B & T cell Development + Antigen Presentation Flashcards
what are the stages of development for a B cell?
pre-pro, pro-B, pre- B,
what occurs during B cell development?
spontaneous recombination with events generate IgM BCR with diverse antigen combining sites
what happens to immature B cells released from the bone marrow?
they express IgM receptors and are antigen reactive, travel to spleen to finish developing
what is BAFF?
B cell activating factor, provides a survival signal
What occurs during T2?
maturation with IgD, B cell fully mature, some stay in follicles of spleen while others migrate to the blood and peripheral lymph organs
what happens during receptor editing?
modifications to #D structure of binding site initiate a new round of VJ recombination
what occurs during T1 in the spleen?
negative selection, B cells that react with self molecules get deleted, rest go to T2
what is expressed of the surface of B cells?
IgM and IgD
what happens if a follicular B cell encounters an antigen?
recognizes it and gets help from helper T cell and divide exponentially
what happens with the C region of the B cells
gene expression changes as it matures and proliferates after stimulation with antigen under help from helper T cells
what is a plasma cell?
secrete large number of antibody but lose cell surface immunoglobulin
what is somatic hypermutation?
selection of B cells producing antibodies with increased affinity for the antigen
how do we get IgM and IgD?
RNA splicing (in spleen T2 has both, they generate two RNA transcripts which get processed differently)
how can different classes of Ig switch?
helper T cells guide the switch to CG, CE, CA to make IgG, IgE, IgA
what is the difference between the classes of AB?
all have same antigen binding specificity (V regions) but different constant regions on the heavy chain so they have different biological regions
what is a B1 cell?
primitive subclass of B cell, in peritoneal cavity, no IgD, have IgM w/o HT cell, more ike innate immunity- no specificity
what commits them to the T cell lineage?
a receptor called notch (it makes the assemble TCR)
when T cells arrive at the thymus what happens?
TCR not assembled, do not express CH4 or CD8 (so called double negitive)
What is significant about the TCRab cells?
CD4&8 positive, predominant in the lymph nodes and spleen
what are the two types of T cell receptors?
AB and GD
what do TCRab recognize?
proteins antigens and bind to antigen derived peptides and MHC,
diverse antigen characteristics
what do the TCRgd cells do?
CD4&8 negative, predominant on skin and mucosal surfaces recognize lipid antigens but do not use MHC, less diverse
what are the four mechanisms used by T cells to produce a diverse range of receptors?
- selection from many mini gene segment
- rocomb to join to randomly selected mini segments
- addition and deletion of nucleotides during joining of mini segments
- association of two different chains to form binding sites
what happens when the B chain rearrangement is productive?
the T cells rearrange the α chain, and the Cells become Tαβ cells
what happens when the B chain arrangement is non productuve?
the cell will rearrange the γ and δ chains to make TCRγδ and Tγδ cells
what happens after TCRab mature and go through cortex?
In the journey, they are
selected according to their affinity for MHC class I and II molecules (pos/neg selection), and self-reactive clones are deleted
what happens so singe positive TCs?
that enter the periphery to carry out functions
describe MHC selection for Tab cells?
The developing Tαβ cells “browse” through the cortical thymic epithelial cells, which express high levels of MHC class I and II molecules (the ID molecules) in
the thymus
What are Major Histocompatibility
Complex (MHC) molecules?
These are self-identity molecules that have broad binding specificity. The same MHC molecule can carry many different peptides, including self-peptides
MHC molecules have peptide-binding domains, which bind to the TCR and CD4/CD8 binding domains
where is the MHC I found?
every cell (nucleated). CD8 molecules on T cells bind to its α3 domain of MHC I
where are MCH II found?
antigen-presenting cells. CD4 molecules on T cells bind to its β2 domain MHC II
CD4+CD8+ DP thymocytes make up ______ of thymic cells
80% of thymic cells
A T cell is positively selected if:
its TCR can bind the MHC-peptide with moderate affinity and shifts from DP to SP
If the TCRαβ can bind to an MHC class II molecule, it also binds with:
the CD4 molecule, selecting the cell to the CD4+ subset (T helpers)
what happens if theTCRab binds to MHC CI?
The opposite happens if the TCRαβ binds to an MHC class I molecule, resulting in selection to the CD8+ subset (CTL/Tc
what happens if T cells with TCRs can’t bind MHC-peptide
die of neglect
what happens to the negative selected cells
move to medulla for further screening
The medullary thymic epithelial cells (mTEC) have a unique protein autoimmune regulator, what does it do?
induces them to express, process, and present many tissue-specific proteins
Thymocytes bearing high-affinity receptors for self-MHC/peptide complexes are
deleted
why is this deletion important?
ensures self-tolerance (elimination of self-reactive clones)
CD4+ and CD8+ thymocytes that survive the selections migrate into the bloodstream and
complete their maturation in the periphery AND DO WHAT?
They recognize foreign antigenic peptides presented to them on the MHC molecules.
When T cells have TCRαβs that bind too strongly to self-peptide/MHC complexes:
apoptosis occurs
why doesn’t hyper mutation occur after MHC section?
Somatic hypermutations do not occur because after MHC selection, mutations lead to loss of MHC recognition, and then the T cells cannot receive signals from antigen-presenting cells.
Recognition of self-antigens by immature T cells in the thymus may lead to what two possibilities?
death of the cells OR the development of regulatory T cells that enter peripheral tissues
when are autoreactive T cells removed?
Removes autoreactive cells before T cells are released into the peripheral bloodstream
Do most cells make it through positive section?
Most cells (95%) fail positive selection and fail to receive needed survival signals,
and die by apo
T cells that are released into the peripheral bloodstream, will be ones activated by what, that then does what?
by foreign peptides presented to them on these MHC molecules (i.e. they are MHC restricted).
Functionally, they become T helper cells and cytotoxic T lymphocytes that carry out immune defense
what occurs within peripheral control?
A small percent of the thymocytes that see self-antigens in the thymus differentiate to CD4+, regulatory T cells.
They leave the thymus and inhibit responses against self-tissues in the periphery.
Among those that bear TCRαb, a small percent of the thymocytes commit to become ______
NKT cells
(if b non productive can become gd or nkc)
where are TCRgd seen?
Appear in the circulation early in ontogeny
Required for protection of the young, and they decline afterbirth
TCRgd do not go through _____
double pos section
TCR join ___ immune system in first time of attack
innate
what is recognized by tcrgd?
lipids on the surface of the antigens do not need shock proteins
what are natural killer cells?
A heterogeneous group of T cells with TCR assembled with an
invariant α chain and a limited number of chains (They do
not have very many specificities, not very diverse)
what do natural killer cells bind?
oreign and self-lipids and glycolipids (such as mycobacterium, which causes tuberculosis)
NKC react with:
lipid antigens presented by CD1, a non-polymorphic MHC class I-like antigen-presenting molecule
Allelic forms of MHC are inherited in
linked groups called
HAPLOtypes
how are haplotypes expressed?
Both alleles are co-dominantly expressed, meaning a person will express the MHC class from the maternal and the paternal simultaneously. (Double the
number of molecules a person can have.
describe Genetic polymorphism of MHC in human population
There are 6 different classes of class I and 12 different classes of class II molecules within a person (6 x 12 x 2 alleles) allows for tremendous genetic variations
describe the process of antigen presentation
process of generating the fragments and putting them on major histocompatibility copes molecules for presentation to the T lymphocytes
Where is polymorphism exhibited?
region that binds peptides
what is the structure of a class I molecule?
A peptide with 3 domains (α1, α 2, and α 3) and a transmembrane C-terminal
+
β2-microglobulin (not encoded in MHC)
a1 and a2 domains form a
cleft that faces toward the cell membrane
may carry antigenic peptides
class I molecules have what type of specificity?
broad, many peptides can fit the same MHC molecule
which amino acid groups on class one molecules are highly polymorphic and which are non-polymorphic
1 & 2 are polymorphic
3 is non
what binds to the a3 domain?
CD 8 molecules
where are class one molecules found?
almost all nucleated cells
MHC Class one molecules present what?
endogenous antigens to CD8 cytotoxic T cells
what does the MHC I present?
endogenous antigens to CD8 to cytotoxic T cells
what is the progression after a cell gets infected by a virus and viral proteins get syn inside the cell?
processed into proteosomes
what happens when peptide MHC molecules and T cell receptors bind?
CD8 enhances the binding at non polymorphic non-peptide binding regions
what do CD8 CTL’s do?
lyse the virus infected cells and eliminate the virus
what is the structure of a MHC II molecule?
a peptide with a1 and a1
b peptide with b1 and b2
(both have transmembrane C terminal)
the a abd b domains form a ______
cleft (faces outward from the cell membrane
which part of the MHC II is polymorphic and which is non-polymorphic?
a 1 and b1 are polymorphic
a2 and b2 are nonpolymorphic
what binds to the b2 domain?
CD4
which MHC has CH4 and which has CH8?
MHC I has CD8
MHC II has CH4
where are MHC II found?
surface of antigen presenting cells
(remember MHC I is found on the surface of almost all nucleated cells)
what do MHC II do?
present antigens to CD4 and helper T cells
what are examples of professional antigen presenting cells?
dendritic cells, macrophages, B cells
(cells that always express MHC II molecules)
what are examples of macrophage like cells?
Langerhans (skin/mucosa)
dendritic cells (Fc or c3 receptors of antigens)
what are examples of occasional presenters?
cytokines, keratinocytes, endothelial cells
what do MHC II molecules present?
exogenous antigens to CD4 T helpers
recap: what is the function of MHC II?
EXOGENOUS antigens to CD4
constitutively expressed on B cells and induced on non-professional cells when needed
recap: what is function of MHC I?
ENDOGENOUS antigens to CD8
what peptides can be presented on the surface by an MHC molecule?
any MHC can bund numerous peptides, including self (peptides can exchange in and out)
what is brough specificity when it comes to MHC?
many different peptides can bind to the same MHC molecule
how many peptides can bind to a MHC at a time?
one. each T cell only responds to one peptide bound to an MHC
what presents non peptide antigens?
CD 1
(structurally similar to class I functionally similar to class II)
what is population significance?
diversity in the MHC locus imparts an evolutionary survival advantage for a species against mortality from an infectious disease (survival of race not necessarily individuals)
what is the benefit to polymorphism in the region of the peptide
allows each persons MHC to bind different panels allowing individuals to react differently to different pathogens
what is a disadvantage of polymorphism of MHC?
certain alleles are associated with disease like autoimmune
what does CD 1 present? what allows it to do this?
lipid containing antigens
hydrophobic groove
what does the CD1 present to?
NKT cells and Tgd cells
Which of the following is NOT True of MHC class I molecules?
a) Present on all nucleated cells
b) Present endogenous antigen to CTL
c) CD-4 molecules bind to the polymorphic region
d) Beta 2- microglobulin is part of its structure
e) Present peptides of protein antigens
c) CD-4 molecules bind to the polymorphic region
