Pre-Quiz 1 Flashcards
(184 cards)
1
Q
4 stages of female reproductive cycle
A
Proestrus, Estrus, Metestrus, Diestrus
2
Q
hormones associated with proestrus
A
LH, FSH, Estradiol
3
Q
Hormone associated with Estrus
A
Prolactin, little bit FSH
4
Q
hormones associated with metestrus
A
Progesterone steadily climbing, little increase in estradiol
5
Q
hormones associated with diestrus
A
progesterone, slight increase in estradiol at the end
6
Q
does reproductive stage affect circulating immune cell composition?
A
no, very likely not
7
Q
gender-related differences in covid hospitalization etc
A
occupational differences, individual risk taking behaviour differs between genders, access to health care, child care responsibilities, etc
8
Q
sex differences in covid immune response (as an example)
A
males have higher ACE2 and TMPRSS2 = higher viral load, while females have higher TLR7 and IFNs
9
Q
sex differences in myeloid cell responses
A
males have higher inflammatory cytokines, like IL6/8/18/1B, as well as chemokines like CCL5 and MCP1. Leads to higher inflammatory response
10
Q
sex differences in effects of obesity and TNF on monocytes
A
in males, monocytes are increased more, Ly6Chi cells are increased in males but not females, adiposity is higher in males, myelopoiesis increases more in males, males develop insulin resistance, changes in males are TNF dependent but not in females
11
Q
sex differences in TNF treatments
A
they have better efficacy and less side effects in males
12
Q
which antibodies are passed to baby thru placenta and breastmilk
A
IgA and IgG
13
Q
where is IgA localized
A
mucosa
14
Q
where is IgG localized
A
blood
15
Q
when is IgG transferred to baby
A
mostly in last 3 months of pregnancy
16
Q
When is IgA transferred to baby
A
right before birth and in first few months of life
17
Q
why is antibody transfer transient in the baby
A
mom only passes on antibodies, not B or T cells so immunity wanes fairly quickly
18
Q
why are you susceptible to bacterial infection after a viral infection
A
type I IFNs downregulate receptors for bacteria
19
Q
what are some reasons for cold air being good for pathogens and bad for dealing with an infection
A
costs the host energy to deal with the infection and so body temp isn’t regulated as well, in equatorial regions there is no cold season, cold air widens blood vessels allowing viruses in, cilia beating is worse when it’s cold
20
Q
how are infant immune systems different from older people
A
Th2-skewed, weak primary responses, proliferation of T cells without antigen exposure
21
Q
main commensal bacteria in female reproductive tract
A
lactobacillus
22
Q
are immune cells and their functions different based on menstrual stage and location within the reproductive tract?
A
yes
23
Q
what hormone do fertilized eggs release that regulates immune system?
A
HCG
24
Q
HCG immune function?
A
signals other cells to keep releasing progesterone, leading to higher counts of NK cells and macrophages
25
immune regulation pre-ovulation
decreased inflammatory cytokine production, skewed away from Th17, decreased DC antigen uptake, decreased antimicrobial peptides, increased IgG/IgA
26
immune regulation post-ovulation
higher expression of CXCR4 and CCR5, increased Th2 cytokine response, increased Langerhans cells, increased DC antigen uptake, increased antimicrobial peptides, decreased IgG and IgA
27
menstrual cycle stages and their time points
follicular phase D0-14, ovulation D14, luteal phase D14-28
28
follicular phase of menstrual cycle
mediated by FSH and LH, stimulates growth of 15-20 eggs
29
ovulation phase of menstrual cycle
estradiol, FSH, and LH peak, body temp increases, follicle releases egg into fallopian tube, increased mucus in cervix
30
luteal phase of menstrual cycle
empty follicle develops into corpus luteum, secretes progesterone, prepares for implantation. If fertilized, 48h for implantation, if not, egg and lining of uterus releases
31
side effects of contraceptives on reproductive tract
decreased glycogen and lactobacilli, increased inflammation, activated T cells, and HIV susceptibility
32
3 main hypotheses for pregnancy problem (Medawar)
fetal immune system/antigens are immature, maternal immunity is repressed, placenta provides physical barrier b/w fetal and maternal tissue
33
reminder to go study diagram demonstrating invasion in the placenta
DO IT NOW - lecture 3 about halfway through
34
immune cell composition at fetal-maternal interface
70% NK, 20% macrophage, 10% assorted mast cells, DCs, and Tregs
35
role of NK cells and macrophages at maternal/fetal interface
artery remodeling, decidualization, EVT invasion
36
which MHCs are not expressed by placenta at interface?
MHCII, MHCIa
37
which MHC is expressed by placenta at interface
MHC1b, like HLA-G/C/E
38
what cells interact with HLA-G on placenta trophoblast
T cells, B cells, NK, DC, Macrophage
39
what do interactions between immune cells and MHC on placenta trophoblasts do?
promote tissue remodeling and immune tolerance, inhibit antigen-specific responses
40
review microchimerism slide in lecture 3
do it now
41
mechanisms of T cell inhibition at maternal-fetal interface
HLA-G expression, P4/PGE2 secretion, inhibitory cytokines/hormones, TNF superfamily ligands on placenta, IDO cleavage of tryptophan, epigenetic silencing
42
mechanisms of B cell inhibition at maternal-fetal interface
complement regulatory proteins inhibit antibodies, BAFF and APRIL (TNF superfamily) promote plasma cell antibody production, Fc receptors transport IgG across placenta
43
effect of TNF superfamily ligands on T cells
suppress proliferation and promote clonal deletion
44
what do PD-L1, TRAIL, BAFF, APRIL, and FASL all have in common
all TNF superfamily ligands
45
how is IgE passed to baby/fetus
breast milk and amniotic fluid
46
how is breastmilk immunomodulatory?
it contains commensals, immune cells, and antibodies/cytokines/complement
47
what immune cells does breastmilk contain?
60% macrophages, 30% neutrophils, 10% lymphocytes
48
why do autoimmune diseases get worse during pregnancy
antibodies are upregulated
49
what peripheral cells are upregulated in the mother during pregnancy
Tregs, neutrophils, Th2
50
what cells are downregulated in the mother during pregnancy
T cells, NK cells, B cells, Th1
51
what cells are not up/downregulated in the mother during pregnancy
most granulocytes, some CD4/CD8 subsets, some NK subsets
52
differences in serum cytokine composition in the mother depending on sex of their baby
male baby = pro-inflammatory and pro-angiogenic, female baby = anti-inflammatory and regulatory
53
what happens in the immune system when birth starts?
inflammation is triggered (upregulate pro-inflammatory, downregulate anti-), recruit macrophages and neutrophils, inflammatory processes prompt cervical ripening and chorioamniotic membrane rupture and contractions
54
immune content of semen
high concentrations of chemokines and cytokines, recruits NK, DC, macrophages and promotes Tregs
55
definition of aging
progressive loss of resilience due to gradual accumulation of damage leading to increased risk of disease and death
56
immune senescence
progressive cellular deterioration/dysregulation due to age, leads to increased inflammation, lower response to vaccination/immunotherapy, increased susceptibility to cancer/pathogens
57
primary hallmarks of aging
genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy
58
antagonistic hallmarks of aging
cellular senescence, mitochondrial dysfunction, deregulated nutrient-sensing
59
integrative hallmarks of aging
stem cell exhaustion, altered intercellular communication, chronic inflammation, dysbiosis
60
definition of primary hallmarks of aging
progressive accumulation of damage/dysregulation with age
61
definition of antagonistic hallmarks of aging
responses to age-associated damage
62
definition of integrative hallmarks of aging
arise when cumulative damage from primary and antagonistic hallmarks cannot be compensated
63
changes in HSCs with age
accumulate DNA damage and mutations, env'tl and intrinsic factors change and influence their phenotype and function
64
changes in HSC differentiation with age
stem cells could be lost, or become dysfunctional, undergo apoptosis, become senescent, or maybe properly develop into leukocytes
65
which immune cells increase with age
myeloid cells
66
which immune cells decrease with age
T and B cells
67
immune systems of semi-supercentenarians
decreased numbers of stem cells with age, DNA damage repair mechanisms are maintained, most circulating immune cells are from related clones, insufficient numbers of immune cells for homeostasis may cause death
68
how do macrophages change in older people
increased in number, baseline cytokine production is increased, but response to stimulation is decreased, decreased TLR and MHC II, transcription factor expression
69
how do B cell numbers and diversity change with age
fewer cells and progenitors, more senescent cells, decreased BR diversity and class switching and somatic hypermutation
70
changes in antibody production in older adults
decreased numbers, neutralization, affinity, increased autoantibodies
71
how do changes in Fc glycosylation impact infection responses
as it decreases, macrophage activation icnreases
72
why do autoantibodies increase with age
we lose the ability to clear them and their B cells
73
what are the main cellular changes involved in thymic involution
increased adiposity, decreased stromal cells
74
what do twin studies tell us about genetic/environmental factors in immune system and how it changes with age?
twins' immune systems start out very similar but as they grow up and stop living together they change in different ways
75
vaccine definition
modified pathogen or part of a pathogen packaged such that it educates our innate and adaptive immune systems for the purpose of infection or severe disease prevention or control
76
criteria for ideal vaccine
one shot, lifetime protection from infection, induces both innate and adaptive immunity, safe, stable/no cold chain required, cheap, needle and pain free
77
types of human vaccines
live attenuated, inactivated, protein, genetically engineered/vectored (incl. mRNA)
78
some common adjuvants
aluminum, diphtheria toxoid
79
why was AZ the most distributed vaccine in 2021
cheapest and easiest to store
80
infectious diseases with no effective vaccines
HIV, TB, Malaria, RSV
81
pros and cons of BCG vaccine
effective in curbing childhood TB but not lung TB in adults, immunity wanes
82
study steps of vaccine development in lecture 6
Dr. Xing's experience making a TB vaccine
83
was Dr. Xing's TB intranasal TB vaccine successful in trials? How?
yes. more cytokine+ CD4 T cells in airways, like TNFa and IFNy
84
why haven't bivalent vaccines been quite so effective for COVID?
because much of the response still goes towards ancestral spike since there is resident memory in the arm
85
COVID strain most different from ancestral (and thus most evasive to first gen vaccines)
Beta
86
weaknesses of first gen vaccines for COVID
reduced protection against VOCs, declining Ab immunity by 6 months, requires frequent boosters
87
what lasts longer as a result of first gen vaccines, Ab or T cell immunity?
T cell
88
unique aspects of next-gen COVID vaccine strategy
multi-valency, targeting genetically stable T cell Ags, respiratory mucosal route to target Trm, TII, durable immunity against VOCs, needle free
89
why use both human and chimp adenovirus vectors in Mac COVID vaccine
many people are already immune to human adenovirus, using both vectors ensures everyone can mount a proper response to the COVID genetic material rather than just the adenoviral capsid
90
why continue to use Adenovirus 5 in Mac COVID vaccine when immunity is so common
because all that immunity is in resident memory in the deltoids where people have been vaccinated, little to no memory in the lungs though
91
which adenoviral vector was better in the mac covid vaccine study
chimp, it induced higher IgG, higher neutralization
92
effect of intranasal but not intramuscular vaccines on airway memory macrophages
higher MHCII, higher metabolic activity and anti-microbial activity
93
differential roles of B/T/TII cells in protection with chimp adenovirus COVID airway vax
TII by far more protective of lungs, losing B or T cells (or both) hardly impaired lung protection at all, but KOing trained macrophages led to significantly more damage in lung tissue
94
differences in T cells in COVID vs other infections
lymphopenia is a predictor of death, more T cell apoptosis in spleens and LNs in COVID deaths than other infections
95
difference in neutrophils in COVID vs other pulmonary infections
less of an increase of neutrophils in the airway than with other infections
96
is IL6 higher or lower in COVID deaths vs survivals
higher, may explain lower T cell counts in those people but may be correlational
97
neutralizing antibodies
block pathogen entry into cell, usually target surface receptors like ACE2
98
how does fucosylation affect phagocytosis
antibodies that lack fucose are more readily phagocytosed, which is more common in old people
99
self-sustaining inflammatory loop in the lungs that leads to pneumonia in COVID
T cells recruited to lungs, release macrophage-recruiting cytokines, which then recruit more T cells, and it loops
100
why is COVID not associated with subsequent bacterial pneumonia?
macrophages do not spike as highly, and are not suppressed as much following infection, in COVID vs other infections, decreasing susceptibility to bacteria
101
why is macrophage regulation different in COVID than other viruses
SARS is good at shutting off the IFN 1 response, leading to less macrophage activation and less subsequent decrease
102
main two cellular binding targets of SARS-CoV-2
ACE2 and TMPRSS2
103
COVID endosomal entry target and general mechanism
ACE2, virus is endocytosed, endosome acidifies cleaving S2, viral and endosomal membranes fuse, releasing viral RNA
104
COVID cell surface entry target and general mechanism
virus binds ACE2 and TMPRSS2, S2 is cleaved, membranes fuse and viral RNA is released into cell
105
study locations of COVID receptors and effects of disease on different organs slides in lecture 7
106
what is usually the tradeoff of evolving better immune evasion in viruses?
less infectiousness/lower affinity for cellular receptor/less able to replicate
107
why has omicron maintained high infectiousness while also improving immune evasion?
compensatory mutations
108
why has omicron been worse for kids?
its affinity for TMPRSS2 changed, and the virus now preferentially binds in the upper respiratory tract which is typically harder for kids to fight off
109
influenza virus type
enveloped negative sense ssRNA
110
what is unique about influenza's genome?
separated into 8 segments
111
major antigens of flu
hemagglutinin and neuraminidase
112
how many strains of flu A and B are there
18 A, 2 B
113
why does flu B not cause pandemics
it has less antigenic variability and most people have protection against it
114
antigenic drift
minor mutations that change the virus over time, the cause of seasonal flu
115
antigenic shift
2 different strains of the same virus infecting the same cell and forming a hybrid virus that could be much worse than either original virus, can cause flu pandemics
116
flu vaccine types used in Canada
live attenuated, recombinant HA, split virus, and subunit vaccines
117
plant-based VLPs
insert antigen of interest into plant, like HA or NA, it will be expressed on cell membranes and bud off to make particles that resemble flu without the genetic material inside
118
egg-derived vaccines
inject virus into chorioallantoic membrane in the egg, where it grows very quickly and can be isolated for use in injections
119
alternatives to eggs as vehicles for viral growth for vaccines
insect or canine cells
120
what is the antigenic target of next-gen flu vaccines?
the H1 stalk, which is highly conserved across many strains of flu
121
what happened to anti-H1 stalk antibodies after 2009 pandemic?
they got stronger/more numerous in most people because we all already had antibodies to the stalk but not to the new head protein. inspired new vaccines
122
chimeric flu vaccines
combining conserved H1 stalk with different variations of the head domain
123
why are inhaled aerosols preferred to intranasal vaccines (at least for flu?)
they give protection into the lower respiratory tract, which is the site of severe infection and pneumonia
124
how do monoclonal antibodies against flu work
target H1 and induce ADCC
125
why are H1-targeting monoclonal antibodies particularly effective/promising?
they leave the HA head free to bind sialic acid on host/immune cells, which makes binding stronger and improves killing efficiency
126
2 layers of Maternal tissue at maternal-fetal interface
myometrium and decidua
127
other name for fetal layer/tissue at maternal-fetal interface
chorion
128
which maternal layer do EVTs invade into?
decidua (aka decidualized tissue)
129
EVT meaning
extravillous trophoblast
130
how long is the chorion hypoxic for?
until the 2nd trimester
131
what is produced by fetal venules/arterioles at maternal-fetal interface
hCG, progesterone, and estrogen
132
what type of virus is HIV?
RNA retrovirus
133
how many copies of its genome does HIV carry?
2
134
what cell surface marker is required for HIV replication in the cell?
CD4
135
what co-receptors does HIV use to get into T cells?
CCR5 and sometimes CXCR4
136
what do Tat and Rev do for HIV
they allow for faster transcription of HIV genes and splicing of the long polygene that is produced so that virus can be put together
137
3 late proteins that assemble into virus particles and bud from the cell in HIV
Gag, Pol, and Env
138
what proteins does HIV use to bind the cell and enter?
gp120 and gp41
139
does HIV stay undetectable if you go off of medications?
no, it will come back
140
is HIV mucosal?
yes
141
which parts of the body are most responsible for HIV transmission?
female genital tract, followed by male genitalia and the intestinal tract
142
how many viral particles are required for HIV to take hold?
1-3
143
what were the correlates of protection in the RV144 HIV vaccine trial
IgG in serum, low serum IgA, short term antibody mediated protection, IgG had little neutralizing ability, IgG were against V1V2 loop of gp120
144
What is unique about the gp120 loop in HIV?
It mutates incredibly quickly, so fast that the virus you transmit is different from the one you were infected with
145
how does semen change immune landscape of cervix?
has a lot of inflammatory cytokines and chemokines and induces inflammation in the cervix, leads to recruitment of NK, DC, macrophages, promotes Tregs
146
why do older HSCs preferentially develop into myeloid progenitors over lymphoid progenitors?
because of increased CCL5 levels associated with age
147
rate of infection after TB exposure
30%
148
4 main antibiotics for TB
INH, RMP, PZA, and EMB
149
how does TB establish itself in the lung despite slow growth rate?
delays T cell priming and trafficking back to the lung
150
how many TB cells are required for infection?
10
151
first cells infected by TB
alveolar macrophages
152
what is a granuloma
a 'prison for TB', a central core of infected macrophages surrounded by T/B/DCs to prevent spread
153
which macrophage types are infected in the granuloma
alveolar and interstitial
154
hypotheses for why TB becomes active
immunosuppression i.e. from HIV, bacteria might reach a critical mass
155
does co-infection of HIV and TB worsen both diseases?
yes
156
what is unique about TB-specific T cells in people with HIV
they are killed more rapidly than other T cells
157
how does HIV change innate immunity in vitro?
decreased phagocytosis by macrophages against TB but not understood why this happens in vivo
158
how does HIV change adaptive immune function?
changes B and CD8 T cell functionality
159
TB-IRIS meaning
TB immune reconstitution inflammatory syndrome
160
what is IRIS
increased inflammation following ART initiation
161
how does IRIS affect TB
makes it worse or uncovers latent TB
162
how prevalent is IRIS
15% of people going on ART develop it a few days to 6 months after start, assuming you need to have TB though
163
risk factors for IRIS
low CD4 count, short time after TB treatment initiation, extensive TB disease
164
possible mechanisms of IRIS
return of excessive cellular immune responses, too much proinflammatory cytokines, no regulatory repsonses
165
general process for developing humanized mice
take PBMCs from umbilical cords, irradiate mice, inject HSCs into mice
166
what genes are usually KO'd in humanized mice
NSG/NRG, NOD, RAG1, gamma chain
167
study Gillgrass' research
go do it I guess
168
which antigens is Dr. Xing's group using in their aerosol Ad-vectored COVID vaccine?
Spike S1 domain, nucleocapsid, and RNA-dependent RNA Pol
169
environmental risk factors for RA
tobacco, periodontitis, infectious triggers
170
genetic risk factors for RA
HLA-DRB1, female sex, PTPN22, PAD4
171
ACPA meaning and risk for RA
anti-citrullinated protein antibodies, confers 10-fold risk for RA
172
does everyone with ACPA have RA?
no
173
what proteins do ACPA target?
citrullinated epitopes of filaggrin, vimentin, fibrinogen, collegen etc
174
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).
175
post-translational modifications implicated in RA
deimination and citrullination
176
PPAD and RA
peptidylarginine deiminase, P. gingivalis protein, citrullinates host and bacterial proteins, risk factor for RA
177
HLAs implicated in celiac disease
HLA-DQ2.5, DQ8
178
immune response process to citrullinated proteins in the pathogenesis of RA
trigger (i.e. risk factors), ACPA induction, second hit, RA
179
symptoms/effects of scleroderma
causes fibrosis in internal organs, skin tightening, damage to blood vessels, scarring, ulcers on fingers
180
some genes associated with scleroderma
HLA, IL12, STAT4, CSK
181
problem with theory of virus trigger for scleroderma
all the viruses with sequences mimicking autoantibody-epitopes don't infect humans
182
cd247 function
T cell activation
183
CSK function
turns off T cells
184
ERAP2 and plague
homozygosity for the protective allele better fights off Yersinia
