Hematopoiesis, Blood, Inflammation, Danger signals and Response Flashcards

1
Q

Hematopoiesis

A
  • Formation of blood cells
  • Derived from hematopoetic stem cells (HSC) in bone marrow
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2
Q

Areas where hematopoiesis occurs from embryo to adulthood

A
  • Yolk sac in embryo
  • Liver in fetus
  • Bone marrow in adult
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3
Q

Hematopoetic stem cells (HSC)

A
  • Cells that become blood cells
  • Self-renewal capability
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4
Q

Human blood replenishment

A

Humans replenish about 1% of blood per day

~500ml per week

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5
Q

Bursa fabricii

A
  • Located in birds
  • Present instead of bone marrow
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6
Q

Two major lineages of hematopoiesis

A
  1. Myeloid lineage
  2. Lymphoid lineage
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7
Q

Myeloid lineage blood cells

A
  • Generated in the bone marrow (differentiate in bone marrow and then leave bone marrow to go to target destinations)
  • Differentiate into granulocytes, monocytes, and red blood cells
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8
Q

Lymphoid lineage blood cells

A
  • Final differentiation in lymphoid organs (they need to see the antigen before final differentiation)
  • Differentiate into lymphocytes
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9
Q

General steps of Hematopoiesis

A

Occurs in bone marrow:

  1. Hematopoietic stem cells
  2. Pluripotent stem cells
  3. Either Common lymphoid progenitor cells OR common myeloid progenitor cells
  4. Either becomes lymphoid stem cells or myeloid stem cells
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10
Q

Cells formed in the lymphoid lineage

A

Makes lymphocytes
- NK cells
- T cells
- B cells (can become plasma cells when secreting antibodies)

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11
Q

Cells formed in the myeloid lineage

A
  • Megakaryocyte (thrombocytes/platelets, reticulocyte and RBCs)
  • Monocytes (dendritic cells, macrophages)
  • Granulocytes (mast cells, basophils, eosinophils, neutrophils)
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12
Q

Granulocytes

A
  • Mast cells
  • Basophils
  • Eosinophils
  • Neutrophils
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13
Q

Staining tips for granulocytes

A

Have granules in their plasma that allows them to immediately release and cause immediate effect. These granules are stained differently in H & E staining for different granulocytes.

  • Basophil= more blue and basic
  • Eosinophil= more acidic and red
  • Neutrophil= granules don’t stain a colour
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14
Q

What part of immune system do monocytes play a role in?

A
  • Dendritic cells and macrophages
  • Allows for the adaptive immune system
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15
Q

What cell produces platelets?

A

Megakaryocytes

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16
Q

What cells produce RBCs?

A

Megakaryocytes –> reticulocytes –> erythrocytes (RBCs)

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17
Q

Appearance of macrophages and dendritic cells

A
  • Very large cells
  • Irregular shape
  • Both appear the same in blood, but you might be able to tell them apart in the tissues
  • Dendritic cells: round shaped nucleus, dendrites
  • Macrophages: U-shaped nucleus, small dendrites
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18
Q

Lymphocytes

A
  • Includes T-cells, B-cells, NK cells
  • Found in the bursa or thymus (where they differentiate)
  • Large, round nucleus
  • Small plasma
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19
Q

Purpose of platelets

A

Help with coagulation of blood

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20
Q

Where are most immune cells found?

A

In the tissues

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21
Q

Contents of Blood

A
  • One of the smallest immune compartments
  • Contains non-cellular factors (humoral immune response) and immune cells (cell mediated immune response)
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22
Q

Vascular systems role in immune cell transport

A

Allows for the transport of immune cells to the effector sites (cell trafficking). Immune cells will use surface molecules to recognize specific tissue-specific markers and leave the blood by transmigrating across the blood vessel wall

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23
Q

Functions of the blood

A
  • Transport of oxygen, hormones, nutrients, and waste to and from tissues
  • Regulates body temperature
  • Promotes wound healing
  • Transports immune cells and contains humoral effector molecules
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24
Q

Effector molecules of blood

A
  • Antibodies
  • Cytokines
  • Acute phase proteins
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25
Q

Four fractions of blood

A
  • Plasma (fluid)
  • White blood cells (leukocytes)
  • Red blood cells (erythrocytes)
  • Platelets (thrombocytes)
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26
Q

Segregation of spun down blood

A

Plasma
- water, proteins, electrolytes

Platelets and PBMCs (one cell nucleus only)
- Lymphocytes, monocytes

Red blood cells (erythrocytes) and polymorphonuclear cells (looks like multiple nucleus)
- Eosinophils
- neutrophils

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27
Q

Leukocytes and the body breakdown of different types

A
  • Monocytes (1-10%)
  • Dendritic cells (<1%)
  • Neutrophils (40-75%)
  • Eosinophils (1-7%)
  • Basophils (0.5-1%)
  • Lymphocytes (20-40%)
28
Q

Homing/Trafficking & Extravasation

A
  1. Leukocytes moving through blood are attracted to site by chemoattraction
  2. Leukocytes undergo tethering, rolling, and eventually adhesion to slow them down
  3. Cells migrate through endothelium into tissues
29
Q

Homing receptors or addressins

A
  • Molecules such as selectins, integrins, chemokines (CC)- Chemokine receptors (CCR)
  • Enable the immune cells to home from blood vessel into certain tissues
30
Q

3 types of defenses

A
  1. Physical barriers
  2. Innate immunity
  3. Acquired immunity
31
Q

Innate immunity function and recognition

A
  • Function to contain infection and inform adaptive immunity
  • Recognize patterns (danger signals)
32
Q

Adaptive immunity and recognition

A
  • Function to clear infection and establish memory
  • Recognize specific antigens
33
Q

Cells of innate immunity

A
  • Dendritic cells
  • Macrophages
  • Mast cell
  • Granulocytes
34
Q

Cells of Adaptive immunity

A
  • B cells
  • T cells
35
Q

Cells that are required by both innate and adaptive immunity

A
  • Gamma-delta T cells
  • Natural killer T cells
36
Q

Bubble Boy and Pigs

A

Young boy with severe combined immune deficiency (SCID) resulting in total inability to respond to pathogens

Pigs with SCID
- No B or T cells
- NK cells present
- Abnormal primary and secondary lymphoid tissues

37
Q

Inflammation

A

The result of the immediate (within minutes) response of the innate immune system

Brings WBCs to site, fights pathogen, initiates adaptive immunity

38
Q

Cardinal signs of inflammation

A
  • Rubor: redness
  • Tumor: swelling
  • Calor: heat
  • Dolor: pain
  • Functio laesa: loss of function
39
Q

Why do certain signs of infection occur?

A
  • Pain from pressure
  • Loss of function from body killing natural body cells
  • Swelling from increase of cells in area
  • Heat from increased activity
  • Red from lots of pressure and cells present
40
Q

Steps of inflammation

A
  1. Breach of barrier and invasion of foreign material or microorganisms
  2. Sentinel cells have pattern recognition receptors to recognize general types of molecules/invaders
  3. Triggers sentinel cells (macrophages and mast cells) to release signal (chemokines) which causes capillaries to widen and draw other cells to the site
  4. Fluid, antimicrobial proteins, and clotting elements move from the blood to the site. Also phagocytic cells move to the site due to attraction from chemokines
  5. Neutrophils and macrophages phagocytose pathogens and cell debris at site allowing tissues to heal
41
Q

Toll-like receptors (TLR)

A

Specific pattern recognition receptors located on inside and outside of immune cells that recognize PAMPs and DAMPs and trigger a response

TLR= mammals

42
Q

Toll receptors

A
  • Found in basic life forms such as fruit flies; indicates role in innate immune system
  • A specific pattern recognition receptor that recognizes fungus invasion and triggers response
  • Flies without toll are susceptible to fungus
43
Q

PAMPs (danger signals)

A
  • PAMPs (Pathogen-associated molecular patterns)
    o Highly conserved molecular patterns among groups of pathogens
  • Innate immune system recognizes them and triggers a response through proinflammatory response
44
Q

Triacylated lipoprotein

A
  • Ligand for TLR receptor
  • Source: bacteria
45
Q

Lipoproteins

A
  • Ligand for TLR receptor and CD36
  • Source: bacteria, viruses, parasites
46
Q

dsRNA

A
  • Ligand for TLR receptor
  • Source: viruses, protozoa
47
Q

LPS

A
  • Ligand for TLR receptor or CD14
  • Source: bacteria, viruses
48
Q

Flagellin

A
  • Ligand for TLR receptor
  • Source: bacteria
49
Q

Diacylated lipoprotein

A
  • Ligand for TLR receptor
  • Source: bacteria, viruses
50
Q

ssRNA

A
  • Ligand for TLR receptor
  • Source: viruses, bacteria
51
Q

CpG DNA

A
  • Ligand for TLR receptor
  • Source: viruses, bacteria, protozoa
52
Q

Toxoplasma profiling-like molecules

A
  • Ligand for TLR receptor
  • Source: protozoa
53
Q

Short dsRNA

A
  • Ligand for RLRs
  • Source: RNA viruses
54
Q

Peptidoglycans

A
  • Ligand for NLRs and peptidoglycan recognition proteins
  • Source: bacteria
55
Q

Muramyl dipeptide

A
  • Ligand for NLRs (NODs)
  • Source: bacteria
56
Q

Glucans

A
  • Ligand for CLRs
  • Source: fungi
57
Q

Glycoproteins

A
  • Ligand for mannose-fructose receptor
  • Source: bacteria
58
Q

Glycolipids

A
  • Ligand for CD1
  • Source: bacteria
59
Q

Fimbria

A
  • Ligand for CD48
  • Source: bacteria
60
Q

What happens when TLRs bind their ligands?

A

Many different pathways that lead to the expression of pro-inflammatory cytokines

Different combinations of the danger signals binding will result in different responses.

61
Q

Types of pattern recognition receptors

A
  • TLRs
  • RLRs
  • NLRs
  • CLRs
  • Mannose-fructose receptor
62
Q

DAMPs

A

Damage-associated molecular pattern that cause activation of immune system

  • Injuries, trauma, cell death, toxins, irradiation
  • Can be intracellular and extracellular
  • Display certain patterns that are recognized by the immune system to initiate wound healing
63
Q

Examples of DAMPs

A
  • Serum amyloid A (SAA)
  • Calgranulin A
  • High mobility group box-1 proteins
64
Q

Pro-inflammatory mediators

A
  • Released in response to DAMPs, PAMPs, and pain
  • Purpose is to prepare tissue for inflammation, stop microbial growth and initiate the first steps of adaptive immunity
    o Increase blood flow
    o Attract immune cells
    o Promote vascular permeability
    o Kill invading microbes
65
Q

Examples of pro-inflammatory mediators

A
  • Tumor necrosis factor
  • Interleukins 1
  • Interleukin 6
  • Antimicrobial peptides
  • Acute phase proteins