Humoral Immunity II - Ab Effector Functions

Question 1

what designates Ab isotype

Answer 1

H chain

Question 2

what leads to B cells with IgM and IgD on the surface

Answer 2

alternative splicing

Question 3

what is the BCR?

Answer 3

surface IgM

Question 4

what occurs once a B cell encounters an Ag?

Answer 4

new IgM and IgD are produced in plasma cell and secreted

Question 5

first Ab secreted in response to any pathogen

Answer 5

IgM

Question 6

what is CSR

Answer 6

isotype switching, permits DNA recombination of rearranged V region with another H chain gene

Question 7

what drives IgG production?

Answer 7

IFN gamma

Question 8

what drives IgA production?

Answer 8

TGF beta

Question 9

what drives IgE production?

Answer 9

IL-4

Question 10

what drives IgM production?

Answer 10

IL-2, IL-4, IL-5

Question 11

when does CSR occur?

Answer 11

when GC B cells engage TFH cells, usually after affinity maturation

Question 12

what is produced when GC B cells engage TFH cells

Answer 12

cytokines and AID are produced

Question 13

describe the order of TFH and GC B cells interacting

Answer 13

1. TFH activated in interfollicular zone by DC
2. DC gives TFH signal 3
3. signal 3 triggers gene expression of corresponding cytokines to drive specific Ig isotype production

Question 14

what triggers cytokine production by TFH?

Answer 14

engagement of TFH with B cell or with FDC by ICOS

Question 15

what are switch regions

Answer 15

S regions are highly repetitive sequences that mediate recombination

Question 16

what activates AID

Answer 16

ligation of CD40 on GC B cells

Question 17

what directs AID to selected S regions?

Answer 17

TFH cytokines

Question 18

what does AID do

Answer 18

targets cytosines in S regions for deamination to uracil

Question 19

what happens to uracil that was produced by AID?

Answer 19

uracil dna glycosylase removes it, leaving a gap

Question 20

what makes a nick in the DNA strand where the gap is ?

Answer 20

APE1 (endonuclease)

Question 21

what occurs once there are nicks on both sides of the DNA strand

Answer 21

circular DNA is made, which is excised

Question 22

1st step of successful microbial infection

Answer 22

attachment to host tissues and colonization

Question 23

what is neutralization?

Answer 23

Ab prevent microbe attachment and therefore the infectious process

Question 24

where does influenza virus bind?

Answer 24

surface glycoproteins of respiratory epithelia via HA hemagglutinin

Question 25

what does the flu vaccine generate?

Answer 25

protective Ab (IgG) which are present in mucus of resp tract

Question 26

how does flu vaccine work?

Answer 26

IgG made are present in mucus of resp tract and bind to flu virus H and prevent attachment, virus is coughed up and swallowed, and destroyed in stomach

Question 27

how does neutralization of toxins work with vaccines?

Answer 27

vaccine formulates Ab that bind toxin, but don't prevent attachment and colonization. just prevent toxin

Question 28

how do Ab perform opsonization

Answer 28

IgA and IgG bind ag on microbe surface, and Fc receptors on the phagocytes bind Ab. this ligation promotes phagocytic uptake of the Ab coated microbe.

Question 29

what is antibody dependent cell cytotoxicity

Answer 29

1. NK cells express Fc gamma receptor that can be used to activate cytotoxic functions of NK

Question 30

steps of ADCC

Answer 30

1. Ab are attached to Ag on cell 2. NK cell FCgamma receptor binds to Fc regions of IgG1 or IgG3 3. ligation signals NK cells to release granzyme/perforin to induce apoptosis on target cells

Question 31

when is ACDD used?

Answer 31

parasitic worm killing! IgE binding to Fc epsilon receptor

Question 32

what cells express Fc alpha receptors for opsinization in mucosa

Answer 32

1. macrophage 2. neutrophil 3. eosinophil

Question 33

what cells express Fc epsilon receptors for degranualation

Answer 33

1. eosinophil 2. mast cell 3. basophil

Question 34

what cell expresses Fc gamma receptor for ADCC?

Answer 34

NK cell

Question 35

what cell expresses Fc gamma receptor for opsinization

Answer 35

macrophage

Question 36

what is the most common serum Ig

Answer 36

IgG1

Question 37

what are IgG used for?

Answer 37

1. neutralization 2. opsonization 3. complement activation 4. ADCC in NK cells

Question 38

what IgG can cross placenta

Answer 38

1,3,4

Question 39

what triggers CSR to IgG

Answer 39

IFN gamma

Question 40

how does IgG1-3 activate classical pathway of complement

Answer 40

pentameric structure of IgM activates complement 1. staple form permits C1 binding to Fc parts of IgM 2. C1q binding activates C1r which cleaves C1s, which cleaves C4 and C2. 3. C4b fragments covalently bond to pathogen surface 4. C2a fragments bind to C4b. 5. C4bC2a is classical C3 convertase! 6. C3 convertase cleaves C3 to C3b and C3a. 7. C3b binds to pathogen surface 8. C3bBb generated from fragments and coats surface with C3b

Question 41

what occurs once pathogen is coated with C3b?

Answer 41

neutrophils and macrophages can phagocytose using CR1

Question 42

what if phagocytosis is difficult?

Answer 42

membrane attack complex forms after C3b turns into C5 convertase

Question 43

how does IgG mediate activation of complement?

Answer 43

C1q crosslinks with 2 or more surface bound IgG to activate classical complement

Question 44

how are soluble Ag removed by IgG?

Answer 44

IgG has higher affinity than IgM, making stable immune complexes with soluble antigen

Question 45

what can immune complexes do?

Answer 45

activate classical pathway! and also develop during course of immune response

Question 46

what occurs if IC build up in small blood vessels or glomeruli?

Answer 46

complement activation due to IC can cause glomerulonephritis, increased neutrophil and macrophage recruitment, frustrated phagocytosis where they spew their contents into the environment and cause vasculitis and hemorrhaging

Question 47

how can RBC capture immune complexes?

Answer 47

IC activates complement, so they are coated with C3b. | RBC express CR1 and capture IC!

Question 48

how are IC removed from the blood stream?

Answer 48

1. RBC captures IC via CR1 attaching to C3b 2. blood passes through the spleen and liver 3. splenic macrophages use Fc receptor to attract IC 4. then produce protease to cleave RBC CR1 and eat it

Question 49

which IgG cross placenta?

Answer 49

IgG1, IgG3, Ig4

Question 50

what ab provide main protection for baby up to 1 year

Answer 50

IgG1, IgG3, IgG4.

Question 51

what Ab does fetus produce before birth

Answer 51

IgM but is not a lot

Question 52

what Ab is provided through breast milk

Answer 52

IgA to protect mucosal surfaces from infection

Question 53

what is the main function of IgA1 and IgA2

Answer 53

1. neutralization especially on mucosal secretion

Question 54

structure of IgA

Answer 54

1. secretory piece | 2. j chain

Question 55

what does secretory piece do on IgA

Answer 55

it is made by epithelia, translated from basolateral to luminal surface of epithelia, and protects from proteolysis

Question 56

what does J piece of IgA do

Answer 56

structural stability and aids in translocation

Question 57

how does secretory piece on IgA protect from proteolysis?

Answer 57

interacts with mucins in mucus and holds IgA in place in mucosa

Question 58

what does IgM do

Answer 58

1. complement activation | 2. agglutination of microbes (use in diagnostics)

Question 59

which is the first BCR expressed on naive mature B cells

Answer 59

IgM (monomer)

Question 60

which is the first Ig synthesized by B cells

Answer 60

IgM (pentamer)

Question 61

functions of IgE

Answer 61

1. immunity to parasites | 2. allergic responses

Question 62

what occurs in an allergic response?

Answer 62

basically, cell makes Th2 response instead of a Th1 response. 1. TFH makes IL-4 2. IgE released from Plasma cell 3. IgE binds to mast cell and eosinophil where allergen is 4. triggers degranulation immediately