Antigen recognition Flashcards

1
Q

what is an antigen

A

antibody generator - a molecule that can elicit a response from the adaptive immune system

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2
Q

what are antigen recognition molecules

A

B cell receptor (BCR) and T cell receptor (TCR)

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3
Q

what is an immunoglobulin and what two forms of the molecule exist?

A

Y shaped molecule with a transmembrane tail anchored in the plasma membrane of B cells - with 2 identical antigen binding sites. 1st form -> BCR (expressed on B cells) and 2nd is the secreted immunoglobulin = lacking the transmembrane tail

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4
Q

what happens upon antigen recognition?

A

B cells -> differentiate into their active form = plasma cells
T cells -> several functions: active CD8 T cells kill human cells infected with a virus or intracellular bacteria. CD4 T cells mediate an appropriate immune response

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5
Q

what are the different regions of an immunoglobulin and their functions

A

constant (C) region - transmembrane region with the effectr function because it interact with the effector molecules of the immune system. the variable (V) region is the antigen binding site

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6
Q

what are the different chain of the immunoglobulin molecule

A

2 heavy chains and 2 light chains

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7
Q

what is the function of the hinge region

A

it is flexible - ties the heavy chain first domain to heavy chain second domain

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8
Q

what is the structural difference of different subclasses of IgG molecules

A

4 subclasses - they vary in the length of the hinge region –> the longer the length, the more flexible the antibody is

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9
Q

structure of the IgG molecules

A

4 polypeptide chains -> 2 heavy chains and 2 light chains. heavy chains are linked by disulphide bonds and each heavy chain is linked to a light chain by diuslphide bonds

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10
Q

what is the 3D structure of each domain (C and V regions of Ig)

A

the strands of polyppetide chains are beta sheets which run in opposite direction = forming a beta barrel structure (also called the immunoglobulin fold)

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11
Q

what ensures the ability of the Ig to bind an epitope?

A

the variable domains (both heavy chains and light chains) have 3 areas of hypervariability = HV1, HV2, HV3 (these areas allow the Ag-binding site to be so unique). altogether, 6 hypervariable regions in each arm of the Y shape

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12
Q

CDRs?

A

complementarity determining regions

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13
Q

FRs? what is their function?

A

framework regions are the regions in between complementarity determning regions -> they provide the structure of the V domains

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14
Q

what is a paratope?

A

the unique antibody combining site –> the combination of H + L chain CDRs

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15
Q

where do antigen/epitope bind?

A

antigen-binding site also called the peptide binding groove

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16
Q

briefly describe what happens after BCRs recognize an antigen

A

there are multiple BCRs on the B cell which recognize the antigens at once = creating a cluster of BCRs. that activates the BCR complex = Ig-alpha and Ig-beta. They contain ITAMs inside the cell which when brought together are phosphorylated by the Lyn kinase. Now ITAMs are ready to bind the adaptor molecule BLNK which triggers the MAPK pathway

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17
Q

what is the purpose of the MAPK pathway

A

transduction cascade which allows the transcription factor Ap1 to enter the nucleus and start replication and cell cycle progression. meaning the ativated B cell can now divide and proliferate

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18
Q

wha are the 3 signals that activate the B cell?

A
  1. the binding of several BCR to an antigen
  2. the recognition of the complement opsonizing the pathogen (B cells have complement receptors)
  3. secreted cytokines from T helper cells (T follicular cells promote class switching to the antibody isotype that is useful for the particular infection)
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19
Q

TCR structure

A

consists of 2 chains - TCR alpha and TCR beta chain

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20
Q

what are the regions of a TCR

A

constant (C) region, variable (V) region - conains Ag-binding site, transmembrane region and cytoplasmic tail

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21
Q

ITAM ?

A

immunoreceptor tyrosine kinase activator motif

22
Q

what is the function of a TCR

A

only recognition - because the heterodimer is a part of a large multiprotein complex (6 additional subunits)

23
Q

how does the antigen recognition differ between BCRs and TCRs

A

BCRs bind the intact antigen whereas TCRs bind to short amino acid sequences = peptides (that are usually buried within the structure of the protein - that is why they need to be degraded)

24
Q

structural difference between CD4 and CD8

A

CD4 has 4 identical domains and a transmembrane area
CD8 consists of an alpha nad beta chain connected with disulphide bonds

25
Q

what is CD3 and the function?

A

CD3 is a co-receptor complex which starts the signalling transduction for T cell activation. it contains ITAMs = same singalling role as in B cells

26
Q

what MHC class I molecules bind to

A

they are recognized by CD8 cytotoxic T cells -> because MHC class I are on all human cells (except RBCs). the CD8 T cells recognize peptides of virally infected cells and then kill them

27
Q

what size peptides do MHC class I present

A

small peptides - around 8 amino acids

28
Q

structure of MHC I

A

3 alpha chains + beta-2 microglobulin. the peptide binding groove is made up of alpha 1 and alpha 2 subunits

29
Q

how big peptides can MHC II present

A

at least 13 amino acids - because the peptide is anchored into the peptide-binding groove (not contained inside)

30
Q

MHC class II structure

A

2 alpha subunit and 2 beta subunits

31
Q

where is the peptide anchored in MHC II

A

in specific pockets of the peptide binding groove -> pockets 1, 4, 6, and 9 interact with side chains of the peptide = holding it in place

32
Q

can B cells act as APCs?

A

yes, B cells can directly bind a pthogen which activates the B cell - production of cytokines - activation of T helper cells to mediate a bigger production of antibodies

33
Q

TAP?

A

transporter associated with antigen processing

34
Q

what is the role of calnexin?

A

it hold partially bound MHC class I alpha chains together until beta-2 microglobulin binds

35
Q

what are chaperone proteins and what is their function?

A

calreticulin and ERp57 they hold the MHC class I complex together and also bind to tapasin and TAP - to facilitate peptide loading onto the peptide binding groove

36
Q

what is the function of the invariant chain?

A

when MHC class II are produced in the ER of cells they contain the invariant chain attached to the Ag-binding site. this ensures that a viral peptide does not get loaded onto MHC class II

37
Q

function of clip molecule

A

facilitates the binding of the invariant chain to the MHC II peptide binding groove

38
Q

3 signals of T cell activation

A
  1. TCR direct recognition of the peptide presented by an MHC molecules –> activation of the CD3 complex sends the 1st signal
  2. the interaction of co-receptors: CD28 and CD80/CD86
  3. cytokine release from APCs
39
Q

what is MHC polymorphism

A

there are regions of hypervariablity in the peptide binding groove (the same principle as a BCR)

40
Q

CD4 T helper subsets

A

Th1, Th2, Th17, Tfh, and Tregs

41
Q

what is the purpose of Tfh cells?

A

Tfh are always activated with another T helper cell. they mediate antibody class switching in response to the specific pathogen (this ensures the correct antibodies are produced)

42
Q

what cytokine is characteristic for Th1 cell subset and what does it interact with (function)?

A

IFN-gamma, enahnces macrophage activity

43
Q

in response to what pathogens is the Th1 cell subset activated

A

intracellular microbes -> certain viruses, protozoa, and bacteria (sometimes bacteria gets engulfed by macrophages and then can avoid the macrophage bactericidal activity)

44
Q

what cytokines are characteristic for Th2 cell subset

A

IL-4, IL-5, and IL-13. they act on eosinophils, mast cells, mucus-producing cells = epithelial cells

45
Q

in response to what pathogens is the Th2 cell subset activated

A

multicellular microbes -> helminths or intestinal parasites

46
Q

what cytokines are characteristic for the Th17 cell subset

A

IL-17A and IL-17F -> they amplify neutrophilic and monocytic responses + the production of antimicrobial peptides from epithelial cells

47
Q

in response to what pathogens is the Th17 cell subset activated

A

extracellular bacteria and fungi

48
Q

what is the antibody isotype characteristic for Th1 response

A

IgG3

49
Q

what is the antibody isotype characteristic for Th2 response

A

IgE

50
Q

what is the antibody isotype characteristic for Th17 response

A

IgG3