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402 Exam 2 > B and T cell development > Flashcards

B and T cell development Flashcards

1
Q

What does innate immune system recognize compared to adaptive immune system?

A
  • Innate: patterns of non-self or altered self (PAMPs and DAMPs)
  • Adaptive: specific epitopes on antigen that are non-self.
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2
Q

Compare innate immune cell receptors to adaptive immune cell receptors.

A
  • Innate: express the SAME set of PRRs.
  • Adaptive: B and T are generated with unique antigen specificity.
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3
Q

Identify heavy chain, light chain, variable regions, constant regions, transmembrane region on immunoglobulin (B cells) and TCR (T cells).

A
  • B cell: Y shape
  • T cell: 2 column shape
  • Heavy chain: in Y shape that running from inner branch down the body (symmetrically).
  • Light chain: in Y shape outer branches (symmetrically).
  • Variable regions: distal region from membrane.
  • Constant regions: proximal region from membrane.
  • Transmembrane region: region that in direct contact with membrane.
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4
Q

What are the special/identifiable features on Ig structures?

A
  • 2 identical light chain.
  • 2 identical heavy chain.
  • Disulfide bridge (connect upstairs and downstair)
  • Carbohydrate added (glycosylated Ig change efficacy, T1/2)
  • Constant region
  • Variable region has antigen binding site.
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5
Q

Compare Fab vs. Fc

A
  • Fab = fragment antigen biding, it binds antigen.
  • Fc = fragment crystallizable, it interacts with other cell surface proteins. Act as cell surface receptor.
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6
Q

Name 5 classes of Ig and what are their unique features? (hint: hinge regions, dimers, pentamers)

A
  • Classes: G/A/M/E/D
  • Hinge regions in D, A, G.
  • Non-hinge regions M,E.
  • Form dimers: A
  • Form pentamers: M
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7
Q

What kind of antigens can B cells bind? And in what kind of geometry can they bind?

A
  • Antigens can be proteins, lipids, carbohydrates, nucleic acid DNA.
  • Can bind to linear or conformation/discontinuous epitope.
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8
Q

What is the unique properties that B cell has that affect how they interact with epitope? (hint: region name)

A

Hyper-variable (HV) region interacting with antigen, surrounded by Frame Region.
AKA complementarity-determining regions.

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9
Q

How many antibody can each B cell produces?

A

ONE

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10
Q

List the step of generation of lymphocyte antigen receptors of Ig.

A
  • Start with heavy chain: D-J combine; V to the DJ; Transcription to make mRNA; Splicing to select only portion needed; Translation to make protein.
  • Then with light chain: V-J combine; Transcription to make mRNA; Splicing of mRNA; Translation.
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11
Q

How does DJ combine?

A
  • RAG (!!!) cleave heptamer, yield hairpins, open hairpins, nick DNA to create palindromic overhangs (P-nucleotides).
  • Add nucleotides randomly to ends of single strands (NOT encoded by the genome).
  • Gap filled by TdT (Terminal deoxynucleotidyl transferase).
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12
Q

Compare membrane bound Ig to secreted Ig.

A
  • Membrane-bound Ig: Ig alpha and Ig beta serve as B cell receptor. Splicing to remove the region “SC sequence” and join “MC exons” in heavy chain. (Think of M = marriage = stay = membrane bound!)
  • Secreted IG: primary transcript is cleaved at polyadenylation site, eliminate MC, keep SC. (Think of S = separate = secreted!)
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13
Q

What are the results and consequences of Pre-B cell test (1)?

A
  • Test heavy chain
  • Weak signal: cell proliferate and undergo light chain rearrangement (pass!)
  • Signal too strong: cell eliminated, reacts with antigens in bone marrow.
  • No signal: apoptosis.
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14
Q

What are the possible outcome of immature B cell? What step is this in testing B cell functionality and self reactivity?

A
  • Test how BCR (surface expression) functional (step 2)
  • Weak signal: cell proliferate and leave bone marrow.
  • Signal strong: cell rearrange on light chain.
  • Signal too strong: apoptosis.
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15
Q

What are the results and consequences of transitional B cell (3)?

A
  • Test BCR reactive to antigens in spleen.
  • Weak signal: fully mature resting B cells
  • Too strong: apoptosis.
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16
Q

Prevalence of antibody (rank their abundance)

A

G > M > A > E

17
Q

What is changed during class switch recombination?

A

Constant region portion of heavy chain changed, but variable region portion of heavy chain stay the same.

18
Q

What is the elimination of cells that recognize self-antigens called? (hint: bone marrow vs. spleen)

A
  • Central tolerance in bone marrow.
  • Peripheral tolerance in spleen.
19
Q

What happened to immature B cells? Mature B cells? Activated B cells?

A
  • Immature B cells who bound to self-cell surface antigens is removed.
  • Mature B cell bound to foreign antigen got activated.
  • Activated b cell give rise to plasma cell and memory cells.
20
Q

What is the critical difference in B and T cell receptors?

A

The way they bind antigen
- TCR can bind a diverse array/antigens.

21
Q

Features of TCR (hint: region, chains)

A
  • 2 variable regions [top run horizontally]
  • 2 constant regions [bottom run horizonally]
  • Encoded by T-cell a and b (or g and d) chains
  • Disulfide bridge.
  • 1 antigen binding site
  • Never secreted
22
Q

Which TCR is the majority of T cells? ab or gd?

A

ab by >95%
gd only in ruminants 35%

23
Q

Explain recombination to produce TCR

A
  • DJ, then V
  • Rearrange alpha chain and Beta chain (rearrrange DNA)
  • Thymic selection: test if TCR recognize antigen
24
Q

What kind of epitopes are recognized by T cells: linear or discontinuous? Naive or processing state?

A

Linear, in the context of APC. They only recognize antigens/epitopes that already processed.

25
Q

What is MHC? And where do you find them?

A
  • Located on APCs.
  • MHC 1 is intracellular vs. MHC 2 is extracellular
  • Both use ER to synthesize MHC molecules to present antigens.
26
Q

What does it mean when “MHC locus is highly polymorphic”?

A

MHC is highly variable, present varying peptides to T cells.

27
Q

Compare/contrast MHC 1 and 2 structures

A
  • MHC1: 8-10 amino acid long
  • MHC2: 13-25 amino acid long, more open, no rings.
28
Q

What is anchor residue?

A

Anchor residues are amino acids that help anchor the peptides to the MHC molecule.

29
Q

What does CD4 binds to? What does CD8 binds to?

A

CD4 to MHC2 = class 2 restricted ; CD8 to MHC1= class 1 restricted

30
Q

What is the flow of immune system (T cells) in terms of organs?

A

Start as T cell progenitor from bone marrow, then goes to thymus. Once selected, it goes to periphery (secondary lymphoid organ). They start surveying what antigens being presented.

31
Q

Steps of T cell selection.

A
  • Happened in thymus
  • Enter through corticomedullary junction cortex.
  • Move up to cortex as 4(neg)8(neg)TCR(neg) = double negative, then interact with cortical epithelial cell. Then if it’s interact with MHC1, it becomes CD8; if it interacts with MHC2, it becomes CD4. This interaction is a positive selection.
  • Once became, it is committed.
  • Negative selection: if T cell interact with mTEC that has AIRE in it, T cell undergoes apoptosis because it interact with host antigens.

Additional note: immature T cells come in naked, no CD4, no CD 8, no TCR. Once entered thymus, chemokines promote T cell to express TCR, CD4 and CD8. Antigens presented on MHC1 or MHC2 will bind to T cell. If antigen on MHC1 binds, it will bind to T cell with CD8, and down regulate CD4. If antigen on MHC2 binds to T cell with CD4, CD8 will be down regulated. Lastly, self antigens will be released to test T cells. If T cells bind antigens, it will be eliminated.

32
Q

What can TCR recognize?

A

1 single TCR can recognize a range of related peptides in a context of MHC. Governed by CD3.

33
Q

The components of the T cell receptor complex are:

A
  • The TCR alpha and beta chains
  • Coreceptor CD4/CD8
  • Signaling molecule CD3
34
Q

During B cell development, B cell receptors are tested for self reactivity by _____. (Hint: what happened to heavy chain and light chain).

A
  • PreBCR to test heavy chain giving weak signal allowing B cell survival.
  • Rearranged light chain given weak signal = B cell survival to move out of bone marrow
  • Rearranged light chain given strong signal = B cell death
35
Q

Immunoglobin class-switch recombination changes _______ of the antibody.

A

Functionality. NOT specificity!!

36
Q

During T cell development in the thymus, what events occur to T cell?

A
  • T cell that strongly bind antigens presented by MHC 1 and 2 are eliminated.
  • T cell that can bind MHC 1 OR 2 are positively selected.
  • T cell change from expressing both CD4 and CD8 to express only one or the other.

402 Exam 2 (3 decks)

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