B3.004 - Innate Immunity Flashcards
1
Q
What is a pathogen
A
a microbe that is causing disease
2
Q
Necrotic
A
dead cells or tissue from injury or disease
3
Q
Apoptosis
A
cell death as a normal and controlled part of an organisms growth and development
4
Q
Cytokines
A
soluble proteins important in cell signaling
5
Q
Chemokines
A
cytokine that attracts a particular cell into an environment
6
Q
What is opsonization
A
coating a microbe with molecules that can be recognized by receptors on phagocytes
7
Q
What is phagocytosis
A
process by which a cell engulfs a solid particle
8
Q
What is at the initiation of inflammation
A
macrophages, dendritic cells, mast cells secrete cytokines
9
Q
Viruses induce production of what
A
interferons from from infected cells to inhibit infection of other cells
induce killing by NK cells
10
Q
What is the cardinal feature of adaptive immunity
A
memory response
11
Q
What are components of innate immunity
A
epithelial barriers dendritic cells phagocytes mast cells NK cells and ILCs complement
12
Q
How does adaptive immunity work
A
lymphocytes express receptors on their cell surface that recognize specifiic antigens
13
Q
What are PAMPs
A
pathogen associated molecular patterns
Shared by microbes of the same type
not on norma host cells
stimulate innate immune response
14
Q
What are some examples of PAMPs
A
LPS
Peptidoglycans
Terminal mannose residues
Unmethylated CG rich DNA
15
Q
What are DAMPs
A
Damage associated molecular patterns
Released from damaged or necrotic host cells
present in injury or infection
16
Q
What are PRRs
A
innate immune receptors that recognize PAMPs and DAMPs
17
Q
What are TLRs
A
Toll Like Receptors
Specific for microbial components
18
Q
What do TLRs do
A
activate transcription factors to stimulate expression of genes encoding cytokines, enzymes and other proteins
19
Q
What is NFkB
A
promotes other items involved in fighting infections
20
Q
Which TLRs are extracellular
A
1,2,4,6
21
Q
Which TLRs are intracellular
A
3,7,8,9
22
Q
What are the steps of TLR signaling
A
- TLR engages
- Recruits proteins that activate transcription
- Increased expression of cytokins, adhesion mols,
- Production of type 1 interferon alpha and beta
- Generate inflammation
- Stimulates adaptive immunity
- antiviral activity
23
Q
What are NLRs
A
NOD like receptors
Family of cytosolic receptors that sense DAMPs and PAMPs in the cytoplasm that contain central NOD and different N terminal domains
24
Q
NOD 1 and NOD 2 contain
A
N terminal CARD
Bacterial peptidoglycans in the cell wall
Activated NFkB
25
NLRP3
Recognizes microbial products, substances associated with cell damage and endogenous substances in cells in large quntities
Enhances production of IL-1bBeta
26
What does IL-1bBeta cause
inflammation, fever
27
What are the steps of inflammasome
1. NLRP-3 oligomerizes with inactive form of caspase 1 inlammasome
2. activation
3. active caspase 1 cleaves an IL-1beta precursor
4. activation
5. IL-1beta generates fever
28
What can inflammasome dysregulation cause
Gout
| autoinflammatory syndromes
29
components of innate immunity
```
Epithelial varrier
Phagocytes
dendritic cells
mast cells
innate lymphoid cells
NT cells
lymphocytes with limited diversity
complement
plasma proteins
cytokines
```
30
what are PMNs
polymorphonuclear leukocytes
| Neutrophils
31
what is pus made out of
dead phagocytes
32
what do neutrophils do
```
First cell to respond to infections
dominant cell of inflammation
phagocytose microbes in the blood and tissue and destroy them
recruited to tissues to remove debris
Live for only a few hours
```
33
what are band neutrophils
immature neutrophils
34
What are dendritic cells?
Antigen presenting cells that produce cytokines
| Bridge innate and adaptive immunity
35
What are mast cells
abundant cytomplasmic vasoactive granules located in the skin and mucosal epithelium
36
What are mast cells activated by
microbial products binding to TLRs
| Antibody dependent
37
What do mast cells synthesize and secrete
prostaglandins and ctyokines (TNF)
38
What do NK cells do
Identify infected and stressed cells and kill them
| CD16/56+
39
What do NK cells secrete
IFN gamma to through microphage activation
40
What activates NK cells
cytokines from macrophages and dendritic cells
41
What does IL-15
development and maturation of NK cells
42
What do IL-12 and type I IFNs do
enhance NK cell killing function
43
How do NK cells prevent killing human cells
Block signaling by receptor activation specific for self MHC I molecules to protect healthy cells
44
What are ITIMs
block NK cell activation, counteracting ITAMs
45
When there is a virus presented to an NK cell what happens
NK is activated
| ITAMs activated
46
What is ADCC
Antibodies recognize viral glycoproteins expressed on the surface of cells infected with enveloped viruses
Therapeutic intervention in treating tumor cells
47
NKT cells and B-1 B cells are what
innate lymphocytes
48
What three pathways are in the complement system
Alternative, Classical, Lectin
49
What is the Alternative pathway
Triggered when activated complement proteins on microbial surfaces are uncontrolled due to lack of regulatory proteins
50
What is the classical pathway
Triggered by antibodies bound to microbes/antigens
51
What is the lectin pathway
Mannose binding lectin binds to terminal mannose residues on microbial cell surface glycoproteins
52
What do C3a and C5a do
they are inflammatory components
53
What does C3b do
opsonization and phagocytosis through CR1
Plays a role in complement mediated cytolysis
Stimulates inflammatory reactions
54
What does the MAC do
punctures a pore in the microbe to kill it
| When C5b combines with C6, C7, C8 and multiple C9
55
As part of the plasma protein innate immunity what are collectins
Mannose binding lectins
| Surfactant
56
What is MBL
recognizes microbial carbohydrates, coating them for phagocytosis
activation of complement by lectin pathway
57
What does surfactant do
soap like substance in the lung protective from infectious microbes
58
What is CRP
C reactive protein
Binds phosphorylcholine on microbes, opsonizes them for phagocytosis by macrophages
Activates classical complement pathway proteins
59
What are interleukins
soluble proteins that cause cell signaling to generate immune and inflammatory reactions - stimulated by infection
Produced by activated and act on leukocytes
Communication between cells
60
What cytokines help in recruitment of neutrophils and monoytes
TNF
IL-1
Chemokines
61
What cytokines cause fever by acting on hypothalamus
IL-1 predominantly
| TNF
62
What cytokine causes an acute phase response protein synthesis from the liver: CRP and fibrinogen
IL-6
63
What cytokine causes thrombus formation
TNF at high concentration
64
What cytokine causes hypotension
TNF at high concentration
65
What cytokines causes septic shock
High TNF, IL-12 from dendritic cells and macrophages
66
What are Type 1 Interferons
released from DCs, macrophages, fibroblasts
| It binds to the virus blocking enzymes necessary for viral replication
67
What do Type 1 Interferons do
Inhibit protein syhtnesis
Degrade viral RNA
Inhibit viral gene expression
68
What are the cellular targets and biologic effects of TNF
```
Endothelial cells - Activation
Neutrophils - activation
Hypothalamus - fever
Liver - synthesis of acute phase proteins
Muscle/fat - catabolism
Many cell types - apoptosis
```
69
What are the principal cellular targets and biological effects of IL-1
Endothelial cells - activation (inflammation, coagulation)
Hypothalamus - fever
Liver - sythesis of acute phase proteins
T cells - Th17 differentiation
70
What are the principal targets and biologic effects of chemokines
Leukocytes - increased integrin affinity, chemotaxis, activation
71
What is the principal target and biological effect of IL-12
NK cells and T cells - IFN gamma production, increased cytotoxic activity
T cells - Th1 differentiation
72
What does IFN gamma do?
Activates macrophages
| Stimulation of some antibody responses
73
What do Type I IFNs (alpha and beta) do?
```
All cells - antiviral state, increased class I major histocompatibility complex expression
NK cells - activation
```
74
What does IL-10 do
Macrophages and dendritid cells - inhibition of cytokine and chemokine production, reduced expression of costimulators and class II MHC molecules
75
What does IL-6 do
Liver- sythesis of acut phase proteins
| B cells - proliferation of antibody producing cells
76
What does IL-15 do
NK cells - proliferation
| T cells - proliferation
77
What does IL-18 do
NK cells and T cells: IFN gamma synthesis
78
What does TGF-beta do
inhibits inflammation
| T cells - differentiation of Th17, regulatory T cells
79
Which disease has defective production of reactive oxygen intermediates by phagocytes
Chronic granulomatous disease
80
What is the mechanism of defect of chronic granulomatous disease
mutations in genes encoding components of the phagocyte oxidase enzyme, most often cytochorme b558
81
What disease has absent or deficient expression of Beta 2 integrins causing defective leukocyte adhesion dependent function
Leukocyte adhesion deficiency - 1
82
What is the mechanism of defect of Leukocyte adhesion deficiency - 1
Mutations in gene encoding the beta chain CD28 of beta 2 integrins
83
What disease has absent or deficient expression of leukocyte ligands for endothelial E and P selectins, causing failure of leukocyte migration into tissues
Leukocyte adhesion deficiency -2
84
What is the mechanism of defect of leukocyte adhesion deficiency -2
mutations in gene encoding a protein required for synthesis of sialyl-Lewis X component of E and P selectin ligands
85
What disease has a defect in complement cascade activation
Complement C3 deficiency
86
What disease has deficient activation of classical pathway of complement leading to failure to clear immune complexes and development of lupus like disease
Complement C2, C4 deficency
87
What disease has a defective lysosomal function in neutrophils, macrophages, dendritic cells, and effective granule function in natural killer cells
Chediak higashi syndrome
88
What mechanism of defect is there for Chediak Higash syndrome
Mutation in a gene encoding a lysosomal trafficking regulatory protein
89
What disease has a defective antiviral immunity in the CNS
HSV-1 encephalitis
90
What mutation can lead to worse outcomes for HSV-1 like encephalitis
Mutations in TLR3 gene
91
What disease has defective innate immune responses to pyogenic bacteria
recurrent pyogenic bacterial infections
92
What doe PRRs do
recognize nucleic acids but they are located in cellular components where healthy cells are not accessible
