Innate Immune Cells Flashcards
1
Q
What has the immune system evolved to do?
A
- to sculpt colonization to benefit the host
2
Q
How do single-celled organisms fight microbes?
A
- by harnessing toxic peptides to thwart invading microbes
- this mechanism is still found in complex animals
3
Q
How have multicellular organisms evolved their immune system to fight invaders?
A
- they devote specialized cells to engulf bacteria and viruses
- evolved from nutritive phagocytes in gutless animals
4
Q
How have higher vertebrates evolved their immune system to fight invaders?
A
- the big bang of immunology
- evolved second form/ adaptive immunity where specialized WBC exquistely target a specific pathogen and maintain the body as an immune memory
5
Q
What does immediate innate, early induced innate and adaptive immune response all have in common?
A
- they all have the same end goal to remove the infectious agent
6
Q
What cells are in innate immunity?
A
- macrophage
- dendritic cell
- mast cell
- NK cell
- complement protein
- neutrophil, eosinophil, basophil (grouped together into granulocytes)
7
Q
What cells are in adaptive immunity?
A
- B-cell
- T-cell
- antibodies
- CD4+ T cell
- CD8+ T cell
8
Q
What cells are in both innate and adaptive immunity?
A
- y T cell
- NK cell
9
Q
Where do pluripotent hematopoietic stem cells live?
A
- in the bone marrow
10
Q
T/F: there are a lot of pluripotent hematopoitic stem cells
A
- False
- there’s a small number in the body, but they’re self-renewing, so any amount is good because they can regenerate
11
Q
What do pluripotenet hematopoietic stem cells respond to?
A
- stromal cells, cytokines, colony stimulating factors (CSF)
12
Q
What are the lineage development and cell diferentiation of pluripotent hematopoietic stem cells mediated by?
A
- coordinated and regulated expression of transcription factors
13
Q
What’s the cellular lifespan of red blood cells?
A
120 days
14
Q
What’s the lifespan of T-cells?
A
30 years
15
Q
What’s the lifespan of neutrophils?
A
1-2 days
16
Q
T/F: normally hematopoiesis is steady state but can increase 10-20 fold in hemorrhage or infection
A
- True
17
Q
What are the 5 colony stimulating factors?
A
- IL-3 (used to be multi-CSF)
- Macrophage-CSF (M-CSF)
- Granulocyte-CSF (G-CSF
- Granulocyte-macrophage- CSF (GM-CSF)
- Erythropoietin (EPO)
18
Q
T/F: the environment cannot affect the innate immune system
A
False, it can affect the regulation of different cells
19
Q
Can cells going through different stages of differentiation able to give rise to all blood cell types?
A
- no, they can still make multiple cell types but are no longer able to differentiate into all types of blood cells
20
Q
What are the intermediate stages referred to as?
A
- common progenitor cells
21
Q
T/F: pluripotent hematopoietic stem cells do not directly differentiate into immune cells
A
True, they have to pass through different stages of differentiation
22
Q
What’s the dependent lineage from transcription factor GATA-1?
A
- erythroid
23
Q
What’s the dependent lineage from transcription factor GATA-2?
A
- erythroid
- myeloid
- lymphoid
24
Q
What’s the dependent lineage from transcription factor PU-1?
A
- erythroid (maturation)
- myeloid (late stages)
- lymphoid
25
What's the dependent lineage from transcription factor Bmi-1?
- all lineages
26
What's the dependent lineage from transcription factor Ikaros?
- lymphoid
27
The transition between various stages of differentiation is driven by what?
- exposure to cytokines, including CSFs
28
What does the activity of the transcription factor induce?
- all developmental changes involved in cell differentiation
29
T/F: neutophils, basophils, lymphocytes and eosinophils look very similar
False, they look very different
30
What's the activated function of macrophages?
- phagocytosis and activation of bactericidal mechanisms
| - antigen presentation
31
What's the activated function of dendritic cells?
- antigen uptake in peripheral sites
| - anitgen presentation
32
What's the activated function of neutrophils?
- phagocytosis and activation of bactericidal mechanisms
33
What's the activated function of eosinophils?
- killing of antibody-coated parasites
34
What's the activated function of basophils?
- promotion of allergic responses and augmentation of anti-parasitic immunity
35
What's the activated function of mast cells?
- release of granuoles containing histamine and active agents
36
T/F: monocytes can give rise to phagocytes
- true
37
Where are monocytes present?
- in the blood where they traffic to various tissues
38
When does the monocyte differentiate? What does it Differentiate into?
- once it enters a tissue the monocyte differentiates into a macrophage
- named according to tissue
39
Is monocyte differentiation specific?
- it's very organ specific so it can fight off invaders
40
How much do monocytes account for in every organ in the body?
- 10-15%
41
What is the name of the macrophage/monocyte that captures and kills pathogens through phagocytosis?
- mononuclear phagocytes
42
What is the name of the macrophage/monocyte that processes and presents pathogen molecules to the T-cells?
- antigen presenting cells (APC)
- they present pathogen to cells in the adaptive immune system (like TOLLs) so T cells can activate and know how to attack
43
T/F: monocytes/macrophzges are 1st class of phagocytes
True
44
What's the difference between monocytes and macrophages physically?
- macrophages have more lysosomes, phagosomes and pseudopodia (things sticking out)
45
What are the 5 changes that occur in a monocyte when it differentiates into a macrophage?
- enlarges 5-10x
- increases intracellular organelles
- increases phagocytic ability
- increased amount of hydrolytic enzymes
- begin to secrete a variety of soluble factors
46
T/F: macrophages serve the same functions in different tissues
False, macrophages serve different functions in different tissues
47
What are the 4 things macrophages do?
- detect pathogens (PRRs)
- clear infection (phagocytosis)
- activate adaptive immune system (MHC-T cells)
- shape/direct adaptive immune response (cytokines)
48
What are the receptors on macrophages?
- LPS receptor CD14
- Toll-like receptors (TLR)
- Fc receptors
- mannose receptor
- complement receptors
- IFNg receptor
- Chemokine receptors
49
How do macrophages clear infections through direct clearance?
- phagocytosis of pathogen, killing it
50
How do macrophages clear infections through enhanced inflammatory response?
- contain/isolate pathogen
- secrete cytokines
raise body temperature
- recruit additional cells (neutrophils)
51
What are the 2 methods macrophages use to clear infections?
- direct clearance
| - enhance inflammatory response
52
Where are dendritic cells located?
- skin
53
Do dendritic cells move?
- no they're stationary
54
What do dendritic cells look like?
- unusually shaped phagocytic cells with long, spindly membrance processes
55
What do dendrtic cells (DC) express high levels of?
- MHCII
56
Why do DC express high levels of MHCII?
- DC are antigen presenting cells (like macrophages) and these high levels allow the cell-surface molecule to present the pathogens to the CD4+ T-cells
57
T/F: DC are most important cell type for the activation of naive T-cells
True
58
Where do dendritic cells develop?
- there are many different types of DC so different areas
- subset from lymphoid lineage
- subset from myeloid lineage
59
What are non-lymphoid dendritic cells called?
- depends on where it is in the body
- skin - Langerhans
- other organs - interstitial dendritic cells
60
What happens if a dendritic cell encounters a pathogen?
- after it picks it up in the tissue the DC will change its morphology in the blood and lymph to be veiled
- moves to lymph node
61
What do lymphoid dendritic cells called?
- depends on here it is in the body
- interdigitating DCs in T-cell rich organ sites
- follicular DCs in B-cell rich lymphoid organ site
62
How do Langerhans cells drain into the lymph node?
1) antigen uptake by Langerhans cells in the skin
| 2) Langerhans cells leave the skin and enter the lymphatic system
63
How do dendritic cells drain into the lymph node?
1) mature dendritic cells enter the lymph node from infected tissues and can transfer some antigens to resident dendritic cells
2) B7-positive dendritic cells stimulate naive T cells
64
How many functions do dendritic cells serve?
- one, they just want to pick up pathogens and take them to the lymph node
65
What are a couple physical features of neutrophils?
- lots of granules, have a primary and secondary granule
| - odd shaped nucleus, like a U
66
What's a metaphor for neutrophils?
- they're like the front line horsemen of the innnate immune system
67
How long do neutrophils live for?
- relatively short-lived
- about 1-2 days and die naturally
- if they fight something then only hours
:''(
68
Where do neutrophils live?
- in the blood
69
Where are neutrophils recruited from?
- from the blood vessels into the infected tissues
70
T/F: neutrophils are voracious phagocytes
- true
| - they eat and digest invaders
71
What does polymorphonucelar cells (PMNs)?
- multiobed nucleus
| - always refers to neutrophils
72
Are neutrophils granulocytes?
- yes
| - they contain a lot of pre-synthesized effector molecules that are stored in granules
73
What happens during neutrophil extravasation?
1) endothelial activation
2) tethering and rolling
3) firm adhesion
4) tranmigration and chemotaxis
- goes from round to pancake shape
74
What are the 5 effector mechanisms used by neutrophils?
- phagocytosis
- degranulation
- oxidative burst
- cytokines
- NETs
75
Define phagocytosis
- eat the infecting pathogen
76
Define degranulation
- dump cytotoxic granular contents on the target
77
Define oxidative burst
- generation of reactive oxygen species (ROS) and reactive nitrogen species (NOS) that can be used to make hydrogen peroxide and hypochloric acid which is toxic to bacteria
78
Define cytokines
- inflammation, activation of other cells
79
Define NETs
- Neutrophil Extracellular Traps
| - cell pokes out its own DNA to capture and contain bacteria
80
What are the thress types of granules in neutrophils?
- azurophilic (primary)
- specific (secondary)
- gelatinase (tertiary)
81
What makes granules a great risk for collateral damage?
- the granules in neutrophils can either fuse with the phagosome or it can be released into the extracellular environment (i think this is the dangerous part)
82
How long is the life span of neutrophils?
- once fully mature 1-2 days
83
What are the stages of formation for neutophils?
1) myeloblast
2) promyelocyte
3) myelocyte
4) metemyelocyte
5) band cell
6) PMN
84
How can a neutrophil suicide be useful?
- by killing themselves they release the contents of their nuclei and mitochondrial DNA
- the nucleic acid + bactericidal enzymes makes a lethal network outside the cell to trap and kill bacteria
85
What are some physical features of eosinophils?
- lots of granules
| - contains large red-staining granules
86
What specific type of infection are eosinophils primarily used for?
- parasitic infections
| - the number of eosinophils increase to 10-20% of blood leukocytes during a parasitic infection
87
How is the recognition of parasites enhanced?
- by the addition of an antibody to an eosinophil
88
What are some physical features of basophils?
- lots of large granules
- horse-shoe shaped nucleus
- lobed nucleus and heaily granulated cytoplasm
89
What reactions are basophils primarily used in?
- allergic responses
| - antiparasitic immunity
90
T/F: basophils are phagocytes
- False
| - they aren't phagocytes
91
How do basophils attack invaders?
- they aren't phagocytes so instead release large amount of pharamacologically active compunds from in their granules
92
What are basophils important mediators for?
- hypersensitivity
| - allergic responses
93
What are some physical features of mast cells?
- normal nucleus
| - large granules
94
What activates mast cells?
- IgE
- bacterial products
- parasites
95
What are mast cells coated with? How does this help them?
- IgE
| - the cell can bind with up to 200 different IgE to its surface
96
What's a granule content in mast cells?
- neurotransmitters that regulate blood vessel tone
97
What are mast cells known for?
- fighting infections
| - ability to cause allergies
98
Where do mast cells differentiate?
- in the tissue
| - phenotype varies on location
99
Where are mast cells located?
- at host-environment interfaces
| - skin, lungs, gut
100
How involved are mast cells in immune responses?
- very involved
| - they're responsible for telling other cell types to make aware that something is happening and they need to help
101
T/F: natural killer cells are clonal
- False, they are not clonal
102
Are NK cells more responsive to bacterial or viral invaders?
- viral
| - other cells are primarily bacterial
103
Do NK cells have markers for B or T-cells?
- no
104
Why are NK cells names natural killer cells?
- they can kill target cells without prior immunization
105
How are NK cells regulated?
- by a balance of activating and inhibiting receptors
106
How do NK cells recognize targets?
- they can recognize targets labeled with antibody
| - known as antibody-dependent cellular cytotoxity (ADCC)
107
What is the negative feedback loop seen in NK cells?
- MHC class I on normal cells is recognized by inhibitory receptors that inhibit signals from activating receptors
- NK cell does not kill the normal cell
108
When would a NK cell kill another cell?
- altered or absent MHC class I cannot stimulate a negative signal, the NK cell is triggered by signals from activating receptors
- activated NK cell releases granule content, inducing apoptosis in the target cell
109
T/F: NK cells are readily potent helpers available to fight against virus
True
110
What is the endothelium?
- a single cell layer that forms continuous lining to contain the blood
111
What are 3 things the endothelium is important for?
- plays critical role in homeostasis
- it's a barrier
- it's responsive to many mediators
112
How does the endothelium help maintain homeostasis?
- helps maintain coagulation and vascular tone (aka blood pressure)`
113
How does the endothelium act as a barrier?
- it regulates the movement of both fluids and macromolecules and leukocytes
114
How is the endothelium responsive to mediators?
- can actively engage in recruitment of different cells
115
When the endothelial cells are activated what can they do?
- produce oxidants, lipid mediators, cytokines, NO
- promote coagulation and regulate vascular tone
- increase microvascular permeability
- express adhesion and activation molecule resulting in increased leukocytes recruitment
116
Where are platelets derived from?
- bone marrow
| - megakaryocyte "bits"
117
Do platelets have a nucleus? Granules?
- no nucleus but lots of granules
118
What are 2 major responses platelets are responsible for for?
- homeostasis (critical)
| - inflammation (participates)
119
Do platelets bind to neutrophils or can neutrophils adhere to platelets?
- both!
120
How deos removing platelets affect inflammation?
- it can reduce the inflammatory response
121
What do platelets help the body with?
- helps to shield the body from infections
| - can enhance the effector function of other cells (NET production by neutrophils)
