EXAM 2 Induced Immunity: Cellular Responses and Cytokines Flashcards
(145 cards)
1
Q
what are the effector functions of immediate innate immunity?
A
- barriers
- antimicrobial peptides
- opsonization
- isolation
- pore formation
- targeting
- inflammation
- cellular recruitment
2
Q
what are the effector functions of induced innate immunity?
A
- phagocytosis
- targeted killing
- antimicrobial peptides
- cytokine release
- inflammation
- cellular recruitment
- B and T cell activation
3
Q
the immediate innate immune response occurs in what time frame?
A
0-4 hours
4
Q
the induced innate immune response occurs in what time frame?
A
4 hours to 4 days
5
Q
what are the cells of the innate immune system?
A
- monocyte
- macrophage
- dendritic cell
- mast cell
- eosinophil
- neutrophil
- basophil
- NK cell
6
Q
which cell of the innate immune system is the circulating precursor cell to macrophages and dendritic cells?
A
monocyte
7
Q
which cell of the innate immune system functions in phagocytosis and killing of microorganisms; activation of T cells and initiation of immune responses
A
macrophage
8
Q
which cell of the innate immune system is responsible for activation of T cells and initiation of adaptive immune responses?
A
dendritic cells
9
Q
which cell of the innate immune system functions in the expulsion of parasites from the body through release of granules containing histamine and other active agents?
A
mast cell
10
Q
which cell of the innate immune system is responsible for the killing of antibody-coated parasites through release of granule contents?
A
eosinophil
11
Q
which cell of the innate immune system kills cells infected with certain viruses?
A
NK cell
12
Q
which cell of the innate immune system functions in phagocytosis and killing of microorganisms?
A
neutrophil
13
Q
which cell of the innate immune system is responsible for controlling immune responses to parasites?
A
basophil
14
Q
what are the local, tissue resident immune cells that respond in the initiation of the induced immune response?
A
macrophages, dendritic cells, mast cells, and specialized T cells
15
Q
what are the 4 components involved in the initiation of the induced immune response?
A
- local, tissue resident immune cells
- complement system
- pro-inflammatory signaling
- infected, damaged, or diseased tissues
16
Q
what are the 3 pro-inflammatory signals involved in initiation of the induced immune response?
A
cytokines, eicosanoids, and acute phase response
17
Q
infected, damaged, or diseased tissues can help initiate the induced immune response via ___ and ___
A
interferon response and altered MHC expression
18
Q
___ detect and phagocytose local pathogens
A
macrophages
19
Q
most tissues have resident macrophages. what are the resident macrophages of the brain, bone, liver, and skin?
A
- brain - microglia
- bone - osteoclasts
- liver - kupffer cells
- skin - langerhans cells
20
Q
macrophages induce and direct ___, and activate the ___ immune system
A
- inflammation
- adaptive
21
Q
what are the 4 effector mechanisms of macrophages?
A
- phagocytosis
- cytokine release
- degranulation
- antigen presentation
22
Q
macrophages can function as ___
A
pattern recognition receptors (PRRs)
23
Q
describe the extracellular process of innate immune cell pattern recognition
A
macrophage receptors recognize the cell-surface carbohydrates of bacterial cells but not those of human cells
24
Q
describe the intracellular process of innate immune cell pattern recognition
A
NK cell receptors recognize changes at the surface of human cells that are caused by viral infection
25
Pattern recognition receptors are present on most ___ cells
innate
26
PRRs allow local, direct \_\_\_
activate
27
what are the 3 innate phagocytic cells?
macrophages, neutrophils, and dendritic cells
28
describe the steps of phagocytosis
1. bacterium becomes attached to membrane evaginations called pseudopodia
2. bacterium is ingested, forming a phagosome
3. phagosome fuses with lysosome, forming the phagolysosome
4. bacterium is killed and then digested by lysosomal enzymes
5. digestion products are released from the cell
29
what are the common macrophage PRRs that are involved in phagocytosis?
* mannose receptor
* complement receptors 3 and 4
* dectin-1
* macrophage receptor with collagenous structure
* scavenger receptor A and B
* lipopolysaccharide receptor
30
what is the common macrophage PRR that are involved in signaling (production and release of cytokies)?
toll-like receptors (TLRs)
31
what are the 6 antimicrobial mechanisms of phagocytes?
* acidification (macrophage & neutrophil)
* toxic oxygen-derived products (macrophage & neutrophil)
* toxic nitrogen oxides (macrophage & neutrophil)
* antimicrobial peptides (macrophage & neutrophil)
* enzymes (macrophage & neutrophil)
* competitors (neutrophil only)
32
\_\_\_ activate macrophages
TLRs
33
TLR activation requires \_\_\_
dimerization; can be heterodimerization or homodimerization
34
what are the main external TLRs?
* TLR-1
* TLR-2
* TLR-4
* TLR-5
* TLR-6
35
what are the main internal TLRs?
* TLR-3
* TLR-7
* TLR-8
* TLR-9
36
what do internal TLRs detect?
nucleic acid combinations
ds viral RNA (TLR-3), ss viral RNA (TLR-7, TLR-8), CpG DNA (TLR-9)
37
which TLR targets protein?
TLR-5 (flagellin)
38
which TLRs target lipids?
TLR-1, TLR-2, TLR-4, TLR-6, TLR-10
39
the heterodimerization of which two TLRs targets diacyl lipopeptides?
TLR-2 and TLR-6
40
the heterodimerization of which two TLRs targets triacyl lipopeptides?
TLR-2 and TLR-1
41
which TLR targets LPS?
TLR-4
42
NOD receptors detect \_\_\_
degraded antigens
43
what are NOD receptors?
nucleotide-binding oligomerization domains
44
NOD receptors recognize intracellular ___ and \_\_\_
* PAMPs and DAMPs
* microbial toxins
* viruses
* cell stress proteins
45
\_\_\_ induce cytokine expression and release
NOD receptors
46
NOD receptors form the \_\_\_
inflammasome
47
NOD receptors cooperate with \_\_\_
TLRs
48
\_\_\_ are signaling molecules of the immune system
cytokines
49
are cytokines soluble?
yes, mostly
50
what is the main nomenclature of cytokines?
interleukins, chemokines, and others
51
what are the six families of cytokines, based on receptor morphology?
* class I
* class II
* interleukin 1
* interleukin 17
* tumor necrosis factor (TNF)
* chemokines
52
cytokines signal predominantly in what two fashions?
paracrine and autocrine
53
cytokines effect ___ and ___ tissues
immune and non-immune
54
what are the common intracellular signaling pathways that cytokines are involved in?
* JAK-STAT
* MAPK
* NF-kappa B
55
activated macrophages secrete which main pro-inflammatory cytokines?
* IL-1 beta
* TNF-alpha
* IL-6
* CXCL8
* IL-12
56
which pro-inflammatory cytokine has the following function:
local: activates vascular endothelium, activates lymphocytes, local tissue destruction, increases access of effector cells
systemic: fever, production of IL-6
IL-1 beta
57
which pro-inflammatory cytokine has the following function:
local: activates vascular endothelium, increases vascular permeability, which leads to increased entry of IgG, complement, and cells to tissues and increased fluid drainage to lymph nodes
systemic: fever, mobilization of metabolites, shock
TNF-alpha
58
which pro-inflammatory cytokine has the following function:
local: lymphocyte activation, increased antibody production
systemic: fever, induces acute-phase protein production
IL-6
59
which pro-inflammatory cytokine has the following function:
local: chemotactic factor recruits neutrophils, basophils, and T cells to site of infection
CXCL8
60
which pro-inflammatory cytokine has the following function:
local: activates NK cells, induces the differentiation of CD4 T cells into Th1 cells
IL-12
61
what are the systemic effects of IL-1 beta, IL-6, and TNF-alpha on the liver?
acute-phase proteins, activation of complement, opsonization
62
what are the systemic effects of IL-1 beta, IL-6, and TNF-alpha on bone marrow epithelium?
neutrophil mobilization, phagocytosis
63
what are the systemic effects of IL-1 beta, IL-6, and TNF-alpha on the hypothalamus?
increased body temp, decreased viral and bacterial replication, increased antigen processing, increased specific immune response
64
what are the systemic effects of IL-1 beta, IL-6, and TNF-alpha on fat and muscle?
protein and energy mobilization to allow increased body temperature, decreased viral and bacterial replication, increased antigen processing, increased specific immune response
65
what are the systemic effects of IL-1 beta, IL-6, and TNF-alpha on dendritic cells?
TNF-alpha stimulates migration to lymph nodes and maturation, initiation of adaptive immune response
66
inflammatory cytokines stimulate the ___ response
liver acute phase response
67
which acute-phase proteins, produced by the acute phase response, are involved in pathogen recognition?
c-reactive protein, mannose-binding lectin, and lipopolysaccharide-binding protein
68
which acute-phase proteins, produced by the acute phase response, are involved in pathogen elimination?
complement components C3, C4, C9, and factor B
69
which acute-phase proteins, produced by the acute phase response, are involved in the inflammatory response?
granulocyte colony-stimulating factor, serum amyloid A, secreted phospholipase A2
70
which acute-phase proteins, produced by the acute phase response, are involved in coagulation?
fibrinogen, plasminogen, tissue plasminogen factor
71
describe how cytokines initiate leukocyte recruitment
1. cytokines produced by macrophages cause dilation of local small blood vessels
2. leukocytes move to periphery of blood vessel as a result of increased expresion of adhesion molecules by endothelium
3. leukocytes extravasate at site of infection
4. blood clotting occurs in the microvessels
72
cytokine activation:
bacteria induce macrophages to produce \_\_\_, which acts on hepatocytes to induce synthesis of \_\_\_.
one of two steps are taken next:
1. ___ binds phosphocholine on bacterial surfaces, acting as an \_\_\_, and also activating complement.
2. ___ binds mannose residues on bacterial surfaces, acting as an \_\_\_, and also activating complement.
* IL-6
* acute-phase proteins
* c-reactive protein
* opsonin
* mannose-binding lectin
* opsonin
73
extravasation depends on what 3 things?
chemokines, adhesion molecules, and proteases
74
chemokines function as \_\_\_
chemoattractants
75
what are the 4 chemokines?
CL, CCL, CXCL, and CX3CL (CXXXCL)
76
adhesion molecules function to \_\_\_
tether leukocytes
77
what are the 4 types of adhesion molecules?
* vascular addressin (CD34)
* selectin (l-selectin)
* integrin (LFA-1)
* immunoglobulin-like molecule (ICAM-1)
78
proteases function to \_\_\_
open basement membranes
79
what are 2 types of proteases?
matrix metalloproteases and elastases
80
chemokine gradients recruit ___ to tissues
cells
81
how do chemokine gradients work?
as more chemokines accumulate, cells are drawn closer and closer to that chemokine
82
leukocytes extravasate to sites of \_\_\_
inflammation
83
describe how leukocytes extravasate to sites of inflammation
* chemokine receptor activation leads to binding
* binding triggers protease release
* basement membrane degradation and chemokines induce diapedesis and tissue entry
* \*weak selectin-mediated adhesion allows neutrophils to roll along the endothelium; rolling adhesion, tight binding, diapedesis, and then migration
84
chemokine gradients are an ___ mechanism
immune targeting
85
excessive plasma TNF-alpha causes \_\_\_
septic shock syndrome
86
describe how excessive plasma TNF-a causes septic shock syndrome
* often initiated by blood-borne infection
* systemic extravasation
* systemic neutrophil infiltration
* vascular collapse
* rapid multi-organ failure
87
what is the primary cell of the induced response?
neutrophil
88
large reserves of neutrophils are reserved in the ___ and are released when needed to fight infection
bone marrow
89
when neutrophils are needed to fight an infection, they travel from the ___ to the \_\_\_, where they engulf and kill \_\_\_; they then die and are engulfed and degraded by \_\_\_
* bone marrow
* infected tissue
* bacteria
* macrophages
90
\_\_\_ are the primary innate killers
neutrophils
91
what are the 4 effector mechanisms of neutrophils?
* phagocytosis
* degranulation
* extracellular traps
* cytokine release - this actually will happen as a result of any of the previous three mechanisms
92
briefly describe neutrophils
* potent pathogen killers
* innate immunity
* primary cell of the induced response
* small and numerous
* destined to die
93
what are the 4 neutrophil granule types?
* azurophil granules - contain proteases and defensins, respond to pathogens
* specific granules - respond to pathogens
* gelatinase granules - response to pathogens
* secretory granules - respond to tissue damage
94
neutrophil granules serve what dual purpose?
phagocytosis and degranulation
95
the neutrophil oxidative burst does what?
kills pathogens
96
how does the neutrophil oxidative burst kill pathogens?
* bacterium is phagocytosed by neutrophil
* phagosome fuses with azurophilic and specific granules
* pH of phagosome rises, antimicrobial response is activated, and bacterium is killed
* neutrophil dies
97
what are NETs? what are the two types?
* neutrophil extracellular traps
* non-lytic - does not directly destroy the neutrophil itself; mobile
* lytic - directly destroys the neutrophil (turns inside out); immobile
* can happen in both tissues and vasculature
* its a way of rapidly stopping an infection from spreading, and keeping it localized
98
dendritic cells initiate \_\_\_
adaptive immunity
99
are dendritic cells resident in tissue?
yes
100
dendritic cells process pathogens into \_\_\_
antigens
101
dendritic cells present antigens to \_\_\_
lymphocytes
102
dendritic cells are involved in ___ regulation
cytokine
103
dendritic cells have an enormous range of PRRs. why?
different PRRs induce different responses
104
activated NK cells target ___ cells
infected, diseased, and stressed
105
\_\_\_ are large, cytotoxic lymphocytes
NK cells
106
\_\_\_ cells target and kill diseased self cells
NK cells
107
NK cells have diverse combinations of receptors that can be both ___ and \_\_\_
activated and inhibited
108
NK cells respond to what 3 things?
interferons, MHC class I, and unique stress ligands
109
\_\_\_ cells regulate the shift from induced innate to the adaptive immune response
NK cells
110
do NK cells die after killing other cells?
no
111
NK cells undergo a process of bone marrow education to select \_\_\_
functional receptor patterns
112
viral infections cause the ___ response
interferon
113
describe the interferon response
* a virally infected cell releases interferon cytokines (INF-alpha and beta), which directly activate NK cells
* induce resistance to viral replication in all cells
* increase expression of ligands for receptors on NK cells
* activate NK cells to kill virus-infected cells
114
describe interferons
* cytokines
* released by diseased or stressed cells
* intracellular infection, cancer
* released by leukocytes
115
what do interferon cytokines do?
* reduce viral replication
* prevent cell division
* induce apoptosis
* activate NK cells, T cells, and macrophages
116
interferons activate ___ cells
NK
117
describe how interferons activate NK cells
* virus ifnection of cells triggers the interferon response
* type I interferon drive the proliferation of NK cells
* type I interferon drives the differentiation of NK cells into cytotoxic effector cells
* effector NK cells kill virus-infected cells by inducing them to undergo apoptosis
118
\_\_\_ cells regulate dendritic cell recruitment of adaptive immunity
NK cells
119
\_\_\_ cells locally activate NK cells
dendritic cells
120
describe how NK cells function as a checkpoint on adaptive immune activation
* if there is a large NK cell response, then dendritic cell presentation is inhibited
* if there is a small NK cell response, then dendritic cells are activated (adaptive immune response)
121
\_\_\_ protect local tissues
granulocytes
122
what are the 3 granulocytes?
mast cells, eosinophils, and basophils
123
\_\_\_ are predominant in tissues and rare in the blood
granulocytes
124
granulocytes express \_\_\_, usually as a result of being primed by prior adaptive responses
PRRs
125
granulocytes ___ when activated, as a result of cell-type specific granule components
degranulate
126
granulocytes respond to ___ organisms
parasitic
127
\_\_\_ are responsible for initiating type I hypersensitivity (allergic reactions)
granulocytes
128
macrophages have ___ that bind microbes and their components. bound material is internalized in phagosomes and broken down in \_\_\_.
* phagocytic receptors
* phagolysosomes
129
pattern recognition receptors are present on most ___ cells, and provide \_\_\_, ___ activation
* innate
* local, direct
130
describe how TLR signaling initiates cytokine production through NF-kappaB
131
NOD receptor recognition of bacterial cell wall components leads to activation of \_\_\_
NF-kappaB
132
\_\_\_ drives the production of cytokines
NF-kappaB
133
inflammasomes activate and promote ___ release
cytokine
134
what are the chemokines that are released by targets?
CXCL
135
what are the chemokine receptors present on immune cells?
CSCR
136
cells detect viral infections by recognizing viral \_\_\_. ultimately, ___ is activated, which causes synthesis and secretion of \_\_\_.
* RNA
* NF-kappaB
* inflammatory cytokines
137
describe macrophage and NK cell bidirectional regulation
* macrophage activated by viral infection secretes inflammatory cytokines that recruit and stimulate NK cells
* NK cell and macrophage form a conjugate pair with a synapse in which IL-12 and IL-15 activate the NK cell
* NK cells proliferate and differentiate into effector NK cells secreting IFN-gamma
* IFN-gamma binds to its receptor on macrophages and activates them to increase phagocytosis and secretion of inflammatory cytokines
138
most cytokines are in the ___ form when they are produced (they have little activity, and are not great at signaling).
NOD proteins come together, bind \_\_\_, and activate it.
procaspase-1 activates ___ (go from pro form to active form).
this drives and enhances the release of ___ and functions as a \_\_\_.
* pro
* procaspase-1
* cytokines
* cytokines
* checkpoint
139
local infection with gram negative bacteria causes macrophages to secrete ___ in tissue.
this ultimately results in the removal of infection via ___ immunity
* TNF-alpha
* adaptive
140
systemic infection with gram negative bacteria (sepsis) results in macrophages in the ___ and ___ to secrete TNF-alpha into the blood stream.
this ultimately results in multi organ failure and \_\_\_
septic shock syndrome
* liver and spleen
* death
141
neutrophils produce \_\_\_-defensins
alpha
142
how do NETs work?
neutrophils release NETs (lytic and non-lytic), which are basically chromatin with attached proteases that form a fibrous structure that captures and binds bacteria and pathogens
143
activated NK cells target infected, diseased, and stressed cells:
MHC class I on normal cells is recognized by inhibitory receptors that inhibit \_\_\_
NK cell does not kill the ___ cell
* signals from activating receptors
* normal
144
activated NK cells target infected, diseased, and stressed cells:
altered or absent MHC class I cannot stimulate a ___ signal. the NK cell is triggered by \_\_\_.
activated NK cell releases ___ contents, inducing ___ in the target cell
* negative
* signals from activating receptors
* granule
* apoptosis
145
cells detect viral infections:
viral replication in cytoplasm prduces uncapped RNA with a \_\_\_
\_\_\_ binding to viral RNA induces association with ___ and dimerization
dimerization initiates signaling pathways that activate ___ and \_\_\_
IRF3 causes synthesis and secretion of type I interferons, and NF-kappaB causes synthesis and secretion of \_\_\_
* 5'-triphosphate
* retinoic-acid-inducible gene (RIG)-I-like receptor (RLR)
* mitochondrial antiviral signaling protein (MAVs)
* IRF3 and NF-kappaB
* inflammatory cytokines
