Lec 02- Cells and Tissues of the Adaptive Immune System Flashcards
What is CD?
cluster of differentiation
Defined subset of cellular surface receptors that identify cell type and stage of differentiation
Myeloid lineage of Pluripotent Stem Cell
Myeloid pregenitor
- Megakaryocyte
- Erythroblast
- Myeloblast
- Monocyte
Lymphoid lineage of Pluripotent Stem Cell
Lymphoid progenitor
- T-cell precursor
- B-cell precursor
Megakaryocyte»_space; ______
Megakaryocyte»_space; Platelets
Erythroblast»_space; ________
Erythroblast»_space; Erythrocytes
Myeloblast»_space; ______, _____, ______
Myeloblast»_space;
- Basophils
- Eosinophils
- Neutrophils
Monoblast»_space; ______, _____
Monoblast»_space;
- Monocytes
- Dendritic cells
T-cell precursor»_space; ________, _______
T-cell precursor»_space;
- Natural killer cells
- T lymphocytes
B-cell precursor»_space; ______
B-cell precursor»_space; B lymphocytes
All blood cells develop from _______.
Common pluripotent stem cells
At what week of gestation do some stem cells migrate to the 1’ lymphoid organs (thymus and bone marrow)?
13th week of gestation
If naive lymphocytes do not recognize Ag, how long does it take for them to die?
1-3 months
What are resting lymphocytes?
- Naive and Memory B and T lymphocytes
- Not actively dividing
- Not performing effector functions
What are small lymphocytes?
- Naive and Memory B and T lymphocytes
- 8-10 um in diameter
Which lymphocytes are in a state of rest/ in the G0 stage of cell cycle?
Naive lymphocytes
When do naive lymphocytes enter the G1 stage before going on to divide?
in response to stimulation
What are large lymphocytes or lymphoblasts?
- activated lymphocytes
- 10-12 um in diameter
What do immature T cells make contact with in the thymus?
- specialized epithelial cells
- dendritic cells
- MO
T lymphocyte cell-to-cell interactions provide mechanisms for ______.
The selection and differentiation of T cells that can be used in the immune system
What are cytokines?
- soluble regulatory factors
- messengers for the immune system
Which cytokines play an important role in T cell development?
IL-1
IL-2
IL-6
IL-7
Following migration from the thymus, most mature naive T cells are maintained in ______.
the periphery without proliferating
The number of naive T cells in the ______ remains fairly constant in young adults.
in the periphery
Naive lymphocyte survival depends on ______.
Signals generated by:
- Ag receptors (TCR or BCR)
- cytokines
What can general survival signals even in the absence of Ag?
Ag receptor of naive B cells (BCR)
Naive TCRs weakly recognize self Ags, enough to generate survival signals but without triggering _____.
Without triggering:
- Clonal expansion
- Differentiation into effector cells
What is the most important cytokine for survival of naive T cells?
IL-7
What does IL-7 do?
promotes low-level cycling of naive T cells
What is required for naive B cell survival?
BAFF
B cell-activating factor
-a cytokine that belongs to the TNF family
T cell receptors are generated by ______ from multiple, inherited germ line genes.
gene rearrangement
T cells undergo selection to _______.
remove those that are highly self-reactive
What 2 types of T cells develop from selection?
- Helper T cells
- Cytotoxic T lymphocytes (CTLs)
What do helper T cells express?
CD4
What is the function of helper T cells?
provide help for B cell growth and differentiation
What do cytotoxic T lymphocytes (CTLs) express?
CD8
What is the function of cytotoxic T lymphocytes?
recognize and kill virus-infected cells
Where do functionally mature T cells migrate to, to mediate protection?
secondary lymphoid tissues
B cells start to develop from stem cells around what week of gestation?
14th week of gestation
Where does differentiation into B cells occur in a fetus and in an adult?
Fetus = liver Adult = bone marrow
What are important for development of B cells?
-Contact with stromal cells in bone marrow
-Cytokines:
> IL-1
> IL-6
> IL-7
As compared to the development of T cells, which cytokine is not required for proliferation of B cells?
IL-2
In the bone marrow, B cell precursors ________ multiple, inherited, germ line genes that encode B cell receptors (Abs) for recognition of Ag.
rearrange
Which B cells are eliminated?
B cells with BCRs that react with self-Ags = eliminated
What is the lifetime production site of B lymphocytes?
bone marrow
What are the 2 types of B cells?
B1 (fetal)
B2 (adult)
What is the first Ab that is expressed on B cells?
IgM
What is the second Ab that is expressed on B cells?
IgD
Where do mature B cells migrate to?
2’ lymphoid tissues
respond to foreign Ags
What happens when B cells are activated by Ag (sometimes with the help of T cells)?
- proliferate in germinal centers
- mature into memory or plasma cells
What are plasma cells?
- terminally differentiated B cells
- produce and secrete large amounts of Abs
What is a key step in the cooperation of Th cells with B cells for Ab responses to protein Ags?
B cells presenting Ags to helper T cells
What % of the bone marrow white cell count is comprised of plasma cells?
- 2-2.8%
- rarely found in the peripheral blood
Lymphocytes mature in _______ organs.
Generative lymphoid organs
B lymphocyte lineage
- Common lymphoid precursor
- (Generative lymphoid organ) Bone marrow
- Immature B lymphocytes
- (Blood, lymph) Mature naive B lymphocytes
- Recirculation
- (Peripheral lymphoid organs) Lymph nodes, spleen, mucosal and cutaneous lymphoid tissues
T lymphocyte lineage
- Common lymphoid precursor
- (Generative lymphoid organ) Thymus
- Naive T lymphocytes
- (Blood, lymph) Naive T lymphocytes
- Recirculation
- (Peripheral lymphoid organs) Lymph nodes, spleen, mucosal and cutaneous lymphoid tissues
Which parts of the body do lymphocytes not circulate through continuously?
- eyes
- brain
- testicles
How do lymphocytes reach the lymph nodes, skin, and intestine?
via High Endothelium Venules (HEVs)
-a specialized endothelium of postcapillary venules
Characteristics of cells of HEV
- much higher than normal endothelial cells
- express high levels of adhesion molecules which serve as homing receptors for lymphocytes
What do the lymphocytes do in response to chemokines?
migrate into the tissue
via diapedesis
How do lymphocytes reenter the circulation?
via efferent lymph vessels that merge into the thoracic duct
What do naive lymphocytes do when in the 2’ lymphoid tissues?
- may respond to foreign Ags
- return by lymphatic drainage to the blood and recirculate through other 2’ lymphoid organs
Steps of Lymphocyte Activation
1- Entry of infectious agents and/or environmental antigens
2- Collection of Ags from tissues via lymph and blood to 2’ lymphoid organs
3- Activation of lymphocytes
4- Initiation of adaptive immune responses
5- Migration of effector cells
6- Blood delivery of Abs to infection site
Where do fully-mature naive T cells and immature B cells migrate to?
2’ lymphoid organs
Ex: Lymph nodes and spleen
Where do B cells complete their maturation?
In lymph nodes and spleen
Naive B and T cells activated by Ags differentiate into _____ and _____.
effector and memory lymphocytes
Where do some effector and memory lymphocytes migrate into?
peripheral tissue infection sites
What are secreted by effector B cells in lymph nodes, spleen, and bone marrow and then enter the blood and are delivered to the infection sites?
Abs
What are antigen-presenting cells (APCs)?
- capture, process, and display microbial Ags to lymphocytes
- provide signals that stimulate the proliferation and differentiation of lymphocytes
Why do APCs usually refer to cells that display Ags to T lymphocytes?
Because B lymphocytes DO NOT need APCs for their activation
What major type of APC is involved in initiating T cell responses?
Dendritic cell (DC)
What are 2 other types of APCs?
Macrophages and B cells
Both present Ags to T lymphocytes
What specialized cell type displays Ags to B lymphocytes during particular phases of humoral immune responses?
Follicular DCs
What 2 types of cells are part of innate immune responses and provide a link between innate and adaptive immunity?
- Dendritic cells
- Macrophages
What cells are the most important for activation of naive T cells?
Dendritic cells (DCs)
DCs have long _______ and _______ capabilities.
long membranous projections
phagocytic capabilities
What lineage are DCs a part of?
Myeloid lineage
What is the maturation of DCs dependent on?
FIt3 ligand
- a type of cytokine
- binds to the Flt3 tyrosine kinase receptor on precursor cells
Macrophages and DCs express receptors that recognize Ags that are typically made by _____
Microbes
NOT mammalian cells
What do activated DCs also secrete?
cytokines
Where do Classical DCs reside?
- skin
- mucosa
- organ parenchyma
Upon activation by microbes, Classical DCs migrate to lymph nodes where they __________.
display microbial protein Ags to T lymphocytes
What are Plasmacytoid DCs?
early cellular responders to viral infection
What do plasmacytoid DCs recognize?
nucleic acids of intracellular viruses
What do plasmacytoid DCs produce?
- soluble proteins
- type I interferons (IFN-a,b)
IFN-a/b have __________ activities
potent antiviral
During inflammatory response in the tissues, DCs may also be derived from ________.
circulating monocytes
What are FDCs?
Follicular Dendritic Cells
-have membranous projections intermingled in collections of activated B cells
Where do FDCs reside?
In lymphoid follicles of:
- Lymph nodes
- Spleen
- Mucosal lymphoid tissues
FDCs are ______ to the DCs that present Ags to T lymphocytes
unrelated
FDCs bind and display protein Ags on their surfaces for recognition by ________
B lymphocytes
FDCs can retain ________ on their cell surfaces for extended periods of time
complement-fixed Ags
What do the retained immune complexes on the FDCs provide?
the antigenic stimulus that drives Ab affinity maturation
Innate Lymphoid Cells (ILCs) include _______ derived cells with lymphoid morphology.
bone marrow-derived cells
3 ILC Functions
- Early defense against infectious pathogens
- Recognize stressed/damaged host cells and help eliminate them
- Influence the nature of subsequent adaptive immune response
What are the first and best characterized innate lymphoid cells?
Natural killer cells
What do natural killer cells secrete?
Cytokine IFN-gamma
What do natural killer cells do?
kill infected and damaged cells
The HSC niche contributes to the control of ______, ______, _______, and ______.
contributes control of:
- HSC quiescence
- proliferation
- self-renewal
- differentiation
What region supports hematopoietic stem cells (HSCs) and other types of hematopoietic cells (progenitors)?
bone marrow
What does the niche within the bone consist of?
Network of:
- vessels
- nerve fibers
- bone remodeling cells
- subpopulations of hematopoietic cells
HSC»_space; _____ and _____
HSC»_space; Myeloid and Lymphoid progenitors
HSC function to ____ and ____.
- increase homing to bone marrow
- increase proximity to endosteum
Lymphoid and Myeloid progenitors function to _____ and ____.
- increase regenerative capacity
- balance differentiation
What 2 cell zones make up the white pulp of the spleen?
T cell and B cell zones
What is adjacent to the trabecular artery of the spleen?
- periarteriolar lymphoid sheath (T cells)
- a lymphoid follicle with a germinal layer (B cells)
What is the naive lymphocyte pathway in the lymph node?
- enter lymph node through artery
- leave by moving across wall of high endothelial venule
What draws B cells and T cells to migrate to different zones of the lymph nodes?
chemokines that are produced in the area
What picks up Ags from the sites of Ag entry of lymph nodes?
dendritic cells
What type of lymphatic vessels in the lymph nodes do Ags enter through?
afferent lymphatic vessels
Where do dendritic cells migrate to in lymph nodes?
T cell-rich areas of the lymph node
Inactive vs. Active lymph node
Inactive = primary follicle
Active = secondary follicle
