Lecture 3. Cells of Innate Immunity Flashcards

1
Q

What are the cells found in the bone marrow ?

A
  1. Pluripotent hematopoietic stem cell
  2. Common lymphoid progenitor
  3. Common myeloid progenitor
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2
Q

What does the common myeloid progenitor differentiate into in the bone marrow ?

A
  1. Granulocyte/macrophage progenitor
  2. Megakaryocyre/erythrocyte progenitor
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3
Q

What does the megakaryocyte/erythrocyte progenitor differentiate into in the bone marrow ?

A
  1. Megakaryocyte
  2. Erythroblast
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4
Q

What does the megakaryocyte differentiate into in the blood ?

A

Platlets

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5
Q

What does the erythroblast differentiate into in the blood ?

A

Erythrocyte

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6
Q

What does the common lymphoid progenitor differentiate into in the blood ?

A
  1. B cell
  2. T cell
  3. Natural killer cell
  4. Immature dendritic cell
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7
Q

What does the common myeloid progenitor differentiate into in the blood ?

A

Immature dendritic cell

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8
Q

What is the family name for granulocyte/macrophage progenitor differentiate into in the blood ?

A

Granulocytes/ polymorphonuclear leukocytes

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9
Q

What does the granulocyte/macrophage progenitor differentiate into in the blood ?

A
  1. Neutrophil
  2. Eosinophil
  3. Basophil
  4. Unknown precursor of mast cell
  5. Monocyte
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10
Q

What is found in the blood ?

A
  1. B cell
  2. T cell
  3. Natural killer cell
  4. Immature dendritic cell.
  5. Neutrophil
  6. Eosinophil
  7. Basophil
  8. Precursor of mast cell
  9. Monocyte
  10. Platelet
  11. Erthrocyte
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11
Q

What is found in the lymph nodes ?

A
  1. B cell
  2. T cell
  3. Natural killer cell
    4, Mature dendritic cell
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12
Q

What is found int the effector cells ?

A
  1. Plasma cell
  2. Activated T cell
  3. Activated natural killer cell
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13
Q

What is found in the tissues ?

A
  1. Immature dendritic cell
  2. Mast cell
  3. Macrophage
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14
Q

What does the B cell differentiate into ?

A

Plasma cell

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15
Q

What does the T cell differentiate into ?

A

Activated T cell

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16
Q

What does the natural killer cell differentiate into ?

A

Activated natural killer cell

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17
Q

What does the monocyte differentiate into ?

A

Macrophage

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18
Q

What is ontogeny ?

A

Tracing immune cells

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19
Q

What does hematopoiesis originate from ?

A

Pluripotent stem cell - HSC

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20
Q

What does the pluripotent stem cell branch toward ?

A

Lymphoid/myeloid progenitor

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21
Q

What is the pluripotent stem cell regulated by ?

A

Growth factors/Cytokines (CSF-1, GM-CSF)

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22
Q

What appears in blood cancer ?

A

Myeloid derived suppressor cells - block pro-inflammatory functions in T cells

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23
Q

What are most myeloid cells ?

A

Phagocytes

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24
Q

What do myeloid cells form ?

A

An innate response

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25
Q

What are phagocytes ?

A

Cells which sample extracellular environment

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26
Q

What is the end result of phagocytes ?

A
  1. Destruction of cargo
  2. Generation or liberation of antigens
  3. Linked to signalling
  4. Metabolic activities
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27
Q

What is phagocytosis ?

A

Highly regulated cellular process involving multiple proteins and rearrangements of the actin cytoskeleton

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28
Q

What is a macrophage known as ?

A

Professional phagocyte

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29
Q

What is the neutrophil known as ?

A

Highly phagocytic professional killer

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30
Q

What is the activated function of macrophage ?

A

Phagocytosis and activation of bactericidal mechanisms

Antigen presentation

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31
Q

What is the activated function of dendritic cell ?

A

Antigen uptake in peripheral sites

Antigen presentation

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32
Q

What is the activated function of neutrophil ?

A

Phagocytosis an activation of bactericidal mechanisms

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33
Q

What is the activated function of eosinophil ?

A

Killing of antibody coated parasites

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34
Q

What is the activated function of basophil ?

A

Promotion of allergic responses and augmentation of anti-parasitic immunity

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35
Q

What is the activated function of mast cell ?

A

Release of granules containing histamine and active agents

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36
Q

Where is bound material internalised ?

A

Phagosomes

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37
Q

Where is bound material broken down in ?

A

Phagolysosomes

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38
Q

What are antigen presenting cells ?

A

Cells which liberate cargo to generate antigens and present antigens on cell surfaces

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39
Q

What do antigen presenting cells present to ?

A

Antigen specific lymphocytes

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40
Q

What is the special machinery required for antigen presentation ?

A

MHC/CO-stim molecules

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41
Q

What is the professional antigen presenting cell ?

A

Dendritic cell

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42
Q

What can acts as an antigen presenting cell ?

A

Macrophages

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43
Q

What are most antigen presentation cells ?

A

Phagocytes

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44
Q

What are the cell surface markers of macrophages?

A
  1. CD11b
  2. CD14
  3. F4/80
  4. CD68
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45
Q

What is the shape of macrophages ?

A

Large, single lobed nucleus, ruffled shape

46
Q

What are macrophages derived from ?

A

Myeloid progenitor in bone marrow via monocyte

47
Q

What are common at mucosal surfaces ?

A

Patrolling/tissue resident macrophages

48
Q

What do macrophages have ?

A

Innate phagocytic capacity

49
Q

What are macrophages enhanced by ?

A

Expression of phagocytic receptors and pattern recognition receptors

50
Q

What do pattern recognition receptors rely on ?

A

Discrimination of non-self by conserve molecular patterns and orchestrate inflammation

51
Q

What are the cell markers of dendritic cells ?

A
  1. CD11c
  2. C80/CD86
52
Q

What may dendritic cells be generated from ?

A

Monocytes

53
Q

What are most dendritic cells recruite by ?

A

Monocyte

54
Q

Where to dendritic cells migrate away to ?

A

Lymph node

55
Q

What do dendritic cells express to migrate towards lymph nodes ?

A

CCR7

56
Q

What do epithelial cells express ?

A

Pattern recognition receptors

57
Q

How may epithelial cells express pattern recognition receptors ?

A
  1. Apically
  2. Basally
  3. On intracellular vacuoles
58
Q

What are epithelial cells not ?

A

Phagocytic

59
Q

What can epithelial cells do ?

A

Specialised transport function

60
Q

What is used by epithelial cells to restrict infection ?

A

Xenophagy

61
Q

What do epithelial cells trigger ?

A

Cytokine/chemokine production to promote inflammation

62
Q

What are the resident cells in the intestinal epithelium ?

A
  1. iECs (Enterocytes
  2. Paneth cells
  3. Goblet cells
63
Q

What are the functions of iECs ?

A
  1. Sensing functions - express TLRs
  2. Engage autophagey to restrict pathogen growth
  3. Have microvilli
64
Q

Where are panteth cells found ?

A

Small intestine

65
Q

What do paneth cells produce ?

A

AMPs (RegIII and defensins) when activated

66
Q

What is function of goblet cells ?

A

Produce mucin when activated

67
Q

Where are microfold cells found ?

A

In follicular associated epithelium in gut

68
Q

What is the smaep of microfold cells ?

A

Folded/ruffled luminal surface

69
Q

What do microfold cells not make ?

A

Mucin or digestive enzymes

70
Q

What are microfold cells often associated with ?

A

Luminal antigen presentinc cells (dendritic cells, macrophages) in lamina propria

71
Q

What is the function of microfold cells ?

A

Facilitate transport of antigen - transcytosis

72
Q

Where are mast cell mature ?

A

Tissues

73
Q

Where are mast cells common ?

A

Skin, gut and aroun blood vessels

74
Q

What is the key activation signal of mast cells ?

A

C3a or IgE

75
Q

What releases contents of mast cells ?

A

Degranulation

76
Q

What is a key mediator of inflammation ?

A

Histamine

77
Q

What does endothelial cells activation involve ?

A
  1. Decreae tight junction expression - for vasodilation
  2. Increase adhesion molecules - capture specific cells
  3. Odema - fluid enters from serum to tissues (swelling) carry complement, clotting and other immune proteins
78
Q

What do cytokines act on ?

A

Endothelial cell

79
Q

What do cytokines promote ?

A

Vasodilation

80
Q

What do cytokines up regulate ?

A

Adhesion molecules on endothelial cells

81
Q

What is rolling ?

A

Loose interactions involving CHO polymers/selections

82
Q

What is firm adhesions ?

A

Tighter specific interactions

83
Q

What do chemokine gradients promote ?

A

Trans-migration into tissue via diapedesis

84
Q

Look at slide 23

A
85
Q

What does monocyte recruitment involve ?

A

Cell surface expressed ligand and endothelium expressed receptor/binding partner

86
Q

What does activated edothelium increase expression of ?

A

chemokine gradients which up regulate monocyte expression

87
Q

What is the rolling/attachment step of monocyte recruitment ?

A

Selectin expressionon endothelial cell non-specifically attracts leukoycte/monocyte

88
Q

What is the arrest/ adhesion step of monocyte recruitment ?

A

CR3 also known as Mac1 (CD11b/CD18)
Bind ICAM1/2

89
Q

What does integrin activation alter ?

A

cytoskeleton dynamics and facilitate diapadesis

90
Q

What is the key factor of macrophage differentiation ?

A

CSF-1

91
Q

What is the neutrophil marker ?

A

Gr1

92
Q

What is the neutrophild derived from ?

A

CMP via myeloblast

93
Q

What does phagocytosis of neutrophils lead to ?

A

Fusion with granules - degranulation leads to death

94
Q

What is the respiratory burst ?

A

Liberates toxic radical triggered by presence of bacteria

95
Q

Where is phagocyte oxidase inactive ?

A

In resting cells

96
Q

What does activation of cell trigger in respiratory burst ?

A

Localisation of other subunits p40, p47, p67

97
Q

What happens in respiratory burst in presence of oxygen and NADPH ?

A

Generates superoxide

98
Q

WHat is chronic granulomatous disease ?

A

Deficiency of NADPH oxidase

99
Q

What is the steps of macrophage phagocytosis ?

A
  1. Contact with solid trigger/cargo
  2. Formation of phagocytic cup
  3. Internalisation and formation of the phagosome
  4. Intracellular fate
  5. Fusion with acidic lysosome for degradation of cargo via catabolic enzymes, respiratory burst, acidic environment
100
Q

What are macrophage receptors ?

A

Slowly evolving, germ lined encoded

101
Q

What are macrophage receptors homologous to ?

A

Resistance proteins in plants

102
Q

What do microbes have for pattern recognition ?

A

Pathogen associated molecular patterns (PAMPs)

103
Q

What do hosts have for pattern recognition ?

A

Pattern recognition receptors

104
Q

What are vitaPAMPs associated with ?

A

Active replication

105
Q

What are natural killer cells ?

A

Lymphocytes that are a component of the innate immune system which does not directly attack invaing microbes

106
Q

What do natural killer cells do ?

A

Destroy compromised host cells

107
Q

How do natural killer cells recognise compromised host cells ?

A

A condition known as missing sself

108
Q

What do natural killer cells not require ?

A

Activation pror to killing

109
Q

What do natural killer cells cause ?

A

Lysis of cells infected with intracellular pathogens through release of granule contents

110
Q

What do unique mechanisms of recognition by natural killer cells rely on?

A

Presence or absence of various receptors KIRS and absence of MHC