Final Flashcards
(369 cards)
1
Q
Do you normally find cytokines in the blood stream? What kind of signaling are they?
A
no- only find in blood in sick people
act locally in a paracrine or autocrine fashion
2
Q
After binding to their receptors, what do cytokines produce?
A
changes in pattern of RNA and protein synthesis
3
Q
What two types of pathways do cytokines utilize?
A
JAK-STAT or Ras-MAP kinase pathways
4
Q
Describe the pathway of JAK-Stat pathway
A
cytokines bind receptors which are bound to JAKs
conformational change activates Jaks->trans/auto-phosphorylation of the two bound Jaks
Jaks phosphorylate cytokine receptors
Stat proteins by receptor chains
Jaks phosphorylate Stats
Stats from dimer and translocate to nucleus
5
Q
what are the five critical roles of cytokines?
A
- inflammatory reactions (pro and anti)
- linking innate and adaptive immunity
- activation of T cells (Th1/Th2 polarization)
- activation of B cells and Ab production (isotype switching)
- important for control of hematopoiesis (leukocytosis)
6
Q
What does we mean when we say cytokines are pleiotropic??
A
exhibit multiple effects on growth and differentiation of a variety of cell types
7
Q
What is an example of cytokines being redundant?
A
activated Th cells produce IL-2,4,5 to cause proliferation of B cells
8
Q
What is an example of synergy in cytokines?
A
Th cells produce both IL-4 and IL-5 to induce a class switch to IgE in B cells
9
Q
What is an example of antagonism in cytokines?
A
activated Th cells produce both IL-4 and IFN-y which work against each other. IFN-y blocks class switching to IgE induced by IL-4
10
Q
What does a cytokine cascade look like?
A
one cytokine induces production of another
11
Q
What are the 8 cytokines that promote acute inflammatory?
A
TNF-a, IL-1, IL-6, IL-8, IL-11, IL-12, IL-15, IL-18
12
Q
What type of transcription do pro-inflammatory cytokines have?
A
NF-kB-dependent transcription
13
Q
What are the two main anti-inflammatory cytokines?
A
IL-10 and TGF-B
14
Q
What type of transcription do anti-inflammatory cytokines have?
A
NF-kB-indepdent transcription
15
Q
If the body is overwhelmed by inflammatory cytokines what occurs?
A
systemic inflammation -> severe sepsis -> cardiovascular collapse and multiple organ failure
16
Q
What are the first things macrophages will produce when activated and in what order?
A
TNF, IL-1, IL-6
17
Q
If someone has a genetic abnormality in the synthesis of active TNF, what happens? Why?
A
they’ll be more sensitive to a lower concentration of bacteria
there is a couple hours of delay before IL-1 and IL-6 are produced and that’s enough time for bacteria to reproduce
18
Q
Which is a more powerful inducer of inflammation: IL-1 or TNF?
A
TNF
we need less of it compared to IL-1
19
Q
What are ways of reducing biological activities of TNF and IL-1?
A
neutralizing antibodies, soluble receptors, receptor antagonists
20
Q
What do TNF or IL-1 produce when administered to humans?
A
fever, systemic inflammation, shock, and death
21
Q
In what patients has blocking TNF and IL-1 been highly successful?
A
patients with rheumatoid arthritis, inflammatory bowel disease, GVHD
22
Q
What patients is blocking TNF and IL-1 not successful? Why?
A
patients with sepsis
by the time the patient presents to you they are beyond the stage of just TNF and IL-1
23
Q
What are systemic effects of TNF/IL-1?
A
fever leukocytosis increase in APPs decrease in appetite increase in sleep
24
Q
What are local effects of TNF/IL-1 on vascular endothelium?
A
increase in expression of leukocyte adhesion molecules
production of IL-1, chemokine
increase procoagulant and decrease anticoagulant activity
25
What cells produce TNF-B? What cells produce TNF-a?
macrophages and monocytes ---> TNF-a
T lymphocytes ---> TNF-B
neutrophils, NK cells
26
What is the most potent inducer of TNF?
endotoxin: LPS
27
What occurs when TNF interacts with endothelial cells/
induces ICAM-1, VCAM-1, and E-selectin to permit the egress of granulocytes into inflammatory loci
28
What is the primary mediator for septic shock?
TNF
29
What is a potent activator of neutrophils? What does it mediate?
TNF
| adherence, chemotaxis, degranulation, and respiratory burst
30
What are the TNF receptors?
TNF receptor I (TNFR p75) and TNF receptor II (TNFR p55)
31
How does TNF affect cancerous cells?
induces antitumor immunity through direct cytotoxic (apoptotic) effects
32
What are the primary producers of IL-1? What else produces IL-1?
primary: macrophages and monocytes
| neutrophils, endothelial cells, keratinocytes
33
What is IL-1 the first in line to do?
interact with CNS to produce fever
34
What effects does IL-1 produce?
fever, lethargy, sleep
35
What cytokine produces anorexia?
TNF
36
What is IL-1 second in line to TNF to do?
stimulate ICAM-1, VCAM-1, and E-selectin on endothelial cells and neutrophils
37
What is the only cytokine to induce production of IL-2? In what cells?
IL-1 induces production of IL-2 by and proliferation of CD4 T lymphocytes
38
So what cytokine is only produced by innate immune cells?
IL-1
39
What is IL-1 second in line to IL-6 to do?
stimulate synthesis of APPs
40
What can IL-1 be neutralized by?
natural IL-1 receptor antagonist IL-1ra
41
What is IL-6 primarily produced by? But also by?
primarily: mononuclear phagocytic cells
T and B lymphocytes, fibroblasts, endothelial cells, keratinocytes, hepatocytes, bone marrow cells
42
What is IL-6 the most important inducer of?
APP
43
What stimulates differentiation of B lymphocytes into mature plasma cells?
IL-6
44
What has a primary role in TH17 immune regulation?
IL-6
45
What primarily produces IL-8? What releases IL-8 on the onset of inflammation?
primarily macrophages
| mast cells
46
What is IL-8 a chemotactic factor for?
neutrophils but not monocytes!
47
What cytokine controls cell-mediated immunity? How?
IL-12 by activation of Th1 T cells
48
What does IL-12 stimulate and activate?
stimulates IFN-y production
| activates and induces proliferation, cytotoxicity, and cytokine production of NK cells
49
What does IL-12 synergize with? To do what?
synergizes with IL-18 (aka IFN-y-inducing factor) to stimulate IFN-y release
50
What primarily produces IL-15?
mononuclear phagocytic cells
51
What is the most important activity of IL-15?
activation of NK cells
52
What type of growth factor is IL-15?
T cell growth factor
53
What is IL-15 a chemotactic factor for?
T lymphocytes
54
What interleukin is important for the survival of CD8 memory T cells?
IL-15
55
What cells primarily make IFN-y?
Th1 T cells and NK cells
56
What is the most important cytokine for cell-mediated immunity?
IFN-y
57
How does IFN-y take care of killing intracellular bacteria?
stimulates phagocytosis, secretion, respiratory bursts, and NO production in tissue macrophages
58
Who induces synthesis of IFN-y in Th cells and NK cells?
IL-18
59
What all does IFN-y stimulate?
- killing by NK cells and neutrophils
- expression of MHC class I and II
- Ag presentation by APCs
- cytokine production by APCs
- expression of ICAM-1
60
What does IFN-y inhibit?
allergic responses by suppressing many IL-4-mediated effects
61
What cytokine has modest antiviral activity?
IFN-y
62
What antagonist is a major anti-inflammatory cytokine?
IL-1 receptor antagonist (IL-1ra)
63
What cells primarily produce IL-10?
macrophages, B cells, Treg cells
64
What does IL-10 inhibit?
production of IL-1B, IL-6, IL-8, IL-12, TNF-a by mononuclear phagocytes
expression of class II MHC by APCs
expression of CD80/CD86 by APCs
production of IFN-y and TNF-B by TH1 lymphocytes
production of IL-4and IL-5 by Th2 lymphocytes
65
What cytokine controls tolerance to environmental allergens?
IL-10
66
What is the most pleiotropic of the cytokines? Why?
TGF-B
| has both stimulatory and inhibitory effects on numerous cell types
67
Who primarily produces TGF-B?
macrophages and Treg cells
68
What does TGF-B stimulate?
fibrosis promoting wound healing and scar formation
| apoptosis in B cells and CD8 T lymphocytes
69
What does TGF-B inhibit?
- proliferation of B cells and CD8 T lymphocytes
| - macrophages and NK cells
70
What cytokine regulates the differentiation of Th17 lymphocytes?
TGF-B
71
What type of response causes asthma? Tuberculosis?
asthma is Th2
| Tuberculosis is Th1
72
What are the cytokines of the adaptive immunity?
IL-2, IL-4, IL-5, IL-17
IFN-y
TGF-B
73
What cytokine stimulates Th cells differentiating into Th1 cells? What is their transcription factor?
IFN-y
| T-bet
74
What cytokine stimulates the differentiation of Th cells into Th2 cells? What is their transcription factor?
IL-4, IL-5, IL-13
| GATA-3
75
What cytokine stimulates the differentiation of Th cells into Th17 cells? What is their transcription factor?
IL-17A, IL-17F, IL-22
| RORyT
76
What type of Th cell is big in alternative macrophage activation?
Th2 cells
77
What will Th1, Th2, and Th17 express?
CD4+ since they're all differentiated Th cell
78
What cells will proliferate if exposed to IL-2? Why only these cells?
activated T cells (have antigens)
| naive T cells have low affinity IL-2 receptors
79
What does IL-2 increase the expression of on activated T cells?
IL-2R
80
When the Ag is cleared, what happens to the IL-2R? Who blocks IL-2 induced proliferation to control T cells?
IL-2R numbers decline
| TGF-B blocks IL-2-induced proliferation
81
What interleukin induces differentiation of a Th0 cell into a Th1 cell?
IL-12
82
What do Th1 cells secrete? What do they promote?
IL-2, IFN-y, TNF-B
| cell-mediated immunity
83
What cytokine induces differentiation into a Th2 cell?
IL-4
84
What do Th2 cells activate?
B lymphocytes
85
What does IFN-y inhibit when it comes to T cells? What about IL-10/IL-4?
Th2 cell proliferation
| Th1 cell proliferation
86
What two other cells do Th1 cells support?
produce IFN-y to activate phagocytes to kill
| stimulate the production of antibodies which promote the phagocytosis of microbes
87
How will mice that are infected with M. tuberculosis (intracellular) react if they are (IFN-y+, IL-12+)?
they can control infection and will survive
88
How will mice that are IL-12 knockout mice (IFN-y+) react to infection with M. tuberculosis?
they cannot control infection and die because no TH1-type of adaptive immunity is developing in mice
89
How will IFN-y KO mice (IL-12+) react to infection with M. tuberculosis?
die early because macrophages are not activated properly in the absence of IFN-y
90
What is the association between Th2 cells and IgE antibody?
Th2 cells produce IL-4 which stimulate the production of IgE antibody
91
what is IgE's role in host defense?
participates in the activation of mast cell by protein antigen
binds to helminths
92
What activates eosinophils? What cells produce it?
IL-5 from Th2 cells
93
What cytokine induces the isotype switch to IgG?
IFN-y
94
What cytokines induce the isotype switch to IgA? Where is it produced?
TGF-B, BAFF produced in mucosal tissues
95
What cytokine induces the isotype switch to IgE?
IL-4
96
What receptors do growth factors bind to?
| What kind of receptor is this?
Type I cytokine receptors
| Jak-STAT
97
What receptors do interferons bind to?
type II cytokine receptors
98
What receptors do TNF-a and B bind to?
TNF receptor family
99
What receptors do IL-1 and IL-18 bind to?
IL-1 receptor family
100
What receptors do IL-10 bind to?
Type II cytokine receptor
101
What cells express the enzyme 5-LO?
macrophages, mast cells, basophils, neutrophils
102
What cells can be induced to express 5-LO?
monocytes
103
What is the function of 5-lipoxygenase?
AA ---> leukotriene (LTA4)
104
What is 5-LO's accessory protein?
5-LO activating protein (FLAP)
105
Are leukotrienes hormones?
no they're autocoids!
106
What is the receptor for LTA4?
There is none, it's a biosynthetic intermediate
107
What leukotrienes control bronchoconstriction and mucus secretion? What are their receptors?
LTC4 and LTD4
| CysLT1 and CysLT2
108
What leukotriene is in charge of neutrophil chemotaxis and degranulation? What is its receptor?
LTLB4
| BLT1,2
109
Pyogenic infection have pus that is rich in what?
neutrophils!
110
Why will people who are complement deficient still have neutrophils showing up at infection sites?
5-LO is working and will produce LTB4
111
What is another function of the inflammation mediators produced by phagocytes and granulocytes?
tells epithelial and mesenchymal cells in the area to adapt, migrate or perish
to limit damage that is inevitable with inflammation
112
What cells are in charge of the inflammatory reaction in asthma? What mediators do they produce?
Th2
IL-4, -5, -13
TNF-a
LTB4
113
What does the initial exposure to an allergen generate and what is this called?
IgE antibodies
| sensitization
114
What does a subsequent exposure to an allergen cause in IgEs?
cross links the IgE receptors
115
What does cross-linking IgE receptors trigger?
degranulation (release of histamine)
| activation of eicosanoid biosynthesis (LTC4, LTD4, PGD2)
116
How does histamine effect the capillaries?
increases permeability of the capillaries to other leukocytes and plasma proteins
117
When IgE recognizes an antibody, what does the mast cell it's attached to do?
degranulates- releases histamine
118
What does it mean when we say histamine is pre-formed? Where is it pre-formed?
synthesized and stored
| in granules of mast cells and basophils
119
What is an example of a substance that complexes with histamine to keep it inactive?
heparin
120
What receptor does histamine have to bind to to cause vasodilation and increased permeability?
H1 receptors
121
Why is there pain at sites of infection?
histamine binds to H1 receptors on peripheral nerves
| and mechanical pressure of tissue swelling on nerves
122
What does binding of histamine to H2 receptors cause?
increased gastric acid secretion in stomach
123
What tissues express both H1 and H2 receptors?
heart, blood vessels, skin capillary blood vessels
124
Where do we find mast cells?
nasal passage, trachea, bronchi, lungs, stomach, intestines, skin
125
What does IL1B induces expression of?
adhesion molecules on endothelium
| COX-2 in macrophages, monocytes, connective tissue and endothelium
126
What engulfs uric acid crystals and triggers IL1B and IL8 release?
macrophage/monocytes
127
What eicosanoid causes vasodilation?
PGI2
128
What eicosanoid causes permeability?
PGE2
129
Leaky vessels allow plasma extravasation into interstitial space and causes what?
localized edema
130
What is the most sensitive techniques for labeling?
radioactivity
131
Why isn't radioactivity used more?
presents health hazards
132
What kind of labeling is currently most used in labs?
fluorescence labels
133
What protein used in fluorescence labels is re from cyanobacteria?
PE (phycoethrin)
134
What molecule provides a green light for fluorescence labels?
FITC (fluorescein isothiocyanate)
135
What is the main technique for detecting presence of antigen in tissue?
indirect immunostaining
136
A reaction between Ag-Ab may lead to precipitation and is the basis for what lab technique?
agglutination
137
What does formation of Ag-Ab complexes lead to? How do we observe this?
increase in light scattering
| observed with naked eye or photometrically using turbidimetric or nephelopmetric detection
138
What is the requirement for agglutination?
have to have multiple sites for interaction on both Ag or Ab
139
The more Ag-Ab complexes formed the more transparent or less transparent the liquid will be?
less transparent
140
A polyvalent Ag is a molecule with multiple? What is it capable of?
epitopes
| can react with several Ab molecules
141
As cross linking between polyvalent Ags occurs what will happen?
become less stable ---> agglutination
| eventually complex will precipitate
142
What pH is ideal for the maximum specific agglutination? What happens if the pH is less than idea?
neutral pH
| below 6 proteins will self-agglutinate
143
A polyclonal antiserum is usually used for?
immunoagglutination
144
A direct agglutination assay has high potential for an error when there is an excess of what?
Ag
145
In indirect agglutination assay, why do we measure with an excess of antigen?
Test antigen will displace manufacturer made complexes
146
What do you measure in indirect agglutination assay?
measuring for displacement of manufacturer made complexes
147
Ouchterlony immunodiffusion involves the migration of Ab and Ag towards each other in? What will you see?
semisolid agar gel
| a visual precipitate is formed
148
Where will a visual precipitate form in ouchterlony immunodiffusion?
where the concentrations of Ab and Ag become equivalent
149
How do you set up a plate for Ouchterlony immunodiffusion?
antiserum (Abs) placed in center well
| each Ag in surrounding wells
150
What are three characteristic precipitation reactions that can occur in Ouchterlony analysis?
identity
non-identity
partial identity
151
What technique is used for rapid Ag quantification in complex samples?
immunoelectrophoresis
152
What is the result of the immunoelectrophoresis and what is it proportional to?
each sample gives a "rocket"
| length of which is proportional to the concentration of Ag in sample
153
What is used to identify monoclonal immunoglobulins (M-component) associated with myeloma (plasma cell neoplasia)?
immunoelectrophoresis
154
How are M-components identified? How do we detect this?
abnormal band in the gamma-globulin region (occasionally in the beta)
IEP
155
How is the resolution of IEP improved? What chemical do we use?
staining
| Coomasssie Blue R-250
156
What technique is used for ABO blood grouping?
hemagglutination (Coombs) assay
157
What does Coombs assay detect?
RBC Ags or Abs present in the sample against RBC Ags
158
What technique can be observed and used to make diagnosis with just the naked eye?
coombs assay
| ABO blood grouping
159
What is used to detect Rh in mother and fetal blood?
indirect coombs assay
160
All leukocytes express what CD?
CD45
161
All T cells express
CD3
162
All B cells express
CD19
163
What technique uses a particular cell type to identify, count, separate out cells from a mixture of different cells?
fluorescence-activated cell sorting (FACS)
164
Treg cells express
CD25
165
sIgA (secreted IgA) and sIgM limit the colonization by pathogens. What is this called?
immune exclusion
166
If food proteins and microbiota suppress Th2, Th1 and Th17 responses what is this called?
oral tolerance
167
Production of what pro-inflammatory mediators can cause hyper immunity?
IL-6, IL-12, TNF
168
Mutations in what immune-regulatory proteins can cause immunodeficiency?
NOD2 or IL-10
169
In the absence of commensal Bacteroides, what binds to TLR5 on intestinal cells and activates NF-kB via IKK?
salmonella flagellin
170
What exports activated NF-kB from the nucleus and is associated with Bacteroides?
peroxisome proliferator-activated receptor (PPAR)
171
Where is a chronic immune-inflammatory response NOT triggered?
mucosa
172
What type of cells is tolerance of microflora related to?
tissue macrophages
| dont sense microflora and thus do not secrete cytokines
173
What pathway does commensal microflora suppress?
NF-kB
174
What is it called when genetic factors and environmental factors result in disruption of the microflora?
dysbiosis
175
What does dysbiosis result in?
loss of protective bacteria and accumulation of pathobionts
176
What does an accumulation of pathobionts and loss of protective bacteria result a hyper activation of?
Th1 and Th17 cells
177
Commensal bacteria tend to have anti-inflammatory activities. They induce what/
Greg cells, IL-10, and REGIIIy
178
What is an islet-derived anti-microbial protein that is induced by commensal bacteria?
REGIIIy
179
Segmented filamentous bacteria (SFB) induce the expansion of what cells?
Th17 cells (pro-inflammatory)
180
If a patient has chronic inflammation due to opportunist pathogens in the gut, what should you suspect to be wrong?
reduced immune responses
181
If the levels of regulation and pro inflammatory stimuli are basal, yet there is colitis (inflammation) what should you suspect?
enhanced immune reactivity
182
What happens to expose the immune system to a great amount of pro inflammatory stimuli which can overcome intestinal regulation?
disruption of the intestinal barrier
183
The normal reaction of the immune system to intestinal stimuli can result in chronic inflammation if there's an absence of what?
Treg cells
184
What occurs when the intestinal regulatory mechanisms outweighs inflammatory signals induced by the immune system reacting to the stimuli from the flora?
GI immune homeostasis
185
Prevention of inflammation may be achieved through regulation of what?
epigenetic
186
What controls the balance between tolerance and pro inflammatory responses and are also essential for immunological development?
environmental signals
187
What is markedly decreased in germ-free mice?
IgA-producing cells and Th17 cells
188
What promotes intestinal barrier function and helps to maintain host-commensal mutualism?
SIgA
189
How does SIgA maintain host-commensal mutualism?
coats commensal and pathogenic bacteria to inhibit their binding to the host epithelium and their penetration of the lamina propria
190
Expression of what CD is found in Treg cells?
FOXP3
191
Why does depletion of Treg cells result in intestinal inflammation?
expansion of CD4+ Th cells specific to commensal bacteria
192
What type of bacteria promote the generation of Th17 cells in mice/
segmented filamentous bacteria (SFB)
193
What cytokines do Th17cells produce that play a role in autoimmune disease?
IL-17 and IL-22
194
What cells do Treg cells suppress?
Th1, Th2, Th17
195
The gut lamina prpria contains a lot of what?
J-chain expressing IgA and IgM
196
How doe endothelial cells exert a local gatekeeper function for mucosal immunity?
they direct migration of B and T cells by expression adhesion molecules and chemokines
197
Activation of T cells in intestinal immunity occurs where?
in the MLNs (mesenteric lymph nodes)
198
How do antigens recognized by intestinal immune system?
enters through M cells and transfers to local DCs
| or enters through epithelium covering the villus
199
What cells in the intestines can express MHC II and act as local APCs?
enterocytes
200
Where do blood antigens interact with T cells?
peripheral lymph nodes
201
what cells overlie payer's patches and lymphoid follicles to facilitate luminal sampling?
M cells
202
What do M cells exhibit that allows them to promote uptake and transport of luminal contents?
reduced mucin secretion and modified apical and basolateral surfaces
203
What cells can extend up between tight junctions of intestinal epithelial cells to sample luminal contents?
dendritic cells
204
Where do professional APCs reside in the Peyer's patches and lymphoid follicles?
subepithlial dome (SED)
205
What are the two general functions of neutrophils?
granulocytes and phagocytes
206
How can inflammation aggravate gout?
uric acid precipitates more easily at acid pH
207
What causes systemic inflammation throughout the vasculature?
LPS (bacteria) and cytokines (TNFa)
208
What causes the drop in blood pressure which is a feature of septic shock?
systemic vasodilation and extravasation of plasma from blood to interstitial space
209
In anaphylaxis, what do we see happen due to histamine?
drop in blood pressure
increase in blood vessel permeability
increase in peripheral edema
210
What compounds the effects of histamine in allergy and anaphylaxis?
autocoid lipid mediators such as LTC4, LTD4, PGD2
211
What type of receptors cause bronchoconstriction when stimulated?
PGD2 and DP receptors
212
What are three major areas of diversity related to the mechanisms of immunogenetics?
immunoglobulins, T cell receptors, MHC
213
Will each antibody produced by a plasma cell respond to different antigens?
NO they all respond to a specific antigens
214
If a single plasma cell secretes a bunch of immunoglobulins (different isotopes) what will they respond to?
the same antigen!
215
What are the two light chain isotypes and can they be mixed on the same immunoglobulin?
kappa or lambda
| NO they have to have two of either of them
216
What isytopes have three constant domains in the heavy chain?
d, y, a
217
What isotypes have four constant domains?
u and E
218
Expression of an Ig heavy chain involves what two gene recombination events?
D-J joining
| Joining of V region to DJ complex
219
In Ig light chains and the TCR a chain, a V gene recombines with what?
directly with a J gene segment
220
In what things do you find a D region?
Ig heavy chain
| TCR B chain
221
What's the difference between kappa and lambda light chain genes?
kappa- 1 constant region
| lambda- 4 constant regions
222
What type of diversity is almost unlimited due to the removal of nucleotides from V, D, and J segments by exonuclease at time of recombination? What enzyme helps?
junctional diversity
| terminal deoxyribonucleotidyl transferase (TdT)
223
What diversity is limited by number of available V, D, and J gene segments and involves V(D)J recombinase?
combinational diversity
224
What is the dos important site for antigen recognition on a TCR?
CDR3
225
in isotype switching, what is deleted?
DNA (This rarely happens in other cells)
226
B cells can accumulate point mutations in the DNA encoding their VL or HL regions. These mutations may increase the affinity of the antibody tot he epitope. what is this called?
affinity maturation
227
What are the principle determinants for graft acceptance or rejection between individuals?
MHC proteins (HLA)
228
Peptides in the cytosol are associated with? What are they recognized by?
MHC I
| CD8+ T cells
229
Peptides in vesicles are associated with? What recognizes them?
MHC II
| CD4+ T cells
230
What are the three polymorphic genes of MHC II?
HLA- DR, -DQ, -DP
231
Which class has more diversity: MHC I or II?
II because a and B chains are polymorphic
232
What do CD 8+ T cells bind to on MHC class I?
a3- it does not vary
233
What do CD4+ T cells bind to on MHC class II?
B2 domain
234
Grafts where tissue is moved from on place to another on the same individual are called?
autografts
235
Transplants between genetically identical individuals are called?
isografts
236
Grafts between genetically different members of the same species are called? What's an example?
allogenic grafts
| kidney transplants
237
Grafts between members of different species are called? What's an example?
xenogeneic grafts
| pig heart valves to humans
238
HLA typing for tissue transplants typically focuses on?
HLA-A, -B, -DR
239
What four things do you check for tissue transplants?
ABO blood typing
HLA typing
screening for preformed antibodies
crossmatching
240
What causes apoptosis in cancer cells?
TNF
241
What is a major activator of intracellular killing of pathogens by tissue macrophages?
IL-18
242
What inhibits allergic responses by suppressing many IL-4 mediated effects?
IFN-y
243
What inhibits expression of class II MHC by APCs?
IL-10
244
What transcriptional factor is unique for T reg cells?
FOXP3
245
What induces a Th0 cell to become a Th17 cell?
IL-1, IL-6
246
What blocks IL-2-induced proliferation which is a key mechanism for control of T cells proliferation?
TGF-B
247
What induces a Th cell to become a Th2 cell?
IL-4
248
What inhibits Th2 cell proliferation?
IFN-y
249
What inhibits Th1 cell proliferation?
IL-10, IL-4
250
After naive T cells have been activated by DCs, pathogen-specific T cells are made by?
clonal expansion
251
Loaded DCs move in to the T cell zone located in the?
parafollicular cortex
252
Autoimmunity results from a breakdown of what?
self-tolerance
253
The induced apoptosis of T lymphocytes that react too strongly to self-Ags is called what?
negative selection
254
What type of tolerance is induced in immune self-reactive lymphocytes in generative lymphoid organs?
central tolerance
255
What type of tolerance is induced in mature self-reactive lymphocytes in peripheral sites?
peripheral tolerance
256
What ensures that mature lymphocytes are NOT reactive to self-aga but it's not always perfect?
central tolerance
257
What prevents activation of potentially dangerous lymphocytes (self-reactive)?
peripheral tolerance
258
If a TCR has no affinity for self peptide what happens in the thymus?
cell undergoes spontaneous apoptosis because it does not receive survival signal
259
If TCRs have a high affinity for self peptide what happens in the thymus?
receive death signal and undergo apoptosis
260
Mutations in what gene results in failure of central tolerance?
AIRE
261
What disease results from a mutation in AIRE? How would these patients present?
autoimmune polyendocrine syndrome (APS)
| destruction of endocrine organs by antibodies, lymphocytes
262
What is AIRE's role in the thymus?
it's a transcription factor that is associated with expression of self-Ags by thymic epithelial cells
263
What regulates the expression of tissue-restricted Ags?
AIRE
264
In the absence of fictional AIRE, what are not eliminated?
self-reactive T cells
265
What is another function of T cells that have a strong recognition of Self Ags?
they become Treg cells that enter peripheral tissues
266
Why are Treg cells not eliminated by apoptosis even though they recognize self-Ags?
they produce anti-apoptotic molecules which protects them from negative selection
267
What does some generation of Treg cells require?
TGF-B
268
What do Treg cells express high levels of that other T cells express normal levels of?
CTLA-4- inhibitory analog for CD28
269
What interleukin does the survival and functional competence of Treg cells depend on?
IL-2 and FOXP3
270
Expression of what makes Treg cells regulatory cells?
FOXP3
271
With an increase in differentiation there is a decrease in what in cells?
proliferative ability
272
What cytokine induces a Th0 cell to become a Treg cell?
TGFB
273
What are two ways you can get Treg cells?
natural Treg cells are generated in thymus
| inducible Treg cells are produced by Ag recognition in LNs
274
What stimulates production of IgA by inducing B cells to switch?
TGF-B
275
If there is a FoxP3 deficiency, what is their impaired production of? What is this syndrome called?
Reg cells
| IPEX syndrome
276
What is an intrinsic signal for apoptosis?
Cyt C, Granzyme
277
Defective development, survival or function of Treg cells an cause inflammatory bowel disease, anti-erythrocyte and anti-DNA autoantibodies. What must be mutated?
IL-2 or IL-2Ra/B
278
There is a failure of anergy in CD4+ T cells leading to lymphoproliferation, T cell infiltrates in organs especially the heart, and patient is dead with 3-4 weeks. What must be mutated?
CTLA-4
279
When T cells recognize self Ags they may use a receptor whose function is to terminate T cell responses. What would this receptor be?
CTLA-4
280
What is expressed on Treg cells and mediates the suppressive function of these cells by inhibiting the activation of naive T cells?
CTLA-4
281
T cells enter a tumor microenvironment and they're induced to overexposes CTLA-4 so they cannot induce cell cycle arrest in tumor cells. What would you treat these patients with?
antibodies directed against CTLA-4
282
What would antibodies against CTLA-4 result in?
T cell activation which gives you a strong response against tumor cells
283
What has a higher affinity for CD 80/86 than CD28?
CTLA-4
284
So if you have a patient who is experiencing autoimmunity, what is one way to block it?
give them soluble CTLA-4
285
If a B cell responds to a self Ags with high avidity what happens to it?
either apoptosis or it edits the specificity of its BCR
286
If a B cell has a weak recognition of self Ags in the bone marrow what happens to it?
anergy of the B cells
287
In B cells, CD22 recruits what enzyme to attenuate B cell receptor signaling?
SHP-1 tyrosine phosphatase
288
What is the process called that results from t cells being physically separated from their specific Ag and therefore cannot become activated?
immunologic ignorance
289
The process known as deletion causes T cells to undergo apoptosis due to a signal they receive from APCs. What is this signal?
FasL
290
What is the CD for Fas?
CD95
291
What is the CD for CTLA4?
CD152
292
Suppression of other cells by Treg cells is due to a release of what cytokines?
IL-10 and TGFB
293
How can genetics confer susceptibility to autoimmunity?
influencing maintenance of self-tolerance
294
What has to happen to induce autoimmunity?
an environmental trigger such as infection or other inflammatory stimuli
295
What type of immunity usually dominates autoimmunity?
adaptive immunity
296
What genes have the strongest association with autoimmunity?
MHC genes
297
What type of infection is rheumatic fever triggered by? It's mediated by a cross-reactivity between these bacteria Ags and what?
streptococcal infection
| cardiac myosin
298
In multiple sclerosis, T cells react with what protein from what viruses?
myelin basic protein
| Epstein-Barr virus, influenza virus type A, human papillomavirus
299
What is an example of polyclonal activation?
LPS activating B cells via TLR4
300
What is it called when a microbial infection causes activation of bystander auto reactive lymphocytes via a cytokine field?
polyclonal activation
301
When microbes kill cells what can be released? What can be a result of this?
sequestered Ags
| inflammation and autoimmunity
302
What exacerbates lupus in mouse models by altering B-cell repertoire in the absence of inflammation?
estrogens
303
What's an example of a reason why autoimmune diseases being more common in women than in men?
estrogens alter B-cell repertoire in the absence of inflammation
304
What drugs can bind to RBC membrane and generate a neoantigen that elects an auto-Ag that causes hemolytic anemia?
penicillins and cephalosporins
305
The blockade of what can induce antinuclear Abs and even lupus and multiple sclerosis?
TNF-a
| mechanism is unknown
306
What are three examples of noninfectious triggers of autoimmunity?
- estrogens
- drugs (penicillins and cephalosporins)
- blockade of TNF-a
307
What types of hypersensitivity are antibody-mediated?
Type I, II, III
308
What types of hypersensitivity are cell-mediated?
Type IV
309
Type I hypersensitivity results from the actions of mediators secreted by what?
mast cells
310
In type II hypersensitivity, antibodies are made against what?
tissue Ags
311
In type III hypersensitivity, Abs bind what? Where are these complexes deposited?
circulating Ags
| deposit in vessels causing vasculitis
312
What cells cause the inflammation of type IV hypersensitivity? What cells kill host cells?
Th1 and Th17 cells
| CD8+ CTLs
313
What antibody dominates type I hypersensitivity?
IgE
314
If an individual has a strong propensity to developing allergic reactions they are said to be?
atopic
315
In type I hypersensitivity, IgE Abs are produced against what type of antigens?
environmental
316
IgE Abs bind to what on the membrane of mast cells and basophils? Does it have low or high affinity?
FcER1
| high affinity
317
When there is initial contact with an allergen, what does IgE do?
becomes fixed on the surface of mast cells or basophils
318
When there is second contact with an allergen, where does the reaction predominantly occur?
Ag-Ab reactions occur predominantly on the mast cell and basophil membrane
319
Why does repeatedly exposing a patient to higher concentrations of an allergen usually get rid of an allergic response?
they start producing IgG which will compete with IgE at low concentrations of the allergen
320
What interleukin is big in type I hypersensitivity and what cells produce it?
IL-4
| Th2 cells
321
How long after a first exposure to an allergen will it take to get an allergic reaction to the allergen again?
5-7 days
322
What are characteristics of the immediate phase of type I hypersensitivity?
vascular and smooth muscle reaction: vasodilation, congestion, edema
323
What are characteristics of the late phase of type I hypersensitivity? How long until this reaction develops?
inflammatory infiltrate rich in eosinophils, neutrophils, T cells
2-24 hours later
324
What causes dilation of small blood vessels and increased vascular permeability in type I hypersensitivity?
histamine
325
What causes damage to local tissues in type I hypersensitivity?
proteases
326
What causes vascular dilation in type I hypersensitivity?
prostaglandins
327
What stimulates prolonged smooth muscle contraction in type I hypersensitivity?
leukotrienes
328
What induces the late-phase reaction (inflammation) of type I hypersensitivity?What's an example? By what pathway?
cytokines- TNF
| NF-kB
329
What is the minimum number of receptors that must be engaged to get a strong response in type I hypersensitivity?
two!
330
What are the effectors for anaphylaxis? Antigens?
IgE on basophils and mast cells
| insect venom, drugs, food
331
What are the effectors of asthma and hay fever?
IgE on mast cells and Th2 cells
332
What are the effectors of food allergies?
IgE on mast cell and Th2 cells
333
How can differentiate anaphylaxis from asthma?
vascular collapse and death occurs with anaphylaxis
334
What antibodies are involved in type II hypersensitivity?
IgG and IgM
335
How do IgG antibodies produce and pro inflammatory response?
bind to neutrophil and macrophage Fc receptors and activate them
336
What causes damage in adjacent tissues in type II hypersensitivity?
reactive oxygen species and lysosomal enzymes that are released from neutrophils and macrophages
337
Autoimmune hemolytic anemia is what type of hypersensitivity? What's the mechanism?
type II
| opsonization and phagocytosis of erythrocytes due to Rh blood group antigens
338
Rheumatic fever is an example of what type of hypersensitivity?
type II
339
Vascular inflammation is a result of what type of hypersensitivity?
type III
340
What is the major mechanism triggering tissue damage in type III hypersensitivity?
classical activation of complement
341
What causes serum sickness?
IV administration of anti-serum
342
What is the reaction that is induced by subQ administration of a protein Ag to a previously immunized animal?
arthus reaction
343
What reaction results in the formation of immune complexes at the site of Ag injection and local vasculitis?
arthus reaction
344
Systemic lupus erythematous is what type of hypersensitivity?
type III
345
What are the major causes of T cell-mediated hypersensitivity reactions?
autoimmunity and exaggerated responses to environmental Ag
346
What are the mechanisms of tissue injury for type IV hypersensitivity?
Th1 and Th17 cells producing cytokines ---> inflammation
| killing of host cells by CD8+ CTLs
347
Delayed type hypersensitivity is caused by activated?
Th1 cells
348
Can only extracellular pathogens cause sensitization phase of DTH?
nope intracellular also can
349
Upon re-encounter with Ag, Th1 clones undergo further clonal expansion and secrete what that activates macrophages?
IFNy and TNF-B
350
What hypersensitivity requires the transfer of antigen-specific Th1 clones to be passively transferred?
type IV
351
How can type I, II, III reactions be transferred?
by serum containing Abs
352
What are examples of type IV hypersensitivities?
type 1 diabetes, MS, rheumatoid arthritis
353
What is tissue injury a result of in type IV hypersensitivity?
products of the recruited and activated neutrophils and macrophages such as lysosomal enzymes, ROS, NO, and pro inflammatory cytokines
354
The inflammation associated with T cell-mediated diseases is typically...
chronic
355
How long does delayed type hypersensitivity usually take to develop?
24-48 hours after Ag challenge
356
TB, poison ivy, and diptheria/tetanus toxins are all things that can sensitize humans for what?
DTH reactions
357
Purified protein derivative (PPD) is an antigen of what? and what type of reaction does it elicit?
mycobacterium tuberculosis
| elicits a DTH reaction aka tuberculin reaction
358
How do corticosteroids work?
block NF-kB
359
What would inhibitors of calineurin, Jaks and other kinases do?
inhibit signaling!
| immunotherapy
360
What would an anti-IL-2R immunotherapy do?
block T cell proliferation
361
What would an anti-IL-17 immunotherapy do?
block inflammation
362
What would an anti-p40 immunotherapy do?
block Th1, Th17 responses
363
What would anti-integrins immunotherapy do?
block adhesion
364
What would anti-TNF, anti-IL-1, and anti-IL-6R immunotherapy do?
block inflammation obvi
365
What would anti-CD40L immunotherapy do?
inhibit cell-cell interaction and leukocyte migration
366
What would anti-CD20 Ab immunotherapy do?
depletion of cells and antibodies specifically B cells
367
How do regulatory T cell-based therapies work?
expand and activate Treg cells in culture and transfer them back to the patients
368
What makes a B cell very sensitive to antigens?
CR2
369
What is a requirement for T helper cell to be involved in activation of B cell?
presentation of peptide Ag wishing class II MHC
