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SFM > Adaptive Antigen Recognition > Flashcards

Adaptive Antigen Recognition Flashcards

1
Q

What are the 3 types of antigen recognition receptors?

A
  1. B-cell receptors on B lymphocytes
  2. T-cell receptors on T lymphocytes
  3. antibodies (soluble)
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2
Q

What is the process of clonal selection? (4 steps)

A
  1. lymphocyte clones with diverse receptors arise in generative lymphoid organs
  2. clones of mature lymphocytes specific for many antigens enter lymphoid tissues
  3. antigen-specific clones are activated (“selected”) by antigens
  4. antigen-specific immune responses occur

*gene rearrangement of receptors and combinatorial association of receptor chains occurring during cell development is independent of exogenous antigen

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3
Q
  • the sum of the diversity of BCRs and TCRs clones generated during development in a specific individual
  • what an individual can respond to
A

pre-immune response

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4
Q
  • immunological memory repertoire
  • changes occur within this after an immune response
  • what an individual has responded to
A

post-immune response

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5
Q

What type of antigens are recognized by B-cell receptors?

A
  • carbohydrates
  • DNA
  • lipid
  • protein 3D conformation
  • macromolecule antigens
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6
Q

What type of antigens are recognized by T cell receptors?

A

predominantly linear protein peptide antigens

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7
Q

What immunoglobulin isotypes exist bound to B cells? (2)

A

IgM and IgD

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8
Q

What is the purpose of invariant chains, Igα and Igβ within BCR complex?

A

the heterodimer ensures surface expression of immunoglobulin during development and functions in signal transdunction through ITAM

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9
Q

What is the purpose of invariant proteins CD3 within TCR complex?

A

CD3 (CDγ, CDδ, CDε (2), and CDζ) ensures the cell surface expression of the TCR and is involved in signal transduction (CD3ζ)

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10
Q

How do lymphocytes mature? (5 steps)

A
  1. commitment of progenitor cells
  2. proliferation of progenitors
  3. sequential and ordered rearrangement of antigen receptor genes
  4. selection events
  5. differentiation of effectors
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11
Q

An individual’s preimmune repertoire is large enough to ensure there will be an antigen-binding site to fit almost any potential antigenic deterimant, with low affinity. After repeated stimulation by antigen, B cells can make antibodies that bind their antigen with much higher affinity. What is this process called?

A

affinity maturation

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12
Q
  • major mechanism for lymphocyte receptor diversity
  • somatic recombinations between V-J (light chain) and V-D-J gene segments allow for an insane amout of combinations (aka antigen binding sites)
A

combinatorial diversification

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13
Q
  • major mechanism for lymphocyte receptor diversity
  • addition of nucleotides at random during of D-J joining or V to DJ joining
A

junctional diversity

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14
Q
  • major mechanism for lymphocyte receptor diversity
  • point mutations occurring in fully assembled V-J and V-D-J regions during immune response
  • provides significant source of Ab diversity

- only occurs in B cells (peripheral)

A

somatic hypermutation

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15
Q
  • mechanisms for immune diversity in BCR and TCR are indentical
  • heavy chain BCR = __ chain TCR
  • light chain BCR = __ chain TCR

However ______ _________ does not occur in TCRs

A
  • β
  • α
  • somatic hypermutation
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16
Q

Why is IgM the first antibody secreted during an immune response?

A

Because it is the first constant region on the gene (Cm)

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17
Q

What are IgM and IgD the only 2 antibodies expressed on mature, naive B cell surface?

A

Becuase the IgM and IgD are the 1st and 2nd isotypes coded for on the constant region of the heavy chain gene

18
Q

When does isotype class switching occur for the heavy chain of an antibody?

A

During an immune response

19
Q

developing lymphocytes make the ____ (__) chain first. Correct expression of this chain is necessary for the initiation of ____ (__) chain

A
  • heavy, β
  • light, α
20
Q
  • provide recognition sites for recognition enzymes that cut and rejoin DNA
  • ensure gene segments are joined in the correct order (especially important in heavy chain VDJ rearrangement)
A

recombination signal sequences (RSS)

21
Q
  • enzyme responsible for recombining V, D, and J segments
  • these genes are only made by lymphocytes, encode for two necessary components of recombinase
A

RAG-1 and RAG-2

22
Q
  • between coding segments there is often an insertion of a series of nucleotides which is catalyzed by enzyme TdT (catalyzes random polymerization of nucleo into DNA w/o template)
  • N (non-template) nucleotides are added in a non-template manner between coding gaps
  • P (palindromic) nucleotides are added to sticky ends in a templated manner

- creates random unique sequence between coding gaps, major source of generation of diversity

  • could also lead to frameshifts, junk DNA, stop codons, non-codons
A

junctional diversity

23
Q

What is the difference between heavy (β) and light/κ (α) chain production? (2)

A
  1. there is a lack of diversity coding segments (D) for light chain
  2. TdT may not be upregulated for addition of N nucleotides, cell can use remaining enzyme from production of heavy chain for N nucleotide addition

(this is why light/α do not have as much diversity as heavy/β chains, although the rest of their production is the same)

24
Q

What is the 2nd type of combinatorial diversity? (other than V-J or V-J-D genes coming together in different arrangenents)

A

2nd type occurs after both receptor chains have been successfully rearranged, transcribed, and translated. Any chain can associate with any other chain, creating more diversity.

(will be checked prior to leaving BM/thymus to ensure no self-reactivity)

25
Q

What are the steps in B cell maturation? (3)

A
  1. pro-B cells in bone marrow undergo developmental maturation
  2. immature B-cells with sIgM are deleted if they react too avidly with self-antigen
  3. mature, naive B cells expressing sIgM and sIgD on their surface circulate in peripheral circulation
26
Q

Where do B cells mature?

A

bone marrow

27
Q

What is the process of a bone marrow stromal cell aiding in B cell maturation? (4 steps)

A
  1. stromal cells express adhesion molecules and cytokines (IL-7) (helps cells decide whether they will be B or T cells)
  2. lymphoid progenitor cells initially interact through VCAM-1 (stromal receptor) and VLA-4 (prog cell)
  3. this promotes interaction between stem cell factor (SCF, stromal) and Kit (prog cell) leading to proliferation of early pro-B cells
  4. cytokine IL-7 alters expression of proteins required for development of B and T lymphocytes
28
Q

What does the surrogate light chain do during B cell maturation and BCR production?

A
  • signals activate largest proliferation of B cells during development
  • allelic exclusion occurs of heavy chain (aka: turns off other allele and signals readiness for light chain)
29
Q
  • 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
A

allelic exclusion

30
Q

In what stage of development is the B cell tested for self-reactivity? Where is this tested?

A
  • immature B cell
  • bone marrow and spleen
31
Q

What happens when a BCR is reactive to self antigen?

A
  • if the receptor is highly reactive apoptosis will be induced
  • if it is mildly reactive, the cell will become anergic (express less of the receptor on its surface)
32
Q
  • occurs in developmentally arrested, immature B cell responding to self antigen
  • re-expression of RAG proteins allows additional arrangement of light chain genes
  • if new light chain receptor does not react w/ self antigen, B cell will mature
  • development of central tolerance

- does not occur in T cells

A

receptor editing in BCR light chains

33
Q

What is alternative splicing of heavy chain mRNA in constant regions?

A
  • allows for isotype switching
  • pre-mRNA can be processed in 2 ways, bringing VDJ next to either Cμ or Cδ genes
  • the resulting mRNA will code for either mu (IgM) or delta (IgD) chain respectively
  • both will be expressed on the B cell surface, with the same antigenic specificity and different constant regions (isotypes)
  • the reason M and D are first is because they come 1st and 2nd on the gene sequence
34
Q

Resting mature, naive B cells expresses

BCR:

Co-BCR:

A

BCR: IgM, IgD, Igα, Igβ

Co-BCR: CD19, CD81, CR2 (CD21)

35
Q

What are the steps in T cell development? (3)

A
  1. pro-T cells produced in bone marrow travel to thymus for further maturation
  2. double positive T cells which cannot bind, or fail to bind to MHC/HLA or have an over affinity to MHC/HLA and/or self-antigen undergo negative selection
  3. those that can bind with self-MHC/HLA survive and are selected to become single positive CD4+ T helper cells or CD8+ cytotoxic T cells
36
Q
  • caused by ever increasing amount of involution of the thymic stroma during life
  • as the stroma and space used to develop immature T cells are replaced with adipose tissue, there is a resultant decrease in thymopoieses
  • in humans, thymic activity peaks during puberty and declines thereafter; may be the reason for decreased immunity with age
A

age related immunosensence

37
Q
  • immature T cells that are contained within the thymus
  • embedded in a network of specialized thymic epithelial cells (TEC)
  • express both MHC/HLA class I and II for presentation of self antigens
  • secrete IL-7 and ______ specific cytokines
  • specialized for self-protein expression for education of ______
A

thymocytes

38
Q

The thymus is a primary lymphoid organ responsible for the de novo generation of mature, naive T lymphocytes, not _______ ______ ___________

The only route by which progenitor cells enter the thymus and mature T lymphocytes leave is via the _______

A
  • exogenous antigen presentation
  • blood
39
Q
  • signals from this are responsible for the largest proliferation of T lineage cells during development
  • signals to irreversibly inhibit rearrangement of β chain locus on the other chromosome (allelic exclusion)
A

surrogate α chain of TCR

40
Q

How are CD4+ and CD8+ T cells selected for?

A
  • if the thymocyte reacts to MHC I, it becomes a CD8+
  • if the thymocyte reacts to MHC II, it becomes a CD4+
  • if they are double negative, they will undergo apoptosis
  • after single positive selection, thymocytes are self-MHC/HLA restricted, but they may still be able to react to self antigen
41
Q
  • small population of self-reactive CD4+ T cells that have undergone differentiation
  • function to inhibit self-reactive Th cells in the periphery
  • express both CD4 and CD25 on surface
  • unique transcription factor FoxP3
A

Tregs

SFM (21 decks)

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