lecture 1b Flashcards
1
Q
What includes the second line of defense against the invasion pathogens?
A
phagocytic white blood cells
antimicrobial proteins
inflammatory response
2
Q
Which white blood cells are phagocytes?
A
Monocytes (which differentiate into Macrophages and Dendritic Cells upon entering tissues) and neutrophils.
3
Q
white blood cells:
Granulocytes:
agranulocytes:
A
Granulocytes: neutrophils, eosinophils, basophils
agranulocytes: lymphocytes (B, T, NK) and monocytes (macrophage, dendritic cells)
4
Q
second line of defense is
A
innate or genetic immunity
5
Q
Antigens are presented to B and T cells by antigen-presenting cells (APCs). The primary types of APCs are:
A
macrophages
dendritic cells (most important)
B cells
6
Q
while antigen presentation via _ primarily targets helper T cells, _ facilitate the presentation to cytotoxic T cells
A
MHC II molecules
MHC I molecules
7
Q
sites of action for extracellular pathogens:
A
interstitial spaces (btwn cells), blood, lymph, epithelial surfaces
8
Q
what are the different extracellular pathogens?
A
bacteria, viruses, protozoa, fungi, and worms.
9
Q
protective immunity against pathogens having interstitial spaces, blood and lymph as their site of action:
A
complement activation
antibodies
phagocytosis
10
Q
protective immunity against pathogens having epithelial surfaces as their site of action:
A
antimicrobial peptides
antibodies
11
Q
Antimicrobial Peptides (AMPs): These are
A
small proteins produced by the epithelial cells that have the ability to kill or inhibit the growth of pathogens such as bacteria, viruses, and fungi.
12
Q
sites of action for intracellular pathogens:
A
cytoplasmic and vesicular
13
Q
what are the different cytoplasmic pathogens?
A
viruses and protozoa
14
Q
what are the different vesicular pathogens?
A
bacteria
15
Q
protective immunity against cytoplasmic pathogens:
A
NK cells
cytotoxic T cells
16
Q
protective immunity against vesicular pathogens:
A
T cell and NK cell-dependent macrophages
17
Q
Two types of pattern recognition receptors:
A
receptors for phagocytosis (mainly phagocytes)
receptors for inflammation
18
Q
receptor for phagocytosis:
A
glucan receptor
complement receptor
scavenger receptor
mannose receptors
19
Q
Glucan Receptor:
A
This receptor binds to glucans, which are polysaccharides commonly found on fungal and bacterial cell walls.
20
Q
Complement Receptors:
A
These receptors bind to complement proteins that have opsonized (coated) the bacteria, enhancing the recognition and engulfment by the macrophage.
21
Q
Scavenger Receptors:
A
These receptors are involved in the binding and uptake of a wide range of ligands, including modified lipoproteins and microbial pathogens, aiding in the clearance of cellular debris and pathogens.
22
Q
Mannose receptors:
A
They recognize and bind to mannose sugars, which are common components on the surfaces of many pathogens, including bacteria, fungi, and viruses.
23
Q
_ are the major constituents of the cell
wall of fungi
A
b-glucans
24
Q
b-glucans are the major constituents of the cell
wall of _
A
fungi
25
Complement is a _
system of plasma proteins that destroy pathogens
26
what are the different PRR signaling pathways?
Toll-like signaling pathway
Inflammasome
Nucleic acid sensing
27
Toll-like Receptor (TLR) Signaling:
Found on: Many cell types, including _, _, _, and others.
Function: Recognizes specific molecular patterns from pathogens, such as lipopolysaccharides (_) on _ (via _), viral double-stranded RNA (via _), single-stranded RNA (via _), and others.
Outcome: Activates signaling pathways that lead to the production of _ and _, often via activation of _
macrophages
dendritic cells
epithelial cells
LPS
gram-negative bacteria
TLR4
TLR3
TLR7
inflammatory cytokines
type I interferons
NF-κB and IRF transcription factors.
28
TLR2 has been shown to bind to a wide range of ligands present on a variety of microorganisms, including _ and _ bacteria, fungi, viruses, and parasites.
Gram-positive
Gram-negative
29
NF-κB and IRF transcription factors:
NF-κB is a protein complex that controls the transcription of DNA, cytokine production, and cell survival.
IRFs are a family of transcription factors primarily known for their roles in the regulation of interferons in response to viral infection, as well as in regulating the expression of genes involved in antiviral defense, immune responses, and cell growth regulation.
30
Inflammasome Activation:
Found on: Mainly in myeloid cells like _ and _.
Function: Detects _, leading to the assembly of the_.
Outcome: Activates _, which processes pro-inflammatory _ like IL-1β into their active forms, and can also trigger a form of cell death known as _.
macrophages
dendritic cells
cytosolic danger signals, often products of infection or cellular damage.
inflammasome complex
caspase-1
cytokines
pyroptosis
31
Nucleic Acid Sensing:
Found on: Various cell types, including _ and _.
Function: Recognizes _ within the cytosol via receptors like RIG-I and MDA5 for _, and cGAS for _.
Outcome: These sensors trigger signaling pathways that lead to the production of _ and other _, primarily through activation of _.
epithelial cells
plasmacytoid dendritic cells
viral RNA or DNA
RNA
DNA
type I interferons
antiviral cytokines
IRFs
32
Type I interferons are _ crucial in the immune system's defense against viral infections.
They include various forms of interferon-_ and interferon-_, among others.
Produced primarily by _, these molecules act by _, triggering signaling pathways that lead to the _ and enhance the immune response. Type I interferons also boost the activity of _ and increase the _, enhancing both innate and adaptive immune responses against viruses.
a group of cytokines
alpha
beta
infected cells
binding to specific receptors on neighboring cells.
expression of genes that inhibit viral replication
natural killer cells
antigen presentation capabilities of dendritic cells.
33
receptors for inflammation:
TLR2
TLR3
TLR4
RIG-I (indirect)
34
how different Toll-like receptors (TLRs) on macrophages recognize specific bacterial and viral components, leading to the synthesis of inflammatory cytokines. Key elements include:
TLR4: Recognizes lipopolysaccharide (LPS), a component found on the outer membrane of gram-NEGATIVE bacteria. Upon recognition, TLR4 triggers a signaling cascade that activates TRANSCRIPTION factors inside the nucleus of the macrophage.
TLR2: Typically involved in the detection of peptidoglycan and other components from gram-POSITIVE bacteria. Similar to TLR4, it activates transcription pathways that lead to CYTOKINE production.
TLR3: Specialized in recognizing double-stranded RNA (dsRNA), a molecular pattern often associated with viral infections.
35
TLR1-TLR4 except TLR3 recognize _
bacteria
36
RIG-I receptors (dsRNA/DNA) recognize _
viruses
37
TLR7-TLR9 + TLR3 recognize _
endosomal pathogen (and viruses)
38
NOD1/NOD2 recognise _
a small
fragment of bacterial
peptidoglycan (bacteria in gut)
39
NLRP3 (inflammasome) recognizes _
stress/danger
40
LPS from Gram-negative bacteria is recognized by _, typically in conjunction with _, a co-receptor that enhances _'s sensitivity to LPS.
TLR4
MD2
TLR4
41
Flagellin, a protein found in bacterial flagella, is recognized by _.
TLR5
42
_ is highlighted as a critical component of the immune response, particularly in recognizing cellular stress or damage signals (DAMPs). It assembles in response to a broad range of stimuli, leading to the activation of _, which then cleaves pro-inflammatory _ like IL-1β into _.
NLRP3 inflammasome
caspase-1
cytokines
their active forms
43
the convex surfaces of TLR1 and TLR2 have binding sites for _
lipid side chains of triacyl lipopeptides
44
binding of each TLR to the same lipopeptide induces _, bringing their _
dimerization
cytoplasmic TIR domains into close proximity
45
TLR4 recognizes
_
from _
lipopolysaccharides (LPS)
bacteria
46
TLR3 recognizes
_ from _
double-stranded RNA
viruses
47
TLR1/TLR2 recognizes
_ from _
peptidoglycan
bacteria
48
Structure of Gram-positive bacteria: possess _ cell wall predominantly composed of _
a thick
peptidoglycan (PGN).
49
binding of TLR2 and peptidoglycan results in _
potentially leading to conditions like septic shock
50
Gram-negative bacteria have a _ cell wall but are characterized by an outer membrane rich in lipopolysaccharide (LPS).
thinner
51
Gram- bacterial
septic shock is
induced by LPS
binding to _
TLR4
52
NFkB activates the transcription of genes for _, which are synthesized in the _ and secreted via the _
inflammatory cytokines
cytoplasm
ER
53
Transcription factor NFkB activates a series of _, _ and _
anti-bacterial/fungal AMP
cytokine
chemokine genes
54
which cytokines produce fever?
IL-6
TNF-Ɑ
IL-1β
55
NOD1/NOD2 are cytoplasmic receptors that recognize small fragments of bacterial _.
peptidoglycan
56
Upon recognition of bacterial ligands, NOD1/NOD2 undergoes a conformational change that allows them to recruit and interact with the _ through a _ known as the _.
The binding to _ initiates a cascade of downstream signaling events leading to the activation of _
kinase RIPK2
domain
CARD
RIPK2
NF-κB
57
Under normal conditions, NOD2 helps maintain _ by recognizing bacterial peptidoglycan from the microbiota.
gut homeostasis
58
NOD2's role in physiological inflammation includes _, which are crucial for controlling the _, thus maintaining _ health.
promoting the production of antimicrobial peptides (AMPs).
growth and composition of gut microbiota
intestinal
59
Mutations in NOD2 that impair its function lead to reduced production of _. This deficiency disrupts the _ (dysbiosis) and decreases _. The resulting microbial imbalance and barrier dysfunction facilitate _ and _, which can manifest as chronic inflammation typical in _ disease.
AMPs
microbial balance in the gut
mucosal barrier function
pathogen invasion
excessive immune response
Crohn's
60
Both RIG-I and TLR3 upon recognizing viral _, initiate signaling pathways that converge on the activation of transcription factor _(Interferon Regulatory Factor 3).
Activated IRF-3 travels to the nucleus to promote the _.
dsRNA
IRF-3
transcription of Type I Interferon genes
61
what do type I IRFs do?
- help induce resistance to viral replication
across all cells
- enhance MHC class I expression and promote
antigen presentation in all cells
- activate dendritic cells and macrophages
- activate NK cells
62
Activated plasmacytoid dendritic cells (pDCs) produce very high
amounts of _.
Therefore, they have a strongly
developed rough _ (like plasma cells)
type I interferon
endoplasmatic reticulum (RER is studded with ribosomes and is essential for protein synthesis)
63
TLR3 and RLRs, located _, activate the _ pathway leading to the _ of _ and subsequent activation of _. This cascade results in the production and secretion of _, which are crucial in _.
intracellularly
TRIF
phosphorylation
TRAF3
IRF3
Type I interferons (IFN-α and IFN-β)
antiviral defense
64
TLR2 and TLR4 are _ and utilize the _ pathway, activating IRAK4 and TRAF6, culminating in the activation of _. This pathway primarily leads to the synthesis and secretion of _ and other _, playing a key role in _ responses. The figure emphasizes the distinct yet crucia
cell surface
MyD88
NF-κB
TNF-α
pro-inflammatory cytokines
antibacterial
65
TNF-α is a _ and is involved in the regulation of _, can induce _, _, _ (in response to infection), and _, as well as inhibit tumorigenesis and _.
cytokine
immune cells
fever
apoptotic cell death
sepsis
inflammation
viral replication
66
the chemokine CXCL8 is anti-_. and does the following:_
bacterial
mobilizes, activates, and degranulates neutrophils and ANGIOGENESIS (the formation of new blood vessels)
67
the chemokine CXCL10 is anti-_
viral
68
what causes redness, heat, and swelling?
vasodilation and increased vascular permeability
69
what causes pain?
inflammatory cells migrate into tissues releasing inflammatory mediator that cause pain
70
Selectins are specialized _ that facilitate the initial contact and rolling of immune cells along the_, which is crucial for _. This process is _ and varies between different tissues, such as _.
adhesion molecules
vascular endothelium
their migration into tissues
selective
mucosa versus skin
71
selectin adhesion system:
interaction between L-selectin on an immune cell and vascular addressin (CD34) on a blood vessel.
72
Integrins provide a _ adhesion, acting like _ to stabilize the immune cell on the _ after the initial capture by _. This strong adhesion is essential for the immune cell to _.
firmer
velcro
endothelial surface
selectins
transmigrate across the endothelium
73
integrin adhesion system:
LFA-1 integrin on the immune cell binds to ICAM-1, an immunoglobulin-like molecule on the endothelial cell
74
Neutrophil immigration
requires 4 steps: _,
involving three molecular
bridges
_
_
_
Rolling adhesion (1)
Tight binding (2,3)
Diapedesis
Migration
1. Selectin/Addressin
2. CXCL8R/CXCL8
3. LFA-1/ICAM-1
75
mode of action of neutrophil:
bacterium phagocytosed
phagosome fuses with azurophilic and specific granules.
pH of phagosome rises --> antimicrobial response activated --> bacterium killed.
pH of phagosome decreases, fusion with lysosomes --> acid hydrolases to degrade the bacterium completely
neutrophil dies and is phagocytosed by a macrophage.
76
Activated neutrophils' functions:
* Phagocytosis
* Degranulation
* Release mediators, cytokines
* Reactive oxygen species (ROS) production
* Release neutrophil extracellular traps (NETs)
77
ROS production:
The efficiency of intracellular killing can be temporarily enhanced
through the _ within _
spiking of production of toxic reactive oxygen
species (H2O2 and O2-)
phagolysosomes
78
NETs are networks of fibers composed primarily of _ from neutrophils that _. The NETs not only physically _ the microbes but also concentrate _ at the site of infection. This mechanism is beneficial as it helps contain the spread of infection and targets the pathogens for destruction, aiding in the clearance of infections, especially those caused by _.
DNA
extrude these webs to trap and kill pathogens
trap
antimicrobial agents
bacteria and fungi
79
CGD (Chronic granulomatous disease ) is mostly due to mutations in NADPH-oxidase which induces _
ROS
80
Eosinophils and basophils are short-lived cells that fight _
nematodes (worms)
81
eosinophil kills _ parasites
antibody-coated
82
basophils induce _
Augmentation of anti-parasitic response and promotion of allergic responses
Produce heparin (A substance that slows the formation of blood clots)
83
the function of mast cells:
release of granules containing histamine (allergies also) and active agents
84
Fc epsilon receptors (FcεR) are a class of receptors on the surface of certain immune cells, like _, that bind to the Fc region of immunoglobulin E (IgE) _. This binding is crucial for initiating cellular responses to _ and _, leading to the release of inflammatory mediators such as _.
mast cells and basophils
antibodies
allergens
parasitic infections
histamine
