immunotoxicology Flashcards
1
Q
what are 3 immune mechanisms that are modulated by xenobiotics
A
immune cell activation
immunosuppression
immune recognition
2
Q
what is immunotoxicity
A
the study of adverse effects on the immune system resulting from exposure to drugs or chemicals
3
Q
what are the 2 components of the immune system
A
innate and adaptive
4
Q
what are the 4 types of cells that come from common lymphoid progenitor
A
NK B T and dendritic cells
5
Q
what are the 6 types of cells that come from common granulocyte/macrophage progenitor
A
eosinophil, basophil, macrophage, neutrophil, mast cell and dendritic cell
6
Q
what is the cellular components of the innate immune system
A
macrophages, dendritic cells, granulocytes, mast cells, NK cells
7
Q
what is the cellular components of the adaotive immune system
A
T cells B cells
8
Q
what is the efferent mechanisms of the innate immune system (4)
A
cytokine production, inflammatory response, phagocytosis, pathogen killing
9
Q
what is the efferent mechanisms of the adaptive immune system (3)
A
antibody production, cytokine production, cell killing
10
Q
how fast is the innate response
A
quick
11
Q
how fast is the adaptive response
A
slow
12
Q
does innate have specific memory
A
no
13
Q
does adaptive have specific memory
A
yes
14
Q
what is the main important differences between innate and adaptive (2)
A
antibody formation and immune memory
15
Q
where are macrophages
A
in tissues (only called macrophages when there)
16
Q
what are kupffer cells
A
resident macrophages in the liver
17
Q
what is the largest macrophage population in the body
A
kupffer cells
18
Q
what do kupffer cells do main mechanism
A
remove foreign material from portal circulation that streams into liver
19
Q
what is a secondary mechanism of kupffer cells
A
synthesize and release proinflammatory mediators like cytokines, ROS, RNS
20
Q
what is the main enzyme of macrophages
A
using NADPH oxidase
21
Q
what do macrophages produce
A
NO
22
Q
what do macrophages release (2)
A
proteases and cytokines
23
Q
what cytokines do macrophages release (3)
A
TNFa, IL-1B and IL-18
24
Q
what does cytokine release from macrophages do
A
signal for neutrophil recruitment
25
what are the 2 waves of attack in hepatic cells
- macrophage catalyzed
| - neutrophil catalyzed
26
why do neutrophils come in wave 2
because cytokine signals tell them do
27
how do neutrophils fight in wave 2
indiscriminately, even will damage host tissue
28
what is an example of toxicity of a xenobiotic that macrophages play a role in
CCl4
29
what happens do CCl4 in the body
CYP2E1 turns it into *CCl3
30
what happens when you deplete macrophages and then give CCl4
there is less liver injury, so it is protective
31
how did they get rid of macrophages to test for CCl4 effects
give them GdCl3 cause it depletes macrophages
32
what happens if you give GdCl3 and CCl4 + why
then there wont be any injury (no macrophages to cause more damage)
33
what 2 pathways can happen to *CCl3
-add O2 to make *OOCCl3 -add lipid to make lipid radical and CHCl3
34
what are 2 drugs that the depletion of macrophages attenuates the toxic effects
acetaminophen and CCl4
35
what is immunosuppression
impairment of maturation and development of immune cells
36
what is a main example of something used for immunosuppression (xeno)
halogenated aromatic hydrocarbons
37
what is pancytopenia
low rbc wbc and platelets
38
what are 4 causes of immune suppression
xenobiotic-induced, panytopenia (bone marrow), thymic atrophy/involution
tumor
39
what is thymic atrophy/involution / what happens (5)
less T cells being made, less proliferation differentiation cytokine production and cell responses
40
what is TCDD (another name)
dioxin
41
what does dioxin do
decreases thymus mass
42
what does TCDD do
decreases thymus mass
43
which drugs decreases thymus mass
TCDD/dioxin
44
what happens if you give dioxin then influenza A
they get more pulmonary damage than mice who werent exposed
45
what does dioxin do to T cells (4)
t-cell depletion, less t-cell differentiation and proliferation
but more regulatory T cells
46
what does AhR stand for
aryl hydrocarbon receptor
47
where is the aryl hydrocarbon receptor
in the cytosol
48
where is there a lot of aryl hydrocarbon receptor
in the thymus
49
what happens with aryl hydrocarbon receptor knockout
the mice are resistant to thymic atrophy caused by TCDD/ dioxin
50
what does TCDD need to activate for it to cause a bad response
the aryl hydrocarbon receptor
51
what does trp depletion cause
T cell death
52
what does trp breakdown into
kynurenine
53
what do tumor cells upregulate
enzymes that breakdown trp
54
what does kynurenine do
binds to aryl hydrocarbon receptor
55
what happens when kynurenine binds to aryl hydrocarbon receptor (3)
induces IL-10 release and regulatory T cell development which leads to immune suppresion
56
what is the role of regulatory T cells
role in regulating or suppressing other cells in the immune system
57
what does more regulatory T cells lead to (2)
less T cell proliferation, less killer t cell formation
58
how does trp depletion lead to immunosuppression in cancer
tumor cells upregulate enzymes to turn it into kynurenine, which binds to aryl hydrocarbon receptor to increase IL-10 and T regulatory cells
59
what is type 1 hypersensitivity
immediate-type hypersensitivity
60
what is type 2 hypersensitivity
antibody mediated cytotoxic hypersensitivity
61
what is type 3 hypersensitivity
immune complex mediated hypersensitivity
62
what is type 4 hypersensitivity
cell mediated hypersensitivity
63
which type of hypersensitivity is anaphylaxic
type 1
64
what are the 2 fragments of the IgG molecule
the Fc and the Fab fragments
65
is the Fc or Fab fragment the one that looks like the two ends sticking out from 1
Fab
66
is the Fc or Fab fragment the one that looks like main one that 2 things brach from
Fc
67
which fragments only has constant regions
Fc
68
which fragments has variable and constant regions
Fab
69
which one is the heavy and light chain
heavy is on the outer one and light is the inner one
70
where are the variable regions
right at the end of the Fab fragments
71
what part of IgG binds to the antigen
the variable region on Fab
72
what part of IgG activates complement and phagocytes
Fc
73
what is the main type of antibody we are learning about
IgG
74
which side is the amino terminal of IgG
the Fab regions
75
which side is the carboxy terminal of IgG
the Fc regions
76
which type of populations get lots of type 1 hypersensitivity
in developed nations
77
what is a prerequisite of type 1 hypersensitivity
need prior sensitization to antigen (so you have antibodies the second time)
78
what is the specific antigen in type 1 hypersensitivity
IgE
79
what specifically happens in type 1 hypersensitivity
binding of antigen to antigen specific IgE bound on mast cells, then rapid liberation of active chemicals such as histamine
80
what do mast release once activated
active chemicals such as histamine
81
what happens in type 1 hypersensitivity when they are first exposed to the antigen
they make IgE antibodies, they bind to surfaces of mast cells and basophils(by Fc portion), and these cells are now primed to react the next time the cells come into close proximity with the allergen
82
how does IgE bind to mast cells
by its Fc portion onto a Fc receptor for IgE (which is already on the mast cell)
83
how does degranulation occur in type 1 hypersensitivity
exposure to antigen causes cross-linking of cell-bound IgEs, so then degranulation happens
84
which cell type is sensory and decides what is foreign
the B cell
85
what does the B cell do once it notices a foreign thing
processes it, presents it to T cell
86
which cell type secreted IgE
plasma cells
87
what are 2 examples of primary mediates in degranulation in type 1 hypersensitivity + what do they . cause
histamine, proteases
| can cause vasodilation
88
what are 2 examples of secondary mediates in degranulation in type 1 hypersensitivity + what do they . cause
leukotrienes and prostaglandins
89
what is the mechanism of antihistamines
block H1 and H2 receptors
90
what is the mechanism of cromolyn sodium
blocks Ca++ influx into mast cells
91
what is the mechanism of theophylline
prolongs high cAMP in mast cells by inhibiting phosphodiesterase
92
what is the mechanism of ephinephrine
stimulates cAMP production in mast cells
93
what is the mechanism of cortisone
blocks histidine to histamine conversion and stimulates cAMP in mast cells
94
why do lots of drugs to treat type 1 increase cAMP
because degranulation is prevented if cAMP levels remain high
95
what happens in type 2
specific IgG or IgM antibodies bind to antigens on cells via their Fab regions
96
what happens once the IgG binds to the cell in type 2
complement activation via Fc region
97
what does complement activation cause (type 2)
attracts phagocytes, causes damage and lysis
98
how does IgG cause complement (type 2)
bridges complement via Fc regions
99
what are 3 examples of complement mediated lysis in type 2
hemolytic anemia, ABO transfusion, Rh disease
100
what are the antigens in type 2
it can be part of the cell naturally, or a drug!
101
what are 2 examples of drugs that can be used as antibodies in type 2
penicillin, quinidine
102
what is opsonization
coating of a particle with proteins that facilitate phagocytosis (targets and tags the cell)
103
which type of hypersensitivity involves opsonization
type 2
104
which type of hypersensitivity involves IgE
type 1
105
which type of hypersensitivity involves mast cell
type 1
106
which type of hypersensitivity involves cell bound antigen
type 2
107
which type of hypersensitivity involves immune complex
type 3
108
what is the first step of type 3 hypersensitivity
antigen and antibodies form complexes in blood
109
what happens to the immune complexes
they are deposited on blood vessels wall
110
what happens once the immune complexes are deposited on blood vessels wall
complement is activated and C3a and C5a are released
111
what happens once C3a and C5a are released
neutrophils are attracted by C5a, they release enzymes that destroy endothelium and RBC escape the vessels
112
what do neutrophils do it type 3 and how do they come around
attracted by C5a and they release enzymes that destroy endothelium and RBC escape the vessels (inflammation, leaky vessels)
113
what does procainamide do (which type)
lupus like syndrome (type 3)
114
what is the mechanism of procainamide in type 3 + what does it cause
forms anti H2A-H2B-DNA antibodies which causes abnormal T cell maturation and proliferation
115
how does procainamide cause T cell activation
because its reactive metabolite activates T cells
116
what does procainamide do to T cells
abnormal T cell maturation, proliferation, T cell activation
117
what is a main serious thing that procainamide can cause (1 word)
agranulocytosis
118
what is agranulocytosis
lowered WBC count
119
which type causes agranulocytosis
3
120
what kind of antibodies does procainamide make
against histones and DNA (H2A-H2B-DNA)
121
which type of hypersensitivity is T-cell mediated
4
122
what is the first thing that happens in class 4
macrophages ingests antigen, processes it, and presents it with class 2 MHC protein
123
what happens after macrophage presents antigen with MHC 2
T helper-1 gets activated, gabba-INF, activates macrophages
124
what are some things that may be involved with class 4
CD4 and CD8 cells
125
what is involved with poison oak, ivy, drugs, soaps and heavy metals
CD8 cell is involved (type 4)
126
what can CD4 cells do
delayed-type hypersensitivity and immune inflammation: induce cytokines and recruit neutrophils, inflammation
127
what can CD8 cells do
cell mediated cytolysis: granzymes, express Fas ligant - both apoptosis
128
what are granzymes
proteases that induce apoptosis
129
what are the 3 main components of type 4
macrophage (APC)
MHC class 2
helper t cells
130
what cell type has CD4
helper t cells
131
what cell type has CD8
killer t cells
132
can xenobiotics activate the immune system
yes
133
can xenobiotics suppress the immune system
yes
134
are immune activation mechanisms simple + explain
no they are simple and can involve various types of hypersensitivity reactions or direct cytotoxic mehcanisms
135
what are 2 things that immunosuppression primarily efects
the thymus (via AhR) and the bone marrow
