Secondary Immuno Def. Flashcards
1
Q
diagnosis of multiple myeloma depends on
A
10% of cells in bone marrow being plasma cells
monoclonal protein in serum/urine and end organ damage
2
Q
MGUS may progress to
A
myeloma
3
Q
IL-6 produced by
A
bone marrow stromal ells & by myeloma
4
Q
what promotes survival by myeloma cells
A
IL-6
5
Q
activation of osteoclasts is mediated by what chemokine
A
CCL3 & RANKL
6
Q
CCL3 w/ RNKL stimualtes
A
development of osteoclasts & activation of osteoclasts
7
Q
final phase of multiple myeloma is similar in presentation to
A
agammaglobulinemia
8
Q
pts w/ multiple myeloma have increased susceptibility to
A
encapsulated infections esp. pneumococcus (strep pneumoniae)
9
Q
pts with multiple myeloma have a lot of antibodies but they are
A
monoclonal
10
Q
when does multiple myeloma present
A
later in life - 65-70
11
Q
myeloma growing in bone and taking up marrow space, so what is often symptom of multiple myeloma
A
bone pain in lwoer back
12
Q
defining feature of multiple myeloma is detection of
A
monoclonal band of Ig
13
Q
upon electrophoresis what will you find in multiple myeloma
A
monoclonal paraprotein, often IgG and sometimes IgA
14
Q
monoclonal protein band is sometiems called
A
paraprotein
15
Q
where can monoclonal paraprotein be found
A
serum and urine
16
Q
when multiple myeloma replaces bone marrow it produces
A
anemia and eventual bone marrow failure
17
Q
activation of osteoclasts leads to
A
bone resorption
18
Q
why is there hypercalcemia in multiple myeloma
A
b/c of the bone resportion
19
Q
light chains are referred to as
A
bence jones proteins
20
Q
bence jones proteins are
A
excess light chains
21
Q
bence jones proteins are often what kind of chain
A
excess kappa chains
22
Q
carpal tunnel is frequent in individuals of pts with
A
multiple myeloma
23
Q
normal Ig production is decreased which is what gives rise to immunedeficiency in
A
multiple myeloma
24
Q
monoclonal protiens are also called
A
paraproteins or M proteins
25
what are paraproteins
immunoglobulins produced by monoclonal plasma cells
26
in majority of cases paraprotein produced is
IgG
27
if not IgG paraprotein it will be
IgA paraprotein
28
bence jones proteins are usually what class of light chain
kappa
29
what test do you do to person if you suspect multiple myeloma
serum protein electropheresis
30
describe serum protein electropheresis
gamma goes toward negative electrode
gamma globulins contain all of the Igs (M, A, D, E, G)
you are interested in gamma globulin peak b/c that is where IgG and IgM will be
31
if somebody has protracted b cell stimluation what will you see in serum protein electropheresis
bigger band and darker spread out (pg 8)
32
somebody w/ multiple myeloma what will you see in serum protein electropheresis
monoclonal band b/c its not diffuse it is very tight and dark.
33
immunofixation electropheresis, describe
agarose gel electropheresis, get albumin stain toward positive and Ig toward negative eletrode
add antibodies to identify the bands
34
diffuse band is indicitive of
polyclonal
35
tight band is indicitive of
monoclonal
36
in multiple myeloma what happens to bone marrow
myeloma cells take over
37
review pg 10
10
38
what does presentation of multiple myeloma look like
```
they will be older, 70 or so
plasma protein is elevated
high plasma protein
low white blood cell
much high IgG
serum electrophoresis - monoclonal protein
MRI: bone destruction
```
39
Waldenstrom’s Macrogobulinemia is characterized by
monoclonal IgM
40
Waldenstrom’s Macrogobulinemia when is onset
older 60-70
41
womeno r men more likely to get Waldenstrom’s Macrogobulinemia
men
42
what are symptoms of Waldenstrom’s Macrogobulinemia
fever, anemia, splenomegaly, weight loss, weakness, fatigue
43
cells in Waldenstrom’s Macrogobulinemia
plasmacitic lymphocytes - not quite plasma and not quite b cells
44
lots of IgM in Waldenstrom’s Macrogobulinemia leads to
hyperviscotiy of plasma - lots more protein and lots more high weight protein
45
how is Waldenstrom’s Macrogobulinemia treated
plasmapheresis and stem cell transplant
46
many of the symptoms in Waldenstrom’s Macrogobulinemia are due to
the increased viscosity of the plasma which will impair blood flow
47
HIV not only virus that can cause immunosuppression, what else can?
EBV
Measles
CMV
48
EBV how does it suppress imune system
binds IL-10 and can also make B cell to make IL-10 which suppresses CD8 anti-viral reactions
49
how does measles immunosuppress
inhibits production of IL-12 and prevents a Th1 response
50
how does CMV immunosuppress?
many other viruses can inhibit antigen processing pathways and prevent presentation of viral antigens
51
EBV, measles, CMB are all what kind of immunosuppression
transient
52
most individuals infected with HIV progress to
AIDS
53
CD4 is expressed where
surface of t cells, amcrophages, dendritic cells
54
HIV infects
CD4 cells, so t cells, macrophages, dendritic cells
55
HIV RNA is transcribe by viral reverse transcriptase into:
DNA that integrates into the host-cell genome.
56
replication of HIV occurs only when
t cells are activated
57
resting t cells will not allow what regarding HIV
HIV replication
58
dendritic cells take HIV to t cells and this causes
spread of HIV to lympho nodes and a reservoir for the HIV
59
during beginning of HIV it is actually
controlled by the immune system, it isn't until loss of CD4 that virus gains control
60
destruction of immune function by HIV leads to
opportunistic infection
61
drugs that block HIV replication lead to decrease in
infectious virus and increase in CD4T cells
62
HIV is what kind of virus
RNA
63
HIV accumulates lots of what
mutations
64
b/c HIV has so many mutations it allows them to become
drug resistant
65
is there a vaccine against HIV
no
66
HIV is what kind of virus
retrovirus
67
what does HIV infect
CD4T ell and macrophage
68
spike glycopotein of HIV is
gp120 head
| stalk: gp41
69
what is what allows HIV to bind to CD4
the head glycoprotein gp120
70
what does gp120 in HIV bind to
CD4 co-recptor CCR5 or CXCR4
71
what cells aquire HIV
dendritic cells
72
what on DC bind to HIV
DC-SIGN
73
what allows DC to pick up HIV
DC-SIGN
74
once DC pick up HIV what do they do
take HIV to the lymph nodes
75
what cell responsible for spreading HIV to CD4 T clls
DC
76
first step in replication cycle of HIV
binding of the gp120 to CD4 and to chemockine receptor - this induces conformation change so it enter cell
77
reverse transcriptase in HIV does what
conversion of viral RNA into double stranded cDNA then uses DNA to amke complementary starand and degrade the DNA
78
how is HIV integrated into HIV
integrase that was packaged in the virus
79
when is HIV activated
when T cell is activated
80
if T cell with HIV is activated what happens
transcription and translation of the HIV
81
after transcription and trnlsation what will HIV do
bud from the cell membrane
82
gp120 initiall binds to
CD4
83
following binding to CD4 of gp120 causes
conformational change
84
after gp120 to CD4 what happens
conformation change that allows it to bind to CCR5 or CXCR4
85
what part of HIV drives fusion
gp41
86
HIV RNA is transcribed by
viral reverse transcriptase
87
activity of reverse transcriptase:
Complementary DNA transcribed from RNA genome
RNase activity destroys RNA strand
Complementary DNA from DNA template
(RNA dependent DNA polymerase and DNA dependent DNA polymerase)
88
what pH does HIV have fusion
neutral PH
89
resting t cells are not ____ to HIV
permissive
90
review pg 37
don't have to memorize all that stuff just review env
91
is HIV virus ever eliminated
no
92
why is there elecation of CD4 t cells afte the first drop in untreated HIV infection
cytotoxic t cell response, but the CD4 will never go back up to the normal CD4 levels w/out drug treatment
93
how long are ppl infected with HIV asymptomatic
10 years
94
even though CD4 t cells increase w/ untreated HIV, eventually
they will slowly declinign and will enter to symptomatic phase and AIDS
95
why can't immune system clear HIV
b/c the CD4 T cells die due to the infection
96
there is latent viral reservoir for HIV in
lympohid tissue
97
evidence of exhaustion of what cells during HIV infection
cytotoxic t cells
98
infected CD4 t cells die as a result of what in HIV
the budding
99
b/c HIV induces fusion @ plasma membrane it can lead to formation f
syncytia
100
syncytia in HIV, describe
uninfected CD4 t cells can aquire by fusing with the infected CD4 t cells
101
can get exhaustion f CD8 cells and what cells in HIV
CD4 T cells
102
what is the window period of HIV
high viral titers but will test negative for ELISA for HIV but pt is very infectious
103
cell responsible for maintaing HIV virus at low level is
cytotoxic T cells
104
what are constitutional symptoms of HIV
non descriptive, just like loss of eight, night sweats, etc. can appear with variety of infections
105
in brain HIV can lead to formation of
syncitia
106
how can you get formation of synctia in brain due to HIV
gp120 expressed on infected cell binds CD4 uninfected cell and they fuse
107
what infections will pt with aids be vulnerable
things taht need Th1 and cell mediated immuniti. some fungi, virus
108
review pg 47
47
109
what is first test to see if somebody has HIV/AIDS
elisa
110
if pt is positive in elisa for HIV/AIDS you will do
western blot
111
what are you coating wells with in elisa for HIV
HIV antigen
112
why are you coating wells w/ HIV antigen in elisa
if they are infected they will have antibodiy against HIV antigens
113
in western blot for HIV you are looking for
body antibodies against it
114
if pt has HIV specific antibody in elisa what will it look like
it will be colored
115
describe western blot for HIV
virus and run it on gel to separate the viral proteins
transfer viral proteins onto membrane, they will bind to membrane
viral proteins separted from one another
if somebody has HIV they will have antibodies against more than one viral protein
have to have antibodies to at least 2 viral proteins
add serum to membrane
116
western blot for HIV is
confirmatory -gives more info than elisa can
117
review pg 49
49
118
if you cannot determine if person is HIV pos or neg for HIV 1 and HIV2 you will do
nucleic acid test
119
new elisa's can detect HIV
much earlier
120
how can you detect HIV earlier than 3rd generation immunoassay
4th generation that looks for actual viral detection or nucleic acid test
121
goals of antiviral thearpy for HIV
supress HIV viral load
improve quality of life
preserve future therapeutic options
prevent HIV transmission
122
when you suppress HIV load for HIV it allows
restoration of CD4
123
the lower the level of HIV virus the less likely
they will transmit the virus
124
how do antiretroviral drugs block virus entry of HIV
block CCR5
block fusion
inhibit gp41 fusion
125
when HIV proteins are made there is polyprotein gp160 that has tobe
cleaved into gp120 and gp41
126
how does antiretroviral drugs block HIV maturation
blocks the protease from cleaving gp160 into active gp120 and 41
127
what are the classes of antiretroviral durgs
Nucleoside (and nucleotide) reverse transcriptase inhibitors (NRTIs)
```
Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
Protease inhibitors (PIs)
Integrase inhibitors (IIs)
CCR5 antagonists
Fusion inhibitors target gp41
```
128
what is HAART stand for
highly active anti-retroviral therapy
129
what is in HAART
HAART = 2 NRTIs + a PI/NNRTI/II
| pg 55
130
use of multiple inhibitors for HIV means that
less likely the HIV will mutate and avoid suppresion
131
regardless of CD40 t cell number in HIV you will
go on hard treatment of HIV
132
whyat has been the issue with HIV vaccine development
Rapid generation of HIV variants.
Vaccines to elicit neutralizing antibodies fail to protect against the diverse HIV subtypes and quasi-species.
Vaccines designed to elicit CTL responses fail to provide protection.
Difficult to generate neutralizing antibodies in vivo.
133
clinical presentation of omenn syndrome?
completel block: SCID
usually not complete block, present with SCID but there are some t and b cells. oligoclonal, elevated IgE
eosinophilia
134
phenotype of DiGeorge syndrome?
thymus affected
complete will have thymic aplasia (rare)
usually thymic hypoplasia
135
x linked proliferative syndrome clinical presentation?
fulminant EBV infection
136
Wiskott-aldrich syndrome clinical presentation?
classic triad: small plaetlets and thrombocytopenia, severe eczema, recurrent pyogenic infections
137
ataxia telangiectasia clinical presentation?
ataxia
recurrent infections largely lung and thymic
increase alpha fetoprotein
sometime decreased IgA (not understood)
138
multiple myeloma clincal presentation?
back/bone pain
deposition of light chains
recurrent infections, renal failure
139
serum abnormaility of multiple myeoloma
monolonal spike IgG
140
waldernstrom's macroglobulinemia clinical presentation
no bone pain or renal failure
141
waldernstrom's macroglobulinemia serum?
monoclonal spike IgM
| plasma hyperviscosity
142
receptor for HIV?
CD4
143
coreceptor for HIV?
CCR5 or CXCR4
144
non-permissive and permissive host cells for HIV
activated T celsl are permissive
| resting are non permissive
145
window period for HIV
period b/w when person infected and when they have antibodies/serum positive
can have high viral titers but screen as serumnegative
146
agglutination reaction done for what two things
ABO blood typing
| Rheumatoid factor test (it is IgM antibody specific for Fc portion of IgG)
147
indirect and direct coombs test does what
if mom has antibody against recess G antigen
148
what coombs test would you do to test mom for the recess b antigen
indirect
149
in antibody excess or antigen excess do not get formation of
precipitant - cannot form lattice structure
150
when antibody binds to antigen at zone of equivalence they will
percipitate in gel
151
describe ouchterlony analysis
poke holes
if they are specific they will precipitate
will form line of perciptate in gel called percipitate line
antibody defuses out from well
review on pg 67
152
line of identity says
what is coming out of the wells is the same
153
line of non identity says
what is coming out of wells is not the same
154
line of partial identity
they share epitopes but not exactly the same
155
spur is line of
partial identity - antigens share an epitope
156
Immunoelectrophoresis describe
add serum in two wells from testing individual and control
albumin goes towards positive electrode
Ig go toward negative electrode
in central part add anti-serum against human serum and allow it to diffuse out
when antibodies (antihuman serum) meets components in serum they are reactive against they will form percipient lines
157
what is one of initial test to see if someone has XLA
Immunoelectrophoresis
