Microenviroment

Question 1

what is an example of a Specialized microenvironments that is essential for
immune cell development

Answer 1

eg. “Stem cells niches”:
Supportive network of
stromal cells in the bone
marow

Question 2

where is the major site of hematopoeisis in adults

Answer 2

bone marrow in the large bones in the medullary cavity

Question 3

what is found in the bone marrow and what happens to it as we age

Answer 3

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

Question 4

where does hematopoesis happen in the developing fetus

Answer 4

In the developing
fetus, hematopoiesis
occurs in the yolk
sac, aorta-gonad-
mesonephros (AGM)
region, placenta and
fetal liver

Question 5

where do hematopeitic stem cells move as they mature

Answer 5

HSC move from
Endosteal niche to the
Vascular niche as they
mature

Question 6

where do mature myeloid and lymphoid cells circulate

Answer 6

Mature lymphoid and myeloid cells
can re-circulate between the BM and
secondary immune organs

Question 7

what do stromal cells do and what are the stromal cells

Answer 7

provide support for HSC growth and development

osteoblasts
endothelial cells
reticular cells
sympathetic neurons
adipocytes

Question 8

osteoblasts

Answer 8

generate bone and control HSC differentiation

Question 9

endothelial cells

Answer 9

line the blood vessels, regulate HSC differentiation

Question 10

reticular cells

Answer 10

connect cells to bone and blood vessels via long processors (arms)

Question 11

sympathetic neurons

Answer 11

can control the release of HSC from the bone marrow

Question 12

adipocytes

Answer 12

regulatory? space filling?

Question 13

where do T cells mature

Answer 13

they migrate to the thymus to mature

Question 14

thymus growth

Answer 14

is largest at puberty and then shrinks dramatically

Question 15

important stromal cells for thymocyte development

Answer 15

cTEC and mTEC

Question 16

cTEC

Answer 16

Cortical thymic epithelial cells (cTEC)
* enable positive selection; select for T cells
that can interact

Question 17

mTEC

Answer 17

medullary thymic epithelial cells (mTEC)
* enable negative selection; remove T cells that
interact with self antigens

Question 18

what happens to the number of thymocytes as they mature

Answer 18

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

Question 19

how do immune cells interact with pathogens and become activated

Answer 19

1. Leukocytes move from the circulation to the site of infection
2. Specialized organs trap antigens

Question 20

what are the specialized organs that trap antigens

Answer 20

• Spleen
• Lymph nodes
• Peyer’s patches

Question 21

how are the lymphatic organs connected tot he lymphatic system

Answer 21

via the lymphatic vessels and nodes

Question 22

what does the lymph do

Answer 22

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.

Question 23

what do lymph nodes trap

Answer 23

tissue borne antigens

Question 24

what does the spleen trap

Answer 24

blood borne antigens

Question 25

the lymph node

Answer 25

* Highly organized structure * B cell zones and T cell zones * Follicular DC maintain follicular and germinal center structures

Question 26

where do antigens go

Answer 26

1. Ag enters via the afferent lymphatics 2. Empties into the supcapsular sinus 3. Trapped by APC; either migrating though the LN OR resident

Question 27

delivery of antigens to t cells

Answer 27

1. antigen capture, activation of migratory DC 2. migration of DC through afferent lymphatics 3. migraino of DC into paracortex 4. assocatiion of DC with FRC 5. interaction of DC with naive T cells

Question 28

delivery of antigen to B cells

Answer 28

1. opsonized antigen enter afferent lymphatics 2. SCSM bind antigen with complement receptors and transort it into the follicle 3. nonantigen specific B cell grabs antigen with comlement receptor s 4. FDC grabs antigen with complement receptors 5. antigen specific B cell recognizes antigens with BCR

Question 29

The T cells experience

Answer 29

1. Ag enters via the afferent lymphatics 2. Empties into the supcapsular sinus 3. Trapped by APC; either migrating though the LN OR resident 4. Naïve T cells enter the LN from the blood via the high endothelial venules (HEV) 5. Spend 16 to 24 h in the LN browsing antigen on APC 6. 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 6. b) If find an Ag match, will stay in the node where it proliferates and differentiates into effector cells (kill or direct the killing)

Question 30

The B cells experience

Answer 30

1. Ag enters via the afferent lymphatics 2. Empties into the supcapsular sinus 3. Trapped by APC; either migrating though the LN OR resident 4. Enter the LN via HEVs 5. migrate through the paracortex into the follicles 6. a) Leave via efferent lymphatics if no Ag match Follicular dendritic cells provide the support for B cells to encounter Ag 6. b) If encounter Ag, becomes partially activated and internalizes Ag 7. Moves to paracortex to allow full activation by interacting with T cell 8. 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 9. Some B cells become plasma cells; reside in the GC OR in the bone marrow

Question 31

how do lymphocytes exit the LN

Answer 31

Lymphocytes exit the LN via efferent lymphatic vessels- follow cytokine gradients

Question 32

how do antigens enter and leave the spleen

Answer 32

All Ag’s and cells enter via the splenic artery and leave via the splenic vein

Question 33

red versus white pulp of the spleen

Answer 33

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

Question 34

Ag in the spleen

Answer 34

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.

Question 35

mucosa contains what

Answer 35

Mucosa contains regions of highly specialized immune tissue (MALT: Mucosal-associated lympoid Tissue)

Question 36

what does MALT respond to

Answer 36

muscosal antigens (gut, bronchial, nasal) peyers patches trap intestinal antigens

Question 37

what is the skin assocaited with

Answer 37

The skin is associated with lymphoid tissue

Question 38

what are interepidermal lymphocytes specialized to do in the skin

Answer 38

Intraepidermal lymphocytes may be specialized to respond to pathogens that enter via the skin Langerhans cells- tissue resident dendritic cells

Question 39

what cells become memory cells

Answer 39

Some T and B cells become memory cells

Question 40

where are memory cells found

Answer 40

Can reside in secondary lymphoid organs or bone marrow (B cells) * central memory cells

Question 41

memory cells and tertiary lymphoid tissue

Answer 41

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