Panic Flashcards
(106 cards)
1
Q
What 2 things do phagosomes fuse to?
A
Lysosomes and granules
2
Q
What three ways can phagosomes use to kill pathogens?
A
Enzyme degradation, antimicrobial peptides, toxic effects of reactive oxygen and nitrogen free radicals
3
Q
How many TLRs are in mice and humans?
A
13
4
Q
What part of the TLR dimers bind PAMPs and DAMPs?
A
The extracellular leucine rich repeats (LRRs)
5
Q
Where are TLRs located?
A
In lysosomes/endosomes and surface bound
6
Q
What pathways do TLRs trigger?
A
NF-kB transcription factor production
Interferon regulating factor (IRF) pathways
MAP kinase downstream transcription factors such as AP-1
7
Q
Are C-type lectin receptors (CLRs) a heterozygous or homozygous population of surface PRRs?
A
Heterozygous
8
Q
What part of the cell do CLRs recognize?
A
Cell wall components, such as the sugars/polysaccharides of bacteria/fungi
9
Q
What is the structure of RLRs and where are they located in the cell?
A
RNA helicases and they are cytosolic PRRs
10
Q
What type of molecules do RLRs recognize?
A
Double stranded viral RNAs
11
Q
What signalling pathways do RLRs activate?
A
Interferon regulatory factors (IRFs) to trigger antiviral interferon responses
NF-kB transcription factor
12
Q
Where are NOD-like receptors located in the cell?
A
Cytosolic PRRs
13
Q
What does the NOD-like receptor activate?
A
Caspase-1 protease
14
Q
What does caspase 1 cleave? Why is this important?
A
IL-1 and IL-18. Important because IL-1B is the major cytokine for inflammation
15
Q
What 5 main things does signalling of PRRs activate the expression of (particularly in macrophages)?
A
Antimicrobial peptides
Cytokines (inflammatory IL-1, TNF-a, and IL-6)
Chemokines
Type 1 interferons (potent antiviral activity)
Enzymes (iNOS and COX2)
16
Q
What are acute phase responses (APRs)?
A
Detectors of systemic inflammation.
17
Q
When do acute phase responses occur?
A
After injury, trauma, or infection of a tissue.
18
Q
What induces acute phase responses?
A
Proinflammatory cytokines (IL-1, TNF-a, and IL-6).
19
Q
What category of cytokines do macrophages and blood monocytes secrete (generally)?
A
Pro-inflammatory
20
Q
What is the purpose of acute phase proteins?
A
Prevent ongoing tissue damage and activate the repair process.
21
Q
When do fever and leukocytosis occurs?
A
Systemic acute inflammation
22
Q
What is the mechanism behind acute phase responses?
A
Increases synthesis/secretion of antimicrobial proteins from the liver (MBL, CRP, and complement components).
23
Q
What two cytokines induce fever?
A
IL-1 and IL-6
24
Q
What two functions do NK cells perform?
A
Kill altered self-cells
Produce cytokines that induce adaptive responses against the altered self cell.
25
During the first stages of the immune response for viruses, which cytokines and which cells do we primarily rely on?
IFN and NK cells.
26
What is the Fc receptor on NK cells called?
CD16
27
What two molecules do NK cells release into the lytic synapse?
Perforin and granzymes
28
What are NETs stimulated by?
PAMPs and cytokines
29
What two main mechanisms connect the innate and adaptive immune responses?
Opsonisation and complement activation
30
What are TLRs on lymphocytes used for?
Costimulation receptors
31
What are the three groups of PRRs?
Extracellular
Cell surface
Intracellular
32
What is LPS recognized by?
TLRs
33
What TLR recognizes bacterial parasites? What about viral dsRNA?
TLR2/1 and TRL3/3
34
Describe what happens during TLR signalling (in detail).
A PAMP or DAMP binds the LRR of the TLR dimer which causes a conformational change -> association of MyD88 to TIR domain of the TLR -> assembly of IRAK1/IRAK4 complex -> IRAK 4 phosphorylates IRAK1 -> creates docking site for TRAF6 -> IRAK1-TRAF6 complex dissociates and activates the TAK1 protein kinase complex -> leads to activation of 2 different pathways:
- > phosphorylates IKK -> phosphorylates IkB-> siddociation of NF-kB -> translocation to nucleus to activate NF-kB dependent genes
- >phosphorylates/activates component of the MAP kinase pathway -> MAP kinase cascade leads to transcriptional activators translocating to the nucleus and activating MAPK dependent genes (like AP-1).
35
Describe what happens during TLR signalling in general.
Detects PAMP -> signalling through adaptor proteins -> recruitment of ubiquitin, ligases, and kinases -> phosphorylation and ubiquitination -> activation of nuclear factors -> inflammatory gene expression
36
What does NFkB stand for?
Nuclear factor kappa-light-chain-enhancer of activated B cells
37
What does activation of NFkB and AP-1 lead to?
Expression of most immune genes
38
What does IRF do?
Regulates type 1 (IFNa and IFNB) antiviral interferon genes.
39
What cytokines does TLR signalling produce?
TNF, Pro-IL1, and anti-viral cytokines (IFNa and IFNB)
40
What does ITAM stand for?
Immunoreceptor tyrosine-based activation motif
41
How do CLRs signal and what is the result of the signalling?
Signal via ITAMs ->leads to activation/modulation of NFkB and AP-1
42
What receptor does HIV use to infect T cells?
CLR
43
What signalling pathways do RLRs trigger?
IRFs to trigger antiviral interferon responses.
| NF-kB transcription factor
44
What is the main purpose for RLR signalling?
Interfere/ shut down viral replication using interferons (interferon = interfere with viral replication)
45
How does influenza avoid RLR signalling?
Binds and sequesters dsRNA to inhibit RLR activation
| Interacts directly with RIG-I to prevent activation
46
How does the Ebola virus prevent RLR signalling?
Inhibits IRF phosphorylation which inhibits RIG-I pathway signalling
47
How does PRR signalling impact antigen presenting cells?
Increases MHC levels on APCs
48
True or false: PRR signalling can cause complement activation?
True: this is stimulated by extracellular PRR binding (MBL through the lectin pathway)
49
Where are CAMs/ICAMs expressed?
Endothelium and leukocytes
50
What two molecules make up CAMs?
Selectins and integrins
51
What are CAMs
Proteins on the cell surface that bind with other cells or the ECM in adhesion.
52
What are the sour families of CAMs?
Selectins
Mucin-like
Integrins
Ig superfamily
53
What is Sialyl Lewis?
E-selectin ligand carbohydrate
54
Where is Sialyl Lewis expressed?
Granulocytes, activated Th1 cells, and monocytes
55
What is the purpose of Sialyl Lewis?
Partner for selectins that bind leukocytes and endothelial cells; important in leukocyte tethering and rolling.
56
Where are integrins expressed? Give an example of an integrin.
Expressed on leukocytes. LFA-1
57
What do integrins bind to?
ICAMs (Ig superfamily)
58
Where are ICAMs expressed?
Endothelium
59
What provides the activating signal to neutrophils during extravasation?
IL-8 from the endothelium
60
What is leukocyte extravasation analogous to in lymphocytes?
T cell migration into the lymph node
61
List the steps involved in leukocyte extravasation
Tethering (slow down, contact) recognition of inflamed tissue -> rolling -> activation -> conformational change in leukocyte integrins -> strong adherence to ICAMs/Ig superfamily on endothelium (arrest and adhesion) -> trans endothelial migration
62
Where do lymphocytes extravasate specifically?
High endothelial venues (HEV)
63
Where in the lymph node do dendritic cells pick up most of the antigens?
Subcapsular sinus (SCS
64
What integrins and chemokine receptors do T cells moving to the intestine have?
LPAM, LFA-1, and CCR9
65
What chemokine receptors and integrins fo T cells moving to the skin express?
CLA, LFA-1, CCL1, CCL17, and CCL27
66
What induces mast cells and basophils during inflammation?
Activated complement proteins
Histamine-releasing proteins made by WBCs
Inflammatory cytokines (IL-1 and IL-8)
In hypersensitivity reactions, by binding of soluble IgE to the FcR
67
True or false: endothelial cells contain histamine receptors that activate endothelium and increase vascular permeability
True
68
True or false: mast cells are key mediators of inflammation.
True
69
True or false: Eicosinoids act on targets far away from the site of formation?
False
70
What produces eicosanoids (specifically)?
Endothelium, granulocytes, macrophages, platelets
71
What do prostaglandins do?
Promote vascular permeability/dilation, platelet aggregation and increased pain sensitivity
72
What do leukotrienes do?
Promote vascular permeability and chemotaxis.
73
What are the 3 main mediators of inflammation-induced activation of coagulation?
Pro-inflammatory cytokines (I’ll-1, IL-6, and TNF-a)
74
What are pyrogens? List the 4 examples given in class.
Substances that induce fever; IL-1, Il-6, TNF-a, and LPS from bacteria
75
List the 7 benefits of fever.
Increased lymphocyte response to mitogens
Increased bactericidal activity of neutrophils
Increased motility, activation, and proliferation of leukocytes
Increased phagocytosis
Higher production of interferon
Increased liver functions (acute phase proteins)
Active excretion of toxins
76
What are the side effects of fever?
Functional overload of organs
Hypo hydration and blood hemolysis (blood clotting)
GI disturbance due to increased level of toxins
77
Why does acute inflammation cause neutrophilia?
IL-1 and TNF-a promote the accelerated release of neutrophils in the bone marrow.
78
What does prolonged infection cause in terms of neutrophils?
Causes the production of colony stimulating factor (G-CSF) which leads to the release of immature neutrophils into the blood
79
True or false: acute inflammation shuts itself down passively.
False: active termination is required (otherwise leads to chronic inflammation).
80
What are the mechanisms for shutting down acute inflammation?
Short half life of inflammatory mediators (ex. C3a and prostaglandins)
Production and release of anti-inflammatory cytokines (IL-10 and TNF-B) and molecules (cytokine signalling blockers that bind to the cytokine or its receptor)
Apoptosis of pro-inflammatory cells (ex. Neutrophils have short half life)
Desensitization (down regulation of pro-inflammatory receptors such as those for prostaglandins and histamine)
81
How can macrophages cause tissue damage during acute inflammation?
Prolonged production of IL-1, IL-6, and TNF-a.
82
What is fibrosis characterized by?
Lymphocytes and plasma cell infiltration of tissues with cell necrosis and fibrosis.
83
What is affinity?
The strength of all the non-covalent interactions between the antigen binding site on the antibody and a single epitope
84
What determines affinity?
The antigen-antibody fit and the number of interactions.
85
True or false: the Kd changes during an immune response
True
86
What is affinity equilibrium dialysis good for?
Good for determining the affinity of different antibodies for an antigen. Can be used for vaccine development for determining which antibody is the best for a particular antigen .
87
What is avidity?
The strength of multiple interactions between an antibody and an antigen.
88
What determines the strength of avidity?
The affinity and number of antibody-antigen interactions
89
When can antibodies bind 2 different antigens?
When the different antigens share common epitopes, or when the epitopes are different but share similar chemical properties
90
Which theory is the correct one for BCR diversity: germline theory or somatic hypermutation?
Trick question: both are correct
91
How do enzymes know where to cut in the germ line DNA when forming BCRs?
The gene segments are flanked by short conserved recombination signal sequences (RSS)
92
What are RSS’s comprised of?
A conserved heptamer
A 12 or 23 bp nonconserved spacer sequence
A conserved nonamer
93
What does TdT do?
Adds N region nucleotides to the joints between gene segments in the Ig heavy chain and at all joints between TCR gene segments
94
What is junctional flexibility?
Refers to the imprecise joining of VDJ gene segments
95
What is the potential mechanism behind allelic exclusion?
Inhibition of rearrangement may be due to signalling through the pre-BCR (stops H chain rearrangement) and BCR (stops L chain rearrangement)
96
What 2 signals do activated B cells need to undergo class switch recombination?
Cytokines and a co-stimulators signal from CD40
97
What classes of IgG do IFN-y, IL-4, and mucosal tissue cytokines generate?
IgG subclasses, IgE, and IgA
98
What part of the antibody determines the specificity on the antibody response?
The antigen binding site
99
What part of an antibody determines the effector action of an antibody?
The heavy chain of the constant region
100
What does class switch recombination do for an immune response?
Allows you to generate antibodies with the same antigen specificity but with different effector functions and distributions.
101
What is the area in the variable region that is hypervariable called?
Complementarity determining regions
102
Why are the hinge regions of antibodies flexible?
Rich in proline residues
103
What do the cysteine residues in Ig’s do?
Allow for heavy chain dimerization through interchain disulfide bond formation
104
How many T cells express 2 different alpha chains paired to the same beta chain from loose allelic exclusion?
1/3
105
True or false: MHC molecules are members of the Ig superfamily
True
106
How are MHC genes inherited?
In linked groups called haplotypes
