Antigen Recognition in Adaptive Immune System

What type of antigen does TCR recognize

Peptide on MHC

What antigen does BCR recognize

Free antigen

What type of response is TCR involved in

Cellular immunity

What is cellular immunity

T cell activation, cytokine release, cytotoxicity

What type of response is BCR involved in

Humoral immunity

What is humoral immunity

Antibody production

What activation is required for TCR

Antigen presentation by APC

What activation is required for BCR

Can directly bind to antigen

What is the name for the antigen binding region on B cell

Paratope

What is the name for the part of the antigen that binds with paratope

Epitope

What chains are present in B cell

Heavy and Light chains

What isotopes are on the heavy chain

IgG, IgA, IgD, IgE, IgM

What must T cells have

TCR and CD3

What are the 3 segments of genes in somatic recombination

V, D, J

B cell heavy and light chain has what segments

VDJ, constant region and kappa and lambda on heavy chain

What segment on the alpha chain

V and J

What segment on the beta chain

VDJ

What is the arrangement for alpha genes (chain)

V → J → C

What is the arrangement for beta genes (chain) and immunoglobulin

D → J → V → C

What mediates recombination of immunoglobulin

VDJ recombinase

What is the first expressed isotype

IgM, IgD (rare)

What is junctional diversity

VDJ recombination/somatic recombination process

What enzymes are used in junctional diversity

RAG, TdT

What does RAG do

Binds and cleave sequence to create DNA hairpin

What does TdT do

Add N-nucleotides to hairpin

What is the precursor (and its location) of T and B cell

Common lymphoid progenitor cell from HSC in bone marrow

Where do immature B cell mature

Spleen (secondary lymphoid organ)

Where do immature T cell (thymocyte) mature

Thymus

What are the stages of B cell development

HSC → Pro-B → Large Pre-B → Small Pre-B → Immature B

What happens to IgH, IgL chain gene and Ig protein at the Pro-B stage

IgH D to J rearrangement, no IgL production or Ig protein expressed

What happens to IgH, IgL chain gene and Ig protein at the large pre-B stage

IgH V to DJ rearrangement, expression of pre-BCR and surrogate receptor, no IgL

What happens after large pre-B stage

Allelic exclusion

What is the allelic exclusion phase

Shut off recombination of Ig heavy-chain genes on second chromosome

What is the function of BTK

Mediate pre-B cell stage and beyond survival, proliferation and maturation

What is XLA

Def of BTK

What happens to IgH, IgL chain gene and Ig protein at the small pre B stage

IgH has rearranged VDJ, IgL has V to J rearrangement, there is intracellular miu

What happens to IgH, IgL chain gene and Ig protein at the immature B cell stage

IgH has rearranged VDJ, IgL has rearranged VJ, Ig protein is IgM

What is receptor editing

B cell that bind to self antigen with high affinity change the receptor

What are two types of receptor editing

Positive and negative selection

What occurs during positive selection

B cell live since the edit produces B cell receptor that doesn’t bind to self antigen

What happens during negative selection

B cell are killed if the edit produces another B cell receptor that binds to self antigen at high affinity

What are the 3 outcomes of central tolerance

Clonal deletion, receptor editing, anergy

What is clonal deletion

Apoptosis of strongly self-reactive B cell

What is anergy

Some self-reactive B cell become unresponsive instead of being killed

Where in the thymus can a large amount of HSC be found

Thymus capsule

What happens in the sub capsular region

T cell development

What triggers Pro T development from double negative common myeloid progenitor cell

IL2 and IL7 from thymocyte

What changes double negative CMP into double positive CMP

Expression of both CD4 and CD8 on cell surface

What occurs in the thymus cortex

Positive selection

What is positive T cell selection

Removal or either CD4 or CD8 based on binding affinity

What will happen if there is strong binding to MHC class II of cortical epithelial cell

Downregulation of CD8 and increase CD4

What will happen if there is weak binding to MHC class II of cortical epithelial cell

Downregulation of CD4 and increase CD8

Where does T cell self tolerance/negative selection occur

Corticomedullary junction

What is T cell negative selection process

AIRE forces T cell to show receptor to DC to ensure no self-reactive T cell

What does AIRE do

Activate TEC/Hassell corpuscle

What sends activation on BCR and TCR

BCR has Ig protein cluster and TCR has CD3

What does BCR binding do

Lead to tyrosine pshophrylation event

What does ITAM do

Give phosphate to adaptor protein

What is the process of signal transduction in B lymphocytes

Cross linking → Tyrosine phosphorylation events → Biochemical intermediate activation → Active enzyme → Transcription factor activation

Anti-calcineurin mechanism of action and indication

Reduction of T cell function for dry eyes

What is the function of NFAT

Encode T cell growth factor IL2 and IL2 receptor component

Function of AP-1

Enhance t cell gene transcription

Function of NF-kb

Activate T cell, stimulate cytokine and cytokine receptor transcription

What are the 2 signals needed for T cell activation

MHC antigen binding, APC expression of costimulatory molecule

What happens if T cell is missing one signal

Become anergic or apoptosis

What is the function of Coinhibitor

Limit/terminate immune response, inhibit T cell response

What is the mechanism of costimulation pathway

Dephosphorylation of signal components