Lecture 4: HSC-Derived Cells

Question 1

Blood components

Answer 1

1. Plasma (serum, clotting factors)
2. Platelets
3. RBCs
4. Leukocytes

Question 2

Hematopoietic stem cells

Answer 2

HSCs are pluripotent progenitors of all blood cells

Question 3

Diapedesis

Answer 3

Process by which leukocytes leave circulation and enter the CT

Question 4

Types of diapedesis

Answer 4

1. Paracellular extravasation
2. Transcellular intravasation

Question 5

Paracellular extravasation

Answer 5

Leukocytes transiently break junctional complexes to squeeze between endothelial cells and exit circulation

Question 6

Transcellular intravasation

Answer 6

Leukocyte pierces the endothelial cell body (fenestration) and leaves blood via the donut hole. Most common in bone marrow.

Question 7

Cytokines

Answer 7

Secreted small proteins that act as signals for HSC cells in CT

Question 8

MSC-derived vs HSC-derived cells

Answer 8

MSC-derived cells are capable of forming an ECM; HSC-derived cells are not and are therefore motile. HSC-derived cells instead interact by transmembrane proteins.

Question 9

Celsus tetrad of inflammation

Answer 9

1. Calor (heat)
2. Dolor (pain)
3. Rubor (redness)
4. Tumor (swelling)

Question 10

How is swelling in inflammation mediated?

Answer 10

Swelling occurs when fluid plasma filtrate is added to the CT through local vessel dilation and endothelial leakage. It helps with cell motility.

Question 11

Rolling adhesion

Answer 11

Process by which circulating leukocytes slow down and attach to endothelium for diapedesis. Mediated by selectin/ICAM proteins

Question 12

Acute vs chronic inflammation

Answer 12

In acute inflammation, local leukocytes secrete cytokines. In chronic inflammation, stromal cells acquire/are entrained to this function and are less easily regulated.

Question 13

Inflammatory cells

Answer 13

1. Mast cells
2. Basophils
3. Eosinophils

Question 14

Mast cells

Answer 14

Contain histamine and heparin granules. Found in CT, have mechanisms for compound exocytosis, and are activated via surface IgE

Question 15

Histamine

Answer 15

Inflammatory protein

Question 16

Heparin

Answer 16

Glycosaminoglycan anti-coagulant

Question 17

Compound exocytosis

Answer 17

Process for rapid, simultaneous degranulation where granules dock with other granules at the membrane surface

Question 18

Basophils

Answer 18

Have blood stream and CT roles in immune modulation; granules contain histamine and heparin

Question 19

Eosinophils

Answer 19

Have granules containing cationic proteins e.g. major basic protein. Mediate allergy and anti-parasite responses. Eosinophil degranulation creates EC Charcot-Leyden crystals

Question 20

Innate immune cells

Answer 20

1. Macrophages
2. Neutrophils
3. Natural Killer cells

Question 21

Macrophages

Answer 21

-Phagocytose unwanted material
-Derive from circulating monocytes (stored in spleen)
-Can form Langhans giant/foreign body giant cells (syncytia)
-Many tissue specific forms (MPS)

Question 22

Mononuclear phagocytic system

Answer 22

Refers to the system of tissue specific/resident macrophages around the body. Many of these come from monocytes seeded in the fetal stage (e.g. brain to avoid BBB).

Question 23

Neutrophils

Answer 23

-Kill phagocytosed microorganisms by respiratory burst
-Capable of chemotaxis and cytokine secretion
-Act by phagocytosis or EC granules
-Capable of NETosis
-Storage by adhering to vessel walls

Question 24

Types of intracellular neutrophil granules and their contents

Answer 24

1. Azurophilic (primary; lysozymes)
2. Specific (secondary; antimicrobial)
3. Tertiary (gelatinase, cathepsin, collagenase; migration)

In order of production

Question 25

NETosis

Answer 25

Specialized cell suicide process used by neutrophils; chromatin is expelled to create toxic areas ("nets")

Question 26

NK cells

Answer 26

Lymphocyte that primarily functions in innate immunity

Question 27

Adaptive immune cells

Answer 27

1. T-lymphocytes 2. B-lymphocytes 3. Dendritic cells

Question 28

Mucosal-Associated Lymphoid Tissue

Answer 28

MALT are large CT congregations of lymphocytes found under mucosal surfaces. Within, B cells colocalize into lymphoid follicles as areas of monoclonal expansion

Question 29

B-lymphocyte

Answer 29

Antigen-specific antibody recognition and production. On antigen recognition, become plasma cells and undergo clonal expansion

Question 30

T-lymphocyte

Answer 30

Recognize self vs non-self w/ MHC molecules and TCRs. Characterized by their cell surface proteins; e.g. CD4+ Th, CD8+ Tc

Question 31

Lymphocyte development

Answer 31

Lymphocytes initially develop in hematopoietic areas (e.g. marrow) and then undergo immunocompetence training to prevent auto-reactivity; B-cells in h-poietic tissue and T-cells in the thymus

Question 32

Dendritic cells

Answer 32

Motile professional APCs

Question 33

Immune defenses other than cells

Answer 33

1. Surface secretions (e.g. stomach acid, antimicrobial peptides in saliva/mucus) 2. Barriers (e.g. junctional complexes, basement membranes, fiber matrices) 3. Proteoglycans (ZIP codes)

Question 34

Mexican hat plot of inflammation

Answer 34

Plot of spatial inflammation regulation. Pro-inflammatory mast cell activity in area surrounded by limiting eosinophil activity.

Question 35

Rolling adhesion/diapedesis process

Answer 35

1. Rolling adhesion via upregulated selectin ("lectin-like" Cell Adhesion Molecule) 2. Tight binding to endothelium via ICAM-1 (intercell. AM) and CD31 3. Diapedesis 4. Migration

Question 36

Leukocyte signaling by cell type

Answer 36

Each leukocyte responds to a unique but overlapping ligand constellation, enabling responses to be general or specific, local or widespread

Question 37

Macrophage life cycle

Answer 37

1. Born in marrow as monocyte 2. Release to circulation or "reserve" pool stored in spleen 3. Enter CT and become mature macrophage

Question 38

Timeline of cellular infection/damage response

Answer 38

1. Local macrophages respond to cytokines 2. Neutrophil numbers peak around 24 hours in 3. Circulating monocytes enter the CT space ~36-48 hours in

Question 39

Neutrophil life cycle

Answer 39

1. Born in marrow 2. "Marginal pool" stored in marrow as adults or pre-mature band cells 3. Released to circulation 4. Enter tissue by rolling adhesion/diapedesis 5. Activated then dies later

Question 40

Lymphoid follicle structure

Answer 40

1. Cortex (B-cell) 2. Germinal center (plasma cells) 3. Paracortex (T-cells)