Stromal Immunology

Question 1

What are stromal cells?

Answer 1

-connective tissue cells of any organ
-develop from embryonic mesenchyme tissues
-low mobility
-generally slow growing in culture

Question 2

How do stroll cells promote tissue repair?

Answer 2

example: broken bone

1) hematoma formation: leakage of bone marrow -> drives immune response
2) fibrocartilaginous callus formation: formation of blood vessels so there is blood flow between parts of the bone
3) bony callus formation: filling of gap in the bone by osteoblasts and osteoclasts
4) bone remodelling: healed fracture

Question 3

Which cells are activated in a bone fracture?

Answer 3

innate- macrophages
adaptive- T cells and b cells
- stroma progenitors and osteoblasts: soft callus formation
-osteocytes: bone remodelling

Question 4

What is a common connective tissue injury?

Answer 4

tendonitis

Question 5

Why is tendon repair not always successful?

Answer 5

healing can leave scarring of tissues or build up of fibroblasts which can cause thickening of the tendon

Question 6

What is one function of stromal cells that relates to the immune system?

Answer 6

they can release large amounts of chemokines to sites of inflammation

Question 7

What are the stromal cells in the thymus?

Answer 7

cortical epithelial cells
stromal epithelial cells

Question 8

What are the stromal cell populations in the lymph nodes?

Answer 8

follicular dendritic cells: antigen capture, presentation of immune complexes

follicular reticular cells: structural support, produce reticular fibres, lymphocyte migration

Question 9

What are the stromal cells in bone marrow?

Answer 9

• lymphoid progenitor cell
• early and late pro b cell
• immature b cell

Question 10

Why are fibroblasts important?

Answer 10

• most common stromal cell
• important in wound healing and preventing pathogens
• central to fibrosis
• provides structure
• can respond to multiple environmental signals

Question 11

What happens to fibroblasts when they’re exposed to TGF-Beta?

Answer 11

they turn into myofibroblasts which secrete more chemokines for inflammation and also changes morphology which allows the cell to repair any breaches

Question 12

How do fibroblasts down regulate the immune response?

Answer 12

drive naive T cells to become regulatory T cells

Question 13

How do fibroblasts control immune cells?

Answer 13

once immune cells reach tissues fibroblasts then release different signals that determine how the immune cells should act

Question 14

What is the downside to fibroblasts?

Answer 14

there are no distinguishing markers between subsets so its difficult to tell the difference between them

Question 15

What are the main functions of myofibroblasts?

Answer 15

• important in wound repair, its structure allows it to pull tissues together (exerts a stronger mechanic force)

Question 16

What kind of stress activates fibroblasts?

Answer 16

mechanical stress

Question 17

What are the 4 main steps in wound healing?

Answer 17

1) clot formation: platelets
2) innate immune response: macrophages, blood vessel
3) fibroblast activation: fibroblasts proliferate and remodel area
4) recovery: epidermis and dermis is healed

Question 18

What happens in scar formation?

Answer 18

• there is an increase in myofibroblasts
• excessive extracellular matrix deposit = scarring

Question 19

What are features of a keloid scar?

Answer 19

• thick collagen bundles
• raised surface
• occluded blood vessels

Question 20

How does diabetes affect wound closure?

Answer 20

• high blood glucose levels impair wound healing
• reduced keratinocyte proliferation
• reduces fibroblast factors = less immune cell recruitment

Question 21

How do fibroblasts drive IBD and Crohn’s disease?

Answer 21

• fibroblasts become activated during inflammation and secrete cytokines
• activated fibroblasts produce excessive ECM components = FIBROSIS

= CHRONIC INFLAMMATION, DISRUPTION OF NORMAL TISSUE ARCHITECTURE AND FIBROSIS

Question 22

What role do fibroblasts play in rheumatoid arthritis?

Answer 22

1) stop emigration and death of immune cells so they are retained and constantly carry out an inflammatory immune response
2) break down cartilage bone = JOINT DAMAGE
3) cause thickening of the joint lining = SWELLING, STIFFNESS, REDUCED MOBILITY

Question 23

What is the consequence of reduced apoptosis in arthritis?

Answer 23

thickening of synovium (joint lining) - reduces functionality of tissue

Question 24

What are the features of a tertiary lymph node?

Answer 24

• induces clonal expansion of b and T cells
• causes germinal centre reaction
• drives autoimmunity

Question 25

What are cancer associated fibroblasts?

Answer 25

• increase metastasis
• reduce chemotherapy effectiveness
• can be recruited from other sites

Question 26

How do fibroblasts contribute to tumour formation?

Answer 26

increase ECM -> stabilises tumour
increased angiogenesis -> tumour has stable blood supply
increased recruitment of cells -> increases mass

create PHYSICAL BARRIER- PROTECTS TUMOUR

Question 27

What are pericytes?

Answer 27

• associated with blood vessels
• can release soluble factors to influence flow of blood
• increased vascular permeability during inflammation leads to pericytes

Question 28

What are the immune-modulatory functions of pericytes?

Answer 28

• important part of blood brain barrier
• regulate immune cell migration from blood into tissues
• down regulate T cell activity