Exam 2 Flashcards
1
Q
2 basic elements of the immune system
A
- White Blood Cells or leukocytes
- Soluble mediators
2
Q
Types of leukocytes (name/list)
A
- neutrophil
- eosineophil
- basophil
- lymphocyte
- monocyte
3
Q
3 types of lymphocytes
A
- B cells
- T cells
- Natural killer cells
4
Q
B cell function
A
- binds to antigen
- multiplies and differentiate into plasma cells
- plasma cells make antibody
5
Q
Th1 T cells function
A
interacts with monocytes and helps them destroy introcellular pathogens
6
Q
Th2 T cells function
A
interacts with B cells and helps them divide
7
Q
Cytotoxic T cells function
A
destructs host cells that have become infected by viruses or other things
8
Q
Regulatory T cells function
A
- help control the development of immune responses
- decrease reaction against self tissues
9
Q
Natural Killer cells function
A
- recognize surface changes on tumor & viral-infected cells
- damage those cells
10
Q
Monocytes function depends
A
on location
11
Q
Monocytes _ antigens
A
internalize antigens
12
Q
B cell _ antigens
A
bind to antigens
13
Q
Monocytes are derived from
A
bone marrow stem cells
14
Q
Monocytes/Macrophages destroy by
A
engulfing and internalizing agents and tissue debris
15
Q
Monocytes release _
A
inflammatory mediators (like Cas 1)
16
Q
Antibodies structure
A
- 4 polypeptide chains
- 2 identical light chains, 2 heavy chains
- 3 domains
17
Q
Circulating antibodies are
A
soluble glycoproteins that recognize and bind antigens specifically
18
Q
5 classes of antibodies in mammals
A
- IgG
- IgM
- IgA
- IgD
- IgE
19
Q
Complement proteins are
A
a group of 20 soluble proteins who control inflammation
20
Q
Alternative pathway
A
pathway in which a number of microorganisms
spontaneously activate the complement system
21
Q
Classical pathway
A
complement system activation pathway that is activated by antibodies bound to the
pathogen surface
22
Q
The classical pathway of activating the complement system depends on
A
antibodies
23
Q
the complement pathway kills pathogens by
A
decreasing membrane integrity
24
Q
Functions of complementary proteins
A
- Lead to efficient development of antibody responses.
- Kill microbial microorganisms.
- Attract phagocytes by chemotaxis, triggering and amplification of inflammatory reactions.
25
Cytokine is the general term for
a large group of secreted molecules involved in signaling between cells during immune response.
26
all cytokines are
proteins or glycoproteins
27
Name some of the cytokine groups
* interferons (IFN)
* interleukins (IL)
* chemokines
* colony-stimulating factors
* tumor necrosis factors
* transforming growth factors
28
type 1 IFN
| interferons
IFN⍺
IFNβ
* can be produced by any cell
29
type 2 IFN
IFN𝛾
* stronger than type 1
* must go through antigen presenting
30
IFN that starts with a virus
IFN⍺
IFNβ
31
IFN that starts with an antigen
IFN𝛾
32
Th0 makes _ with _
Th0 makes Th1 with IL12 and IFNy
* makes Th2 with IL4
33
Th1 promotes B cell what stages with what
Th1 promotes B cell *division* with *IL2* and *differentiation* with *IFNy*
34
Th2 promotes B cell which stages and with what
Th2 promotes division with IL4
and differentiation with IL 4,5,6,10,13
35
innate immune response definition
* does not depend on immune recognition
* unspecific
* provides immediate defense
* not long last immunity
36
innate immune response mechanisms/symptoms/characteristics
* inflmmation
* phagocytosis
* clearance of debris & pathogens
* remodeling and regneration of tissues
37
adaptive immune response definition
* depends on immune recognition by lympocytes
* uses specific entigens
* pathogens that do not have patterns can still be recognized
* allows vaccines
38
T cells only recognize antigen peptides bound to
HLA encoded molecules
39
4 types of T cell activation
* adhesion
* Ag specific
* costimulation
* cytokine signaling
40
memory cells are
B cells that do not differentiate into plasma cells
* in an inactive state in host for a while
41
vaccines use
a modified pathogen that has antigens but cant do damage
| called toxoids
42
purpose of inflammation
* eliminate initial cause of injury
* clear out necrotic cells
* initiate tissure repair
43
acute inflammation is initiated by
resident immune cells like macrophages
44
macrophages contain _ so initiate inflammation
toll like receptors which recognize pathogen and damage associated molecular patters (PAMP and DAMP)
45
cytokine and chemokine lead to
leukocyte margination and enthelial adhesion
46
chemokines function as _
chemotactic mediators and attract leukocyte to infammatory sites
47
in response to inflammation, leukocytes
destroy pathogens and remove damaged tissues
48
lymhocytes are activated by
antigen presenting cells
49
chronic inflammation definition
* persistent inflammation due to non degradable pathogens, viral infections or autoimmune reactions
* adaptive immunity plays a major role
50
chronic inflammatory sites are characterised by
simultaneous destruction and repair of the tissue
51
Glia in the CNS
* oligdendrocytes
* microglia
* astrocytes
52
Glia in the PNS
schwann cells
53
microglia are major in
brain and spinal cord
54
_ are derived from bone marrow stem cells
microglia
55
microglia are derived from
bone marrow stem cells
56
microglia can
* act as first form on innate immune response in CNS
* function as a APC and activate adaptive imm res in CNS
57
functions of microglia
* Scavenging, survey CNS on a regular basis.
* Phagocytosis, engulf tissue debris and invading pathogen.
* Cytotoxicity, release cytotoxic substances to damage cells.
* Inducing inflammation, release inflammatory mediators.
* Antigen presentation, activate adaptive immune response.
* Synaptic stripping, remove dysfunctional synapses.
* Promoting repair, release growth factors.
58
M1 microglia are activated by
LPS and IFNy
59
M1 microglia promote
* ROS
* inflammatory cytokines
* TNFa, IL1 & IL6
* iNOS
60
M2 microglia activation
* *alternative activation*: IL4 & IL13
* *aquired deactivation*: IL10 & TGF beta
61
M2 microglia does what
* engulfs pathogen
* inhibits the things M1 does
* activate neurotrophic growth factors
* activate ECM reconstruction & tissue repair
* activate Arg1
62
Arg 1 inhibits
iNos
| and visa versa
63
functions of astrocytes
Structural: Maintain the physical structuring of the brain.
* Glycogen fuel reserve buffer: contain glycogen and are capable of
glycogenesis, can fuel neurons with glucose.
* Metabolic support: provide neurons with nutrients such as lactate
* Blood–brain barrier.
* Transmitter uptake and release: glutamate, GABA, etc.
* Regulation of ion concentration in the extracellular space: potassium
* Modulation of synaptic transmission.
* Nervous system repair.
* Long-term potentiation, modulate synaptic plasticity.
64
Blood brain barrier structure
endothelium then pericyte on tope then astrocyte on top
65
Gliosis
* nonspecific reactive change in response to damage to the CNS
* involves the proliferation and/or hypertrophy
* lead to the formation of a glial scar
66
astrocyte end feet purpose
* Providing biochemical support to endothelium.
* Act as a physical barrier against unwanted cells or molecules
attempting to enter the CNS.
67
functions of BBB
* Restricts **ionic and fluid movements** between the blood and the brain, allowing specific ion transporters and channels to
regulate ionic traffic, to produce a brain interstitial fluid that
provides an optimal medium for neuronal function.
* Act as a **physical barrier against pathogen** to enter the CNS.
* **Restricts** entry of **cytokines and chemokines** into the CNS.
* Restricts entry of **leukocytes** into the CNS.
68
_ are too large to cross the BBB.
Antibodies
69
why is the CNS have bad immunity
* BBB too good
* low levels of leukocyte into CNS
* low level of MHC moleculed (not enough antigen presentation)
* no lymphatic drainage system
70
MRI measures
water in the tissue
71
MRI how it works
* magnetic properties of the protons in the water
* put water in magnetic field, they line up with the field
* then you send radio frequency to exicte and watch how they move back to alignment
72
in MRI, higher magnetic fields...
give higher resolution
73
TH1 weighted MRI images mechanism
uses the interaction of nuclei with its surroundings (lattice)
* T1 is time constant
74
T2 MRI images mechanism
uses spin spin interactions between nuclei
75
T1 vs T2 weighted: CSF
* T1: Dark
* T2: Bright
76
T1 vs T2 weighted: White Matter
* T1: light
* T2: dark grey
77
T1 vs T2 weighted: inflammation
* T1: dark
* T2: bright
78
_ is good for watching real time effects in brain
fMRI
79
fMRI mechanism
BOLD effect:
* when brain part is activated, blood flow increases in that region
* decrease in deoxyhemoglobin
* increase in fMRI signal
80
_ is good for mapping connections in the brain and seeing axonal damage
diffusion MRI
81
diffusion MRI mechanism
* neasures anisotropic water diffusion in the brain
* water diffuses along axons
82
low anisotrophy =
slower diffusion
83
diffusion in isotropic vs anisotropic samples
* isotropic diffusion is all directions
* anisotropic diffusion down axons
84
magnetic resonance spectroscopy (MRS) mechanism
* supress H2O signal
* get NM signal from other things
85
PET requires a _
substrate labeled with positron emitting tracer
86
PET mechanism
* tracer emits positron
* positron collides with electron
* produces 2 photons traveling in oposite directions
* 360 detectors used to map the photons and creat 3D images
87
the _ is very important in PET tracers
half life
| tells you how long between admin tracer and doing scan
88
way to asses atrophy
structural MRI, T1 weighted
89
thing for assessing neuronal loss
MRI: volumetry, cortical thickness or MRS w/NAA, Glu
90
microstructural changes can be assesed by
non-conventional MRI
91
way to asses neuronal viability
MRS
| looking at ratio of neurotransmitters (ex)
92
assessing synaptic dysfunction
| espicially in parkinson's
* dopamine PET or
* MRS (MRI) with Glu, Gln or GABA
93
_ can be used to asses _ in PD
PET to asses dopamine function in striatum
94
demylination can be imaged by
MT MRI
95
MRI can noninvasively image...
* anatomy
* blood flow
* neuronal activation
* connectivity
* axonal damage
* demylination
* chemical levels
96
PET can image...
* metabolism
* ligand binding
97
Way to assess oxidative stress
MRS with glutathione (GSH) and ascorbate (Asc)
98
_ are the most abundant antioxidants in CNS
GSH and Asc
99
way to assess impaired energetics
* FDG-PET
* 31P-MRS (phosphate tracking)
* 13C-MRS (Glu/GLn cycle rate)
100
how does FDG PET assess what it does?
PDG PET traces wither glucose is phosphorylated or not which shows whether energetics (glucose uptake) are impaired
101
Low FDG uptake is an indicator of _ in what diseases?
* low FDG uptake = impaired energetics
* could mean atrophy
* AD, Dementia with Lewy Bodies (DLB), Frontotemporal Dementia (FTD)
102
FDG-PET is useful in HD for...
detection of hypometabolism before symptoms
103
what is a good technique for telling what ype of dementia patients have
FDG-PET
104
phosphoros nuclei can help differentiate as specific as
different phaspates in ATP, so can see when ATP -> ADP or visa versa
105
31P-MRS is useful for _ in PD
looking at levels of ADP and ATP (to assess energetics) in PD patients
106
13C-MRS mechanism and what it shows
* label C 13 on glucose to trace
* can measure glutamate and glutamine levels with MR
* can show if glucose metabolism is impaired (in AD)
107
13C-MRS can show _ in AD
13C-MRS can show energy deficiets and slower metabolism as a cause of demetia that is in AD
108
AD pathology
* amyloid plaques
* neurofibrillary tangles (NFTs)
* diagnosis based on ^ and age and medical history
| NFTs from tau protein aggregates
109
_ can be used to asses toxic protein accumulation
11C-Pittsburgh compound B tracing with PET
| PiB
110
**11C-Pittsburgh compound B** binds to
Aβ plaques (extracellularly)
| markers of AD
111
order of biomarkers in AD progression
1. Aβ amyloid plaques *(PiB)*
2. tau NFTs *(in CSF)*
3. Dementia *(MRI & FDG-PET)*
4. Cognitive impairment
112
tau deposition can be imaged by
using PET to see the density of NFT
113
way of assessing gliosis
* MRS with myo-inositol & Glutamine
* PET w/ MAO-B
114
way to assess reactive astrocytosis
* MAO-B by PET
* MRS MRI with myo-inositol and Gln
115
MOA-B is localized in..
astrocytes
| but people have them in other places too, increased MOA-B = AD
116
MOA-B is localized in..
astrocytes
| but people have them in other places too, increased MOA-B = AD
117
way to assess neuroinflammation
* TSPO by PET *(acute inflammation)*
* Dynamic contrast enhanced (DCE) MRI *(show BBB breakdown)*
118
TSPO is localized in _ and functions
glial cells and is upregulated with microglial activation
119
DCE MRI requires...
a gadolinium based contrast agent
120
DCE MRI shows _ by _
* use agent to see leakage of in BBB
* enhanced signal - BBB broken down
121
MRI or PET uses ionizing radiation
PET
122
MRI mostly does not use a tracer except
* DCE MRI *(contrast agent)*
* 13C-MRS *(metabolism)*
123
PET does or does not use a tracer
always uses a tracer
| non endogenous signal
124
does MRI or PET have specific, molecular binding
* MRI: depends
* PET always does
125
is MRI or PET more sensitive and why
PET is more senitive due to the tracer concentration (can be little)
126
does MRI or PET have better resolution
MRI
127
is MRI or PET cheaper/more available and why
MRI because tracers are expensive
128
demylination can be imaged by
MT MRI
129
anticipation is
a clinical phenomenon describing progressively earlier onsent of the disease in successive gnerations
130
symptoms of fragile X syndrome
* abnormal facial feature
* cognitive defiecits
* disability
* shyness, poor eye contact
131
TRE in gene FMR1 causes *gain or loss* of the FRMP1 protein
causes loss of FRMP1 protein function
| this causes Fragile X syndrom
132
TRE in gene DMPK causes *gain or loss* of DMPK RNA function
causes gain of DMPK function
| this causes Muscular Dystrophy 1
133
_ in the DMPK gene is responsible for what disease
TNE in DMPK causes Muscular Dystrophy 1
134
TRE in gene FMR1 causes
fragile X syndrome
135
HD is caused by
an TNE in the HTT gene
136
Ataxia is a disease that effects
the cerebellum
137
HD effect
| brain part
basal ganglia
138
In HD, up to 95% of _ are lost
GABAergic medium spiny projection neurons
139
factors influencing TNR diseases' phenotypes
1. germline instability *(not stablely transmitted mutation)*
2. larger expansion = earlier onset
140
anticipation
progressively earlier onset of diease in sucessive generations
| happens in TNR diseases
141
TNR in promoter
| (effect and disease example)
* transcriptional silencing
* loss of function
* **fragile X syndrome**
142
TNR in intron
| (effect and disease example)
* impaired transcription
* ** friendreich ataxia**
143
TNR in coding region
| (effect and disease example)
* expanded PolyQ
* gain of function
* **huntington disease**
* **SCA 1, 2, 3**
144
TNR expansion at end of exon
| (effect and disease example)
* new RNA properties
* gain of function
* **mytonic dystrophy**
145
fragile X syndrome is _ function due to TNR in _ gene
* loss of protein function
* FMR1 gene
146
Fragile X syndrome features/symptoms
* abnormal facial structure
* anxiety
* hypersensitivity
* disability
* autistic features: *shyness, poor eye contact*
147
Fragile X syndrome genetic pattern
* X linked dominant
* less penetrance in females
148
pathological hallmark of FX Syndrome
* in cortex abnormal spines
* *elongated shafts and small heads*
* immauture spines
149
FXS molecular mechanism
* methylation and transcriptional repression of FMR protein
* FMR protein blocks mRNA in binds to, decreasing signaling and endocytosis
**in FXS**
* FMR protein loss of function = ↑ signalling through mGlu *(LTD)* = ↑ mRNA = ↑ endocytosis of AMPA-R = immature spines
150
lowering _ expression for FXS helped symptoms
lower mGlur expression with knock out mice
151
treatment of FXS
mGluR antagonists
152
Mytontonic Dystrophy Type 1 (DM1) clinical signs
* Myotonia *(impairement of relaxing muscles)*
* Muscular dystrophy
* cardiorespitory problems
* cataract
* cognitive problems
153
DM1 inheritance pattern
autosomal dominant
154
DM1 is caused by TNR in and is a _ function mutation
* DMPK gene
* RNA mediated gain of toxic function
155
MD1 mechanism
* repeats in DMPK cause sticking of RNA spilicing factors (MBNL) to it
* less MBNL = no splicing of certain genes
* unstable proteins are expressed, toxic gain of function
* loss of CIC-1 channel
156
how does MD1 mechanism lead to mytonia
DM1 TNR
= ↓ MBNL splicing factor
= ↑ function of toxic gene
= ↓ CLC channels
= ↓ Cl permebaility
= ↑ excitability of muscle cells *(no repolarization)*
157
DM1 therapeutic approaches
* inhibition of RNA polymerase
* other molecules that bind the repeats
* ASO to post transcriptionally silence
158
ataxia
loss of full control of bodily movements
159
adult onset SCA1 clinical signs
* ataxia
* dysphagia *(no swallow)*
* dysarthia *(speech)*
* cognitive changes
160
SCA1 pathology
* atrophy of cerebellum *(ataxia)* and brain stem
* loss of Purkinje neurons
161
SCA1 inheritience
autosomal dominant
162
Sca1 TNR is _ gene and causes _ function mutation
TNR in Sca1 causes gain of function in ATXN1 protein
163
Decreasing ATXN1 during _ stage is beneficial
early and middle stages of Sca1
164
decreasing ATXN1 in _ stages does not help _
decreasing in late stages does not help motor deficits in Sca1
165
Sca1 therapies should be
| what time
before onset of symptoms
166
SCA1 mechanism
* TNR = ↑ ATXN1
* ATXN1 go in nucleus
* ATXN1 regulates transcription and RNA splicing
167
SCA1 therapeutic approaches
* inhibit ATXN1 through phsphorylation
* ASO to cut out TNR
168
how does ASO work
ASO makes dsRNA to cut out a specific TNR extra parts
169
HD is cause by _
caused by TNR in exon 1 of **HTT gene** which makes **polyQ expansion** in **huntington** protein
170
HD inheritence
autosomal dominant
171
HD genetics phenotypical differences
* more repeats = ↓ age of onset
* risk factors affect age of onset
172
3 stages of HD
1. presymptomatic
2. predromal
3. manifest
173
Presymtomatic and prodomal stages of HD characterized by
* subtle effects
* cognitive
* motor alternation
* weight loss
174
Manifest stage of HD characterized by
* Motor symptoms: *chorea, fine moter bad, slurring, akinesia later*
* cognitive symptoms
* mood symptoms
| chorea = involuntary movement, jerking
175
Neuropathological hallmakrs of HD
* volume & cell loss in striatum
* dysfunction and death of MSN
* presence of huntington protein aggregates
176
CNS motory systems mechanism in HD
* **loss of indirect pathway MSN = loss of D2 receptors**
* D2 receptors inhibit GPe, so **GPe uninhibited**
* STN activates Gpi, so GPi inhibited
* GPi inhibits thalamus so **disinhibition of thalamus s0 increase in motor cortex**`
| D2 ↓ = ↑ GPe = ↓ STN = ↓ GPi = ↑ thalamus = ↑ motor cortex
177
loss of HTT gene causes
embryonic death
178
mechanism of transcriptional problems in HD
TNR in Htt gene = polyQ expansion = Htt cannot associate with REST = no BDNF transcription
| REST is repressor elemement
BDNF is a neurotrophic factor
179
dysregulation of heat shock response in HD
mutant Htt = ↑ CK2⍺ = ↓ HSF1 = ↓ proteasomal degredation = ↑ protein misfolding = ↑ huntington aggregates
180
HD palliative care techniques
* tetrabenazine to treat chorea
* things for cognitive
* speech/physical therapy
181
possible cures in animal models of HD
* neuronal stem cell transplanation
* Cas9 editing of gene
* ASO gene silencing
182
MS symptoms clinical
very wide variety
183
clinical subtypes of MS
| list off
1. Relapsing Remitting MS (RR MS)
2. Secondary progressive MS
3. primary progressive MS
4. progressive relapsing MS
184
relapsing remitting MS
* most common
* no progressive decline
* random episodes of severeness then nothing
185
secondary progressive MS
* bad episodes that are random with nothing in between
* constant episode with variable severity
* severity never to nothing but still declines and inclines constantly
186
primary progressive MS
starts and gets worse without ever declining
187
progressive relapsing MS
* relapses worse over time
* constant symtoms, no return to normal
* small declines after relapse episode
188
MS **plaques** pathology hallmarks
| the cracks
* inflammation
* demyelination
* oligodendrocyte death
* axon degeneration
189
symptoms in MS are variable because
pathology is localized by where in brain
190
MS general pathology
* demyelination
* neurodegeneration
* volume loss
* cell death
191
_ occurs early in MS
neurodegeneration
192
causes of MS
| list
* genetics
* enviromental factors
* infectious factors
* sex hormones
193
genes involved in MS
* HLA *antigen presentation*
* T cell *receptor antigen presentation*
* receptor for IL1, 2, 17
* TNF⍺, β *inflammation*
194
enviromental factors for MS
* sunlight help increase good T cell activity
* make vitamin D to inhibit autoimmune response (allergies)
195
infectious factors for MS
* epstein-barr virus
* Human herpes simplex virus 6
196
immune pathogenesis of MS
* T cell mediated autoimmune demylination
* myeline reactive T cells should only be in PNS, MS patients have in CNS also
197
hypotheses of MS pathogenesis
1. molecular mimicry
2. by stander activation of APC which activate reactive T cells
3. BBB breakdown
4. oligodendrocyte death
198
_ is decreased in the progressive stage of MS
inflammation
199
progressive MS results from
neurodegeneration
200
neurodegeneration in MS happens because
oligodendrocytes lost so demylination and MS has no remyelination so neuron is lost gradually
201
MS can be diagnosed with _ to view _
* MRI to see inflmmaion
* CSF tests to see level of T/B cells
* EP tests to see demylination
202
short term treatments for acute relapse in MS
IV of glucocorticoids to inhibit inflammation by
* inhibition of antigen presentation
* reduction of edema
* decrease of proinflammatory cytokines
* inhibition of lymphocytes
203
long term treatments of MS
* **IFN-β**: inhibit T cell activation
* **Tysabri**: block entry of lymphocytes in CNS
204
treatmentss that _ are not available in MS
treatments that delay disability progression
205
list animal models of MS
* EAE
* ciral models
* neurotoxin models
206
Q2. Antibodies are produced by
Plasma cells
207
What type of cells initiates acute inflammation?
REsident monocytes (Macrophages)
208
What form of energy is important for MRI?
Radiowaves
209
The hallmark MR imaging biomarker for Alzheimer's Disease is
hippocampal atrophy
210
The most widely used approach to assess presynaptic dopamine function
imagining membrane dopamine transporters
211
abnormal shape of the substantia nigra can be seen in _ with _
seen in PD with an MRI
212
SCA1 is characterized by _ in _
severe loss of Purkinje neurons in the cerebellar cortex
213
functional imaging can be used in HD to...
* identify molecular biomarkers
* assess brain atrophy
* measure striatum volume
214
Most common form of MS is
relapsing remitting MS
215
treatments of MS aim to:
* supress inflammation
* protect oligodendrocytes and myeline
* protect neurons and axons
216
ATXN1[82Q]A776 mice
| cannot be phosphorylated
no disease
217
Gliotic activity can be imaged by
* PET with TSPO
* mI MRS MRI
* PET with MAO-B
218
mechanisms for remyleination failier in MS
* chronic inflammation kills oligodendrocytes
* microenviroment doesn't allow O precursor cells to differentiate
* OPC depletion
* aging reducing OPC ability to remylinate
219
animal Models of progressive MS
1. EAE
2. TMEV
3. Caprizon
220
immune players in MS
* Th1, Th17
* B cells
* microglia
* macrophages
