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SFM Exam 1 > Adaptive Ag Recognition > Flashcards

Adaptive Ag Recognition Flashcards

1
Q

What are the two membrane bound lymphocyte receptors?

A

BCRs on B cells and TCRs on T cells

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2
Q

What is an example of a soluble antigen recognition receptor?

A

Antibodies

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3
Q

The process of gene re-arrangement of the lymphocyte receptors and the combinatorial association of the receptor chains occurring during lymphocyte development is independent of what?

A

The exogenous Ag

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4
Q

Describe clonal selection

A

Lymphocyte clones expressing all of the possible specificities are produced during development and the Ag selects those clones which have the appropriate receptor
The selected clones are then activated, proliferate (clone themselves) and differentiate into lymphocyte effector cells

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5
Q

What is the pre-immune response?

A

The sum of the diversity of BCRs and TCRs clones generated during development in a specific individual

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6
Q

What is immune repertoire?

A

What the individual can respond to

The pre-immune response

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7
Q

What is the post immune response?

A

Memory repertoire
Changes to the repertoire after an immune response
What the individual has responded to

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8
Q

Describe a BCR

A

Four chains
Two Ag binding sites, bivariant
Carb, DNA, lipid, protein 3D conformation macromolecule Ags
Can recognize free soluble Ags
Can react to any particle in a fluid
Secreted upon activation
Somatic hypermutation and class switching

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9
Q

Describe a TCR

A

Two chains (alpha/beta or gamma/delta)
One Ag binding site (monovalent)
Predominately linear protein peptide antigens
Peptide must be bound to HLA to be recognized
Restricted to interacting with other cells
Not secreted upon activation
No change during or after response to Ag

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10
Q

Describe the BCR structure

A

Surface bound IgM and IgD
Ig-alpha and Ig-beta (CD79A/CD79B) that has two invariant chains
Ig alpha and beta heterodimer ensures surface expression of immunoglobulin during development and functions in signal transduction

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11
Q

Describe TCR complex structure

A

Alpha/beta chain heterodimer
CD3: a complex of invariant proteins (CD fetal, gamma, epsilonx2 and zeta)
CD3 complex ensures the cell surface expression of the TCR and is involved in signal transduction
TCR complex is TCR plus CD3 complex proteins

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12
Q

Broadly describe lymphocyte maturation

A
  1. Commitment of progenitor cells
  2. Proliferation of progenitors
  3. Sequential and ordered rearrangements of Ag receptor genes
  4. Selection events
  5. Differentiation of effectors
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13
Q

What is combinational diversification?

A

Multiple germ line genes
Re-arrange genes to create diversity
V-J or V-D-J somatic recombinations
Start with heavy chain locus first

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14
Q

What is junctional diversity?

A

Addition of nucleotides at random during the process of D-J or V to DJ joining

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15
Q

What are the major mechanisms for generation of lymphocyte receptor diversity?

A

Combinatorial diversification, junctional diversity and somatic hypermutation

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16
Q

What is somatic hypermutation?

A

Occurs in B cells only
Point mutations curing in fully assembled V-J and V-D-J regions during an immune response
Provides a significant source of Ab diversity

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17
Q

Does somatic hypermutation occur in TCRs?

A

No

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18
Q

Mechanisms accounting for immune diversity for BCR/Abs and TCRs are

A

Identical
Production of heavy chain BCR = production of beta chain TCR
Production of light chain BCR = production of alpha chain TCR

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19
Q

What does the immunoglobulin heavy chain contain?

A

Constant regions for all Ab isotypes

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20
Q

Mu (Cm) is the first isotype expressed as

A

BCR because it is the first constant region on the gene

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21
Q

Class switching to different isotype constant regions can occur during an

A

Immune response (heavy chain only)

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22
Q

Kappa light chain is preferentially

A

Expressed

Majority of BCRs have a kappa light chain

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23
Q

What are TCR beta and delta chains constant regions analogous to?

A

BCR heavy chain

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24
Q

What are TCR alpha and gamma chain constant regions analogous to?

A

BCR light chain

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25
Q

Alpha/beta T cells

A

Majority of expressed TCRs in peripheral T cells

Gamma/delta TCRs are expressed on a subset of T cells specific for mucosal and other specialized responses

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26
Q

What is necessary for initiating the generation of the light (alpha) chain?

A

Correct expression of the heavy (beta) chain

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27
Q

What is the first rearrangement in combinatorial diversity (VDJ rearrangement)?

A

DJ

V-DJ is second

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28
Q

What is the role of recombination signal sequences?

A

Provide recognition sites for recognition enzymes that cut and rejoin DNA and
Ensure gene segments are joined in the correct order (esp. important in heavy chain VDJ rearrangement)

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29
Q

The recombination of gene segments is directed by what?

A

Recombination signal sequences (RSS)

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30
Q

What enzyme is responsible for recombining V, D and J segments?

A

Recombinase RAG-1 and RAG-2 (recombination activating genes)
Only made by lymphocytes
Encode for these two necessary components of recombinase

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31
Q

At the junction between coding segments there is often an insertion of a series of nucleotides which is catalyzed by what enzyme?

A

TdT

32
Q

TdT catalyzes the random

A

Polymerization of nucleotides into DNA without the need for a template

33
Q

What are N (non-template) nucleotides?

A

Added in a non-template random manner between coding joints

34
Q

What are P (palindromic) nucleotides?

A

Added to asymmetrically cleaved hairpins in a templated manner to complete unpaired nucleotides
Repair enzymes

35
Q

Making the light chain

A

Kappa/alpha (for TCRs)
V-J rearrangement occurs the same way as heavy chain
Lacks the diversity coding segments (D)
Same players: RRS, RAG 1 and 2
TdT: N nucleotides (maybe or maybe not added)
TdT may not be upregulated for the addition of N nucleotides but the cell can use any remaining enzyme from the production of the heavy chain

36
Q

What is the second type of combinatorial diversity?

A

Occurs after both receptor chains have been successfully rearranged, transcribed and translated
The two different receptor chains are combined to make the Ag-binding site

37
Q

Broadly describe B cell maturation (didn’t really go over)

A

Pro-B cells in bone marrow undergo developmental maturation ->
Immature B cells with sIgM are delegated if they react too avidly with self Ag ->
Mature, naive B cells expressing sIgM and sIgD on their surface circulate in peripheral circulation

38
Q

Where do follicular B cells come from?

A

The bone marrow (they are B2 cells)

39
Q

Describe bone marrow stroma cell support

A

Stromal cells express adhesion molecules and cytokines
Lymphoid progenitor cells initially interact through VCAM1 and VLA4 which promotes interaction between the stem cell factor (SCF) and Kit leading to proliferation of the early pro-B cells
The cytokine IL-7 alters the expression of proteins required for the development of B and T cells

40
Q

What are signals from the pre-BCR responsible for?

A

The largest proliferative expansion of B cells during B cell development
Signals to irreversibly inhibit rearrangement of the Ig heavy chain locus on the other chromosome (allelic exclusion)

41
Q

Describe allelic exclusion in B cells

A

An individual B cell can express one heavy chain encoded by only one of the two inherited alleles
Ensures that every B cell will express a single receptor thus maintaining clonal specificity

42
Q

What is tolerance?

A

Selection deletes or functionally inactivates cells that display Ag receptors that are self reactive
Tolerance is acquired by immature B cells that do NOT become activated when challenged with self Ag

43
Q

What is rescue of self reactive B cells by receptor editing?

A

Occurs in developmentally arrested immature B cell responding to self Ags
Re-expression of RAG proteins for additional rearrangement of light chain genes
If new light chain receptor specificity does not react with self Ag B cell will mature
Development of central tolerance

44
Q

Does receptor editing occur in T cells?

A

Receptor editing does NOT occur in T cells

45
Q

What markers do resting mature naive B cells express? *****

A

BCR expresses IgM, IgD, Ig-alpha and Ig-beta
Co-BCR: CD19, CD81 and CR2 (CD21)
HLA class II (and I)
CD40 and CD20

46
Q

What are the two major subsets of B2 cells?

A

Follicular B cells (re-circulating B cells) which are the majority
Marginal B cells which reside in the spleen and respond to blood borne polysaccharide Ags

47
Q

B1 cells

A

Mucosa — limited Ag specificity

48
Q

What are thymocytes?

A

Immature T cells contained within the thymus

49
Q

What are thymocytes embedded in?

A

A network of specialized thymic epithelial cells (TEC)

50
Q

Describe thymic epithelial cells

A

Express both HLA class I and II for presentation of self Ags
Secrete IL-7 and thymocytes specific chemokines
Specialized for self protein expression for education of thymocytes (AIRE)

51
Q

The thymus is a primary lymphoid organ responsible for what?

A

The de novo generation of mature naive T cells and not exogenous Ag presentation** (primary lymphoid organs should not have exogenous Ags)

52
Q

What is the only route by which progenitor cells enter the thymus and mature T cells leave is via what?

A

The blood

53
Q

What is junctional diversity?

A

Creates random unique sequences between the coding joints

Major source of generation of diversity

54
Q

How can additional diversity occur during the junctional diversity process?

A

By errors that occur in the recombination event that brings the V region next to the J or D regions or the D region next to the J region
Can lead to frameshifts*
Can triple the diversity generated by D-J and V-D/J joining
The diversity created by this mechanism occurs in the hypervariable* region

55
Q

What are the two different ways the heavy chain pre-mRNA can be processed?

A
  1. To bring the VDJ next to the C-mu gene
  2. To bring the VDJ next to the C-delta gene
    With the resulting mRNA coding for a mu (IgM) and delta (IgD) respectively
    Both will be expressed on the surface of the mature naive B cell and both have the same antigenic specificity (only difference is the constant region)
56
Q

What is the microenvironment for T lymphocyte development?

A

Thymic stroma

57
Q

Describe the organization of the thymus

A

Different regions of the thymus are distinguished by the cells present and influence the developmental events of T cells
Thymic cortex = outer cortical region
Medulla = inner cortical region

58
Q

What are signals from the pre-TCR responsible for?

A

The largest proliferative expansion of T lineage cells during T cell development
Signals to irreversibly inhibit rearrangement of the beta chain locus on the other chromosome (allelic exclusion)

59
Q

Describe CD4/8 positive selection for HLA restriction

A 
The TCR interacts with either a class I or II HLA molecule 
CD4 or CD8 must recognize and bind to HLA as part of the recognition by TCRs 
If they dont recognize either class I or II they will undergo apoptosis
60
Q

After positive selection, thymocytes are self MHC/HLA restricted but they may still be able to react to

A

Self Ags

61
Q

What must occur after positive selection to MHC restriction?

A

Negative selection to self Ags

62
Q

A small population of self reactive CD4+ T cells undergo differentiation to become what type of cell?

A

Treg cell which function to inhibit self reactive Th cells in the periphery

63
Q

What cell surface markers do Treg cells express?

A 
TCR/CD3 signaling complex
CD4+ 
MHC class I 
CD25 
CTLA-4
64
Q

What TF is unique to Treg cells?

A

FOXP3

65
Q

What surface markers are present on CTLs?

A

TCR/CD3 signaling complex, CD8+ and MHC/HLA class I

66
Q

What surface markers are expressed on Th cells?

A

TCR/CD3 signaling complex, CD4+ and MHC/HLA class I

67
Q

When does proliferation occur during T cell development?

A

Stem cell into beginning of pro-T cell phase

Middle to end of Pre-T cell phase

68
Q

What surface markers are expressed on a double positive T cell during development?

A

CD4+CD8+

TCR/CD3

69
Q

What surface markers are expressed on a single positive (immature T cell) and a naive mature T cell during development?

A

CD4+CD8- or CD4-CD8+

TCR/CD3

70
Q

At what stage of development is the surrogate alpha or beta chain present during T cell development?

A

Pre-T cell

71
Q

During what stage of maturation does proliferation occur in B cell development?

A

Mid stem cell phase to mid pro-B cell phase

Mid to end pre-B phase

72
Q

At what stage of B cell maturation does RAG and TdT expression occur?

A

In between pro-B and pre-B cell stage

73
Q

What surface markers are expressed by mature naive B cells?

A

CD19+ and IgD

74
Q

What is an immature B cell’s response to an antigen?

A 
Negative selection (deletion) 
Receptor editing
75
Q

What is a mature naive B cell’s response to an antigen at the end of maturation?

A

Activation (proliferation and differentiation)

76
Q

What surface markers are expressed by a pro-B cell during maturation?

A

CD43+, CD19+ and CD10+

SFM Exam 1 (8 decks)

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