Innate Immunity Flashcards

1
Q

opsonization

A

the process of locating a microbe with molecules that can be recognized by receptors on phagocytes, which proceed to engulf and kill microbes

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2
Q

sites of microbial entry

A

epithelium of skin, GI tract, and respiratory tract

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3
Q

cells that show up at site of microbial entry

A

macrophages, dendritic cells, mast cells, phagocytes

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4
Q

plasma proteins

A

complement proteins that circulate in the blood promoting microbial destruction

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5
Q

cardinal feature of adaptive immunity

A

memory response, somatic rearrangement of gene segments during lymphocyte development leading to clonal expansion of B and T lymphocytes

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6
Q

innate microbial recognition

A

structures shared by classes of microbes not present on host cells are recognized

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7
Q

adaptive microbial recognition

A

lymphocytes express receptors (antibodies) on their cell surface that recognize specific antigens, activating phagocytosis, an innate property

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8
Q

PAMPs

A

microbial molecules shared by microbes of the same type that are not on normal host cells, that stimulate immune responses

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9
Q

examples of PAMPs

A

lipopolysaccharides (gram - bacteria), peptidoglycans (bacteria), terminal mannose residues (opportunistic infections), and unmethylated CG rich DNA (viruses)

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10
Q

DAMPs

A

damage-associated molecular patterns released from damaged or necrotic host cells present in injury, infarction, or infection

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11
Q

PRRs

A

pattern recognition receptors, recognize PAMPs and DAMPs, present on phagocytes, dendritic cells, and others

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12
Q

PRRs can be located in different places in the cell

A

cell surface to detect extracellular microbes, vesicles where microbes are ingested, and the cytosol to sense cytoplasmic microbes

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13
Q

Toll-Like Receptors are PRRs detecting microbial components located

A

extracellularly, recognizing proteins, lipids, and polysaccharides on cell surfaces, and in endosomes, recognizing nucleic acids

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14
Q

What do toll-like receptors do

A

activate transcription factors to stimulate the expression of genes encoding cytokines, enzymes and NF kappa B, which promotes other infection-fighting agents

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15
Q

what is the result of a defect in TLR signaling

A

recurrent and highly severe infections

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16
Q

which toll-like receptors are found extracellularly and what do they find

A

1,2,4,5,6 look for proteins, lipids, and polysaccharides on microbial membranes

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17
Q

which toll-like receptors are found intracellularly in endosomes and what do they find

A

3,7,8,9 look for nucleic acids, both single and double stranded RNA and CG rich DNA (viruses)

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18
Q

how do toll-like receptors signal inflammatory responses

A

engage with bacteria or virus on leucine-rich repeats, signaling domain recruits transcription factors NF kappa B and interferon regulatory factors, which lead to increased expression of inflammatory cells and antiviral cells

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19
Q

what does NF kappa B do

A

transcription factor, increases expression of cytokines, adhesion molecules, and costimulators, leading to acute inflammation and the stimulation of adaptive immunity

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20
Q

what do interferon regulatory factors do

A

transcription factor, increases expression of type 1 interferons IFN alpha and beta, which lead to the antiviral state

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21
Q

what is the role of NOD-like receptors

A

sense DAMPs and PAMPs in cytoplasm containing nucleotide oligomerization domain, and different N-terminal domains

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22
Q

Nod1 and Nod2

A

contain N-terminal caspase related domains (CARD), found in bacterial peptidoglycan in cell wall, activated NF kappa B

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23
Q

NLRP3

A

recognizes microbial products, substances associated with cell damage, and endogenous substances in too large of quantities e.g. crystals, enhances production of IL1b beta, which leads to fever

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24
Q

genetic defect in NLRP3

A

enhances production of IL1b beta, leads to periodic fever syndrome

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25
how do patients with gout get a "fever" in their toe
NLRP3 oligomerizes with inactive form of caspase 1 inflammasome in response to crystal buildup, activating caspase 1, which cleaves IL1 beta precursor, which gets activated and generates fever locally
26
chemical barrier on epithelium
peptide antibiotics like defenses and cathelicidins which kills some microbes locally
27
intraepithelial lymphocytes
limited diversity, lymphocytes embedded in barrier kill microbes before they breach epithelium
28
chemokines
call leukocytes to cell surface and to the site of injury
29
selectins
allow for leukocyte to slow down and adhere to cell surface in process known as rolling
30
integrin
allows for stable adhesion of leukocytes to cell wall
31
PMNs
polymorphonuclear leukocytes, or neutrophils, most abundant leukocyte in the blood, rapidly increase in number during infection, first responders, dominant cell of inflammation, phagocytose microbes in blood and tissue and remove debris leading to pus formation
32
Band Neutrophils
immature neutrophils, unsegmented nucleus, released prematurely indicating desperate situation
33
oxidative burst
PRR recognizes microbe and phagocytosis occurs, membrane closes and forms phagosome, fuses with lysosome forming phagolysosome, phagocyte oxidase converts O2 to superoxide and ROS, works with lysosomal proteases to destroy microbes
34
patients who can't produce ROS
can't properly destroy microbes using the phagolysosome, experience chronic granulomatous disease
35
Mononuclear phagocytic system
monocytes differentiate into macrophages in the tissues, found in all connective tissue and organs, ingest microbes, clear dead tissues, initiate repair
36
some macrophages are derived from
the yolk sack or fetal liver during development, particularly those in the brain (microglial cells), liver (kupffer cells), spleen (sinusoidal macrophages), and lungs (alveolar macrophages)
37
Classical macrophage activation
toll-like receptor ligands and interferon gamma lead to production of phagolysosomal killing of bacteria and fungi
38
alternative macrophage activation
IL13 and IL4 lead to macrophage production of IL10, which is anti-inflammatory and TGF beta, which leads to tissue repair
39
role of dendritic cells
antigen presenting cells, activated by cytokines, move through lymphatic vessels, connect to and activate t cells in lymph nodes, bridge between innate and adaptive immunity
40
role of mast cells
contain vasoactive granules i.e. histamine, which increase capillary permeability at site of injury, and synthesize and secrete prostaglandins and cytokines (TNF), which stimulate inflammation
41
where do mast cells reside
skin and mucosal epithelium
42
role of natural killer cells
combat intracellular microbial infections by identifing infected or stressed cells and killing them by emptying their cytoplasmic granules in the extracellular space nearby, which enter the cell and induce apoptosis, also secrete IFN gamma to activate macrophages
43
what activates natural killer cells
cytokines from macrophages and dendritic cells, particularly IL 15 and IL 12
44
IL 15
develops and matures natural killer cells
45
IL 12
enhance natural killer cell killing function, as well as type I interferons alpha and beta
46
inhibitory role of natural killer cells
block signaling by receptor activation specific for "self" MHC I molecules, protect healthy cells
47
ITIMs
inhibitory receptors of natural killer T cells, blocking ITAMs, preventing NK activation
48
CD94/NKG2 lectin subunit
block NK cell activation
49
KIRs
killer cell immunoglobulin-like receptors, block NK cell activation
50
NK cell ADCC
antibody-dependent cellular cytotoxicity, antibodies recognize viral glycoproteins on cells infected with enveloped viruses, leads to killing of antibody-coated cell
51
NKT cells
shares properties of both NK cells and T cells, recognizes lipids on CD1 molecule, not adaptive immunity
52
B-1 B cells
B lymphocytes in the peritoneal cavity and mucosal tissue that produce IgM, not adaptive immunity
53
complement system: alternative pathway
activated complement proteins on microbial surface are uncontrolled due to lack of regulatory proteins, innate immunity
54
complement system: classical pathway
antibodies bound to antigens, adaptive immunity, C3a and C5a are inflammatory, C3b is responsible for opsinization
55
complement system: lectin pathway
mannose binding lectin binds to terminal residues on microbial cell surface glycoproteins, innate immunity
56
3 main functions of complement system
opsonization and phagocytosis (C3b), inflammation (C3a and C5a), and cell lysis via membrane attack complex
57
complement membrane attack complex formation
C5 cleaved to C5b, binds with C6,7,8 and multiple C9, forms a pore in membrane, influx of water and ions, cell death
58
collectins
plasma proteins including mannose binding lectin and surfactant
59
mannose binding lectin
recognizes microbial carbohydrates, coats them for phagocytosis, activation of lectin complement system, not clinically relevant
60
surfactant
soap like protective coating on lung against infectious microbes, important in premature babies
61
c-reactive protein
binds phosphorylcholine on microbes, opsonizes them for phagocytosis, activates classical complement pathway proteins, can be measured in blood to prove active infection
62
interleukins
soluble proteins cause cell signaling to generate immune/inflammatory reactions, stimulated by infection, produced by, activated, and act on leukocytes
63
interleukin role in innate immunity
communicate with mast cells, dendritic cells, and macrophages
64
interleukin role in adaptive immunity
communicate with helper T lymphocytes
65
cytokines responsible for monocyte/neutrophil recruitment
TNF, IL1, and chemokines
66
cytokines responsible for fever
TNF and primarily IL-1b
67
cytokines responsible for acute phase response protein synthesis in liver
IL6, leads to production of C-reactive protein and fibrinogen
68
cytokines responsible for hypotension
TNF, at high concentrations
69
cytokines responsible for septic shock
TNF at high concentrations, IL12 from dendritic cells and macrophages, in response to LPS and other microbial molecules
70
type 1 interferon role in viral infection
binds to the virus, blocks enzymes necessary for viral replication, preventing protein synthesis, degrading viral RNA, and inhibiting gene expression
71
TNF produced from
macrophages, T cells, and mast cells
72
TNF effect on endothelial cells
inflammation and coagulation
73
TNF effect on neutrophils
activation
74
TNF effect on hypothalamus
fever
75
TNF effect on liver
synthesis of acute-phase proteins
76
TNF effect on muscle/fat
cachexia
77
Tissue types/cells effected by TNF
endothelial, neutrophils, hypothalamus, liver, muscle/fat
78
Interleukin 1 produced by
macrophages, dendritic cells, endothelial cells, epithelial cells, mast cells (MDEEM)
79
Tissue/cell types effected by interleukin 1
endothelial cells, hypothalamus, liver, and T cells
80
Interleukin 1 effect on endothelial cells
inflammation coagulation
81
Interleukin 1 effect on hypothalamus
fever, particular IL1b
82
Interleukin 1 effect on liver
synthesis of acute-phase proteins
83
Interleukin 1 effect on T cells
Th17 differentiation
84
Th17
produces IL17, pro inflammatory cells, found in joints of arthritis patients
85
chemokines produced by
macrophages, dendritic cells, endothelial cells, T cells, fibroblasts, platelets
86
tissue/cell types effected by chemokines
leukocytes
87
chemokine effect on leukocytes
increased integrin affinity, chemotaxis, activation
88
Interleukin 12 produced by
dendritic cells, macrophages
89
tissue/cell types effected by interleukin 12
NK cells, T cells
90
effect of interleukin 12 on NK cells
interferon gamma production, increased cytotoxic activity
91
effect of interleukin 12 on T cells
interferon gamma production, increased cytotoxic activity, Th1 differentiation
92
interferon gamma produced by
NK cells and T lymphocytes
93
interferon gamma role
activates macrophages, stimulates some antibody response
94
type 1 interferons produced by
alpha: dendritic cells and macrophages, beta: fibroblasts
95
type 1 interferon role
antiviral state, increased class I MHC expression, activates natural killer cells
96
interleukin 10 produced by
macrophages, dendritic cells, T cells
97
interleukin 10 effects which cells?
macrophages and dendritic cells
98
role of interleukin 10
inhibition of cytokine and chemokine production, reduced expression of costimulators and class II MHC molecules
99
interleukin 6 produced by
macrophages, endothelial cells, t cells
100
interleukin 6 effects which tissue/cell types?
liver and B cells
101
interleukin 6 effect on liver
synthesis of acute-phase proteins
102
interleukin 6 effect on B cells
proliferation of antibody-producing cells
103
interleukin 15 produced by
macrophages
104
interleukin 15 role
promote proliferation of NK cells and T cells
105
interleukin 18 produced by
macrophages
106
interleukin 18 role
cause NK cells and T cells to produce interferon gamma
107
TGF beta produced by
many cell types
108
role of TGF beta
inhibition of inflammation, leads to tissue repair
109
chronic granulomatous disease
defective production of ROS leads to inability to produce phagocytic oxidase, leading to low immunity, many infections, mostly skin and some pulmonary
110
leukocyte adhesion deficiency
defective leukocyte adhesion-dependent functions leads to high WBC count in patients
111
complement C3 deficiency
can prevent the full cascade, other times it's just defective and slow
112
Chediak-Higashi syndrome
defective lysosomal function in neutrophils, macrophages, dendritic cells, and defective granule function in NKs, diagnosed very early, patients have silver hair, effects phagocytosis, bad long-term infections
113
HSV1 encephalitis
mutation in toll-like receptor 3 leads patients with HSV1 to have defective CNS antiviral effects
114
Positive selection of reactive cells
check to see if the T cells are able to interact with MHC, if they are, they will survive and move on to maturity
115
negative selection of reactive cells
check to see how capable the T cells are of binding with self, if it's too strong, cell will be told to undergo apoptosis, way to prevent autoimmunity