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SFM Quiz 2 > Antigen Presentation > Flashcards

Antigen Presentation Flashcards

1
Q

Antigen presenting molecules use MHCs aka

A

human leukocyte antigen (HLA)

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2
Q

Type I MHC on

A

all nucleated cells in the body

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3
Q

Type II MHC on

A

professional antigen presenting cells: Dendritic cells, macorphages, B lymphocytes and some thymocytes

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4
Q

two receptors for MHC

A

B cell receptors and T cell receptors

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5
Q

T cells do not recognize

A

antigens in free/soluble forms

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6
Q

T cells only recognizes antigens associated with

A

MHC/HLA

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7
Q

differences in HLA/MHC molecules expressed by an individual will influence the

A

repertoire of antigens to which T cells can respond

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8
Q

MHC/HLA has an unprecedented extent of

A

polymorphism

more then 150 separate alleles have been identified within the MHC

many alternative versions of each MHC gene

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9
Q

MHC location is on chromosome

A

6 and divided into three classes

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10
Q

MHC haplotype

A

encode protein antigens central for immune system to discriminate between self and non self

most humans are heterozygous (one from mom, one from dad) and both are codominant to generate more diversity

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11
Q

transplanation

A

want the best match possible between donor and recipient for both class I and II genes

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12
Q

Class I MHC genes

A

encoded by three separate gene regions in the MHC locus

  • HLA-A
  • HLA-B
  • HLA-C

these are membrane bound glycoproteins
expressed on all nucelated cells
inhibitory receptor for NK cells

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13
Q

MHC I

A

present antigen to CD8 CTL

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14
Q

MHC I structure

A

membrane bound glycoprotein
4 extracellular domains
conserved
heterodimer of a chain and B2 microglobulin

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15
Q

MHC 1 a chain

A

encoded by the MHC class locus

forms three of the fourh globular domains

a1, a2, and a3

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16
Q

MHC I B2 microglobulin

A

non MHC encoded

forms fourth fomain

associates noncovalently with the a3 domain of the a chain

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17
Q

the area between a1 and a2 domains of the MHC I has teh

A

peptide binding groove

greatest polymorphism

peptides are bound and presented on teh surface of cells

bunds pepetides 8-10aa in length

closed ends limit size

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18
Q

key features of MHC I

A

all alleles of class I can be expressed at the same time on each cel (6 different MHCs)

slightly different shape –> present a differnt set of peptides

conformation of this forrve dictates what peptides can bind

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19
Q

each allele of class I MHC has a differetn range of peptides that can

A

bind in the groove

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20
Q

synthesis of a chain of MHC I

A

translated into ER as glycoproteins

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21
Q

in the ER, alpha chain of MHC I interacts with

A

B2 microglobulin and associates with peptides derived from cytosolic proteins

then MHC I peptide complex are transported to cell surface

22
Q

class II genes are encoded by the

A

HLA-D region with three sets of genes

HLA-DP
HLA-DQ
HLA-DR

23
Q

Class II MHC genes have an

A

A and B chain
membrane bound glycoproteins
antigen presenting cells only

24
Q

MHC II present to

A

CD4 T cells

25
Q

MHC II structure composed of

A

two proteins
a chain and b chain, strongly associated
four globular domains
NOT covalently linked

26
Q

MHC II peptide binding groove

A

formed by the a1 and b1 globular domains
binds peptides 13-18aa long
open end allows for larger peptides

27
Q

each allele of class II MHC has a

A

different range of peptides that can bind in the groove

a1 and b1 globular domains have greatest polymorphism

28
Q

in MHC II, all alleles of the a and B chains are

A

expressed

6a chains and 6 b chains

any a chain allele may be associated with any B chain allele

adds to the diversity of the peptide-binding groove

29
Q

greater range of peptides that can bind to

A

Class II MHC

30
Q

antigen-MHC binding is

A

saturateable and low affinity
slow-on rate
very slow-off rate

31
Q

slow MHC-antigen binding allows

A

peptide MHC complex to persist long enough to interact with T cells

32
Q

only one peptide binds to an MCH

A

at any one time, either I or II

same MHC can bind multiple peptides at different times, either I or II

33
Q

peptide bining

A

there are pockets in the peptide-binding cleft

the aa on the antigen peptides fit into these pckets and anchor the peptides in the cleft

the rest of the peptide contains residues that bow upward and are recognixed by the ag receptors on T cells

34
Q

antigens coded on Y chromosome

A

can cause accute rejection on male grafts in female pts

35
Q

capture of antigens

A

microbes enter the body

pahgocytosed by APC in tissues

antigens enter via periphery and filtered by the lymph

antigens in the blood are filtered by the spleen

36
Q

Professional APC express a lot of

A

MHC II and costimulatory molexyles

can activate naive T cells

ex is classical DCs in all tissues
plasmacytoid DCs are in blood and tissues, promote innate and antiviral state

37
Q

activation of DC cells

A

lose adheisve markers and upregulate CCR7

increase MJH and CD80

travel to regional secondary lymphoid tissue

mature as they migrate

present Ag to T cells

38
Q

two processing pathways

A

depends on chemical nature of ag
density of peptide
specific MHC and its binding site
self vs nonself

39
Q

each pathway stimualtes the T cell population most effective, I.E.

A

intracellular pathogens and self: MHC I

extracellular pathogens: MHC II

40
Q

MHC II pathway

A

exogenous proteins are ingested and degraded

a and B and invarient chains are made in the ER and sent ot Golgi

peptide is not loaded until late endosome

41
Q

invariant chain MHC II pathway

A

Ii occupies the peptide binding cleft, probotes folding, assembly, trafficking and place holder

Ii is degraded to CLIP by lysosomal enzymes

HLLA-DM acts as peptide exchanger, remvoing LCLIP and adding peptide to MCH II

unbound MHC are no displayed

42
Q

MHC I pathway

A

cytosolic antigens

proteasome foind in cytoplasm of most cells, degrades damaged proteins, and targeted by ubiquitin

TAP-transports peptides from cytosol to ER where peptide is trimmed and loaded into MHC I

43
Q

MHCs carry peptides from normal self proteins that are degraded but these do not normally

A

provoke an immune respone

44
Q

cross presentation

A

dedritic cells ingest virally infected or transformed cells and display antigens to CTLs

can also display to Th cells

45
Q

transplantation

A

a major factor limiting the success of transplantatino is the imune response of teh recipient to te donor tissue

46
Q

HLA associated diseases

A

many autoimmune diseases and susceptibilty to infectinos are assocaited with HLA alleles

most HLA associated idseases have unknonw etiologies that contribute to the immunologic abnormalities

47
Q

HLA associated disease: ankylosing spondylitis

A

inflammation over the spine

88% of poeple have HLA-B27 allele

each allele has limitined number of peptides it can present

possible that HLA B27 allele cnanot bind a critical antigenic peptide
or
present a critical antigenic peptide against the agent causing the disease

48
Q

HLA associated disease: rheumatic fever

A

sequela of strep pyrogenes infection

generation of ab against the streptococci, cross reacti with cardiac tissue

patients with HLA-DR4 allele are more prone

49
Q

other HLA assocaited diseases

A

Sjorgren’s syndrome: associated with HLADr3, defect in salivation and lacrimation

insulin dependent DM: associated with HLA-DQ w8 and others

psoriasis: associated with HLA-B3

50
Q

class I antigen processing defects

A

renal cell carcinoma

transporter assocaited with antigen processing is down regulated (TAP)

51
Q

bare lymphocytes syndrome (Class I MHC)

A

TAP protein is nonfunctional, so no peptides can enter the ER

class I molecules cannot leave the ER unless they have bound a peptide, cells cannot present antigens on their surface

chronic resp. infections, poor responses to viruses

52
Q

bare lymphocyte syndrome class II MHC

A

caused by inherited decfect in CIITA leading to def. in HLA class II expression on cells and nonfunctioning T cels

HLA II genes are turned on by CIITA which induces IFNy.

mutations in any Tf lead to decrease in class II gene prpducts

reduced Th cell count due to failed thymic selection

reduced antigen presentation to mature T cells

decreased humoral and CMI repsonses incluting DTH

pt have severe recurrent infections

SFM Quiz 2 (25 decks)

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