Unit 4 + Final Flashcards
(243 cards)
1
Q
What is the lingo?
A
2
Q
What causes transplant rejection?
A
3
Q
How are antigens recognized?
A
4
Q
What immune mechanisms lead to rejection?
A
5
Q
What is hyperacute rejection and what is its cause?
A
6
Q
What is acute rejection and what is its cause?
A
7
Q
What is chronic rejection and what is its cause?
A
8
Q
Donor APC are also presenting with _____ ___
A
donor MHC
9
Q
What is graft rejection?
A
activation of immune response against donor tissue
10
Q
What is the greatest barrier to transplantation as a therapeutic option for organ failure?
A
availability of organs
11
Q
What methods can be used to reduce the immunogenicity of allografts?
A
sourcing transplants and minimize allogeneic differences between donor and recipient we test for compatibility
12
Q
HLA genes code for what?
A
MHC
13
Q
What is hematopoietic stem cell transplantation used for?
A
treat lethal diseases caused by intrinsic defects in one or more hematopoietic lineages in a patient
14
Q
What is immunodeficiency?
A
doesn’t make the immune cells (or lack thereof)
15
Q
What are the three strategies in development to induce donor-specific tolerance?
A
costimulatory blockade, hematopoietic chimerism, and transfer or induction of Tregs
16
Q
What is costimulatory blockade?
A
All T cells will not be activated to react to self-antigen (peripheral tolerance)
17
Q
What is hematopoietic chimerism?
A
take donor cells and mix it in culture. Those cells are put into recipient (peripheral tolerance)
18
Q
________________ can be used to prevent or treat allograft rejection
A
immunosuppression
19
Q
What are the two instances when graft versus host disease (GVHD) occurs?
A
the host is immunocompromised and therefore unable to reject the allogenic cells in the graft and solid organs that contain significant numbers of T cells are transplanted
20
Q
What is transplantation?
A
process of taking cells, tissues, or organs from one individual and placing them into a different individual
21
Q
What is a graft?
A
the cells, tissue, or organs you are transplanting
22
Q
What is a donor?
A
the individual who provides the graft
23
Q
What is a recipient?
A
the individual who receives the graft
24
Q
What is orthotopic transplantation?
A
graft is placed in its normal anatomical site
25
What is heterotopic transplantation?
graft is placed in a different anatomical site
26
What is transfusion?
the transfer of circulating blood cells or plasma from one individual to another
27
What is autologous graft?
graft transplanted from one individual to the same individual
28
What is syngenic graft?
graft transplanted between two genetically different individuals
29
What is allogenic graft (or allograft)?
graft transplanted between two genetically different individuals of the same species
30
What is xenogenic graft (xenograft)?
graft transplanted between individuals of different species
31
What are alloantigens or xenoantigens?
molecules that are recognized as foreign in allografts or xenografts
32
What is alloreactive or xenoreactive?
lymphocytes and antibodies that react with alloantigens or xenoantigens
33
What are the 3 ways alloantigens are recognized by T cells?
direct presentation, indirect presentation, and antibody mediated recognition
34
When does direct recognition occur?
when the T cell of the host recognizes that the MHC of the donor is not the same
35
Every APC found in the transplanted tissue is going to be ________ ___, which explains why MHC is so important for transplant
non-self MHC
36
Intact MHC molecules displayed by cells in the graft are recognized by _________ _ _____ without a need for process by host APCs
recipient T cells
37
Why are T cell responses very strong?
because there is a high frequency of T cells that can directly recognize any single allogenic MHC molecule
38
What is indirect recognition of alloantigens?
picks up antigens from the donor and presents antigen on surface to the self T cell to recognize the foreign antigen from donor tissue
39
Each allogenic MHC molecule can have _______ ________ that are foreign for the host, each recognized by different clones of T cells
multiple peptides
40
True or False: T cell rejection can happen even if the MHCs are matched really well
True
41
The direct pathway is....
the APC from the donor presenting to the TCR of the recipient
42
What two things are required for triggering the T cell response for the direct pathway?
antigen itself and MHC
43
The indirect pathway is when...
the APC of the host is presenting foreign antigen only to the host T cell
44
If the MHC is matched really closely between donor and host, then the direct pathway is...
unlikely to stimulate donor rejection, but the indirect pathway is almost impossible to avoid
45
What APCs transport alloantigens to the lymph node?
dendritic cells
46
What types of cells cause rejection by distinct mechanisms?
Alloreactive CD4+ and CD8+ T cells that are activated by graft alloantigens
47
What is the outcome of sensitization in activation of alloreactive T cells?
activation of T cells, generation of effector T cells by direct and indirect antigen presentation
48
CTLA-4 induces what?
an inhibitory signal that downregulates T cell activation and is the target of induction regiments
49
Leukocyte depletion strategies use what?
antibodies such as thymoglobulin designed to bind to peripheral alloreactive lymphocytes allowing an allograft to settle in
50
Most of the antibodies produced in graft recipients that undergo rejection are usually target at what?
foreign MHC proteins (MHC mismatch), leading to strong antigen stimulation of B cells, T cells, and rejection
51
What is the most significant factor for why there is rejection in transplants?
MHC matching
52
High affinity alloantibodies are mostly produced by what types of cells?
helper T cell-dependent activation of alloreactive B cells
53
Label the rejection stages of allograft rejection in order
hyperacute → acute → chronic
54
What happens during hyperacute rejection?
once graft is put in, there are antibodies already there that react to it. Then, those antibodies will bind to their antigen and activate complement and platelets leading to blood clots
55
What is vascular occlusion?
blood clots will prevent blood flow to the new organ and grafted organ will suffer ischemic necrosis
56
What is ischemic necrosis?
no blood flow and no oxygen so tissue will die
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What is acute cellular rejection?
activation of CD4+ helper T cells and CD8+ CTLs and cytokines produced by helper T cells that lead to inflammation and CTL-mediated killing of graft cells
58
What is acute antibody-mediated rejection?
activation of B cells with T cell help with high affinity antibodies specific to that donor tissue lead to binding of tissue and complement activation
59
B cells with high-affinity antibodies are targeted at what in acute antibody-mediated rejection?
a donor tissue that results in loss of the graft tissue
60
When does chronic rejection happen?
when we don't have preexisting antibodies
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What is chronic rejection?
accumulation of chronic inflammatory responses
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In chronic rejection, alloantigen-specific CD4+ T cell start interacting with APCs. This results in what?
The APCs present antigens on self MHC and over time there are some antigens that cause a small response leading to release of some proinflammatory cytokines causing muscle cells to proliferate reducing O₂ capacity to the organ
63
What immune mechanism mediates blood transfusion reactions?
complement
64
Which individual's immune cells are responsible for GVHD?
the donor
65
Which protein is tested when recipients are looking for a "match" for organ or stem cell transplantation?
HLA genes
66
What is the main challenge in xenotransplantation?
human immune cells and antibodies react to antigens from other species
67
What is an allograft?
tissue from an individual is transferred into another of the same species
68
If a transplant recipient already has antibodies against the donor tissue when the transplant occurs, what type of rejection would you expect?
hyperacute
69
In mice, if a donor mouse is genetically identical to the recipient mouse, what is the result of a transplant?
no rejection
70
If a donor mouse gives a tissue transplant to a recipient mouse that is 1/2 the same strain and 1/2 a different strain, what is the result of the transplant?
no rejection
71
What are the general characteristics of the microenvironment?
72
How can the immune system recognize cancer?
73
What T cell types are important for cell-mediated
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How to target cancer cells if they are "self"?
mutations lead to a change in proteins to form neoantigens, which are cancer-specific and exempt from central tolerance
75
______ ____ ________ can also be detected along with neoantigens
normal self antigens
76
What is the main mechanism for killing tumors?
CD8+ CTLs
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Antibody significance may kill tumor cells by what two methods?
activating complement and ADCC
78
What innate cells can contribute to immune surveillance against cancers and kill tumor cells?
NK cells
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What are two ways innate immune cells can promote tumor growth
M2 macrophages and innate cells generate free radicals causing DNA damage and leading to mutations
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What adaptive immune cells can contribute to tumor growth?
Increase in Tregs and Th1
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What are the different ways your immune system fights tumors?
blocking T cell inhibitory pathways, vaccination with tumor antigens, adoptive cellular therapy with antitumor cells, passive immunotherapy with antibodies, cytokine therapy, and non-specific inflammatory stimuli
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What happens in blocking T cell inhibitory pathways?
Inhibiting the inhibitor to activate the cell
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What is the goal of inhibiting inhibitors?
activate T cells in site of the anti-activation environment around tumors
84
Vaccines with tumor antigens are composed of what?
killed tumor cells, recombinant tumor antigens, or dendritic cells incubated with tumor antigens
85
What is the process of personalized tumor
86
What are the three types of adoptive cellular therapies?
tumor infiltrating lymphocyte therapy (TIL), chimeric antigen receptor (CAR) T-cell therapy, and endogenous T-cell (ETC) Therapy
87
What happens in chimeric antigen receptor (CAR) T-cell therapy?
design a specific receptor that binds to a specific antigen and T cells react strongly against that antigen which are infused back into patient and those T cells bind to cancer cells and kill them
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What is the drawback of CAR T cell therapy?
potential off target toxicity effects if CAR T cell can bind to other things besides the cancer cell
89
What are the three ways to develop passive immunotherapy with antibodies?
direct tumour cell killing, immune-mediated tumuor cell killing, vascular and stromal cell ablation
90
T cells cannot proliferate without what cytokine?
IL-2
91
High doses of ___ is clinically approved treatment for advanced melanoma and renal cell carcionoma
IL-2
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___ and ____ are effector antitumor agents in animal models
TNF; IFN-ɣ
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What is the mechanism responsible for hypersensitivity disorders?
94
How soon after the exposure of hypersensitivity disorders does the response occur?
95
What is immunodeficiency?
underactivation of the immune system
96
Type I is an ______ type of reaction and based on ___ mediation
allergic; IgE
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Type II involves ___, ___, and ________ cells
IgG; IgM; Cytotoxic
98
Type III is an _____ ______-_______ , in which antibodies and antigens are stuck together causing inflammation
immune complex-mediated
99
Type __ results in production of cytokines?
IV
100
_____ ________ happens when you don't have a response, but you will have antibodies the next time you're exposed
First exposure
101
When __-______ happens, ____ binds causing release of histamines
re-exposure; IgE
102
IgE antibodies respond to what types of organisms?
helminths
103
What are the two ways antibody-mediated diseases are produced?
1. antibodies bind to antigens on particular cells or in extracellular tissues 2. antigen-antibody complexes that form in the circulation and are deposited in cell walls
104
Immune complexes that can cause disease may be composed of what?
antibodies bound to either self antigens or foreign antigens
105
Many systemic immunological diseases in humans are caused by what?
the deposition of immune complexes in blood vessels
106
Type __ is the only type of hypersensitivity that does not involve antibodies
IV
107
Type IV is a classic _________ response
autoimmunity
108
_______-____ ________________ is another type of type IV hypersensitivity
Delayed-Type Hypersensitivity (DTH)
109
In tuberculosis, T cells can only be activated if...
you have previously encountered that pathogen
110
chronic DTH reactions happen when
innate immune cells throw themselves on top of the phagocytosed microbes
111
granulomatous inflammation is caused by what?
prolonged cytokine signals
112
What antibody isotype is associated with Type I hypersensitivity?
IgE
113
Which Hypersensitivity type is associated with antibody immune complexes?
Type III
114
How do T cells mediate hypersensitivity reactions?
CD8 T cell direct killing, CD4 T cells produce cytokines, and induce inflammation
115
Will a delayed type hypersensitivity response occur in an individual the first time they are exposed to an antigen?
No
116
Which hypersensitivity type is associated with IgM and IgG antibodies that attach to cells and induce complement and cytotoxic responses?
Type II
117
Cytochrome c is present in the ___________ _____________ _____ during normal cell function and is released into the _________ when apoptosis is initiated
mitochondrial intermembrane space; cytoplasm
118
What is the basic mechanism of general anti-inflammatory drugs (NSAIDS and SAIDS)?
inhbiit the secretion of cytokines and other mediators of inflammation
119
What type of hypersensitivity do general anti-inflammatory drugs target?
Bring down the inflammation and reduce symptoms (not sure abt this one)
120
What are the four the basic mechanisms of anti-cytokine therapy?
soluble cytokine receptor, anti-cytokine antibodies, cytokine receptor antagonists, and small molecule inhibitors (JAK kinases)
121
What type of hypersensitivity does anti-cytokine therapy target?
Type IV
122
What is the basic mechanism of depletion of cells/antibodies?
CD20 (depletes B cells), CD3 (depletes T cells), and CD52 (depletes B and T cells)
123
What type of hypersensitivity does depletion of cells/antibodies target?
124
What are the three basic mechanisms of other biologic agents (anti-receptor anti-integrin antibody treatment)?
Blocks B7 costimulators (CTLA-4-IG), inhibits leukocyte migration into tissues (Anti-c4 integrin), and block T cell-mediated activation of B cells and macrophages (Anti-CD40)
125
What type of hypersensitivity does other biologic agents (anti-receptor anti-integrin antibody treatment)?
126
What are the five basic mechanisms of intravenous Ig (IVIG) therapy?
- inhibits activation and function of -DCs, monocytes, macrophages, neutrophils, and NK cells
- neutralizes activated complement components
- modulates B-cell functions and plasma cells
- reciprocally regulates Treg cells and effector T cells, such as Th2 and Th17 subsets
- downregulates the production of inflammatory cytokines
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What type of hypersensitivity does intravenous Ig (IVIG) therapy target?
128
What is the basic mechanism of tolerance inducing therapies?
induce tolerance in disease-producing T cells (promote activation of regulatory cells without activating effector cells)
129
What type of hypersensitivity do tolerance inducing therapies target?
130
What are the two functions of integrins?
help cytotoxic T cells bind to their antigens and help with cells get to the place via diapedesis
131
What drugs can strongly prevent inflammation?
corticosteroids
132
What is an example of a tolerance-inducing therapy?
induce Tregs with low dose IL-2
133
Which type of hypersensitivity does anti-cytokine therapy primarily target?
type IV
134
Which type of hypersensitivity does antibody depletion therapy most likely target?
type II and III
135
How might low-dose IL-2 induce tolerance to treat autoimmune disorders?
promoting activation and proliferation of Tregs
136
What kind of antibodies are part of an IVIG treatment?
all immunoglobulins isolated from the blood plasma of donors
137
What is the main mechanism of corticosteroids to suppress inflammatory signals?
reduce cytokine release
138
What is the difference between immediate allergic reactions and late-phase reactions?
139
How is Th2 cells involved in
140
How are mast cells involved in allergy?
141
What does granulation do in early allergy?
142
What does granulation do in late allergy?
143
Allergy is also known as
Type I hypersensitivity
144
What is an allergen?
an antigen that causes a response in an inappropriate way?
145
What happens during first exposure to antigen (none of which are noticeable)?
T-cell dependent production of IgE, Th2 cells stimulate class switching in B cells, plasma cells secrete IgE, and IgE binds to high affinity IgE receptors on Mast cells
146
FcεR1 represents what?
constant region of IgE
147
IgE comes from what?
B cells that are activated by T cells
148
Eosinophils are identified based on what?
granules contain basic proteins that bind acidic dyes
149
Polyvalent means what?
multiple epitopes that bind to the same antigen
150
What happens upon second exposure to allergen?
antigen binds to mast cell, cross-links the antibody, and releases all the granules inside
151
Vascular and smooth muscle response causes what (histamine and other mediators)?
immediate reaction
152
True or False: Mast cells respond only to cross-links
False, mast cells do not respond only to cross-links
153
Cytokine has to be expressed from the _____
genes
154
What are the two outcomes of the signaling pathway of granule exocytosis?
vascular dilation, smooth muscle contraction and tissue damage
155
What are the two outcomes of the signaling pathway of enzymatic modification of arachidonic acid?
vascular dilation and smooth muscle contraction
156
What is the outcome of the signaling pathway of transcriptional activation of cytokine genes?
inflammation (leukocyte recruitment)
157
After second exposure, there is an _______ reaction and a ___ ____ reaction
immediate; late phase
158
Late phase is driven by _________
cytokines (causing inflammation)
159
Immediate phase is driven by __________
histamines
160
Upon first exposure to an allergic antigen, what key cell types are activated?
Th2 and B cells
161
Upon second exposure to an allergic antigen, what cells are activated?
eosinophils, basophils, and mast cells
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What antibody isotype is associated with allergic responses?
IgE
163
What mechanisms lead to the immediate allergic reaction?
mast cells degranulate vasoactive amines and lipid mediators
164
What mechanisms lead to the late-phase allergic reaction?
cytokines produced by mast cells recruit leukocytes
165
What are the differences and similarities between primary (congenital) and secondary (acquired) immunodeficiency?
In primary immunodeficiency, genetic defect results in an increased susceptibility to infection that is frequently. In secondary
166
What are the general principles behind innate cell deficiencies?
167
What are the general principles behind
168
Serum Ig levels test whether or not you can make what?
antibodies
169
What is T cell receptor excision circles?
during VDJ, VDJ recombinase brings two combinases and forms a loop and then cuts off that loop
170
______ and ______ are your first line of defense
phagocytes; complement system
171
Complement is responsible for what three purposes?
172
Chronic Granulomatous Disease is caused by what?
mutations in components of the phagocyte oxidase (phox) enzyme complex
173
Another example of immunodeficiency is
leukocyte adhesion deficiencies
174
What is leukocyte adhesion deficiency?
inflammation doesn't work the way it's supposed to
175
APCs are triggered by ___
toll-like receptor signaling
176
What is severe combined immunodeficiency (SCID)?
any immunodeficiency that affects both B cells and T cells
177
What types of cells lead to SCID?
T cells
178
Genetic defects that cause SCIDs are _________ ________ or ________
autosomal recessive; X-linked
179
RAG1, RAG2, and artemis are involved in what process?
VDJ
180
MHC class II is involved in what process?
positive or negative selection of the thymus
181
What is the consequence of RAG1 and RAG2 being knocked out in a patient?
no mature B cells or T cells
182
________ __________ can be a major part of causing immunodeficiency
cytokine signaling
183
A severe type of SCID is
no VDJ recombination
184
No signaling from TCR stage, then what happens to the T cell?
the T cell will not continue
185
MHC class II deficiency, or Bare lymphocyte syndrome, results in what?
no CD4+ T cells (and also no B cells)
186
SCID can be caused by what type of defective cell activation?
defective T cell activation
187
What are selective immunoglobulin isotype deficiencies caused by?
a problem of the signaling of certain cytokines in B cells
188
How does early phase response differ from late phase response?
189
Why do people get allergies?
190
How do different modes of entry alter the immune response to allergens?
191
How do antihistamines work?
192
What is anaphylaxis and how is it treated?
193
What is bronchial asthma and how is it treated?
194
What is sensitization/desensitization?
195
Immediate phase is driven by what?
histamines
196
Late phase is characterized by what?
inflammation, primarily by eosinophils
197
Immediate reaction is the [first or second] exposure to antigen?
second
198
Immediate reaction is also known as what?
Wheal and Flare Response
199
Why do individuals develop allergies?
genetics, microbiota, and exposure to environment
200
People are more likely to have allergies when they develop strong ___ responses
Tₕ2
201
Responses to the [same or different] allergen may have the [same or different] manifestations depending on the tissue targeted
same; different
202
Histamine acts primarily on what receptor?
H1 receptor
203
In chronic allergic inflammation, histamine effects on inflammatory cells cause what?
cellular activation and release of proinflammatory mediators
204
What is anaphylaxis?
a systemic reaction in which a patients come into contact with something they're allergic to
205
Anaphylaxis is driven by what?
histamines and other amines
206
What is a treatment for anaphylaxis?
epinephrine
207
What are the two ways epinephrine treats anaphylaxis?
causes peripheral vasoconstriction and relaxes smooth muscles for bronchodilation
208
What are the two major targets for asthma?
prevention and reversal of inflammation
209
What can reduce bronchial constriction?
leukotriene antagonists and muscle relaxants
210
Antihistamines [are or are not] effective treatments for asthma?
are not
211
What can be used to treat atopic dermatitis?
corticosteroids
212
Desensitization uses the ___ to regulate the environment and prevent inflammation from occuring
gut
213
How does desensitization occur?
by inducing small doses of allergen over time
214
What is the early phase of an allergic response in the skin?
Wheel and flare
215
True or False: There is a strong genetic component to a person's susceptibility to developing an allergic response
True, there is a strong genetic component to a person's susceptibility to developing an allergic response
216
For what type of hypersensitivity are antihistamines the most effective and why?
Type I, because antihistamines counter the effects of degranulation of granulocytes
217
Eczema is an allergic response, but where do allergens (most commonly) come from?
exposure to airborne allergens
218
What allergic response is NOT helped with treatment using antihistamines?
asthma
219
What are some of the causes and mechanisms of acquired immunodeficiency?
220
What is the viral lifecycle of HIV?
221
and how it infects cells and causes diseases at the cellular level?
222
What is secondary (acquired) immunodeficiencies?
immunodeficiency due to something that was acquired during life
223
Malnutrition and immunodeficiency is associated with what?
impaired cellular and humoral immunity to microorganisms
224
All the immune cells come from where?
the bone marrow
225
What are some ways immunodeficiency can cause cancer?
226
What are the two ways to suppress the immune system?
functionally inactivate lymphocytes and inactivate cytokines
227
HTLV-1 infects and transforms what types of cells?
CD4+ T cells, reducing the number of T cells that can fight infection
228
Why would we need the immune system to fight viral tumors?
immune system is responsible for fighting tumors
229
What work to shut down viral production?
restriction factors
230
HIV enters immune cells via what method?
chemokine receptors
231
CD8 T cells responds at what point during the immune response to HIV?
Day 20
232
What types of receptors detect virally infected cells?
TLRs and RIG-I
233
The initial adaptive immune response to HIV infection is characterized what?
expansion of CD8+ T cells specific for HIV peptides
234
What are the two mechanisms of immune evasion by HIV?
HIV has a high mutation rate and down-regulate class I MHC
235
What are the 3 mechanisms that contribute to the loss of CD4+ cells in HIV?
cytopathic effects of viral infection, killing by antigen-specific CTLs, and activation of inflammosome and elimination of infected cells by pyroptosis
236
The most prominent defects caused by HIV are in [humoral or cell-mediated] immunity with results from the destruction of [CD4+ or CD8+] T cells
cell-mediated; CD4+
237
What is the primary form of treatment for HIV?
target replication of the virus (antiretroviral therapy)
238
How do anti-HIV treatments target the virus?
inhibit enzymes and proteins required for viral infection
239
How does HIV lead to immunodeficiency?
it targets and infects CD4 T cells
240
How does HIV evade the immune system?
it has an extremely high mutation rate, preventing detection by antigen-specific T cells & antibodies
241
What about HIV makes it especially challenging to design a vaccine for?
the high rates of mutations makes the target antigen a moving target
242
What is NOT something that leads to acquired immunodeficiency?
genetics
243
No detectable vascular reactions from an immediate reaction happen in what disease?
bronchial asthma
