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Heme/Lymph > Lymphoid Development > Flashcards

Lymphoid Development Flashcards

1
Q

General outline of B and T cell development

A
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2
Q

What can antibodies recognize?

What mediates binding?

What mediates Ab signaling function?

What mediates Ab effector functions?

A

Macromolecules - Conformational and linear epitopes

Antigen recognition mediated by variable regions of heavy and light chains of Ig

Signaling functions are mediated by proteins (Alpha/Beta chains) associated with membrane Ig

Effector functions are mediated by constant regions of secreted Ig

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3
Q

What is the structure of an antibody?

A 
5 different classes (isotypes) that are functionally different due to constant region differences
Light chains are either kappa or lambda (not changed during class switching)
3 regions of hypervariability for heavy and light chain: Contact sites for epitope in the antigen binding site: Complementarity-determining (CD regions) CDR1,2,3
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4
Q

IgA:
Subtypes
Heavy Chain
Serum Concentration
Seerum half-life
Secreted form
Functions

A

Subtypes: IgA 1,2
Heavy chain – Alpha(1,2)
Serum concentration – 3.5 mg/mL
Serum half-life – 6 days
Secreted form – Monomer, dimer, trimer
Functions – Mucosal immunity

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5
Q

IgD
Subtypes
Heavy Chain
Serum Concentration
Seerum half-life
Secreted form
​Functions

A

Subtypes: None
Heavy chain – Delta
Serum concentration – Trace
Serum half-life – None
Secreted form – None
Functions – Naïve B cell antigen receptor

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6
Q

IgE
Subtypes
Heavy Chain
Serum Concentration
Seerum half-life
Secreted form
​Functions

A

Subtypes: None
Heavy chain – Eta
Serum concentration – 0.05 mg/mL
Serum half-life: 2 days
Secreted form: Monomer
Functions: Mast cell activation (immediate hypersensitivity), defense against helminthic parasites

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7
Q

IgG:
Subtypes
Heavy Chain
Serum Concentration
Seerum half-life
Secreted form
​Functions

A

Subtypes: IgG1-4
Heavy chain – Gamma (1,2,3,4)
Serum concentration – 13.5 mg/mL
Serum half-life – 23 days
Secreted form – Monomer
Functions: Opsonization, complement activation, Ab-dep cell-mediated cytotoxicity, neonatal immunity, feedback inhibition

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8
Q

IgM:
Subtypes
Heavy Chain
Serum Concentration
Seerum half-life
Secreted form
​Functions

A

Subtypes: None
Heavy chain – Mu
Serum concentration – 1.5 mg/mL
Serum half-life – 5 days
Secreted form – Pentamer
Functions – Naïve B cell antigen receptor, complement activation

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9
Q

Define the following types of isotypic, allotypic, idiotypic:

A

Isotypic – Large differences in constant regions which determine IgG vs IgA vs etc.
Allotypic – Small differences in constant regions which make the isotypes unique to the individual
Idiotypic – Variable region differences

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10
Q

How does Ig affinity change during immune response?
What is the on-rate and off-rate during immune response?
What is the role of accessory molecules?

A

Affinity of Igs increase during immune response
Rapid on-rate, variable off-rate
No accessory molecules

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11
Q

What do T-cells recognize?
How is antigen recognition mediated by variable regions of alpha/beta chains?
How are signaling functions mediated?
What effector functions do T-cells have?

A

Recognize peptides displayed by MHC molecules on APCs - Linear epitopes

Antigen recognition mediated by variable regions of alpha/beta chains

Signaling functions mediated by CD3 and Zeta proteins associated with TCR

TCR does not perform effector functions

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12
Q

How does Ag recognition change for T-cells during infection?

What is the on-rate and the off-rate?

What molecules also are needed for recognition?

A

No change during immune responses

Slow on-rate, slow off-rate

CD4 or CD8 simultaneously binds MHC molecules

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13
Q

Define affinity vs avidity?

A

Affinity – Specific interaction binding kinetics
Avidity – The combination of all the affinities over an entire process (multiple reactions)

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14
Q

What is the rearrangement sequence of the heavy chain?

A

D-J recombines
V-DJ recombines
VDJ-Constant recombines
VDJC is then expressed within the cell

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15
Q

What is the rearrangement sequence of light chain?

A

V-J recombines
VJ-Constant recombines
VJC expressed and joins heavy chain at the cell’s surface

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16
Q

What are the types of diversity?

A

Combinatorial diversity: V-(D)-J number of combinations
Junctional diversity: Post combination, endonucleases can excise portions of the combined locus creating distinct new loci
Mix and match pairing of light and heavy chains
Somatic hypermutation - Important step of Ig affinity maturation, Not strictly a method of diversity

17
Q

What is allelic exclusion?

A

Only maternal or paternal allelic recombination occurs not both
If one succeeds the other does not occur
If neither succeeds the cell dies
Protects clonal specificity

18
Q

What is the importance of the RAG gene in recombination?

A

Necessary for Pro lymphocyte to reach Pre lymphocyte
Deficiency results in SCID

19
Q

What are the maturation steps involved for lymphocytes?

What are the checkpoints?

A

Proliferation – IL-7 mediated

Pre-B/T antigen receptor expression – First recombination
Failure is the first checkpoint, leads to cell death

Proliferation of Pre-cells

Antigen receptor expression – Second recombination
Failure is second checkpoint, leads to cell death

Positive and negative selection

20
Q

Explain positive and negative selection, and what kind of avidity does it display?

A

Positive selection - Mature cells show weak self-antigen recognition (Low avidity)
Negative selection – Strong self-antigen recognition (High avidity)
Lack of positive selection – No self-antigen recognition (No avidity)

21
Q

Where does T-cell maturation occur?

What CD expression is there for the immature cells?

How does positive selection effect CD?

A

Thymus is the major site
Cortical region – Positive selection
Medullary region – Negative selection

Immature cell are CD4/CD8 double positive

Positive selection – Self reactive MHC+ peptide live and proceed to the next stage
If Class I recognition – CD8+
If Class II recognition – CD4+

22
Q

What are the specific changes in Ig DNA,RNA and Ig expression for B cell maturation?

A

Heme/Lymph (18 decks)

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