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TERM 3- Premidterm > L21, L25, L27- Antigen Presentation, Recognition > Flashcards

L21, L25, L27- Antigen Presentation, Recognition Flashcards

1
Q

B-cells recognize (1) type molecules in (2) form

A

1- proteins (mainly), polysaccharides, lipids, nucleic acids

2- soluble form, or cell surface-associated antigen

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2
Q

T cells recognize (1) type molecules in (2) forms

A

1- peptide fragments

2- presented on specialized molecules (MHCs via APCs)

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3
Q

antigens are usually presented to T-cells via (1) on (2) cells after its migration/maturation in (3) via (4) molecules and (5) signaling

A 
1- MHC-II receptors
2- dendritic cells
3- lymph nodes, paracortical area
4- chemokines
5- TLR-signaling
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4
Q

the most important APC is (1) and usually presents its antigen in the (2) area of (3)

A

1- dendritic cells
2- paracortical area
3- lymph nodes

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5
Q

list the 3 signals that stimulate T-cells via antigen signaling

A

1) antigen presentation: MHC/peptide (dendritic cell) recognized by T-cell receptor
2) co-stimulatory signal: CD28 (T-cell) recognized by CD8o/CD86 (dendritic cell)
3) CK secretion: CKs (dendritic cells) recognized by T-cells

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6
Q

MHC genes are found on the (1) cluster of genes on Chromosome (2)

A

1- HLA (human leukocyte antigen)

2- chr. 6

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7
Q

list the MHC-I gene classes

A

HLA-A, HLA-B, HLA-C

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8
Q

list the MHC-II gene classes

A

DP(αβ), DQ(αβ), DR(αβ)

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9
Q

MHC-I receptors are found on (1) cells

MHC-II receptors are found on (2) cells

A

1- all nucleated cell

2- APCs

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10
Q

MHCs genes are expressed in a _______ fashion

A

co-dominant expression (both parental alleles are expressed)

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11
Q

describe the components of MHC-I

A

α-chain (α1, α2, α3): transmembrane, encoded by A/B/C regions of MHC complex

β2-microglobulin: encoded by highly conserved gene (different chromosome)

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12
Q

Of the MHC-I complex:

  • (1) is the highly polymorphic polypeptide binding region
  • (2) binds to CD8 of T(c) cells
  • peptides that are (3) peptides long are recognized (antigen)
  • antigens presented are processed (endo/exo)-genously
A

1- α1/α2 subunits (target cell) binds to T cell receptor
2- α3
3- 8-10 AAs
4- endogenously

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13
Q

describe the components of MHC-II

A

Heterodimeric protein (Ig superfamily)

  • α1, α2: transmembrane
  • β1, β2: transmembrane
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14
Q

Of the MHC-II complex:

  • (1) is the highly polymorphic polypeptide binding region
  • (2) binds to CD4 of T(h) cells
  • peptides that are (3) peptides long are recognized (antigen)
  • antigens presented are processed (endo/exo)-genously
A

1- α1/β1 (α2 is highly conserved region)
2- β2
3- 13-25 AAs
4- exogenously (via Ig)

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15
Q

list the APCs

A

dendritic cells, macrophages, B-cells

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16
Q

MHC-I receptors are recognized by (1) on (2) cells and will result in the release of (3) and (4) with the following functions, (5) and (6) respectively

A

1- CD8
2- T(c) cells
3/5- perforins: forms pores in cell membrane
4/6- granzymes: protein breakdown + cell lysing

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17
Q

MHC-II receptors are recognized by (1) on (2) cells and will result in the release of CKs resulting in (3) which will produce different CKs activating (4)

A

1- CD4
2- T(h) cells
3- T-cell clones
4- B-cells, T(c) cells

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18
Q

list the two antigen presenting pathways, their alternate names, and their MHC/T-cell association

A

Cytosolic, endogenous, non-lysosomal pathway (produced in cell): MHC-I, CD8 T(c) cells

Endocytic, exogenous, lysosomal pathway (taken via endocytosis): MHC-II, CD4 T(h) cells

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19
Q

In the cytosolic antigen presenting pathway, infected proteins are marked with (1) to be degraded by (2). The resulting peptides will bind to (3).

A

1- ubiquitin
2- proteosome
3- MHC-I

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20
Q

proteosome components in cytosolic antigen presenting pathway are activated via….

A

INF-γ (inc number of proteosome components)

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21
Q

Peptides from the proteosome in the Cytosolic pathway enter the ER via (1) and bind to (2). Once loaded on, (2) will signal for (3) or (4) via the Golgi apparatus.

A

1- TAP1/TAP2
2- MHC-I
3- exportation to cell surface
4- sent to lysosome for degradation (usually if no antigen binds)

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22
Q

list the targets of immunoevasins that interfere with antigen presentation via MHC-I

A

(virus blocks MHC-I presentation to T(c) cells)

  • inhibit peptide transport
  • inhibit peptide loading
  • cause MHC-I degradation
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23
Q

(1) virus blocks it viral peptide from transport into ER via (2) and leads to (3)

A

1- HSV
2- TAP1/TAP2
3- MHC-I degradation via lysosome

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24
Q

(1) virus retains MHC-I in the ER, leading to (2)

A

1- adenoviral protein

2- MHC-I degradation via lysosome

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25
Q

list the mechanisms of exogenous antigen uptake

A

-phagocytosis, pinocytosis
-Fc receptor, Complement receptor, or membrane Ig receptor mediated phagocytosis
(note- all create an endosome)

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26
Q

after uptake of an antigen into an endosome, the pH (inc/dec) to activate (2) in order to produce (3); note some drugs will (inc/dec) the pH to inhibit endosomal antigen processing

A

1- dec (more acid)
2- Cathepsin B, D, L proteases
3- ~24 AA peptides from antigens
4- inc pH in endoome

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27
Q

describe the state of MHC-II when unbound to antigen

A

CLIP is bounded non-covalently to invariant chain to stabilize immature MHC-II complex

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28
Q

(1), which is bounded to immature MHC-II receptors, is removed by (2) and replaces (1) with (3); note (4) may also play a role

A

1- CLIP
2- HLA-DM
3- antigen
4- HLA-DO

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29
Q

________ is when exogenous antigens normally processed by phagolysosomes (MHC-II) are presented via MHC-I

A

cross-presentation

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30
Q

describe presentation of antigen for Rickettsia rickettsia

A
  • organism is endocytosed
  • rapidly lyses endosomal membrane –> escaping phagolysosome formation
  • degraded via proteosome
  • presented via MHC-I (although was in endosome)
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31
Q

______ is the presentation of antigen to and activation of T(c) cells

A

cross-priming

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32
Q

list the mechanism bacteria use to evade MHC-II antigen presentation

A
  • escape endosome
  • neutralize endosomal acidification
  • block fusion with lysosome
  • sequesters MHC-II molecules from fusion / going to the cell surface
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33
Q

(1) lymphocyte recognize antigens to initiate responses

(2) lymphocytes and (3) recognize antigens to perform their function

A

1- Naive
2- effector T cells
3- Abs

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34
Q

B cells recognize antigens via (1); T cells via (2)

A

1- Abs

2- T-cell receptors (TCR)

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35
Q

antigen receptors of lymphocytes have (1) components to capture antigen and it is made of (2) and (3); then there are (4) components to carry out function

A

1- recognition
2- variable/constant regions
3- light/heavy chains
4- signal transduction

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36
Q

BCRs are also (1) and will recognize the following chemical structures: (2). (1) can be expressed as (3) or (4).

A

(B-cell receptors)
1- Abs
2- proteins, lipids, carbs, nucleic acids (microbes, toxins in native form)
3- membrane-bound Ag receptors on B-cells
4- secreted proteins

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37
Q

the (variable/constant) regions are responsible for recognition of antigens

A

variable domains, in secreted or membrane-bound form (constant regions on secreted Abs can play minimal role)

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38
Q

describe composition of BCR

A

4 polypeptide chains: 2 identical heavy chains and 2 identical light chains

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39
Q

the (1) region of the (light/heavy) chain on a BCR recognizes Ag and the (3) region on (light/heavy) chain binds and activates complement

A

1- Fab region
2- light chain (constant and variable)
3- Fc region
4- heavy (constant)

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40
Q

describe domains of light chain on Ab

A
  • N-terminal is variable and site of antigen binding

- C-terminal is constant, defined as λ or κ

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41
Q

describe domains of heavy chain on Ab

A
  • heavy chain variable region determines class: Ig- G, A, M, E, D
  • constant region is nearly invariant, defined as α, γ, δ, µ, ε
42
Q

Ig(1) and Ig(2) have an extra heavy chain domain in the constant region

A

IgM, IgE

43
Q

describe the 3 types of variability found in Igs between people

A

Isotype: 5 major classes of Abs (H/L chains)

Allotype- alleic variants of constant domain (only one parent’s is expressed)

Idiotype- individual variability of H/L chains in Variable regions

44
Q

define function for all 5 Igs

A
  • IgM- 1st responder to new Ag
  • IgG plasma, memory cells produce as secondary responder (most abundant)
  • IgA- present in blood, serous, mucus secretions
  • IgE- allergic responses, parasitic worm infections
  • IgD- receptor on B cells
45
Q

Ig(_)- monomer, produced by plasma cells (primary) and memory cells (secondary), most abundant

A

IgG

46
Q

Ig(_)- monomer/dimer, circulates in blood, present in serous/mucous secretions

A

IgA

47
Q

Ig(_)- pentamer (5 monomers), 1st class synthesized in Ag encounter (not opsonizer, best complement activator)

A

IgM

48
Q

Ig(_)- monomer, receptor of antigen on B cells

A

IgD

49
Q

Ig(_)- involved in allergic responses and parasitice worm infections

A

IgE

50
Q

_____ is the only Ig that crosses the placenta

A

IgG

51
Q

define affinity in a BCR

A

strength of ONE interaction (note- there’s affinity maturation)

52
Q

define avidity in a BCR

A

strength on MULTIPLE interactions (non-covalent)

53
Q

define cross-reactivity in a BCR

A

one Ab binding different epitopes

54
Q

what mediates signalling functions on a BCR

A

Igα and Igβ (+ other co-stimulators)

55
Q

explain monoclonal Abs

A

one clone of B cells makes one Ab specific for one Ag

56
Q

describe composition of TCRs

A 
2α chains- one constant, one variable
2β chains- one constant, one variable
Note- no secreted form, no class switching
57
Q

_____ region of BCRs and TCRs is the most variable region

A

CDR3

58
Q

CD(1) and CD(2) are associated with TCR complex

A

1- CD3

2- CD4 or CD8

59
Q

describe CD3 structure and its role in the TCR complex

A
  • 3 dimers: γε, εδ, ζζ/ζη
  • cytoplasmic tail: ITAMs (immunoreceptor tyrosine-based activation motif) responsible for signal transduction for TCR complex
60
Q

list the 3 phases of B-cell development

A
  • Ag-ind.: generate immunocompetent cells
  • Ag-dep.: activate mature cells
  • differentiation into plasma/memory cells
61
Q

list the steps of Ag-Indep. phase of B-cell maturation

A
  • HSC (hematopoietic stem cells)
  • lymphoid progenitor / stem cell
  • Pro-B cell (B cell progenitor)
  • Pre-B cell
  • Immature B cell
62
Q

Pro B-cells have high expression of (1) and (2), and (3) is critical for its maturation into Pre-B cells

A

1- CD45R
2- CD19
3- IL-7

63
Q

in Pro B cells ______ is present on cell surface

A

Ig-α, Ig-β

64
Q

describe the two outcomes of Pro-B cell maturation (what is the determiner)

A

Rearrangement of Ig H chains:
-successful rearrangement => pre-B cells
-unsuccessful => apoptosis
(mediated by terminal deoxyribonucleotidyl transferase (TdT)

65
Q

Pre-B cells have presence of (1) in cytoplasm and (2) on cell surface. Recombination of (3) on L chain occurs, and with failure recombination of (4) occurs.

A

1- Igµ
2- Igα, Igβ with surrogate L chain
3- Igκ
4- Igλ L chain

66
Q

_______ are expressed in Pro-B cell to Immature B cell phases of development/recombination

A

RAG1, RAG2

67
Q

BTK, aka (1), is involved in (2) and its deficiency leads to (3) with the following characteristic, (4)

A

1- Bruton’s tyrosine kinase
2- B-cell development
3- X-linked agammaglobulinemia
4- no Ab production, normal pre-B cell population (failure to mature, enter circulation)

68
Q

list the three important characteristics of Immature B cells

A
  • IgM expressed on surface
  • functional BCRs appear
  • Negative selection (clonal deletion) occurs
69
Q

Mature B cell, aka (1), expresses (2) and (3) and undergoes further maturation via (4) process

A

1- follicular B cells
2- IgM
3- IgD
4- RNA processing of H chain

70
Q

describe characteristics of Naive B cell

A
  • migration out of bone marrow
  • quiescent (in Go phase)
  • has not encountered antigen
71
Q

CD_ is the key B cell marker

A

CD19

72
Q

CD_ is expressed in all but the first and last stages of B cell development and is a key target of monoclonal Abs in B cell lymphomas/leukemias

A

CD20

73
Q

_____ signaling is a key driver of B cell malignancies

A

dysregulated BCR (note- x targets downstream kinases)

74
Q

list the order of Thymocyte development (include location)

A
  • HSC (hematopoietic stem cells) in bone marrow
  • common lymphoid progenitor, migrates to thymus: IL-7
  • T cell precursor (pro-T cell): no TCR, CD3
75
Q

list 4 outcomes of T cell maturation in the thymus

A
  • weak recognition of MHC-II/peptide => CD4+ T cell (positive selection)
  • weak recognition of MHC-I/peptide => CD8+ T cell (pos. sel.)
  • no recognition of MHC/peptide => apoptosis (failure of pos. sel.)
  • strong recognition of MHC-I/II/peptide => apoptosis (neg. sel.)
76
Q

(1) is a transcription factor expressed in the (2) region of the thymus to drive negative selection of self-recognizing T cells; defective (1) can lead to (3)

A

1- AIRE (autoimmune regulator)
2- medulla
(don’t want cells to recognize self)
3- autoimmune diseases

77
Q

where in the Abs do people differ based on allotype

A

constant regions of H and L chains

78
Q

lymphocytes use (1) number of genes to make over (2) different Abs

A

1- 500

2- > 1 billion

79
Q

list the two types of changes genes of lymphocytes undergo

A

1) somatic recombination (VDJ joining- non-homologous)DNA recombination)
2) Junctional diversity: addition/removal of NTs among VDJ joints

80
Q

the largest contribution to diversity of antigen receptors is…

A

junctional diversity

81
Q

Somatic recombination occurs on (1) of BCRs and (2) of TCRs among the following segments: (3). This occurs during the (4) phase of development / maturation.

A

1- H and L chains
2- α β δ γ chains
3- Variable, Diversity, Joining
4- Ag-independent phase

82
Q

RAG1/RAG2 function to (1) during the following phases of B cell development: (2)

A

1- breakdown and rearrange gene components (H and L chain)

2- Pro-B cell (H chain), Pre-B cell (H chain complete, L chain), Immature B cell (L chain complete)

83
Q

Ig H chain gene rearrangement occurs during (1) phase of development

Ig L chain occurs during (2) phase

A

1- Pro-B cell (progenitor) to Pre-B cell

2- Pre-B cell to Immature B-cell

84
Q

cytoplasmic µ+ is indicative of ____ phase of B cell development

A

Pre-B cell (µ codes for IgM)

85
Q

presence of just surface IgM is indicative of ____ phase of B cell development

A

Immature B cell

86
Q

presence of surface IgM and IgD is indicative of ____ phase of B cell development

A

Mature B cell (not in Bone Marrow)

87
Q

RAG1/RAG2 are critical components of ________ process

A

somatic recombination

88
Q

H chain recombination of (1) occurs during pro-B cell phase, (2) during pre-B cell phase

L chain somatic rearrangement occurs during (3) phase

A

1- DJ
2- VDJ
3- immature cells

89
Q

define allelic exclusion

A

B cells will only express genes from a chromosome from ONE parent- never both

90
Q

junctional diversity includes the following two components…

A
  • junctional flexibility

- P-nucleotide/N-nucleotide addition

91
Q

define junctional flexibility

A

exons are spliced, => slight variation in position of segmental joining

92
Q

describe P-nucleotide addition

A

addition of random NTs to cleaved hairpin during the joining of segments

93
Q

describe N-nucleotide addition

A

-addition of random NTs to 3’ cut end of segments
-TdT (terminal deoxynucleotidyl transferase) adds NTs to heavy chain gene
(Note- V-J, V-DJ, VD-J joints in variable domain inc diversity)

94
Q

list the two methods of BRC variability after maturation and migration out of the bone marrow

A
  • somatic hypermutation

- class switching

95
Q

In somatic hypermutation B cells in the (1) area are proliferating following antigen contact, and (2) mutations occur in the (3) region of the Ig via (4) enzyme in order to (5).

A 
1- secondary lymphoid organs
2- point mutations
3- variable region
4- AID (activation induced cytidine deaminase, C --> U)
5- improve affinity
96
Q

describe class switching of BRCs

A
  • occurs after Ag stimulation
  • V-(D)-J units will stay and be associated with different constant regions
  • IgM(µ) –> A(α), G(γ), D(δ), E(ε)
  • decided by which ever gene is closest (α γ δ µ ε) to variable after rearrangement
  • only occurs once
97
Q

list the regulator(s) of class switching of BRC

A

-IL-4 predominately
-IFN-γ
-somewhat IL-5 (IgE)
(activation of CD40-CD40L)

98
Q

AID is important for….

A

(activation-induced cytidine deaminase)

  • somatic mutation
  • class switching
99
Q

(T/F) B-cells and T-cells both undergo somatic mutation

A

F- only B cells`

100
Q

TCR rearrangement is analogous to BCR where rearrangement of (1) chains occur in pre-T cell, then (2) chains in immature T cell [included segments]

A

1- β chain (D-J joining –> DJ-V joining // analogous to H chain)
2- α chain (V-J joining)

101
Q

list the factors of generating TCR diversity (hint- 6)

A
  • multiple germ-line segments
  • combinatorial V-(D)-J joining
  • Junctional flexibility: imprecise joining at junctions
  • P-region NT addition
  • N-region NT addition
  • combinatorial association of α and β chains (or γ/δ chains)

TERM 3- Premidterm (20 decks)

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