Lecture 4 Flashcards
0
Q
What is the reaction of innate immunity?
A
eliminates damaged cells and initiates the process of tissue repair:
-recognizes and responds to host molecules related to stressed, damaged, and dead host
1
Q
innate immunity
A
initial host defense response to pathogens that prevents, controls, or eliminates infection:
-may keep the infection in check until more specialiezed adaptive immune repsonses are activated
2
Q
What clears cell debris?
A
phagocytosis
3
Q
What stimulates and controls tissue remodeling?
A
innate immunity
4
Q
Innate immunity controls?
A
adaptive responses
- intracellular vs extracellular pathogens
- provides the danger signals that alert the adaptive immune system to response
- reacts in distint ways to different microbes thereby influcencing the type of adaptive immune response
5
Q
cellular and chemical barriers
A
skin, mucosal epithelia, antimicrobial molecules
6
Q
blood proteins
A
complemetn, acute phase proteins, cytokines, others
7
Q
cells
A
phagocytes(macrophages, neutrophils), dendritic cells, natural killer cells, innate lymphoid cells
8
Q
Liver is major responder to these acute phase proteins
A
components
T cells were-natural killer cells, innate lymphoid cells,
9
Q
innate immunity
A
inflammation, physical barriers, anti viral responses
10
Q
leukocytes and plamsa proteins
A
inflammation
11
Q
skin and epithelial cells
A
physcial barriers
12
Q
inhibition of viral replication
A
anti-viral reponses
13
Q
innate immunity specficity
A
pathogen-assocaited mollecular patterns (PAMPs)
damage-associated mollecular patterns (DAMPs)
14
Q
adaptive immunity specificity
A
Fine structures of microbial and non microbial Ags
15
Q
Innate immunity receptors
A
patterna recognition receptors (PRRs)
16
Q
Adaptive immunity receptors
A
greater diversity of BCRs and TCRs generated by somatic recombination
17
Q
Distribution of receptors innate immunity
A
nonclonal: identical receptors on vaious cell
18
Q
Distribution of receptors with adaptive immunity
A
clonal: identical on a single cell, but different btw two cells
19
Q
innate immunity discrimination of self and non self
A
Yes
20
Q
adaptive immunity discrimination of self and non self
A
Yes
21
Q
Nucleic Acids
- ssRNA
- dsRNA
- CpG- unmethylated CpG DNA seuqneces
A
- Virus
- Virus
- Virus, bacteria
22
Q
Protiens
Pilin
Flagellin
A
- bacteria
- bacteria
23
Q
Cell wall lipids Lipoplysaccharides (LPS) Lipoteichoic acid (LTA)
A
- Gram negative bacteria
- gram positive bacteria
24
Carbohydrates
mannan
glucans
fungi, bacteria
| fungi
25
Damage Assocaited molecular patterns
| Stress induced proteins
HSPs
26
crystals
monosodium urate
27
nuclear proteins
HMGB1
28
innate immunity inducers inflammation
pathogens sd
Exogenous ligands (PAMPs)
- nucleic acid
- Lipid
- Proteins
29
Sensors Pattern Recognition receptors inflammation
Toll-like receptors
NOD-like receptors
C-type lectin and so forth
30
mediators inflamation
TNF alpha
IL-6
IL-1Beta
31
Homeostatic inflammation Cell/ECM-derived molecules
| inducers
Nuclecic Acids (ATP)
Lipid
Protein
32
inflammation causes
a lot of macrophages, it is unable to get rid of them.
33
Where can microbial PRRs be located?
extracellular in endososoems or cytosol
34
5 families of microbieal PRRs
```
TLR family: surface, endosomal
CLRs family
NOD-like receptors (NLRs) family
RIG-like receptors (RLRs) family
Cytosolic DNA sensors (CDS) family
```
35
Which cell expresses toll like receptor 9??
macrophages
36
What bind pathogen assocaited molecular patterns from extracellular pathogens?
PRRs on the cell surface
37
What recognize nucleic acids of phagocytized microbes?
endosomal TLRs
38
NOD
nucleotide-binding oligomerization domain
39
CLR
C type lectin receptor
40
RIG
retinoic acid inducible gene
41
TLR's location
surface and endosomal membranes of DCs, phagocytes, B cells, endotheial cells
Ex TLRs 1-9
Ligands= microbial Ags(LPS, peptidoglycans, viral nucleic acids)
42
NLRs llocation
cytosol of phagocytes, epithelial cells and others
43
NLR's example NOD1/2
bacterial cell wall peptidoglycans
44
NLRP family (inflammasomes)
intracellular crystals (urate, silica); changes in concentrations of ATP and ions lysosomal damage
45
RLRs location
cytosol of phagocytes and other cells
ex RIG-1, MDA-5
Viral RNA
46
CDSs location
cytosol of many cell types
ex AIM2; Sing assocaited CDSs
bacterial and viral DNA
47
CLRs location
plasma membranes and phagocytes
mannose receptors
microbial carbohydrates w terminal mannose or fructose
48
homodimers or heterodimers
TLRs
49
evolutionalrily conserved family of PRRs expressed on many cell types
TLRs
50
What do TLRs recognize?
PAMPs and DAMPs
51
Whare TLRs are express on the cell surface?
1,2,4,5,6
52
What TLRs are expressed in endosomes?
3,7,8,9
53
DNA containing un methylated ctyosine-guanosine dinucleotides
CpG
54
receptor homology domain
TIR, TOLL/IL-1
55
TLR1;TLR2
bacterial lipopeptides
56
TLR2
bacterial peptidoglycans
57
TLR4
LPS
58
The only anti inflammatory cytokine is?
L10 not dependent on
59
TLR5
bacterial flagelin
60
TLR2;TLR6
bacterial lipopeptides
61
TLR3
dsRNA
62
TLR7
ssRNA
63
TLR8
ss RNA
64
TLR9
CpG DNA
65
TLR structure
Leucine rich repeat motifs
| cysteine rich flanking motifs, TIR domain
66
What adaptor protein does TLRs 1, 2, 5 and 6 use?
MyD88
67
MyD88 activates?
the transcription factors NF-kB and AP-1
68
What adaptor ptoein does TLR3 use/
TRIF
69
What does TRIF activiate?
IRF3 and IRF7 transcription factos
70
TLRs 7 ad 9 can activate
both pathways
71
TLRs 7 and 9 in the endosome use
MyD88
72
MyD88 activates
NF-KB adn IRF7
73
Major TLF signaling pathways?
MyD88, with expetion of TLR3
74
TLR4 and the TLR2 subfamily(TLF1, TLR2, TLR6) engage?
TIRAP
75
How does TLR3 signal?
TRIF
76
What is TRIF used in conjuction with?
TRAM in the TLR4-MyD88-independent pathway
77
What are functional roles of TLRs?
influence adaptive repsone-->T cells-->cell mediated immunity
direct antimicrobial response--> bacterial death
tissue injury--> apoptosis of host cells or septic shock
78
What is produced in the inflammasome?
secreted form of IL-1B and IL-18
79
What are proinflammatory cytokines?
IL-1B and IL-18
80
What is the main function of caspase-1?
to cleave the inactive ctyoplasmic precursor forms of two homologous ctyokines called IL-IB and IL-18
81
What does inflammasomes activate?
the enzyme caspase-1(a protease w cysteine residue in the active site)
82
a subfamily of 14 NOD-like receptors
NLRP(pyrin-domain-containing protines)
83
What respond to cytosolic PAMPs and DAMPs by binding other proteins and forming signaling complexes?
inflammasomes
84
Caspase
important in apoptosis
85
macrophage mannose receptor (MMR) and DEC-205
a) a cysteine- rich N terminal domain
b) a fibronectin-like domain
c) multiple calcium-dependent (C-type)lectin domains that bind various carbohydrate ligands
86
The scavenger receptor (SR) family
trimeric complexes of type II transmembrane polypeptides
87
Have 3 distince extracellular structural domains
a) SR cysteine-rich (SRCR) domain (absent in SR-A II)
b) the collagen-like domain, which is implicated in the binding of polyanionic ligands
c) the alpha- helical coiled-coil domain (absent in MARCO), which is believed to assist in receptor trmerization
88
What is a group of receptors mediated the uptake of oxidiezed lipoprotiens into cells?
SRs
89
What are expressed on Mo and mediate recognition/phagocytosis of microorganisms?
SR-A and CD36
90
What functions as a coreceptor in TLR2/6 recogintion and repsonse to bactrailly derived lipoteichoic acid and diacylated lipopeptides?
CD36
91
SRs bind various bacterila constituets based on?
negative charges of bacterial LPS, lipoteichoic acid, nucleic acids, B-glucan and proteins.... only bacteria has sugars
92
What are c-type lectin receptors?
receptors for carboydates
93
What is the mannose receptor involved in?
phagocytosis of microbes
94
What do mannose receptors recognize?
terminal D-mannose, L-fucos, and N-acetyl D glucosamine sugars on microbial surface
95
What does carbohydrate receptors contain a conserved carbohydrate recognition domain for?
microbial mannose, N-acetylglucosamine, and B-glucans
96
Some of the lectins are soluble proteins found in?
the blood an dextracellular fluids
97
Other lectins are integral membrane proteins found on
the surfaces of macrophages, dendritic cells, and some tissue cells
98
What doe receptors for carbohydrates facilitate?
the phagocytosis of the microbes and the secretion of cytokines that promote subsequence adaptive immune repsones
99
what prevent approach and deny entry of pahtogens at skin and mucous membranes?
physical barriers for innate immunity
100
What remove debris and pahtogens?
pagocytes
101
destroys absnomal cells
immunological surveillance
102
What immune cells are TLRs expressed on?
mcarophages and dendritic cells
103
What do microbial lipoproteins activate?
mammalian immune cells through TLR2
104
What does LPS activate?
TLR4
105
What do bactreial DNA sequences containing unmethylated cytosine-guanomsine dinucleotides(CpGs) work through?
TLR9
106
What does TLR dependent signaling pathways activate?
NF-KB which results in transcription of pro inflammatory genes
107
What controsl the adaptive T cell immune response?
Cytokine IL-12
108
What does activation of TLRs trigger?
antimicrobial pathways that directly kill the pathogens
109
In what way can actiavtion of the TLRs be detrimental to the host?
- can contribute to tissue injury by inducing apoptosis
| - can lead to life thratening symptoms of septic shock
110
What does epithelia at the portals of entry of microbes provide?
physical barriers, produce antimicrobial substances, and harbor intraepithelial lymphocytes that are believed to kill microbes and infected cells
111
small cationic peptides that contain both cationic and hydrophobic regions
defensins
112
What are defensins produced by?
epithelial cells of mucosal surfaces and by granule containign leukocytes, including neutrophils, NK cells, and CTLs
113
Why is synthesis of defensins stimulated by?
cytokines and microbial products
114
Defensin A and B are produced by
different cell types
115
What have direct toxicity to microbes, including bacteria, fungi and enveloped viruses?
defensins
116
How do defensisn kill microbes?
By inserting into and disrupting functions of the microbail membranes
117
What regualted activation of cells involved in the infalmmatory repsonse to microbes?
antimicrobial peptides defensins
118
What are produced by neutrophils and barrier epithelial cells in the skin, gastrointestinal tract and respiratory system?
antimicrobial peptides cathelicidins
119
What are antimicrobial peptides cathelicidins synthesized as?
18-kD two domain precursor protine and is proteolytically cleaved into two protective peptides
120
Whay would synthesis and cleavage of antimicrobial peptides cathelicidins be stimulated by?
cytokinds and microbial products
121
What are the mechanisms of antimicrobial peptides cathelicidins?
direct toxicity to microorganisms and the activation of leukocytes
122
What can bind and neutralize LPS?
C-termal fragment called LL-37
123
What plays an anti inflammatory role by beinding to DNA and blocking AIM2 inflammasome activation?
LL-37
124
What are common at sites in the body that are exposed to the external environment, such as the skin?
mast cells
125
Why are mast cells found in close proximity to blood vessels?
They can regualte vacular permeability and effector- cell recruitment
126
How can mast cells regulate the behavior of neighboring cells?
Effector cells through the release of mediators
127
What are lipid mediators?
prostaglandins, leukotrienes, platelet-activating factors
128
Mast cells release what preformed mediators?
```
histamine
heparin
proteases
chondroitin sulfates
TNF
antimicribial peptides
```
129
What effect does lipid mediators have?
- recruitment and activation of monocytes and macrophages
| - migration and activation of dendritic cells
130
What effect do preformed mediators have?
- recruitment and activation of T cells
- recuritment and activation of neutrophils, basophils and eosinophils
- phagocytosis and or antimicrobial activity
- effects on epithelial cells, tight juction protiens, etc..
131
Functions of monocyte/macrophages
1.activation
2.chemotaxis, tissue inflammation
3. phagocytosis, scavenger function, tissue repair
4effector function
5. antigen presentation
6. immunomodulation
132
Where do dendritic cells arise from?
A common precursor cell of the myeloid lineage in the bone marrow
133
What do Dcs further differentiate into?
classical DCs and plamacytoid Dcs
134
What may arise from monocytes in infalmed tissues?
inflammatory DCs
135
tissue-redient DCs, the skin, appears early in life and may develop from embryonic precursors
Langerhans cells
136
What is the matruation of DCs dependent on?
Flt2 ligand, which binds to the Flt3 tyrosine kinase receptor on the precursor cells
137
Dendritic cells are the most improtant for activation of?
naive T cells
138
Play a major role in inate responses to infections and in linking innate and adaptive immune repsonses?
DCs
139
WHat have long membraneous projections and phagocytic capabilites?
DCs
140
DCs are part of the .... lineage?
Myeloid and arise from a precursor that can also differentiate into monocytes
141
Does to Mo and Dcs express?
receptors that recognize Ags typically made by microbes and no mammalian cells
142
What do activated DCs also secret?
cytokines
143
Where do classical DCs reside?
The skin, mucosa and organ parenchyma
144
Where do cassical DCs micrate upon actiatioini by microbes?
to LNs where they display microbial protein Ags to T lymphocytes
145
What are early cellular repsonders to viral infections?
plamacytoid DCs
146
What does plamacytoid DCs recgonize and produce?
They recognize nucleic acids of intracellular viruses and produe soluble proteins type I interferons, aka IFN-alpha/beta
147
What have potent antiviral activites?
IFN-ALpha/beta
148
DC may also derive from
ciruclating monocytes
149
What do innate lymphoid cells develop from?
Common bone marrow precursor identified by the Id2 transcription factor
150
What are the 3 major subsets of innate lymphoid cells?
distinguished by expression of distince transcription factors and by cytokines produced
151
ILC1-->
IL-12 and IL-18
defense against viruses
152
ILC2-->
IL-25 and IL-33
allergic inflammation
153
ILC3-->
IL-1 and IL-23
intestinal barrier function; lymphoid organogensesis
154
What is the function of NK cells?
Recgnize ligands on infected cells or cells undergoing other types of stress
155
NK cells kill htos...
infected or stressed host cells
156
what eliminate reservoirs of infection and thus release intracellular pahtoges for phagocytosis?
NK
157
What do NK cells respond too?
IL-12 produced by macrophages and secrete IFN-gamma
158
What activates the macrophages to kill phagocytized microbes?
IFN-gamma
159
When NK cells recognize ligands on targe cells, they?
activate protein tyosine kinases (PTKs)
160
What are NK cell activating receptors called?
killer cell immunoglobulin (Ig) like receptors (KIRs)
161
What do Nk cells not kill?
I MHC expressing healthy cells
