Pre-Quiz 2 Flashcards
(165 cards)
1
Q
type I hypersensitivity reaction characteristics
A
IgE, soluble antigens, mast cell activation, allergy, asthma, anaphylaxis
2
Q
type IV hypersensitivity reaction characteristics
A
Th1/2/CTL, soluble antigens, Th2 activation of eosinophils, chronic asthma and allergies
3
Q
where are mast cells commonly found
A
in mucosa and skin, close to nerves and blood vessels
4
Q
mast cell Fc receptor
A
epsilon-R1
5
Q
Fc-epsilon-RI binding target
A
IgE
6
Q
effects of IgE on mast cells
A
induces degranulation via Fc-epsilon-RI
7
Q
what molecules do mast cells expel during degranulation
A
histamine, heparin, serotonin, leukotrienes, prostaglandins, proteases
8
Q
effects of mast cell degranulation
A
kills pathogens, but also acts on neurons to induce sneezing, itching, allergy symptoms etc
9
Q
what can trigger mast cell degranulation
A
mechanical trauma, chemical agents, heat/cold, stress (like anxiety stress), IgE
10
Q
what molecules tell DCs to take antigens to LNs
A
TSLP, IL-33, IL-25
11
Q
what cytokines polarize to Th2
A
IL-4
12
Q
source of IL-4 during Th2 polarization
A
the Th2 cell itself, DC tells T cell to express IL-4 via OX40L, then IL-4 acts on T cell in autocrine fashion
13
Q
why are food allergies persistent?
A
IgG plasma cells
14
Q
what was a clue that IgE plasma cells don’t work like normal plasma cells
A
IgE levels are almost undetectable in absence of pathogen, but shoot up upon exposure. There should be some baseline detectable level
15
Q
how are IgE plasma cells generated?
A
IgG1 memory cells differentiate into 1 IgE plasma cell and 1 memory cell upon allergen exposure
16
Q
red flags for immunodeficiency
A
recurrent infections with same pathogen, recurrent infection with unusual pathogen, unusual infection of a common pathogen
17
Q
what is an unusual manifestation of staph infection that could be a sign of immunodeficiency
A
infecting the lymph nodes
18
Q
TLR1 target
A
bacterial and yeast proteins
19
Q
TLR3 target
A
dsRNA
20
Q
TLR4 target
A
LPS
21
Q
TLR5 target
A
flagella
22
Q
TLR7/8 target
A
ssRNA and viral particles
23
Q
TLR9 target
A
methylated DNA of specific patterns, preferably bacterial DNA
24
Q
what do the IRF family transcription factors activate
A
IFNs/viral defenses
25
what are some common sources of immunodeficiency (that were normal in Forrester)
oxyburst (ROS production by neutrophils), CH50 and alternative CH50 (complement pathways), immunogloubulins
26
consequence of no IL-6 response
no fever response, so no drop in sociability or activity, no night sweats, etc
27
IRAK-4 immunodeficiency
loss of a protein kinase involved in many TLR pathways, leads to activation of NFkB and IRF
28
IRAK4 mutation causing deficiency
Q293X
29
what other immunodeficiency does IRAK-4 resemble
MyD88
30
what are IRAK-4/MyD88 patients susceptible too?
mostly gram+ bacteria
31
x-linked SCID stats
a range of disorders, affects 1/100,000
32
x-linked SCID effects on immune system (and some different sources of disease)
no T/NK cells due to lack of cytokine signaling, B cell numbers normal but non-functional. Could be ADA or PNP deficiency which cause toxicity to B and T cells. Could be VDJ defects due to RAG mutations
33
mortality rate of X-SCID by 1st birhtday
100% if not treated
34
when is X-SCID usually diagnosed
4-7 months
35
SCID symptoms
infections (usually more viral, fungal lung infections, lung more than GI, strep and staph), underweight/diarrhea due to lack of T cells regulating gut microbiome, family history
36
unusual presentations of SCID
sometimes there are some T cells, maternally engrafted T cells cause reaction, limited VDJ recombination
37
environmental risk factors for RA
tobacco, periodontitis, infectious triggers
38
genetic risk factors for RA
HLA-DRB1, female sex, PTPN22, PAD4
39
ACPA meaning and risk for RA
anti-citrullinated protein antibodies, confers 10-fold risk for RA
40
does everyone with ACPA have RA?
no
41
what proteins do ACPA target?
citrullinated epitopes of filaggrin, vimentin, fibrinogen, collagen etc
42
shared epitope of HLA-DRB1
in the DR-beta chain, a five aa sequence that is conserved across all alleles and is positively charged (P4). P4 accepts Cit because it is neutral, but will reject arginine or lysine (which are what Cit replaces).
43
post-translational modifications implicated in RA
deimination and citrullination
44
PPAD and RA
peptidylarginine deiminase, P. gingivalis protein, citrullinates host and bacterial proteins, risk factor for RA
45
HLAs implicated in celiac disease
HLA-DQ2.5, DQ8
46
immune response process to citrullinated proteins in the pathogenesis of RA
trigger (i.e. risk factors), ACPA induction, second hit, RA
47
symptoms/effects of scleroderma
causes fibrosis in internal organs, skin tightening, damage to blood vessels, scarring, ulcers on fingers
48
some genes associated with scleroderma
HLA, IL12, STAT4, CSK
49
problem with theory of virus trigger for scleroderma
all the viruses with sequences mimicking autoantibody-epitopes don’t infect humans
50
cd247 function
T cell activation
51
CSK function
turns off T cells
52
ERAP2 and plague
homozygosity for the protective allele better fights off Yersinia
53
differences in cytokine levels in healthy vs allergic individuals in response to allergens
more IL-10 in healthy people, very little in allergic people. More IL-4 in allergic people, still some but less in healthy people
54
Tr1 cells
Tregs that produce IL-10 and are Foxp3-
55
Foxp3- Tregs
Tr1 cells
56
what is odd about aeroantigen-specific Tregs?
They are most frequent Tregs, but also we are rarely exposed to these antigens and allergic people are low in these Foxp3+ Tregs. They also tend to be specific for non-allergen particle-associated proteins
57
what is immunotherapy in a nutshell?
repeated challenge with the allergen or antigen
58
beekeeper immunotherapy
after the first couple stings of the year, their response to bee venom plummets because they become tolerant
59
typical course of allergen immunotherapy
start out with a very low dose that increases with each visit, then plateaus at quite a high dose for several years of monthly injections
60
what are common delivery methods for allergen immunotherapy
usually subQ injections or sublingual tablets (tablets under the tongue)
61
why does allergy response decrease soon after starting immunotherapy even though IgE levels do not change until much later?
Immunotherapy increases IgG4, which outcompetes IgE for allergen
62
why does IgG4 outcompete IgE for allergen?
Doesn't bind Fc well, nor itself well, so falls apart easily and recombines with other chains and binds many things basically
63
what cytokine drives IgG4 production?
IL-10
64
which cells cells make IgG4
IL-10 producing BR1 cells (CD25+CD71+CD73-)
65
function of BR1 cells
suppress antigen-specific CD4 T cells
66
common mechanisms of immunotherapy
deletion of effector T cells, induction of Tregs, immune deviation (i.e. shift from Th2 to Th1), induction of Bregs, IgG blocking Abs
67
problems with immunotherapy
adverse events, long duration, low compliance
68
peptide immunotherapy biological characteristics
short synthetic peptides too short to cross-link IgE
69
peptide immunotherapy clinical characteristics
4-8 intradermal administrations, has been shown to be efficacious in phase 2
70
skin patches as immunotherapy
allergen is in the patch and hydrates into skin through sweat I think
71
problems with skin patches as immunotherapy
itchy, needed for up to 2 years, doesn't improve symptoms that much, big compliance issues
72
problems with oral immunotherapy
pills are just peanut powder, prohibitively expensive for consumers, have to take them forever, can cause GI reactions
73
intraplymphatic immunotherapy
subQ injection into groin, results in drainage to LNs, works pretty well
74
B cell epitope vaccines as immunotherapy
stimulate blocking Abs, success in phase 2
75
underlying problem in asthma
bronchoconstriction
76
what is bronchoconstriction?
contraction of smooth muscles in airways, which shouldn't normally happen
77
what are some common triggers of bronchoconstriction?
allergens, infections, cold air, exercise
78
how is asthma severity defined?
based on frequency, how bad constriction gets, and how much treatment is needed
79
what is the thinking of how asthma starts?
people with the right predisposition, who also currently or recently have/had an infection, are exposed to an allergen and DCs initiate a skewed Th2 response to the innocuous antigen
80
how can airway infections improve asthma?
by repolarizing Th2 to Th1
81
why is intrinsic asthma different and difficult to figure out the cause of?
everything about the disease is identical, except there is no driving allergen
82
how is adaptive response generated in asthma?
DCs pick up antigen, go to lymph node, activate and skew to Th2, Th2 does its thing
83
how are eosinophils recruited to airways in asthma?
Th2 cells that are activated in response to the allergen, release IL-5 among others, also can travel to the bone marrow and induce eosinophil differentiation
84
early infections conferring risk for asthma
RSV and rhinovirus
85
hygiene hypothesis and asthma
idea that 'dirtier' living protects, so living in the country, large families, and having other diseases during childhood may be protective
86
when are anti-IL-5 treatments useful?
severe cases only, when steroids manage most of the inflammation but eosinophilia persists
87
changes included in airway remodeling associated with asthma
fibrotic changes, increased smooth muscle, increased goblet cells, increased vascularization
88
what is thought to drive tissue remodeling in asthma
inflammation
89
is IL-13 useful as asthma treatment?
may be helpful in preventing tissue remodeling before it starts but probably not useful in practice
90
what are FEV1 and PC20
FEV1 = volume you can exhale in 1 second. PC20 is provocative concentration, in this case of cholinergic molecules that can induce smooth muscle constriction in the airways
91
what is the PC20 in severe asthmatics vs healthy people
0.03 vs 64 mg/ml
92
why do steroids not completely normalize PC20 in asthmatics?
thought that chronic structural changes limit how much recovery you can get
93
what receptors expressed by smooth muscles in airways interact with mast cell granules for constriction?
histamines bind H1 receptor, leukotrienes bind LTD4 receptor
94
bronchodilators
bind to B-andrenergic receptor on smooth muscle, produces rapid relaxation, can lead to receptor down-regulation
95
corticosteroids for asthma
suppress Th2, need to be taken regularly, usually inhaled which can have side effects
96
immunotherapy and new treatments for asthma
immunotherapy may be efficacious but it varies. anti-IL-5 is a new treatment that may be useful in severe cases
97
what do mast cells release immediately?
histamine, protease, heparin, TNFa
98
what do mast cells release over minutes?
prostaglandins, leukotrienes
99
what do mast cells release over hours?
cytokines
100
when do milk/egg allergies usually resolve?
school age
101
how many people outgrow peanut allergy?
about 20% of young children
102
ImmunoCAP allergy test
in vito blood test looking for allergen-specific IgE, measured in kilounits/liter of blood
103
what does food allergy treatment often focus in without immunotherapy?
avoidance and desensitization, i.e. carry an epi-pen and/or slowly be fed the food to try and build up tolerance
104
epicutaneuous immunotherapy
allergen applied to skin, safe but not that efficacious
105
difference between allergy desensitization and tolerance
desensitization is when you no longer react to (some concentration of) allergen but are eating it regularly. tolerance is when allergic response is gone even when you have stopped eating it regularly
106
is oral immunotherapy good at inducing desensitization?
sort of, while you're on it. it is often lost after stopping treatment though.
107
common causes of anaphylaxis
food (in kids), insect stings, medication (in adults)
108
uncommon causes of anaphylaxis
latex, exercise, allergy shots, idiopathic
109
signs of anaphylaxis
face itching/redness, trouble breathing/swallowing/speaking, stomach pain/vomiting/diarrhea, hives/rash/weakness/paleness/sense of doom
110
why is Emerade dose higher than regular EpiPen
it is for some adults who are over 60kg
111
lessons/reasons for anaphylaxis deaths despite treatments like EpiPens
not carrying EpiPen, thinking the food was safe, asthma, not recognizing symptoms
112
what does epinephrine bind?
alpha and beta adrenergic receptors
113
alpha adrenergic receptor response to epi
increases BP reverses blood vessel dilation
114
beta adrenergic receptor response to epi
increases heart rate and strength of contraction
115
LEAP study
infants at risk for peanut allergy were fed peanuts regularly in first few years of life and had much lower rates of allergy than controls
116
Sir MacFarlane Burnet idea of adaptive response
self/non-self theory, immature lymphocytes with many antigen receptors interact with self antigens and are destroyed if they bind, rest develop into naive lymphocytes and maybe get activated in an infection down the line
117
Charles Janeway infectious non-self
immune system targets non-self stuff but only if it is dangerous
118
Polly Matzinger danger model
immune cells recognize "danger", whether that's self or not
119
study evolving concepts of immunology slide lecture 17
useful info there
120
when were co-stimulatory signals discovered?
late 60s/early 70s
121
are all PAMPs considered dangerous?
no
122
are all DAMPs non-self?
no
123
modern definition for autoimmunity
stems from deficiencies in normal processes and tissue response to DAMPs released as a result of inflammation, continual tissue-injury and impaired repair
124
what happens to T cells with intermediate affinity for self antigen
they become Tregs
125
what happens to T cells with weak affinity for self antigen
they become conventional T cells
126
what cells perform negative selection by presenting thymocytes with self antigen?
thymic epithelial cells in the medulla
127
how do cortical thymic epithelial cells interact with thymocytes?
ensuring TCR is functional
128
transcription factor used by mTECs to present thymocytes with self-antigen
AIRE
129
potentially harmful results of lymphopenia
reduced Tregs, increased autoreactive cells, skewed effector/regulatory ratio
130
which part of antibody binds complement?
the hinge region, where the heavy chain bends outwards
131
which part of the antibody binds Fc?
the base of the heavy chain
132
what are three potential sources of autoantigens?
repeated apoptosis/necrosis = higher chance of presenting autoantibodies to auto-reactive T/B cells. generation of neoantigens by mutation in cells. cross-reactivity with viruses etc
133
study complement slides lecture 17
do it now
134
Which IgG subtype is not involved in the classical complement pathway?
IgG4
135
how does mucus/surfactant protect lung from oxidative stress?
basically traps it and keeps it away from tissue
136
resident protective cells in the lung
epithelium and macrophages
137
COPD
chronic obstructive pulmonary disease
138
how much COPD is caused by cigarette smoking
70%
139
characteristics of COPD
emphysema, chronic bronchitis, recurrent infection and acute exacerbation
140
emphysema
loss of alveolar sacs
141
acute exacerbation
exposure to pathogen or pollutant increases inflammation and mucus production in the lung of COPD patients
142
impact of smoking on pulmonary milieu
neutrophilia/cytokine secretion, surfactant damage and epithelial cell death due to oxidative stress, macrophage dysfunction like reduced pathogen clearance and secretion of MMP
143
general dogma of COPD
neutrophils are primary contributors to smoke-associated lung disease
144
has trying to dampen the immune response helped with COPD?
not even a little bit
145
consequence of low immune reactivity in the lung
spontaneous infection, impaired wound healing, excessive tissue damage
146
does depleting neutrophils help protect against lung damage?
not really. It exacerbates inflammatory response to smoke
147
why were inflammatory cytokines higher in the lungs of smoke-exposed neutrophil-depleted mice?
we keep expressing cytokines to try and recruit neutrophils in response to smoke, but there are none to recruit
148
what is an antimicrobiral peptide that could be used to modulate the immune response in the lungs of smokers while also supporting host defense
h-BD2, which is part of the innate immune system secreted by leukocytes and epithelial cells
149
effects of h-BD2 in smokers (mice)
reduces inflammation, cytokine secretion, but does not impair protection against bacteria
150
effect of CBD or THC from cannabis smoke on lungs
it's actually anti-inflammatory, opposite of tobacco smoke
151
how does cannabis smoke affect response to flu in mice
dampens the immune response, mostly in APCs and IL-4, leads to increased viral load
152
4 things energy is used for in immune system
maintenance and replenishment of immune cells, defense, maintenance of tolerance, immunosurveillance
153
why do animals on antibiotics grow larger?
they don't need to waste as much energy on immune response
154
how much extra energy is spent on inflammation when it starts?
25-60%
155
metabolic cost of raising body temperature for fever
1 degree celsius increase = 10-12% metabolism
156
what does muscle breakdown contribute to change in metabolism during infection
produces glutamine
157
function of transient insulin resistance
regular cells become insulin resistant, leaving more glucose available for immune cells
158
alternative TCA metabolites
fatty acids, glutamine, anything that can become Acetyl-CoA
159
reasons why activated immune cells prefer glycolysis
it's faster, production of cofactors like NADH, production of metabolites, and nutrient availability
160
how does insulin affect immune cell activation
increases glucose receptor expression via Akt
161
example of dysregulated metabolism in macrophages in RA
RA macrophages produce more ATP and ROS (i.e. higher oxygen consumption/metabolism in general), promoting inflammation and tissue pathology
162
how do tumour cells kills CD8 T cells (without PD1)
tumours secrete IDO, which cleaves tryptophan, leaving T cells without a energy source. IDO-trp product, kyn, also activates Tregs, which inhibit the CD8 T cells in the TME
163
sex differences in immunometabolism
male cells prefer glycolysis, females prefer TCA and use of fatty acids for TCA over pyruvate
164
how do sex differences in preference for glycolysis affect survival in glioma?
males who are high-glycolytic die faster, perhaps because they don't initiate insulin resistance as well, leaving less glycolysis for immune cells
165
what cytokine do Br1 cells need to polarize this way, and where to they get it?
IL-10, and they produce it so that they can become Br1 cells. Much like Th2 cells with IL-4
