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COT Part I > Lecture 4: HSC-Derived Cells > Flashcards

Lecture 4: HSC-Derived Cells Flashcards

1
Q

Blood components

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

Hematopoietic stem cells

A

HSCs are pluripotent progenitors of all blood cells

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3
Q

Diapedesis

A

Process by which leukocytes leave circulation and enter the CT

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4
Q

Types of diapedesis

A
  1. Paracellular extravasation
  2. Transcellular intravasation
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5
Q

Paracellular extravasation

A

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

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6
Q

Transcellular intravasation

A

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

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7
Q

Cytokines

A

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

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8
Q

MSC-derived vs HSC-derived cells

A

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.

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9
Q

Celsus tetrad of inflammation

A
  1. Calor (heat)
  2. Dolor (pain)
  3. Rubor (redness)
  4. Tumor (swelling)
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10
Q

How is swelling in inflammation mediated?

A

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

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11
Q

Rolling adhesion

A

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

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12
Q

Acute vs chronic inflammation

A

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

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13
Q

Inflammatory cells

A
  1. Mast cells
  2. Basophils
  3. Eosinophils
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14
Q

Mast cells

A

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

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15
Q

Histamine

A

Inflammatory protein

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16
Q

Heparin

A

Glycosaminoglycan anti-coagulant

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17
Q

Compound exocytosis

A

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

18
Q

Basophils

A

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

19
Q

Eosinophils

A

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

20
Q

Innate immune cells

A
  1. Macrophages
  2. Neutrophils
  3. Natural Killer cells
21
Q

Macrophages

A

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

22
Q

Mononuclear phagocytic system

A

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).

23
Q

Neutrophils

A

-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

24
Q

Types of intracellular neutrophil granules and their contents

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

In order of production

25
Q

NETosis

A

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

26
Q

NK cells

A

Lymphocyte that primarily functions in innate immunity

27
Q

Adaptive immune cells

A
  1. T-lymphocytes
  2. B-lymphocytes
  3. Dendritic cells
28
Q

Mucosal-Associated Lymphoid Tissue

A

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

29
Q

B-lymphocyte

A

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

30
Q

T-lymphocyte

A

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

31
Q

Lymphocyte development

A

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

32
Q

Dendritic cells

A

Motile professional APCs

33
Q

Immune defenses other than cells

A
  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)
34
Q

Mexican hat plot of inflammation

A

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

35
Q

Rolling adhesion/diapedesis process

A
  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
36
Q

Leukocyte signaling by cell type

A

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

37
Q

Macrophage life cycle

A
  1. Born in marrow as monocyte
  2. Release to circulation or “reserve” pool stored in spleen
  3. Enter CT and become mature macrophage
38
Q

Timeline of cellular infection/damage response

A
  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
39
Q

Neutrophil life cycle

A
  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
40
Q

Lymphoid follicle structure

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

COT Part I (13 decks)

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