Chapter 7 b) SHM, isotypes, GC Flashcards

1
Q

what are the parts of the GC

A

the light zone - FDC and ag-specific B cells

the dark zone - Ag specfic B cells

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2
Q

where does B cell activation occur

A

GC

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3
Q

describe cell movement in the GC

A

the dark zone and the light zone approach eavh other so that FDC carrying Ag are able to combine with Ag-specific B cells

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4
Q

are GC homogenous or heterogenous?

A

heterogenous

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5
Q

explain the Somatic hypermutation (SHM) process, it’s purpose, where it occurs, etc

A

so somatic hypermutauion / affinity selction occurs in the GC

it produces point mutauions in the Ig heavy and light chain rearragamnets
- based on these points mutations selection is done for increased affinity for Ag over time

The point mutaions are done by the presence of activation -induced cytosine demainase (AID)
- this is able to create point mutauions by replacing cysteidine with urancil, whihc is recognized as incorrect thus we try to fix this mistake and in doin so we create mutations, of whihc the one with higher affinity will be selcted for

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6
Q

explain the movement of B cells in the GC

A

in the T cell zone
- naive B cells are fully activated with T helper cells and Ig memory cells are created as well as the primary focus

TD antigen activation B cell enter the GC and proliferation and SHM occur

from here those that interact with self die by apaoptosis

cells that don’t interact with T helper cells or interact with FDC die of neglect

cells that recive co-stimulatory signals from T helper cells undergo proliferation, CSr and SHM and differentiate into memory cells or plasmablasts (these scret Ab and proliferate)

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7
Q

what is CSR?

A

class-switch recombination (CSR), is a biological mechanism that changes a B cell’s production of immunoglobulin from one type to another

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8
Q

what is affinity vs avidity

A

affinity is the stregth of one binding sight between the 1 Fab region and the antigen
- undergoes affinity maturation to increase the binding interaction
- affintiy of IgG>IgM
- only bi-valent

avidity is the total binding affinity of 1 ab
- IgM is a pentamer so it increases it’s avidity becasue there are more binding sites
- does not undergo affinty maturation

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9
Q

what is afiiinty maturation?

A

Ab affinity increases as response continues: CDRs undergo SHM

B cells with low affinity are excluded from interaction with T helper cells in GC

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10
Q

what are CDR’s?

A

Complementarity-determining regions (CDRs) are immunoglobulin (Ig) hypervariable domains that determine specific antibody (Ab) binding.

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11
Q

where does SHM occur?

A

dark zone

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12
Q

what is class switch recombination? whos it regulated by? what’s it do? how does it affect antigen binding? what directs it?

A

regulated by T cells
causes a change in the isotype produces by B cell
antigen binding specificity does not change
cytokines direct the switch

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13
Q

for isotypes is the light chain or heavy chain reponsible for the isotype?

A

the heavy chain changing is what determines the isotype

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14
Q

for istopes how do sub-classes exist/

A

sub class exist based on how the heavy chain pairs with either the kappa or lamba light chains

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15
Q

talk about the IgM

A

pentamer

Location:
blood (serum)
first Ig produced in immune response

Function:
most efficient in activating the complement system
Ag agglutination
natural antibodies

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16
Q

talk about IgG

A

location:
bloods, lymph also tissues
longest half life

Function:
four subclasses in mice and humans
precipitaion of antigen (agglutination)
- neutrlaizes toxins
- immobilizes bacteria
- neutrlaizes viruses
opsonization
ADCC
actiavtes complemnt

  • only one that cross placenta
    -produced in memory response
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17
Q

talk about IgA

A

dimer

Location:
secreions - dimer
in serum is a monmer

fucntion:
primary defence against local respiratory or gastro-intestinal infections

has a secretiry compoentn

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18
Q

talk about IgE

A

location:
in the serum, lowest concentration and half-life

Function:
binds with high affinity to mast cells and basophils
hypersenitivity reaction(allergy)

play a role in protection against parasites

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19
Q

talk about IgD

A

location:
serum in low amounts
secretions in upper respiratory tract

Fucntion;
co-expression with IgM on surface of B mature, naive B cells (IgD>IgM)

binds to mast cells and basophils upson Ag binding increase release of antimicrobial peptides and cytokines

20
Q

Explain how IgE binds to cells

A

IgE binds to the Fc receptors of mast cells, with the allergen attached to the cell

this causes degranukation and the release of granule contencts such as histamine and other substances

21
Q

can CSR occur outside the GC

A

yes

22
Q

what aids in CSR?

A

the AID - activation induced deaminase replaces the RAG

and we need switch pitns

23
Q

what should be noted about expressing IgD and IgM?

A

No swithc after C delta so different RNA processing making it possible to have both IgM and IgD not possible for any other isotype

this occurs in the spleen

24
Q

differences between naive b cells and memory B cells

A

naive
IgM IgD
low complemnt recpetor
location - speleen, LN, circulation
lower averge receptor affinity
needs co-stimulation

memory
IgM IgG IgA IaE
high complemnt recptors
location - circulation
high average receptor affinity
doesn;t need t cell stimulation

25
Q

whats the difference between an antigen and an immunogen

A

antigen - substance capable of binding to components of the immune repsonse, B cells, T cells antibody

immunogen - illicits a immune response

all immungens are antigens but not all antigens are immunolgens

26
Q

all proteins are antigenic or immunologenic?

A

immunogenic

27
Q

what are the 4 requirements for immunogenicity?

A
  1. foreigness
  2. high molecular weight
  3. chemical complexity
  4. degradability
28
Q

the more foreign a substance the more what?

A

immunogenic it is

29
Q

what should we know about molecular weight

A

<1000 Da not immunlogenic
1000-6000 Da maybe
>6000 Da is immunognic

30
Q

whats a hapten

A

LMW antigen but if paired to a carrier we can have an immunlogic response

31
Q

Talk about chemical complexity

A

haptens only have one epitopde
polysccahrides and homopolymers have multple epitopes of the same specfificty

portein hoever have various epitopes or varying specficicy, these means these are the most complex and the most immunlogic

32
Q

talk about degradability

A

T cells recognize antigens when they are presented to them by MHC

APC’s degrade antigens to antigenic peptides whihc bind to MHC for presentation to T cell

thus good degradability is key for good immunogens

33
Q

antigenic determinents on Ab

A

can be:

isotypic dterminants
allotypic determinants
idiotypic determinants

34
Q

explain isotypic dertminants

A

vary on the Fc region

35
Q

explain allotypic determinants

A

vary between indivuals so the heavy and light cahin are different

36
Q

explain idiotypic determinants

A

the top region of the fab region has idiotypes on it that bind to only one epitope and these differ, so the variable region differes

37
Q

Whta other fcators affect immunogenicity?

A
  1. Henotype of host
  2. antigen dose
  3. route of antigen administration
  4. Adjuvants
38
Q

genotype of host

A

everyone has differennt MHC complexes some are better at recognizing certain diseases compared to others

if we lack the gentic matieral to syntheseize T or B lymphocytes and are unable to signal an immune response we have a hole in our repertoire

39
Q

antigen dose

A

too low or too high there is no antibody reponse

40
Q

route of administration

A

Sc or Im - lymph nodes
IV - spleen
Gastrointestional - GALT - may induce intolerances
Intranasal route - MALT - may cayse allergic response, good for respiratory virus vaccines

41
Q

T/F repeated exposure to an antigen is needed to stimulate a strong immune response

A

True

42
Q

adjuvants

A

subsatnces that mixed with immunogen enhance the immune response aganist the immunogen

safe to use in human is alum or aluminnum potassium sulfate

mineral oil is used to prolong response/presecens

43
Q

what are nude mice?

A

mice with no hair and no thymus so T -independent Ag antibody production without the need for T-cell help

44
Q

TI-1 Ag

A

bacterial cell wall components, bind to innate immunity pathogen recognition recpetors (PRR) on B cell and BCR

45
Q

TI-2 Ag

A

bind to complement receptors and BCR

BAFF used to produce second signal

46
Q

how do TI-1 Ag induce AB synthese

A
  1. generate IgM (no CSR)
  2. no induction of memory cells

a. polysacharide alone binds to BCR and thru a thymuc independnet reponse IgM is produced

b. Protein conjugate to polysaccahride allows for T helper cell add B cell cooperate to produce IgG

47
Q

differences between B2, b1, and marginal zone B cells

A

B2- T-D

B1 and MZ B cells - T-I