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Flashcards in Lymphoid Development Deck (22):
1

General outline of B and T cell development

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2

What can antibodies recognize?

What mediates binding?

What mediates Ab signaling function?

What mediates Ab effector functions?

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

3

What is the structure of an antibody?

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

4

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

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

5

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

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

6

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

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

7

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

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

8

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

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

9

Define the following types of isotypic, allotypic, idiotypic:

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

10

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?

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

11

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?

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

12

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?

No change during immune responses

Slow on-rate, slow off-rate

CD4 or CD8 simultaneously binds MHC molecules

13

Define affinity vs avidity?

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

14

What is the rearrangement sequence of the heavy chain?

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

15

What is the rearrangement sequence of light chain?

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

16

What are the types of diversity?

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

What is allelic exclusion?

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

What is the importance of the RAG gene in recombination?

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

19

What are the maturation steps involved for lymphocytes?

What are the checkpoints?

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

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

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

Where does T-cell maturation occur?

What CD expression is there for the immature cells?

How does positive selection effect CD?

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

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

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