immuno exam 2 Flashcards
(183 cards)
1
Q
3 pathways of complement activation
A
lectin
classical
alternative
2
Q
complements are activated mostly through
A
alternative pathway
3
Q
major components of lectin pathway
A
MBL
ficolins
MASP-2
C2-C9
4
Q
how is lectin pathway activated
A
when mannose binding lectin (MBL) or ficolin binds to pathogen surface
5
Q
part of the lectin pathway, MASP-2 cleaves
A
C4 into C4a and C4b
C2 into C2a and C2b
6
Q
part of lectin pathway, C4b bound to C2b (C4bC2b) generates
A
C3 convertase
7
Q
part of lectin pathway, C3 convertase cleaves
A
C3 into C3a and C3b
8
Q
part of lectin pathway, C3b binds to C4bC2b (C4bC2bC3b) to generate
A
C5 convertase
9
Q
part of the lectin pathway, there are many ___ molecules on the pathogen surface
C3 convertase can cleave up to 1000 of this molecule
A
C3b
10
Q
major components of classical pathway
A
C1q
C1r
C1s
C2-C9
11
Q
the first component activated in the classical pathway
A
C1
12
Q
C1 is activated by
A
antibody-antigen complexes
13
Q
part of the classical pathway, 3 subunits of C1
A
C1q
C1r
C1s
14
Q
part of the classical pathway, which molecule is converted into an active protease
A
C1s
15
Q
which Ab is most efficient at activating the classical pathway
A
IgM
16
Q
part of the classical pathway, active C1s cleaves C4 into
A
C4a and C4b
17
Q
part of the classical pathway, __ binds to C4b, generating C4b2
A
C2
18
Q
part of the classical pathway, C1s cleaves C42b into
A
C2a and C4b2b
19
Q
part of the classical pathway, C4b2b is also called
A
C3 convertase
20
Q
part of the classical pathway, C3 convertase cleaves C3, generating
A
C4b2b3b (C5 convertase)
21
Q
major components of alternative pathway
A
C3
B
D
P
H
I
C5-C9
22
Q
how is the alternative pathway activated
A
membrane bound C3b generated from lectin/classical pathway; spontaneous hydrolysis of C3
23
Q
part of alternative pathway, B factor binds to C3b on the pathogen surface; B factor is then cleaved by ___ into Ba and Bb, generating C3bBb
A
factor D
24
Q
part of alternative pathway, C3bBb is
A
C3 convertase
25
why does C3b need to be destroyed as fast as it gets generated
to prevent over-activation of the complement
26
part of alternative activation, what molecules bind to C3b on the host cell surface to prevent C3b from binding to other molecules and activating the complement
DAF
I
H
MCP
CR1
27
part of alternative pathway, what molecule stabilizes C3 convertase on the pathogen surface; makes sure the complement can be activated
properdin (factor P)
28
part of alternative pathway, C3b binds to C3bBb to generate
C3bBbC3b (C5 convertase)
29
the last component to be cleaved by the complement
C5
30
first step of forming membrane attack complex (MAC)
activating C5
31
C5 convertase from all 3 complement pathways bind and cleave
C5 into C5a and C5b
32
to form MAC, C5b binds to
C6 and C7
generating C5b67 complex
33
to form MAC, C5b67 binds to pathogen membrane via
C7
34
to form MAC, C8 binds to C5b67 complex and inserts into
pathogen cell membrane
35
to form MAC, C9 binds to C5b678 complex and polymerizes into 10-16 molecules of C9, forming a pore in the pathogen's cell membrane, this is destructive because
it allows water to get into and destroy the cell
36
for complement regulation, what molecule is a C1 inhibitor; binds to C1s
C1NH
37
for complement regulation, what molecules inactivate C3 convertase; displace C2b from C4b2b
DAF
CR1
MCP
C4BP
38
for complement regulation, what molecules inactivate C5 convertase; binds to C3b
CR1
H factor
I factor
39
for complement regulation, which factor cleaves C3b
I factor
40
for MAC regulation, what molecule blocks the formation of MAC; binds to C5b678 to prevent C9 binding
CD59 (Protectin)
41
3 consequences of complement activation
direct killing of pathogens
promote phagocytosis of pathogens
promote inflammation
42
which complement molecule serves as an opsonin to promote phagocytosis
C3b
43
which complement molecule is necessary to stimulate phagocytosis
C5a
44
how do C3a and C5a promote inflammation
binding to cel surface increases vascular permeability and infiltration of inflammatory cells in tissues
45
complement gene clusters of ___ in MHC III region
C4, C2, factor B
46
complement gene clusters of ___ in RCA cluster
C4BP, CD55, CD35, CD21, CD46, factor H
47
pattern of genetic variants in complement genes inherited by an individual
complotype
48
C4-4 allele expression is associated with
low serum C4
autoimmune polyarthritis development in dogs
49
autosomal hereditary recessive C3 deficiency is caused by
deletion of single cytosine
frameshift mutation - pre mature stop codon
shortened C3 chain
50
clinical effect of autosomal hereditary recessive deficiency
seen in brittany spaniels
heterozygous - normal
homozygous - inc susceptibility to bacterial infections
51
porcine factor H deficiency is
autosomal recessive in yorkshire pigs
52
clinical effect of porcine factor H deficiency
healthy at birth
failure to thrive
stop growing
become anemic
die of renal failure due to excess C3b
53
treatment of porcine factor H deficiency
replace factor H by plasma transfusion
54
tests for porcine factor H deficiency
electron microscope
indirect immunofluorescence
55
effect of mannose binding lectin deficiency
inc susceptibility to infections in children
not yet described in domestic animals
56
effect of C6 or C7 deficiency
individuals are healthy
57
what do MHC deliver
pathogen signals to T cells
58
what were MHC originally discovered as
transplantation antigens
59
what do MHC play a role in recognizing
intercellular recognition and self vs. non-self
60
what do T cell receptors (TCR) recognize
an Ag derived peptide combined with MHC on an APC
61
how many classes of MHC molecules are there
3
62
what forms the antigen binding site on MHC I; area the T cell sees
a1 and a2 chain
63
how large are antigenic peptides MHC I binds
8-10 amino acids
64
what forms the floor of MHC 1
B pleated sheet
65
what forms the walls of MHC 1
two parallel alpha helices
66
a3 domain on MHC 1 has a binding site for
CD8 molecules for phagocytosis
67
how many chains does MHC II contain
2, a and B
68
what region of MHC II does a T cell antigen receptor see
a1, B1 and antigenic peptide
69
how large is the antigenic peptide on MHC II
13-25 amino acids
70
the antigen binding site on MHC II is formed by
a1 and B1 domains
71
on MHC II, a2 and B2 domains have a binding site for
CD4 molecules
72
how do MHC molecules bind to peptides
anchor residues; can bind many different peptides
73
MHC III
do not directly participate in antigen processing and presentation
74
what properties of MHC molecules make it difficult for pathogens to evade the immune response
polygenic and polymorphic
75
what makes MHC polygenic
MHC molecules have two major different classes, each with different loci
76
what makes MHC polymorphic
each MHC locus has two alleles in an individual; creates genetic diversity and prevents a pathogen from eliminating an entire species
77
what kind of MHC molecules have similar structure but are less polymorphic in a population
nonclassical MHC I
78
what 2 mechanisms contribute to MHC polymorphism
point mutations
gene conversion
79
gene conversion
small blocks of DNA are exchanged between different class I genes in a nonreciprocal fashion
80
the more diverse MHC molecules an individual has
the higher chance of presenting self-antigens and autoimmune disease, and the smaller the peripheral T cell repertoire
81
ideal number of MHC molecules in humans for maximizing foreign Ag recognition and minimizing self Ag recognition
6
82
presence of HLA alleles DR4 and DRQ are associated with more susceptibility to
type 1 diabetes
83
presence of HLA alleles B57 and B27 are associated with
more susceptibility to psoriasis, ankylosing spondylitis and reiter's syndrome
overrepresented in the HIV elite controllers (undetectable HIV)
84
presence of BoLA-DRB3.2 7, 8, 11, 22, 24 and 28 alleles is associated with
low proviral load for bovine leukemia virus
85
presence of BoLA-DRB3.2 10 allele is associated with
high proviral load for bovine leukemia virus
86
antigen
substance capable of stimulating immune response; activates lymphocytes
87
epitope (antigenic determinant)
portion of Ag that binds to immune cells
88
where do B cell epitopes present
surface of molecule
89
a large molecule with multiple epitopes can
stimulate multiple immune responses
90
what part of epitopes do B cells recognize
conformation of epitope
91
T cell epitopes come from
large molecules like bacteria; can be located anywhere in molecule
92
how do T cells recognize epitopes
if bound to APC on MHC
93
Ag that invade a host from outside and then grow in the host's tissues and extracellular fluid; processed in phagosomes in APCs; typically bacterial
exogenous Ag
94
Ag produced by host cells; processed by proteasomes in the cells they are produced; viral or autoantigens
endogenous Ag
95
two properties of Ag
immunogenicity
antigenicity
96
ability of an Ag to provoke an immune response in the body
immunogenicity
97
capacity of an Ag to bind specific T cells or B cells
antigenicity
98
factors that determine the immunogenicity of an Ag
foreignness
size
stableness
complexity
genetics of recipients
route of Ag administration
dose of Ag
99
has antigenicity but not immunogenicity; only immunogenic when bound to other large molecules; activates immune response when attached to a carrier
hapten
100
what cells can serve as APCs
nucleated cells that express MHC
101
what cells cannot serve as APCs
RBCs
102
MHC class II only present on
professional APCs
103
professional APCs
dendritic cells
macrophages
B cells
104
what is the only APC that can activate naive T cells
dendritic cells
105
DCs are not found in
immune privileged sites
brain, eyes, testes
106
where are DCs prominent
lymph nodes
skin
mucosal surfaces
107
purpose of dendrites on DCs
inc surface area - inc efficiency of Ag trapping and maximize contact between DCs and other cells
108
DC type specialized in taking up, processing and presenting Ag to naive T cells
classical or conventional DCs (cDCs)
109
DC type that responds to viruses by synthesizing type 1 IFN; also synthesizes type 3 IFN; can activate NK cells
plasmacytoid DCs
110
DC type in the skin
langerhans cells
111
DC type found in the germinal centers of spleen, LN and peyer's patches; found in localized infection sites; essential for Ab production and B cell memory
follicular DCs
112
role of immature DCs
capture invading microbes; capture Ags by phagocytosis, pinocytosis and by binding to cell surface receptors; does not completely degrade pathogens
113
how do immature DCs kill invaders
mounting respiratory burst
114
role of activated DCs
present Ags to T cells
activate T cells
115
what do activated DCs respond to
IL-1
TNF-a
PAMPs and DAMPs
116
mature DCs express DC-SIGN that binds ICAM-3, what is the function of this interaction
allows DCs to maintain a prolonged interaction with naive T cells and rapidly screen 1000s of T cells
117
why are macrophages inefficient APCs
most of ingested Ag is destroyed by lysosomal proteases and oxidants
118
B cell antigen receptors (BCRs) enable B cells to
present large amounts of specific Ags to sensitized T cells
119
4 important molecules for MHC II
invariant chain - CLIP
HLA-DM
HLA-DO
MARCH-1
120
CLIP is part of an invariant chain for MHC II, what is its function
binds to MHC II to stabilize before peptides are available
121
function of HLA-DM
catalyzes the release of CLIP and binding of antigenic peptides to MHC II
122
function of HLA-DO
negative regulator of HLA-DM; binds to DM to prevent peptide loading of MHC II
123
function of MARCH-1 (membrane bound E3 ligase)
regulates MHC II Ag processing and presentation
124
important molecules for MHC I Ag processing and presentation
TAP
ERAAP
proteasome
125
function of TAP
transporting peptides generated from proteasome into ER
126
TAP expression is enhanced by
interferon
127
function of ERAAP
trim amino termini of peptides before binding to MHC I molecules
128
ERAAP expression is enhanced by
IFN-y
129
function of proteasome
process Ag under physiological conditions
130
PA28 proteasome-activator complex is induced by
IFN-y
131
exogenous Ag can be loaded on to MHC I molecules via
cross presentation
132
endogenous Ag are loaded on to MHC II molecules via
autophagy pathway
133
4 cytokine families
interleukin
interferon
TNF
chemokines
134
cytokine modes of action
autocrine/intracrine
paracrine
endocrine
135
properties of cytokines allow
cytokines to regulate the activity of immunocompetent cells in a coordinated manner
136
cytokine property: a given cytokine has different biological effects on target cells
pleiotropic action
137
cytokine property: two or more cytokines exert the same biological effect on the same cells
redundancy
138
cytokine property: effect of two cytokines on a particular cell is greater than the additive effect of individual cytokines
synergistic action
139
cytokine property: the action of one cytokine inhibits the effects of another cytokine
antagonistic action
140
ex of two synergistic cytokines
IL-4 and IL-5
stimulate B cell proliferation and induces class switch to IgE
141
ex of two antagonistic cytokines
IL-4 and IFN-y
IFN-y blocks class switch to IgE induced by IL-4
142
cytokine property: action of a cytokine leads to the induction of one or more cytokines which in turn induces the production of other cytokines
cascade action
143
cytokines have at least two functional units on their cell surface receptors; what are they for
ligand binding
signal transduction
144
what type of receptor is not used as a cytokine receptor
channel linked receptor
145
receptors that use tyrosine kinases for intracellular signaling are typical for
growth factor and cytokine receptors
146
immunological receptors that use GPCR
C5a
chemokine receptors
leukotriene receptors
platelet activating factor receptor
147
ligation of sphingomyelinase activating receptors triggers
activation of NF-kB
148
sphingomyelinase activating receptors are often used by
IL-1 and TLRs
149
group 1 cytokine receptors form complexes with
janus kinases (JAKs)
150
what do JAKs do
phosphorylate STAT
151
what does STAT do
dimerizes to form an active transcription factor; may enhance or suppress cytokine signaling
152
central to most cell signaling; reversible modification of proteins by adding a phosphate group to selected amino acids
protein phosphorylation
153
signal transduction systems use __ to modify and send a signal into a cell
ATP
154
amino acids phosphorylated by protein kinases
serine
threonine
tyrosine
155
phosphorylation of this amino acid is key in cytokine receptor signal transduction
tyrosine
156
three major signal transduction pathways in the immune system
NF-kB pathway
NF-AT pathway
JAK-STAT pathway
157
highest distribution of lymphocytes in
lymph nodes
158
discovery of T cells by
thymectomy; loss of cellular immunity
159
discovery of B cells by
bursectomy; loss of humoral immunity
160
what technique can be used to identify molecules expressed by lymphocytes
fluorescence activated cell sorting (FACS) using a flow cytometer
161
types of lymphocyte surface molecules
adhesion molecules
Ag receptor complex
molecules that regulate lymphocyte function
162
how do lymphocytes use adhesion molecules
naive LC use to migrate into lymph nodes
LC use to migrate into inflamed tissues and to interact with other cells
163
ex of adhesion molecules
ICAM-1
VCAM-1
interact with LFA-1
164
chains on T cell Ag receptor complex (TCR)
alpha-beta chain
gamma-delta chain
165
what molecule transmits TCR signal into a cell
CD3
166
what molecule is the coreceptor on CD4+ T cells and necessary for Ag recognition for MHC II
CD4
167
what molecule is the coreceptor on CD8+ T cells and necessary for Ag recognition for MHC I
CD8
168
B cell Ag receptor (BCR) is
membrane bound Ab;
can loosely bind then change to have high affinity
169
what molecules transmit BCR signal into a cell
Iga (CD79a)
IgB (CD79b)
170
2 important B cell co-receptor molecules
CD19 and CD21
171
what molecule is a co-stimulatory receptor and necessary for naive T cell activation
CD28
172
what receptor is an important growth factor for activated T cells
IL-2 receptor
173
what molecule is a marker for an active T cell; naive T cells do not express
CD25
174
lymphocyte surface molecules expressed on naive T cells
CD45RA
CD127
175
lymphocyte surface molecules expressed on effector T cells
CD25
CD45RA/RO (not highly expressed)
176
lymphocyte surface molecules expressed on effector memory T cells
CD45RO
CD127
177
lymphocyte surface molecules expressed on central memory T cells
CD25
CD45RO
C127
178
lymphocyte mitogens
activate lymphocytes in a non-Ag specific way; used to measure lymphocyte functions
179
commonly used mitogens
PHA
Con A
PWM
LPS
180
which mitogen:
from red kidney bean
binds N-acetylgalactosamine
stimulates T cells, a little bit B cells
PHA
181
which mitogen:
from jack bean
binds a-mannose and a-glucose
stimulates T cells
Con A
182
which mitogen:
from pokeweek plant
both T and B cells
PWM
183
which mitogen:
from gram negative bacteria
stimulates B cells
LPS
