Lecture 2 Flashcards
Where doe all blood cells develop from?
common pluripotent stem cells.
What is a primary lymphoid organ?
The thymus and bone marrow where starting from the 13th week, some stem cells migrate there.
Where do T lymphocytes generate?
The thymus where they proliferate, differentiate, and complete their maturation.
Where do B cells proliferate, differentiate, and complete their maturation?
The bone marrow
Where are Ag specific receptors localized?
T and B cells
The sturucture of these receptors vafies from one cell to another but they are all identicall…
on a single cell
How long until a naive lymphocyte dies if they do not recognize an Ag?
1 to 3 months.
Pluripotent stem cells, CD 34 + differentiate into
lyphoid progenitor and myeloid progenitor
meloid progenitor become what 3 things?
mega karyocyte, myeloblast and erythroblast
what 2 things do lymphoid progenitors become?
t cell precurser and b cell pre cursor
CD stands for
cluster of differentiation, which indicates a defined subset of cellular surface receptors that identify cell type and stage of differentitation
What is refered to as resting lymphoctyes?
naive and memory lymphocytes?
Why is something a resting lymphocyte?
it is not deviding, nor are they performing effector functions
Can a person distinguish btw B and T lymphoctes?
No, not morphologically.
WHen observed on blood smears B and T lymphocytes are refered to as?
small lymphocytes (8 to 10 um)
What state of rest are naive lymphocytes in?
the Go stage of the cell cycle
What happens when stimulation occurs?
G1 stage of the cell cycle before dividing
What are activated lyphoctes called?
large lymphoctyes or lymphoblasts 10 to 12 diameter
What does the survival of naive lymphocytes depend on?
Signals generated by Ag receptors (TCR or BCR) and cytokines
What generates survival signals even in the absence of Ag?
Ag receptor of naive B cells (BCR)
What do naive T lymphocytes (TCR) recognize?
Various self Ags weakly, enough to generate surviavl signals but without triggering clonal expansion and differentiation into effecto cells.
What is the most important cytokine for survaval of naive T cells? What does it do?
interleukin IL-7, which promotes low -level cycling of naive T cells
What cytokine is required for B cell survival?
The cytokine in the TNF family, B cell-activating factor (BAFF)
What doe T cells make contact with and where?
epithelial cells, DCs, and Mo in the thymus
What provide mechanisms for the slection and differentition of T cells unful to the immune system?
cell-to cell interactions
What serve as solube regulatory factors or messengers for the immune system ion general?
cytokines
What 4 cytokines play an impotant role in T cell development?
IL-1, IL-2, IL-6, IL-7
Where do most naive T cells go after migration from the thymus?
They are maintained in the periphery without proliferating.
The number of naive T cells in the periphery remains fairly constat in youn adults,
despite continuouis output from thymus, suggesting balanced loss and replacmeent of peripheral naive T cells
What are large numbers of Ag-specifice T cells procuded from?
T cell precursors
Each T cell has receptors specific for only one Ag that is gnereated by…
gene rearrangement from multiple, inherited germline genes
Why does T cells undergo selection?
to remove those that are highly self reactive
What two types of cells are developed in the T cell process?
T helper cells and cytotoxic T lymphocytes (CTLs)
What do T helper cells express?
CD4 and provide help for B cell growth and differentiation
What do cytotoxic T lymphocytes express?
CD8 and recognize and kill virus- infected cells.
Where do mature T cells migrate?
To secondary lymphoid tissues to mediate protection
When do B cells start to develop?
Around the 14th week of gestation.
WHere does differntiation into B cells occur?
The fetal liver, after birth in the bone marrow, which is the lifetime production.
What two different kinds of B cells develop?
B1 and B2
WHat is the first antibody express on B cells/
IgM
What is expressed after IgM on B cells?
IgD
B cells protliferate into … with T cells help.
memory cells or inot plasma cells
What produce and secrete large amounts of Abs?
plasma cells
Who do B cells present Ags to?
helper T cells, which is a key step in the cooperation of Th cells with B cells for Ab responses to protein Ags
What are generatie lymphoid organs?
bone marrow and thymu
What are secondary lymphoid organs?
lymph nodes, spleen, regional lymphoid tissues such as mucosa-associated lymphoid tissue
What is peripheral lymphoid organs?
lymph nodes, spleen, mucosal and cutaneous lymphoid tissues
What parts of the body do lymphocytes not make it to?
eye, brain, and testicles
What specialized venules do the lymphoctes use to get to the lymph nodes, skin, and intestines?
High Endothelium Venules(HEVs)
What is not requried for the proliferation of B cells?
IL 2
Cells of HEVs are much higher than normal endothelial cells and express much high levels of?
adhesion molecules that serve as homing receptors for lymphocytes
What is diapesis?
the passage of blood cells through the intact walls of the capillaries, typically accompanyging inflammation
Why do lymphocytes migrate by diapediesis into the tissue/
In response to chemokines
How do lymphocytes renter the ciculations/
Efferent lymph vessels that merge into the thoracic duct
What are the most important for activation of naive T cells?
Dendritic cells
What is maturation of Dcs dependent on?
The cytokine Flt3, which binds to the Flt3 tyrosine kinase receptor on the precursor cells
What recognize Ags typically made by microbes and not mammalian cells/
Mo and DCs
Where do classical DCs resdie?
in skin, mucosa, and organ parenchyma
What responds to viral infections/
plasmacytoid DCs
What is important contacts for B cells development?
stromal cells and ctyokines IL1, IL6, and IL7
What is not required for the development of B cells, but is needed for the development of T cells?
IL2
How does recognition of Ag occur for B cells?
The B cell precursors rearrange multiple, inherited, germline genes that encode B cell receptors
What is a terminally differentiated B cell which produces and secretes lg amounts of Abs?
plasma cells
B cells present Ags to?
T helper cells
What is the function of a plasma cell?
secretion of Abs
What do lymphocytes develop from?
bone marrow stem cells and then mature in the genrative lymphoid organ
What parts of the body do lymphocytes no reach?
eye, brain, testicles
What area does lymphocytes reach via high endothelum venules (HEV)?
LN, skin and intestines, bc they are much higher than normal endothelial cells and their express high levesl of adhesion molecles that serve as homing receptors for lymphocytes
How do lymphocytes respond to chemokines??
migrate by diapedis into the tissue
How do lymphocytes reenter circulation?
efferent lymph vessels that merge into the thoracic duct
Antigens are captured from a site of infections and transported to?
the draining lymph node, where the immune response is initiated
Where do fully mature naive T cells and immature B cells migrate ?
into lymphoid organs such as LNs and the spleen
Where doe B cells complete there maturation?
LNs and spleen
What do naive B and T cells actived by Ags differentiate into?
effector or memory lymphoctes
WHere do some effector and memory lymphocytes migrate to?
periperhal tissue sites of infection
Abs secreted by effector B cells in LNs, spleen and bone marrow enter?
The blood and are deleivered to sites of infection
What are antigen presenting cells???(APCs)
Cells that capture, process, display microbial Ags to lymphocytes and provide signals that stimulate the proliferation and differentation of the lymphocytes
What do APC usually refer to ?
A cell that displays Ag to T lyphocytes bc B lymphocytes do not need PAC for their activation
What is the major type of APC involved in intitaiting T cell response?
dendrictic cells
What are other types of APCs?
macrophages and B cells, both present Ags to T lymphocytes in cell mediated and humoral immune responses
What does follicular DC display?
Ags to B lymphocytes during particular phases of humor immune repsonses
What provide link btw innate and adaptive immunity?
DCs and Mo
What are the most important for the activation of Naive T cells?
dendritic cells
What have long membranous projections and phagocytic capabilites?
dendritic cells
What linease are DCs from?
myeloid lineage and arise from a precursor that can also differentiate into monocytes
What is matturation of DCs dependent on?
cytokine Flt3 ligand, which binds to Flt3 tyrosine kinase receptor on the precursos cells
Do activated DCs secrete cytokines?
Yes
Fetal hemapoietic stem cells create??
langerhans cells
Adult dendritic precursors create?
classical Dcs, plamacytoid Dcs, and inflammatory DCs
Where do classical DCs reside?
skin, mucosa, and organ parnechyma
Upon activation by microbes, DC migrate to?
LNs where they display microbial protein Ags to T lyphocytes
What do plamacytoid DCs respond to?
viral infections
What does plamacytoid DCs recognize and produe?
nucleic acids of intracellular viruses and soluble proteins type I interferons, aka IFN-alpha/beta
What circulating thing can DCs be derived from?
monocytes
Where are FDCs found?
in collection of activated B cells with membranous projections
Where do FDCs reside?
LNs, spleen, and mucosal lyphoid tissues
What are unrelated to DCs that present Ags to T lymphocytes?
follicular dendirtic cells (FDCs)
What do FDCs bind and display? Why?
protein Ags, for recognition by B lymphocytes
FDCs have the remakable ability to?
retain complement- fixed Ags on tehirf cell surface for extended periods of time
What do FDC immune complexes provide?
antigenic stimulus that drives Ab affinity maturation
What are innate lymphoid cells? (ILCs)
several subsets of bone marrow- derived cells w lymphoid morphology
ILCs functions?
similar to T cells, but lack T cell antigen receptors
What are the 3 major functions of ILCs?
- provide early defense against infectious pahtogens
- recognize stressed and damaged host cells and help to elminate these cells
- influence the nature of the subsequent adaptive immune resposnee
What are the first and best characterized innate lyphoid cells?
natural killer cells
What doe NK cells sectreet?
IFN-gamma and kill infected and damaged cells
What is the HSC nich?
in the bone marrow where there are regions of support for functions of hematopoietic stem cells and other types of hematopoeitic cells (progenitors)
What does the HSC nich contribute too?
HSC quience, proliferation, self-renewal and differentiation
What does the nich consist of?
A network of vessels, nerve fibers, bone remodeling cells and subpopulations of hematopoietic cells, which reslut in a complex three demential architechture
The thymus is made of of??
The cortex and the medulla
What is teh Hassal’s corpuscle in teh thymus?
part of the medulla whose fuction is poorly understood
What makes up the white pulp of the spleen?
the T cell and B cell zones
Naive lymphocytes enter the LN through?
an artery, leave the circulation by moving across the wall of high endothelial venule
How do B and T cells migrate in the LN?
chemokines that are produced in these areas
Where do DC migrate too in the LN?
T cell rich arease
activated to be killing microbes
classical activation
activated to repair and remodel?
alternative activation
What type of receptors to mast cells and baosphils express?
IgE
What promote the maturation of eosinophils in myeloid precursors?
GM-CSF, IL-3, IL-5
