B Cells 8

Question 1

What are the 6 key functions of Ab?

Answer 1

1. neutralization
2. opsonization
3. complement + MAC –> phagocytosis, lysis
4. ADCC on NK cells –> apoptosis of infected cells
5. ADCC on granulocytes –> Ab binds pathogen, then degranulation
6. transport

Question 2

what allows Igs to do their roles?

Answer 2

Fc receptors

Question 3

what are Fc receptors?

Answer 3

transmembrane receptors that bind the Fc portion of Igs

Question 4

what cells are Fc receptors found on? (7)

Answer 4

1. macrophages
2. granulocytes
3. DCs
4. mast cells
5. B cells
6. epithelial cells
7. neutrophils

Question 5

what is each FcR specific for?

Answer 5

specific for the constant Fc region of one class of Ig

Question 6

what is important to trigger signaling?

Answer 6

crosslinking FcR

Question 7

what is crosslinking?

Answer 7

more than 1 FcR binds an Ab that is bound to an Ag –> must occur to have signaling

Question 8

what are the 4 roles of FcR?

Answer 8

1. degranulation
2. opsonization
3. transport/maintenance of serum Ab levels
4. ADCc

Question 9

how do FcR bridge the gap btwn adaptive and innate?

Answer 9

allows non-specific immune cells to take advantage of antigen-specific antibodies

Question 10

describe how opsonization works

Answer 10

aggregation of Ag binding will allow crosslinking of FcRs on phagocyte surface –> triggers intracellular signaling for phagocytosis

Question 11

what Ab are involved in opsonization?

Answer 11

IgG

Question 12

does free IgG trigger opsonization?

Answer 12

no!! it can bind FcR but without Ag there is no signaling

Question 13

since opsonization requires aggregation of IgG, what does this mean about the number of epitopes required?

Answer 13

for opsonization, the phagocyte must have multiple epitopes on its surface to allow multiple IgG to bind and aggregate, thus allowing crosslinking

Question 14

describe IgG subclasses

Answer 14

subclasses have distinct effector capabilities: some are good at complement fixation, some are good at ADCC by NK cells

but ALL bind to FcR and allow opsonization

Question 15

describe ADCC on NK cells

Answer 15

1. IgG binds antigen on surface of target cell
2. NK cells have FcRs for IgG –> FcR recognizes IgG
3. crosslinking –> signaling
4. NK cell releases toxic granules –> apoptosis

Question 16

describe ADCC vs innate activation of NK cells

Answer 16

ADCC requires IgG, innate requires absent MHC I as activating signal

both release the same toxic granules to kill

Question 17

when is ADCC required instead of innate activation of NK cells?

Answer 17

normally, our cells present self-protein to show they’re healthy BUT if a virus hijacks this machinery, viral proteins will be presented and act as epitopes, allowing ADCC and the cell can still be killed

Question 18

what is IgE involved in?

Answer 18

allergy, asthma, helminths, protozoa

Question 19

is IgE made in large or small quantities?

Answer 19

small quantities, but potent effects

Question 20

what is the role of IgE?

Answer 20

induce degranulation of eosinophils, basophils, mast cells to damage large pathogens

Question 21

describe eosinophil and mast cell activation

Answer 21

1. TH2 cytokines activate eosinophils and mast cells
2. IgE binds FcR on eosinophils and mast cells
3. IgE can bind Ag and degranulate

Question 22

describe mast cells at baseline

Answer 22

they do have IgE bound to FcR at baseline but not crosslinked –> no signaling

Question 23

what types of things can be neutralized?

Answer 23

1. toxins
2. viruses –> internalized
3. intracellular bacteria

Question 24

what Ig classes are involved in neutralization? what do they do?

Answer 24

IgG and IgA bind to toxins/pathogens to prevent them from binding their targets

Question 25

where is IgA found (4)?

Answer 25

1. mucous in gut 2. milk from mammary glands 3. tears 4. saliva

Question 26

describe neutralization of toxins

Answer 26

normally, toxin binds cellular receptors and is endocytosed where it has toxic effects Ab binds toxin to BLOCK binding to cellular receptor

Question 27

describe neutralization of bacteria

Answer 27

Ab block colonization of bacteria

Question 28

describe neutralization of viruses

Answer 28

Ab binds virus, blocking binding to virus receptor and fusion

Question 29

what is the result of complement activation?

Answer 29

forms MAC, inflammation, and/or opsonization

Question 30

what complement pathway is involved in complement activation by Ab? how does it work

Answer 30

classical C1q can bind Ab on pathogen surface, triggering signaling cascade to make C3 convertase and cleave C3 --> C3a + C3b

Question 31

how can Ab link adaptive to innate?

Answer 31

thru classical pathway of complement

Question 32

which 2 types of Ig can trigger complement cascade? which is most effective?

Answer 32

IgM and IgG IgM most effective for complement

Question 33

why is IgM most effective for complement? (5)

Answer 33

1. first Ab produced 2. lower affinity --> no SHM 3. pentavalent --> 10 binding sites! makes up for lower affinity 4. good place for C1q to bind 5. forms dense Ab-pathogen complexes that are efficiently engulfed

Question 34

why are FcRs important for transport?

Answer 34

allow targeting of diff Ig classes to diff parts of the body

Question 35

where are IgA, IgE, and IgG each located?

Answer 35

IgA --> found in mucosal tissue, breast milk (passive immunity) IgE --> near epithelial surfaces IgG --> widely distributed everywhere in serum, in fetus

Question 36

what Ab do newborns have in circulation?

Answer 36

IgG

Question 37

how do FcRs allow Ig transport across barriers

Answer 37

ex. Ab bind epithelial surface, endocytosed, then released on the opposite side

Question 38

where is IgD found?

Answer 38

a minor (0.2%) component of blood but is present in higher levels in secretions of upper respiratory tract

Question 39

what is the function of IgD?

Answer 39

bind basophils and mast cells so they release AntiMicrobial Peptides (AMPs), cytokines, and chemokines (not well understood)