody effector functions depend on specific ___

Answer 4

Fc receptors

Question 5

name 7 antibody effector functions

Answer 5

1- neutralization
2- complement fixation
3- immune complex formation
4- opsonization
5- triggers physical mechanisms of pathogen elimination
6- triggers allergic responses, mast cell degranulation
7- antibody dependent cellular cytotoxicity (ADCC)

Question 6

antibody functions sequentially

Answer 6

IgM produced first, pentameric, binds pathogen strongly and activates complement through classical pathway, b/c of large size, stays in bloodstream
- somatic hypermutation, affinity maturation, and isotype switching lead to production of high affinity IgG and monomeric IgA - smaller size of these allows them to leave bloodstream and enter sites of infection
- the receptor FcRN transports IgG from bloodstream to extracellular spaces

Question 7

which Fc receptor transports IgG from bloodstream to extracellular spaces?
explain

Answer 7

FcRN
- acidic pH of endocytic vesicle causes association of IgG with FcRN, protecting it from proteolysis

Question 8

infection in blood elicits what antibody responses?

Answer 8

IgM, IgG, monomeric IgA

Question 9

describe dimeric IgA

Answer 9

• dimeric IgA (held together by J chain) protects mucosal epithelial surfaces
• dimeric IgA made my plasma cells in lamina propria, but needs to be transported across epithelium by Poly Ig receptor (specific for IgA dimers and IgM pentamers because it binds to J chain)
• facilitates transcytosis of IgA

Question 10

which receptor transports dimeric IgA across epithelium

Answer 10

Poly Ig receptor

Question 11

name a few functions of dimeric IgA

Answer 11

• can export toxins and pathogens from lamina propria while being secreted
• able to neutralize antigens internalized in endosomes
• binds pathogen on M-cell surface and takes it to lymphoid tissue

Question 12

locations of dimeric IgA, IgE, IgG

Answer 12

dimeric IgA: respiratory, urinary, digestive, breast milk
IgE: skin and mucosal surfaces
IgG: only one that can cross placenta

Question 13

what happens to antibody levels in infant’s first year of life

Answer 13

declines in maternally transferred antibodies couples with development of their own IgM, IgG, IgA
- at around 3 months, start making own new antibodies (IgM first)

Question 14

pathogen/viral neutralization is done by what antibody

Answer 14

dimeric IgA

Question 15

what is meant by neutralization?

Answer 15

antibody getting in the way/interfering with the interaction between a virus and its preferred receptor on the surface (essential for its ability to infect cell)

Question 16

toxin neutralization- cholera

Answer 16

cholera toxin prefers to bind to a specific cell-surface protein, if neutralized, antibody binds to the part of toxin that wants to bind to receptor (toxin has been neutralized- cannot perform function)

Question 17

describe complement fixation

Answer 17

pentameric IgM is perfect ligand for C1q (classical path)
- initiation of class path by IgM binding to antigen on pathogen surface
- in absence of C1, wouldn’t have classical path- immune complex disease
- IgG also capable of fixing complement- binding of at least two molecules of IgG to pathogen is required for complement fixation

Question 18

describe immune complexes

Answer 18

protein complex formed by binding of antibodies to soluble antigens
- size of immune complex depends on concentration of antibody and antigen
- large complexes also coated with complement and cleared by phagocytes
- smaller complexes tend to accumulate in small vessel walls where they can activate complement and cause damage
. renal podocytes, leads to damage of glomeruli
. patients with deficiencies in early components of complement cascade (C1) cannot coat immune complexes with C4b and C3b and cannot remove them –> kidney damage

Question 19

most important Fc receptor for opsonization is ___, specific for this antibody, ___

Answer 19

FcyRI
IgG

Question 20

describe opsonization (antibody and Fc receptor)

Answer 20

phagocyte expressing FcyRI can bind to IgG that is bound to a pathogen –> leads to efficient internalization and destruction by killing of that microbe

Question 21

Fc receptor for allergic and anti-parasite responses is ___
antibody involved is ___

Answer 21

FcERI
IgE

Question 22

describe allergic and anti-parasite responses

Answer 22

IgE binds to mast cells through FcERI receptor (FcE) –> high-affinity interaction, when antigen they are specific for binds –> leads to degranulation and release of histamine –> variety of symptoms

• eosinophils

Question 23

Antibody-dependent cellular cytotoxicity is mediated by ___ cells that express this receptor ___ that can kill cells coated with ___

Answer 23

NK cells
FcyRIII (CD16)
IgG1 or IgG3

Question 24

the only Fc receptor expressed by NK cells

Answer 24

FcyRIII (CD16)

Question 25

ADCC mechanisms is purely dependent on…

Answer 25

antibodies coating a target cell and expression of FcyRIII

Question 26

FcyRI

Answer 26

opsonization- expressed by phagocytes- can bind to IgG

Question 27

FcyRIII (CD16)

Answer 27

expressed by NK cells - ADCC

Question 28

FcyRIIB

Answer 28

expressed by naive B cells preventing them from participation in secondary responses (inhibition)

Question 29

FcRN

Answer 29

expressed on vascular endothelium - moves IgG across endothelial layer - increased Ig half-life

Question 30

the four subclasses of IgG differ in the structure of the ___

Answer 30

hinge