B3.039 Prework 1 Immune Cell Development Flashcards
what defines a naïve lymphoid cell
express antigen receptors, but cannot do anything
where are naïve lymphoid cells located?
circulate amongst peripheral lymphoid organs
describe the life cycle of naïve lymphoid cells
survey for antigens and differentiate upon exposure into memory and effector cells
undergo apoptosis if they don’t find their antigen within weeks to months
new cells are released
what defines a B Cell effector cell
produce molecules that eliminate antigens
function of plasma cells
produce Abs in the peripheral lymphoid tissues
function of plasmablasts
produce Abs in the blood stream
some migrate to the bone marrow to mature into plasma cells
function of T Cell effector cells
produce molecules that eliminate antigens
short lived and die after elimination of antigen
function of CD4+ T helper cells
produce cytokines to activate B cells, macrophages, and others
function of CD8+ cytotoxic cells
kill infected host cells
what are lymph nodes
encapsulated aggregates of lymphoid tissue
what is lymph
leakage from blood vessels
function of lymphatic vessels
carry the lymph that has drained from the tissues to the lymph nodes
discuss the role of the lymphatic system in immunity
APCs sample the lymph for antigens of microbes
dendritic cells capture antigens and transport them to the lymph node via the afferent vessel
exit lymph node via the efferent lymphatic vessel
where are follicles located in the lymph node
cortex
what is located in cortex follicles
B cells- periphery/cortex
follicular dendritic cells
where are germinal centers located
middle of follicles
light staining areas
what is located in germinal centers
B cells that have recently responded to an antigen
site of antibody production
what is located in the paracortex of the lymph nodes
T cells adjacent to the follicles
dendritic cells
discuss the circulation of naïve T and B lymphocytes
constantly circulate between blood and lymphoid organs where they enter through a high endothelial venule (HEV)
chemokines home them to their respective area
CXCR5
receptor on B cells that homes them to the follicle
CCR7
receptor on T cells that homes them to the paracortex
discuss the circulation of dendritic cells
enter through afferent lymphatic vessels
migrate to the T cell rich areas of the node
how are lymphocytes activated upon stimulation by antigen
change chemokine receptors
T and B cells can move toward each other and meet at the follicular edge to interact
T cells help B cells differentiate into Ab producing cells
what happens after lymphocytes are activated
exit through the efferent lymphatic vessels to travel to sites of infection
some T cells migrate into the follicle to help B cells make high affinity Abs
where are plasma cells located
peripheral lymphoid tissue and bone marrow
do not migrate to sites of infection
function of plasma cells
secrete Abs into the blood stream and onto mucosal surfaces to bind microbes or their toxins
what cells do migrate to sites of infection
effector T cells
other memory T cells will recirculate in the lymph nodes
function of spleen white pulp
trap pathogens and their secreted antigens that have entered the blood stream and present them to naïve lymphocytes passing through
pathogens are coated by Abs generated in the white pulp
function of spleen red pulp
filters and removes microorganisms via phagocytes that recognize the Ab or complement coated microorganism directly
filters blood to remove abnormal or old RBCs
PALS
periarteriolar lymphoid sheath
surrounds splenic arteriole
made up of T cells
what makes up the white pulp
PALS and lymphoid follicles together
where are vascular sinusoids
red pulp
what is the mantle zone
ring of lymphocytes surrounding the germinal center
what is the marginal zone
interface between the red pulp and the white pulp where particulate antigen from circulation is trapped and presented to APCs
GALT
gut associated lymphoid tissue
secondary lymphoid tissue
function of GALT
trap pathogens and their secreted antigens that have entered through the GI tract
presentation to naïve lymphocytes passing through
what creates the innate barrier of the GALT
mucus secreting epithelium
where is gut commensal bacteria located
stays in the lumen
what are M cells
specialized epithelial cells that promote antigen transportation to underlying tissues
where do lymphoid cells encounter antigen in the GALT
lamina propria
Peyer’s patches
organized areas of lymphoid aggregates
which Ig is associated with the GALT
IgA transports into the lumen to neutralize microbes
what prevents reactions to commensal microbes
T reg cells and others suppress T lymphocyte activation
25% of the body’s lymphocytes are in these areas at any given time
GALT/ MALT/ cutaneous lymphoid tissue
makeup and function of the thymus cortex
immature T lymphocytes differentiate
undergo selection
reticular epithelial network
makeup and function of the thymus medulla
less T lymphocytes
undergo further selection and mature prior to leaving
what is Hassal’s corpuscles
within the medulla
flat keratinized degenerate epithelial cells
what are the two primary steps in IgH rearrangement
1st: D to J recombination
2nd: V to DJ
what is V(D)J recombinase
group of enzymes that mediate recombination
lymphocyte specific enzymes and ubiquitously expressed enzymes
what are the primary lymphocyte specific enzymes in V(D)J recombinase
recombination-activating gene-1 and -2 (RAG-1 and RAG-2)
terminal deoxynucleotidyl transferase (TdT)
what are the ubiquitously expressed enzymes in V(D)J recombinase
DNA ligase IV
DNA-PK
combinatorial diversity
mediated by RAG-1/2
many combination of Vs, Ds, and Js can be used
D>J followed by V>DJ
junctional diversity
mediated by TdT
addition/subtraction of nucleotides at the coding joint
describe B cell receptor editing
the autospecific B cell undergoes a second K/L locus rearrangement
second rearrangement replaces the L chain of the self reactive BCR
B cell undergoes another round of selection based on its new BCR
negative selection
if BCR editing does not succeed, cells apoptose
most immature B cells die
positive selection
become mature naïve B cells
must co-express IgM and IgD
pro-B cells
express RAG-1/RAG-2 and TdT
pre-B cells
express IgM + surrogate light chain
re-express RAG-1 and RAG-2
immature B cells
express IgM+ K or L chain
subject to selection or deletion, MOST immature cells die
mature B cells
cells that undergo positive selection, become mature naïve B cells
must co-express IgM and IgD
goals of T cell development
functional lymphocytes
diverse repertoire
limited self reactivity
what are TRECs
T Cell receptor excision circles
circular DNA formed by the genomic rearrangement that occurs during V(D)J recombination
how are TRECs measured
qPCR (reported as number of PRECs per million cells)
diagnostic usage of TRECs
newborn screening for primary immunodeficiency
thymic output after HSCT
double negative thymocytes
ab vs yd lineage commitment
pre-TCR expressed
double positive thymocytes
TCRab, CD4, CD8 expressed
positive and negative selection
single positive thymocytes
TCRab, and EITHER CD4 or CD8 expressed
what is positive selection
TCR binds MHC-peptide complexes in the thymus
only cells expressing a TCR that can bind MHC peptide complexes can be positively selected
what is negative selection
if a cell fails to bind MHC, undergoes apoptosis
if a TCR binds self peptide, it is eliminated to prevent autoreactivity
