B3.084 T Cell Development Flashcards
what types of cells do blood cells arise from?
a common pluripotent stem cell
hematopoietic stem cell
what are the 3 classes that cells differentiate into during early development?
erythroid progenitors (RBCs and platelets)
myeloid committed precursor cells
lymphoid committed precursor cells
what types of cells are made from lymphoid precursors?
T cell
B cell
dendritic cell
NK cell
what types of cells are made from myeloid precursors?
dendritic monocytes neutrophils eosinophils basophils
how long do neutrophils survive in blood?
days or weeks
shorter once recruited to tissues
how long do lymphocytes live in blood?
years
characterize leukocytes
white blood cells
responsible for innate and adaptive immune responses
originate in bone marrow
recognize and destroy foreign invaders
how do NK cells differ from B and T lymphocytes?
do not possess antigen receptors
have some similar qualities to T cells despite this
use antibody to recognize antigen
more a part of the innate immune system
what would happen if clonal selection was uncontrolled?
you would develop a tumor
what is one way clonal selection is regulated?
T cells kill B cells
make you feel bad, but prevent you from developing tumors
what are the two types of antigens MHC molecules can present?
self antigen - ALL THE TIME, do not elicit a response
foreign antigen - when there is an infection
self MHC + foreign antigen = T cell recognition
can a T cell respond to a non-self MHC?
no
only self MHC
different in everyone
what important parts of the immune system are encoded within the human MHC gene on chromosome 6?
Class 2 - DP,DQ,DR Complement C4, C2 TNF Class 3 Class 1 - B,C,A
what cytokines can increase cell surface levels of MHC class 1?
IFN- a,b, gamma
antiviral state
what cytokines can increase cell surface levels of MHC class 2?
IFN gamma
TNF alpha
what does it mean to say that MHC antigens are codominant?
each allele inherited from the parent is expressed
how do TCR and BCR exhibit allelic exclusion?
the product of only one chromosome is expressed
nothing in common with parents due to somatic recombination
what is a haplotype
combination of alleles at linked loci found on one chromosome
often used with reference to the MHC
polymorphism
existence of multiple alleles at a particular gene locus
how many different MHC class 1 molecules does each individual possess?
6
why can each individual have many MHC class 2 molecules?
individual a chains can pair with individual b chains
describe the process of MHC binding and presenting
MHC molecules bind to an antigen
this sits in a cleft within the molecule
antigen within the cleft is presented to T lymphocytes
antigen binds to MHC with broad specificity
antigen binds to TCR with precise specificity
what occurs as T cells pass from immaturity through maturity in the thymus?
develop TCRs
other surface molecules change (CD3, CD4, CD8)
does the T cell develop further after leaving the thymus?
no
which complex does the TCR require to function?
CD3
what is an indicator of a stem cell in the bone marrow?
CD34+
describe the stages of T cell development
- CD3+ and CD4 - CD8 -
- CD3 + and CD4 + CD8 + (DP)
- CD3+ and either CD4+ or CD8+ (SP) (1.7:1 ratio of CD4+:CD8+)
negative selection
getting rid of T cells that respond to self antigen presented by MHC
positive selection
select for functioning T cells that are able to bind to self MHC complexes
central tolerance
occurs in the thymus
cells that respond strongly to self MHC and self antigen are destroyed
peripheral tolerance
outside of the thymus
occurs when self reacting T and B cells are in an unreactive state to self antigens
what are the 4 mechanisms of peripheral tolerance?
- ignorance - autoreactive T cells never encounter their cognate Ag except by accident
- Deletion - self-specific peripheral T cells are destroyed after TCR engagement (negative selection is leaky and some T cells survive until later)
- Anergy - a state of functional unresponsiveness induced upon self Ag recognition
- Foxp3+ Treg cell mediated suppression of dangerous T cell responses against self-Ag
how are Treg cells produced?
stimulation of CD4+ T cells with TGFB
how do Treg cells inhibit T cells?
cytokines IL-10 and TGFB