Microenviroment Flashcards
what is an example of a Specialized microenvironments that is essential for
immune cell development
eg. “Stem cells niches”:
Supportive network of
stromal cells in the bone
marow
where is the major site of hematopoeisis in adults
bone marrow in the large bones in the medullary cavity
what is found in the bone marrow and what happens to it as we age
Cross-section of the bone marrow: full of
osteoblasts, adipocytes, endothelial cells,
reticular cells, neurons, and HSC.
As we age, the bone marrow fills with more and
more adipocytes
where does hematopoesis happen in the developing fetus
In the developing
fetus, hematopoiesis
occurs in the yolk
sac, aorta-gonad-
mesonephros (AGM)
region, placenta and
fetal liver
where do hematopeitic stem cells move as they mature
HSC move from
Endosteal niche to the
Vascular niche as they
mature
where do mature myeloid and lymphoid cells circulate
Mature lymphoid and myeloid cells
can re-circulate between the BM and
secondary immune organs
what do stromal cells do and what are the stromal cells
provide support for HSC growth and development
osteoblasts
endothelial cells
reticular cells
sympathetic neurons
adipocytes
osteoblasts
generate bone and control HSC differentiation
endothelial cells
line the blood vessels, regulate HSC differentiation
reticular cells
connect cells to bone and blood vessels via long processors (arms)
sympathetic neurons
can control the release of HSC from the bone marrow
adipocytes
regulatory? space filling?
where do T cells mature
they migrate to the thymus to mature
thymus growth
is largest at puberty and then shrinks dramatically
important stromal cells for thymocyte development
cTEC and mTEC
cTEC
Cortical thymic epithelial cells (cTEC)
* enable positive selection; select for T cells
that can interact
mTEC
medullary thymic epithelial cells (mTEC)
* enable negative selection; remove T cells that
interact with self antigens
what happens to the number of thymocytes as they mature
The number of thymocytes (immuture T cells)
decline as the they mature.
DN: Double Negative
>DP: Double Positive
>SP: Single Positive
they move from the sucapsular cortex tot he cortex to the medulla
how do immune cells interact with pathogens and become activated
- Leukocytes move from the circulation to the site of infection
- Specialized organs trap antigens
what are the specialized organs that trap antigens
- Spleen
- Lymph nodes
- Peyer’s patches
how are the lymphatic organs connected tot he lymphatic system
via the lymphatic vessels and nodes
what does the lymph do
The lymph picks up cells
and proteins in the
interstitial fluid from the
tissue surrounding the
blood vessels and
lymphatics
Lymph is move through system by movement of surrounding muscles.
what do lymph nodes trap
tissue borne antigens
what does the spleen trap
blood borne antigens
the lymph node
- Highly organized structure
- B cell zones and T cell zones
- Follicular DC maintain
follicular and germinal center
structures
where do antigens go
- Ag enters via the afferent
lymphatics - Empties into the supcapsular sinus
- Trapped by APC; either migrating
though the LN OR resident
delivery of antigens to t cells
- antigen capture, activation of migratory DC
- migration of DC through afferent lymphatics
- migraino of DC into paracortex
- assocatiion of DC with FRC
- interaction of DC with naive T cells
delivery of antigen to B cells
- opsonized antigen enter afferent lymphatics
- SCSM bind antigen with complement receptors and transort it into the follicle
- nonantigen specific B cell grabs antigen with comlement receptor s
- FDC grabs antigen with complement receptors
- antigen specific B cell recognizes antigens with BCR
The T cells experience
- Ag enters via the afferent lymphatics
- Empties into the supcapsular sinus
- Trapped by APC; either migrating though the LN OR resident
- Naïve T cells enter the LN from the blood via the high endothelial venules (HEV)
- Spend 16 to 24 h in the LN browsing antigen on APC
- a) Leave via efferent lymphatics if don’t find an Ag match
In the paracortex (T cell zone): The
fibroblast/follicular reticular cells (FRC) create
processes and conduits to allow T cells to interact
efficiently with APCs - b) If find an Ag match, will stay in the node where it
proliferates and differentiates into effector cells (kill or direct
the killing)
The B cells experience
- Ag enters via the afferent lymphatics
- Empties into the supcapsular sinus
- Trapped by APC; either migrating though the LN
OR resident - Enter the LN via HEVs
- migrate through the paracortex into the follicles
- a) Leave via efferent lymphatics if no Ag match
Follicular dendritic cells provide the support for B cells to
encounter Ag - b) If encounter Ag, becomes partially activated and internalizes Ag
- Moves to paracortex to allow full activation by interacting with T
cell - Some B cells re-enter follicle and establish the germinal center (aka
secondary follicle)
* GC support generation of B cells with increased affinity (binding
ability) for Ag - Some B cells become plasma cells; reside in the GC OR in the bone
marrow
how do lymphocytes exit the LN
Lymphocytes exit the LN via efferent
lymphatic vessels- follow cytokine gradients
how do antigens enter and leave the spleen
All Ag’s and cells enter via the
splenic artery and leave via the
splenic vein
red versus white pulp of the spleen
Red and White pulp separated by the marginal zone
Red pulp: Old red blood cells are removed
White pulp: Lymphoid-rich region
* PALS: periarteriolar lymphoid sheath
* T cells
* B cell follicles & Germinal Centers
Ag in the spleen
Ag enters via the splenic artery, encounters DC in the marginal zone, which trap and process it. DC
migrate to the PALS and activate T and B cells.
mucosa contains what
Mucosa contains regions of highly specialized immune tissue
(MALT: Mucosal-associated lympoid Tissue)
what does MALT respond to
muscosal
antigens (gut, bronchial, nasal)
peyers patches trap intestinal antigens
what is the skin assocaited with
The skin is associated with lymphoid tissue
what are interepidermal lymphocytes specialized to do in the skin
Intraepidermal lymphocytes
may be specialized to
respond to pathogens that
enter via the skin
Langerhans cells- tissue
resident dendritic cells
what cells become memory cells
Some T and B cells become memory cells
where are memory cells found
Can reside in secondary lymphoid organs or bone marrow (B
cells)
* central memory cells
memory cells and tertiary lymphoid tissue
Can return to the tissue(s) that originally encountered Ag
* “tertiary lymphoid tissue”
* includes microenvironments, stromal cells that support immune
cell function
* effector memory cells can reside in this tissue
