Final Exam Flashcards
To pass (833 cards)
1
Q
primary lymph
A
bone marrow, thymus
2
Q
secondary lymph
A
spleen, lymph nodes, mucosal immune tissue
3
Q
humoral components
A
Abs, complement, acute phase proteins
4
Q
HPC
A
hematopoietic stem cell
5
Q
HPC gives rise to
A
myeloid progenitors, lymphoid progenitors
6
Q
myeloid cells originate from
A
bone marrow
7
Q
G-CSF
A
granulocyte colony stimulating factor
8
Q
M-CSF
A
monocyte stimulating factor
9
Q
myeloid cells + G-CSF
A
myeloblast –> basophils, eosinophils, neutrophils (Grow, My BEN!)
10
Q
myeloid cells + M-CSF
A
monoblast –> blood monocytes, dentritic cells (Make More Blood Money, Diamond Collector!)
11
Q
lymphoid cells produce
A
T cells, B cells, NK cells
12
Q
T cell precursor + IL-7 (thymus)
A
T lymphocytes
13
Q
B cell precursor + IL-7 (bone marrow)
A
B lymphocytes
14
Q
major leukocyte morphologies
A
granulocyte, mononuclear
15
Q
granulocytes in the blood
A
basophils, eosinophils, neutrophils
16
Q
granulocytes in the tissue
A
mast cells, tissue eosinophils
17
Q
mononuclear cells in the blood
A
monocytes, T cells, B cells, NK cells
18
Q
mononuclear cells in the tissue
A
macrophages, T lymphocytes, plasma cells, NK cells
19
Q
phagocytic mononuclear cells
A
monocytes, macrophages, dendritic cells
20
Q
in the tissue, monocytes produce
A
macrophages, dendritic cells
21
Q
phagocytic granulocytes
A
neutrophils
22
Q
what cells are indistinguishable on blood smear
A
mononuclear cells
23
Q
CD
A
cluster of differentiation
24
Q
how to distinguish mononuclear cells
A
CDs
25
T cell CD
CD3, CD4, CD8
26
B cell CD
CD19, CD20
27
NK cell CD
CD16, CD56
28
Monocyte CD
CD14
29
phagocytic cell types associated with innate immunity
neutrophils, macrophages, eosinophil (limited)
30
the professional phagocytes
neutrophils
31
granulocyte contents
peroxidase, lysozyme, degrative enzymes, defensins
32
defensin definition
Cys-rich, cationic, active against bacteria, fungi, viruses
33
neutrophils eliminate pathogens by
phagocytosis, degranulation, NETs
34
NETs
neutrophil extracellular traps
35
leukocytosis
elevated WBC count
36
largest component of WBC count
neutrophils
37
neutrophilia
elevated neutrophils
38
left shift
unmatured neutrophils present
39
neutrophil reserves located in
bone marrow
40
leukopenia
reduced WBC count
41
neutropenia, agranulocytosis, granulocytopenia
reduced neutrophils
42
professional APCs
DCs
43
mDCs
monocyte derived, responsible for capture, processing, and presentation of Ag to T cell
44
pDCs
IFN producing DCs in tissue and blood
45
Langerhans Cells (LCs)
DCs in epidermis
46
monocytosis
elevated monocytes
47
causes of monocytosis
chronic infections, autoimmune disorder, sarcoidosis
48
sarcoidosis
proliferation of resident macrophages
49
monocytopenia
reduced monocytes
50
bone tissue resident macrophages
osteoclasts
51
CNS tissue resident macrophages
microglial cells
52
lung tissue resident macrophages
alveolar macrophages
53
liver tissue resident macrophages
Kupffer cells
54
connective tissue resident macrophages
histiocytes
55
remodels tissue after inflammatory response
monocyte derived inflammatory tissue macrophages
56
defend against parasites
mast cells, basophils, eosinophils
57
mast cell granule contents
histamine, serotonin, heparin, cytokines, chemokines
58
normally emerges from bone marrow as immature cell
mast cells
59
matures locally
mast cells
60
sentinel cells definition
ubiquitous first defense cells
61
sentinel cell types
mast cells, DCs, tissue macrophages
62
mastocytosis
elevated mast cells
63
effects of histamine
itching, hives, anaphylactic shock
64
most common cutaneous mastocytosis
urticaria pigmentosa
65
eosinophil granule contents
histamine, peroxides, major basic protein
66
major basic protein associations
defense against helminths, atopic bronchospasm
67
eosinophilia
elevated eosinophils
68
causes of eosinophilia
parasites, atopic reaction
69
only lymphoid innate cells
NK cells
70
NK cell differentiation location
bone marrow
71
specificity of NK cell receptors
broad specificity
72
memory of NK cell response
does not exist
73
NK cell targets
neoplastic cells, infected cells
74
sebum components
lactic acid, fatty acids, low pH
75
microbial agents of milk
lactoperoxidase, lactoferrin, lysozymes
76
Ig found in mucous, tears, saliva, bronchial tissue
IgA
77
effects of vasodilators
contraction of nonvascular smooth muscle, increased vascular permeability, pain
78
pyrogenic cytokines
IL-1, TNFa, IL-6
79
target of pyrogenic cytokines
hypothalamus
80
PRRs
pattern recognition receptors
81
PAMPs
pathogen associated molecular patterns
82
pathogen evasion by alteration of PAMPs
does not exist
83
notable gram negative PAMP
LPS
84
notable gram positive PAMP
lipoteichoic acid
85
notable mycobacterial PAMP
lipoarabinomannan
86
notable fungal PAMP
beta-glucan
87
notable bacterial PAMP
terminal mannose
88
notable prokaryotic PAMP
fMET
89
PRR properties
germline encoded, nonclonal distribution
90
TLRs
toll-like receptors, type of PRR, activate inflammation
91
location of TLRs
cell surface, endosomes
92
cell surface TLRs recognize
extracellular PAMPs
93
endosomal TLRs recognize
nucleic acids
94
TLR1:TLR2 heterodimer
LPS (gram negative), GPI (parasites)
95
TLR2:TLR6 heterodimer
lipoteichoic acid (gram positive), zymosan (fungi)
96
TLR4:TLR4 homodimer
LPS (gram negative)
97
TLR5
flagellin (motile bacteria)
98
TLR3
dsDNA (virus)
99
TLR7
ssDNA (virus)
100
TLR8
viral ssRNA (virus)
101
TLR9
unmethylated CpG rich DNA (bacteria virus)
102
most important transcription factor for inflammation
NF-kB
103
NF-kB stimulates
acute inflammation, adaptive immunity
104
IRFs
interferon regulatory factors, transcription factors
105
IRFs stimulate
anti-viral cytokines IFNa/b
106
TLR adaptor proteins
MyD88, TRIF
107
MyD88 activates
IRAK-4 in TLR4 response to LPS (gram negative)
108
MyD88/IRAK-4 deficiency
susceptible to bacterial and viral infections
109
NLRs
NOD-like receptors
110
inflammasome
cytoplasmic complex containing NLRs
111
NLRs activate
NF-kB and MAPK pathways
112
most important NLR
NLRP3 in the cryopyrin inflammasome
113
NLRP3 activates
NF-kB pathway, caspase-1 mediated, secretion of proinflammatory IL-1b and IL-18
114
Key regulatory proinflammatory cytokine in gout
IL-1b
115
IL-1b promotes
neutrophil influx to synovium
116
NLRP3 associated DAMP
uric acid
117
gout anti-inflammatory therapy
anti IL-1b
118
DAMP
damage associated molecular pattern
119
DAMPs stimulate
NF-kB pathway, release of IL-1 and TNFa
120
DAMPs released by necrotic cells
HMGB1, uric acid, HSPs
121
HMGB1
DAMP, nucleolus protein
122
uric acid
DAMP, diffusible danger signal
123
HSPs
DAMP, cytoplasmic proteins
124
TLR2:TLR3 heterodimer
HMGB1
125
TLR2:TLR4 heterodimer
HSPs
126
autoimmune diseases associated with DAMPs
MS, type 1 DM, SLE, RA
127
PRR-triggered phagocytosis signals
formyl peptide receptor, mannose receptor
128
mast cells + IgE + Ag release
histamine
129
mast cells + PAMP release
proteases
130
mast cells + cytokine release
serotonin
131
mast cells + chemokines release
heparin
132
mast cells + C3a + C5a release
IL-4 and TNFa
133
controller of histamine and bradykinin
mast cells
134
mast cells are located in close proximity to
blood vessels
135
initial mast cell response
granule release (vasoactive amines), lipid-derived eicosanoid production
136
late-phase (2-24 hours after secondary exposure to allergen) mast cell response
vascular smooth contraction, endothelial vasodilation, leukocyte chemotaxis and activation
137
only innate immune cell that survives prolonged periods after activation
mast cells
138
cytokine molecule class
peptides
139
endocrine
long range
140
paracrine
short range
141
autocrine
itself and others
142
macrophages secrete all cytokines except
IFNg (secreted by NK cells and T cells to activate macrophages)
143
anti-inflammatory cytokines
IL-10, TGFb
144
IL-10
inhibits cytokine and chemokine production, reduces MHC-II production
145
TGFb
inhibits inflammation, differentiates Th17 and Treg
146
IL-8
neutrophils recruitment
147
IL-12
stimulates NK cells and T cells to release IFNg
148
C3b
opsonization, immune complex clearance
149
C3a, C5a
anaphylatoxin
150
anaphylatoxins cause release of
histamine
151
C5a
neutrophil recruitment
152
C3d
enhances immune response
153
MAC
membrane attack complex
154
MAC formation kills by
osmotic shock
155
AP
alternative pathway
156
CP
classical pathway
157
LP
lectin pathway
158
AP recognizes
microbes
159
CP recognizes
antibodies
160
LP recognizes
mannose binding lectin
161
CP: C1q binds
IgM or IgG (x2) on microbial surface
162
CP: C1r and C1s of the active C1qrs complex cleave
C2 and C4
163
CP: C4b covalently attaches to
microbial surface
164
CP: C2a binds
C4b (C4bC2a C3 convertase is formed)
165
CP: C3 convertase cleaves
C3
166
CP: C3b binds
microbial surface (C4bC2aC3b C5 convertase is formed)
167
CP: C5 convertase cleaves
C5
168
CP: C5b initiates
MAC self assembly
169
APPs
acute phase proteins
170
APPs act on
hepatocytes
171
major interleukins of APR
IL-6, IL-1, TNFa
172
APR
acute phase response
173
major APPs used to diagnose inflammation
CRP and SAA
174
where do neutrophils enter tissue from blood
post capillary venules
175
endothelial cells (ECs) activated by
IL-1 and TNFa from tissue resident macrophages
176
activated ECs upregulate
adhesion molecules P selectin (PS), E selectin (ES), ICAM-1, VCAM-1
177
adhesion ligands constitutively expressed on neutrophils
PSGL-1 and ESL-1 (static affinity), LFA-1 and VLA-1 (low affinity)
178
IL-8 is displayed on
ECs
179
IL-8 binding chemokine receptor of neutrophil activates
increased affinity of LFA-1 and VLA-4
180
rolling is dependent on
selectins
181
adhesion, crawling and transmigration are dependent on
integrins
182
most important chemoattractant for monocytes
MCP-1
183
classic (M1) macrophages activated by
PAMPs binding TLRs, IFNg
184
alternative (M2) macrophages activated by
IL-4 and IL-13
185
M1 macrophages
microbicidal, pro-inflammatory
186
M2 macrophages
wound repair, produce IL-10 and TGFb
187
M2 macrophage TGFb stimulates
myosin for wound contraction
188
NADPH oxidase
oxygen to superoxide
189
superoxide dismutase
superoxide to hydrogen peroxide
190
catalase
breaks down hydrogen peroxide
191
myeloperoxidase
hydrogen peroxide to hypochlorite
192
IFN-a/b
block viral replication, induce expression of protein kinase RNA (PKR) and ribonuclease L
193
PKR
prevents recycling of GDP (blocks RNA replication)
194
ribonuclease L
mediates viral RNA degradation)
195
type 1 interferons
IFN-a/b
196
IFN-a/b directly activate
NK cells
197
how activated NK cells take care of viruses
kill host cells, release intracellular contents for phagocytosis, secrete IFNg to activate macrophages
198
NK cell activating receptors (KARs)
recognize stress associated molecules on abnormal cell surfaces
199
KARs trigger activation of
protein tyrosine kinases (PTKs)
200
NK cell inhibitory receptors (KIRs)
recognize MHC-I on normal cell surfaces
201
KIR versus KAR, which signal is more important
sufficient KIR overrides KAR
202
NK cell granules contain
granzymes and perforins
203
alloantigen
tissue specific Ag present in one individual of a species but not in others (ABO, HLA)
204
epitope (antigenic determinant)
specific binding site of Ag
205
paratope
specific binding site of Ab or HLA
206
conformational determinant
recognition depends on shape
207
linear determinant
recognition depends on sequence
208
neoantigenic determinant
recognition depends on proteolysis
209
T-dependent Ag
protein recognized by TCR that stimulates T cell and B cell response
210
T-independent Ag
non-proteins recognized by BCR that stimulates B cell response
211
TCRs recognize
linear determinants of processed Ags presented by APCs
212
g/d T cells
recognize free peptides and lipids, reside in epithelial and mucosal compartments
213
immunodominant epitope
elicit T cell response
214
haptens
small molecules that cannot induce immune response alone
215
superantigens (SAgs)
not processed, bind directly to MHC-II and Vb chain of TCR
216
food poisoning SAg
Staphylococcal enterotoxins (SEA, SEB, SEC, SED, SEE)
217
toxic shock syndrome SAg
Staphylococcal toxic shock toxin (TSST-1)
218
scaled skin syndrome SAg
Streptococcal pyrogen exotoxins (shock)
219
general structure of Ab
four polypeptide chains held together by many disulfide bonds
220
heavy chains consist of
variable region (Fab) and constant region (Fc)
221
light chains consist of
variable region (Fab) and constant region (Fc)
222
classes of Abs
IgM, IgG, IgA, IgD, IgE of heavy chain Fab
223
types of Abs
kappa and lambda of light chain Fab
224
papain Ab digestion
branches of tree are removed, separating two Ag binding regions
225
pepsin Ab digestion
tree trunk is removed, leaving single bivalent binding capacity
226
each V domain has how many HV regions
three
227
each HV regions are flanked by how many FR regions
four
228
Ab allotype
allelic differences in C region of H chains
229
Ab idiotype
genetic differences in V region of H and L chains
230
first Ab produced in response to novel Ag
IgM
231
Ab pentamer
IgM
232
Ab efficient binding of C1 complex
IgM and IgG (x2)
233
Ab contains J piece that allows crossover to mucosa
IgM and IgA
234
Ab expressed on B cells as monomer
IgM and IgD
235
predominant Ab of secondary immune response
IgG
236
Ab which more and more produced with each secondary exposure
IgG
237
most abundant Ab in serum
IgG
238
differences between IgG subclasses
small structural differences on H chain
239
Abs of secondary immune response
IgG, IgA, IgE
240
Ab dimer
IgA
241
most abundant Ab in external secretions
IgA
242
Ab contains secretory component that binds Fc domains
IgA
243
bound to blood basophils and tissue mast cells by Fc receptor with high affinity
IgE
244
FcRn
recycles IgG across placental barrier after processing
245
types of interactions between Ag and Ag
hydrogen bonds, electrostatic bonds, van der Waals forces, hydrophobic forces
246
affinity
strength of interaction between univalent epitope and univalent paratope
247
avidity
strength of interaction between multivalent Ag and multivalent Ab
248
monoclonal Ab (mAb or moAb)
monospecific identical antibodies, all clones of single parent cell
249
zymogen
precursor enzyme
250
MAC C5b binds
C6 and C7
251
MAC C5bC6C7 complex attaches to
microbial membrane via C7
252
MAC C5bC6C7 complex attached to microbial membrane via C7 binds
C8, which then inserts itself into cell membrane
253
MAC C5bC6C7C8 complex binds
C9, which then polymerizes with 16 molecules of itself and forms a pore in the membrane
254
AP C3 "tickover"
spontaneous generation of C3a and C3b from C3
255
AP "tickover" C3b opsonizes microbial surface then binds
Factor B (FB)
256
AP FB (bound to C3b) cleaved by
Factor D (FD) (C3bBb C3 convertase is formed)
257
AP C3 convertase is enhanced and stabilized by
properdin
258
AP C3 convertase while stabilized by properdin binds
C3b (C3bBbC3b C5 convertase is formed)
259
compliment "amplification loop"
AP activated by C3b from CP or LP
260
CP: C1q binding Ab:Ag activates
C1r, which in turn activates C1s
261
LP: MBL attaches to
terminal mannose residues on microbial surface
262
LP: after attaching to microbial surface, MBL activates
MASP1 and MASP2
263
LP: activated MASP1 and MASP2 of MBL complex cleaves
C2 and C4, initiating cascade identical to CP
264
C1-INH inactivates
C1r and C1s, MASP1 and MASP2
265
DAF blocks interaction between
C4b and C2a
266
DAF prevents downstream assembly of
C3 and C5 convertases of CP and LP
267
Factor H (FH) binds
C3b
268
Factor H (FH) decay accelerating activity of
AP C3 and C5
269
Factor I (FI) degrades
C3b and C4b
270
Factor I (FI) destabilizes
C3 and C5 convertases of CP and LP
271
MAC inhibitory protein
CD59
272
CD59 blocks
C9 association with C5b-8 complex
273
C3a receptors are found on what type of cells
mast cells and basophils
274
C3a receptor binding induces
secretion of TNFa
275
C5a receptors are found on what type of cells
monocytes and macrophages
276
C5a receptor binding induces
secretion of IL-1, IL-6, prostaglandins, ROS, RON
277
most powerful anaphylatoxin of all complement proteins
C5a
278
CH50 measures
CP and LP
279
AH50 measures
AP and LP
280
low C3 and C4 indicate
chronic consumption in CS
281
mAb Comstatin
removes C3
282
mAb Eculizumab
removes C5
283
paroxysmal nocturnal hemoglobinuria (PNH) treatment
Comstatin and Eculizumab
284
HLA-I found on
all nucleated cells
285
HLA-II found on
macrophages, DCs, B cells, some thymocytes
286
HLA genes located on
chromosome 6
287
HLA-III influences the
inflammatory response
288
HLA haplotype
set of HLA alleles on each chromosome
289
HLA expression
codominant
290
HLA class I are designated with
single letters (A, B, C)
291
HLA class II are designated with
double letters (DMA, DMB, DOA)
292
HLA-I encoded by which three gene regions
HLA-A, HLA-B, HLA-C
293
HLA-I present to
TCR of CD8 CTL
294
HLA-I inhibitory receptor for
NK cells
295
HLA-I structure
heterodimer of a chain (a1, a2, a3 domains) and b2 chain
296
HLA-I peptide binding groove is located
between a1 and a2 domains of a chain
297
HLA-1 b2 binds a chain via
a3 domain
298
HLA-I peptide binding groove fits
peptides 8-10 amino acids in length
299
how many HLA-I alleles can be expressed in a given cell
all alleles expressed simultaneously
300
HLA-I a chain translated into what organelle
ER
301
in the ER, newly synthesized HLA-I a chain noncovalently interacts with
b2 chain
302
in the ER, newly synthesized HLA-I interacts with
peptides derived from cytosolic proteins
303
TAP
transfers cytosolic proteins into ER for association with HLA-I
304
HLA-II genes located in which region
HLA-D
305
HLA-II structure
a chain and b chain
306
HLA-D region encodes which chains of HLA-II
both a and b chains
307
how many HLA-II alleles can be expressed in a given cell
all of them
308
HLA-II peptide binding groove is located
between a1 and b1 domains of a and b chain
309
HLA-II peptide binding groove fits
peptides between 13 and 18 amino acids in length
310
which HLA peptide binding groove has open ends
HLA-II
311
how many peptides bind HLA
binds multiple different peptides (nonspecific) one at a time
312
HLA rate of "on rate" and "off rate"
slow "on rate", very slow "off rate"
313
HLA peptide binding depends on what characteristic of peptide
size
314
TCR peptide binding depends on what characteristic of peptide
linear sequence (recognizes amino acid side chains)
315
H-Y antigen
antigens coded on Y chromosome associated with rejection of male grafts in female patients
316
CD4 binds what domain of HLA-II
b2
317
CD8 binds what domain of HLA-I
a3
318
phagocytic cell types associated with adaptive immunity
macrophages, DCs, B cells
319
DC phagocytic role in adaptive immunity
Ag presentation to naïve T cells
320
macrophage phagocytic role in adaptive immunity
Ag presentation to CD4 effector T cells during CMI
321
B cell phagocytic role in adaptive immunity
Ag presentation to CD4 helper T cells during humoral response
322
HLA-II expression in DCs and macrophages induced by
IFNg
323
costimulatory signal required during Ag presentation to T cell
CD40 from APC binding to CD40L on T cell
324
HLA-II expression in B cells induced by
IL-4
325
free Ags in the periphery are filtered by the
lymph and lymphoid tissue
326
free Ags in the blood are filtered by the
spleen
327
what cell types are located in spleen
macrophages and B cells
328
only cells that can activate naïve mature T cells
DCs
329
classic DCs produce which cytokines
TNFa, IL-6, IL-12, IL-23
330
classic DCs located in
all tissues
331
plasmacytodic DCs produce which cytokines
IFN-a/b
332
plasmacytodic DCs located in
blood and tissues
333
CCR7 expressed by
lymphatic endothelium
334
activated DCs increase expression of
B7/CD80
335
HLA-II pathway processes what type of pathogens
extracellular`
336
HLA-I pathway processes what type of pathogens
intracellular and self
337
HLA-II a and b chains are produced in what organelle
ER
338
where does extracellular pathogen processing take place
phagolysosome
339
where is digested extracellular pathogen first introduced to HLA-II
late endosome
340
invariant (Ii) chain prevents
HLA-II association with intracellular or self peptide in ER
341
Ii degraded to
CLIP by lysosomal enzymes
342
HLA-DM acts as a peptide exchanger in the late endosome during HLA-II processing, replacing
CLIP with extracellular antigen
343
fate of unbound HLA-II molecules
not displayed
344
intracellular or self proteins digested by
proteasome
345
intracellular or self peptides transported into ER by
TAP
346
posttranslational modification of cytosolic proteins destined for HLA-I pathway
ubiquitination
347
what cell type can cross-present
DCs
348
cross-presentation
DC uses both HLA-I for Ag presentation to CD8 CTL and HLA-II for Ag presentation to CD4 Th
349
outcome of HLA-II Ag presentation to CD4 Th
promotes macrophage activation and B cell Ab secretion
350
outcome of HLA-I Ag presentation to CD8 CTL
promotes killing of target cell
351
HLA associated diseases
ankylosing spondylitis, rheumatic fever, Sjorgren's syndrome, type 1 diabetes mellitus, psoriasis
352
HLA associated with ankylosing spondylitis
HLA-B27 (HLA-I)
353
HLA associated with rheumatic fever
HLA-DR4 (HLA-II)
354
HLA associated with Sjorgren's syndrome
HLA-DR3 (HLA-II)
355
HLA associated with type I diabetes mellitus
HLA-DQw8 (HLA-II)
| HLA-DRB1 (HLA-II)
356
HLA associated with Psoriasis
HLA-B3 (HLA-I)
357
Processing defect associated with renal cell carcinoma
downregulated TAP (HLA-I)
358
Processing defect associated with bare lymphocyte syndrome class I
nonfunctional TAP (HLA-I)
359
Processing defect associated with bare lymphocyte syndrome class II
defective transcription factor HLA-II transactivator (CIITA)
360
CIITA induced by
IFNg
361
RFX5, RFXAP, RFXANK are examples of
HLA-II transcription factors
362
abnormal HLA-II or HLA-I expression results in
reduced T cell count due to failed thymic selection, reduced Ag presentation
363
BCR structure
surface Ab and two invariant chains (Iga and Igb)
364
part of BCR responsible for signal transduction
immunoreceptor tyrosine-base activation motif (ITAM) located on Iga and Igb
365
TCR structure
heterodimer (a and b chains) associated with invariant CD3 complexes and homodimer (zeta chains)
366
part of TCR responsible for signal transduction
immunoreceptor tyrosine-base activation motif (ITAM) located on CD3
367
stem cell develops into
pro-lymphocyte
368
pro-lymphocyte develops into
pre-lymphocyte
369
pre-lymphocyte develops into
immature lymphocyte
370
immature lymphocyte develops into
mature lymphocyte
371
clonal selection occurs in the absence of
Ag
372
which alleles can be expressed on BCR or TCR
only one allele per parent per cell (allelic exclusion)
373
allelic exclusion
clones are monospecific
374
combinatorial diversity
multiple genes for each region (germ line), multiple combinations of regions (somatic recombination)
375
junctional diversity
additional nucleotides during process of D-J or V-DJ joining (H chain, b chain)
376
somatic hypermutation
point mutations in fully assembled VJ and VDJ regions (occurs in H chain only)
377
Ig H chain (M, D, G, A, E) B cell is equivalent to
b chain T cell
378
Ig L chain (kappa, lambda) B cell is equivalent to
a chain T cell
379
somatic hypermutation only occurs in
B cells (T cells are nonspecific)
380
Ig H chain locus located
chromosome 14
381
Ig L kappa chain locus located
chromosome 2
382
Ig L lamda chain locus located
chromosome 22
383
Ig H chain (TCR b chain) gene combination order
D-J, V-DJ
384
Ig L chain (TCR a chain) gene combination order
V-J (no D domain in light chain)
385
recombination signal sequences (RSSs)
ensure genes are combined in order (D-J before V-DJ)
386
V(D)J recombinase recombines
V, D, J segments
387
V(D)J recombinase activity initiated by
RAG1 and RAG2
388
RAG1 and RAG2 are only expressed in
lymphocytes
389
V(D)J recombinase tends to lose
nucleotides at sites of hairpin cleavage
390
deoxyribonucleotidyl transferase (TdT) inserts
nucleotides between D and J segments
391
P nucleotides added by TdT to
asymmetrically cleaved hairpins in templated manner
392
N nucleotides added by TdT
in non-templated manner (random)
393
TCR b chain locus located
chromosome 7
394
TCR a chain locus located
chromosome 14
395
TCR d chain locus located
chromosome 14 (remember g/d T cells)
396
TCR g chain locus located
chromosome 7 (remember g/d T cells)
397
B cell development location
bone marrow (mostly), spleen (not as much)
398
stromal cell
connective tissue cell
399
B cell development: B stem cells and bone stromal cells initially interact through
VCAM-1 (bone stromal cell) and VLA-4 (B stem cell), grows into early pro-B cell
400
B cell development: VCAM-1 and VLA-4 promote interaction between
Kit (bone stromal cell) and SCF (B stem cell), grows into late pro-B cell
401
B cell development: Kit-SCF interaction promotes
expression of IL-7 receptors, grows into pre-B cell
402
B cell development: pre-B cell IL-7R stimulation by IL-7 results in
allelic exclusion of Ig H chain, production of surrogate chain, largest proliferative expansion
403
B cell tolerance located
bone marrow
404
B cell tolerance achieved when
immature B cell is not activated when challenged with self-Ag
405
soluble self Ag: self-reactive immature B cells become
anergic
406
B cell development: when fully processed BCR is expressed, the cell matures from pre-B cell to
immature B cell
407
multivalent self Ag: self-reactive immature B cells become
deleted
408
fate of anergic immature B cells
rescue by receptor editing of Ig L chain genes
409
proteins required for anergic immature B cell rescue by receptor editing
RAG1 and RAG2
410
immature lymphocyte rescue by receptor editing occurs in what cell types
only B cells
411
T cell development location
progenitor T cells travel from bone marrow to develop in thymus
412
thymocytes
immature T cells within the thymus
413
how do progenitor T cells travel to the thymus
blood
414
T cell development: pre-T cell IL-7R stimulation by IL-7 results in
allelic exclusion of b chain, production of surrogate chain, largest proliferative expansion, expression of CD4 and CD8
415
T cell development: largest proliferative expansion located
thymic cortex
416
positive selection of pre-T cells occurs in the
thymic cortex
417
positive selection: thymocyte weak recognition of HLA-II presenting self-Ag
self-restricts to become CD4-only thymocyte
418
positive selection: thymocyte weak recognition of HLA-I presenting self-Ag
self-restricts to become mature CD8-only thymocyte
419
negative selection of self-restricted thymocytes occurs in the
thymic medulla
420
negative selection: thymocyte strong recognition of either HLA-I or HLA-II presenting self-Ag
apoptosis
421
negative selection: thymocyte fails to recognize HLA-I or HLA-II presenting self-Ag
death by neglect
422
after positive and negative selection, the T cell is
mature, naïve
423
Treg surface molecules
CD4, CD25 (high affinity IL-2R), CTLA-4
424
Treg unique transcription factor
FOXP3
425
mature naïve T cells surface molecules
CD4 or CD8, CD28, CD40L, HLA-I, TCR, LFA-1, VLA-4, CCR7
426
mature naïve T cells enter peripheral lymph through high endothelial venules (HEV) by
weak adhesion (L-selectin binds L-selectin ligand of HEV) followed by stable arrest (LFA-1 binds ICAM-1 of HEV)
427
first signal between APC and T cell
HLA/Ag binds TCR
428
second signals between APC and T cell
CD40 (APC) binds CD40L (T cell), B7 (APC) binds CD28 (T cells)
429
first and second signals between APC and T cell stimulate APC to release
IL-12 to enhance T cell activation
430
activation of TCR CD3 ITAMs results in
Lck (kinase on CD4 and CD8) activates ZAP-70 (tyrosine kinase on zeta chains)
431
transcription factors stimulated after TCR activation
NF-kB, NFAT, AP-1
432
TCR activation and NF-kB, NFAT, AP-1 production increases: transcription factors
c-Fos and c-Myc
433
TCR activation and NF-kB, NFAT, AP-1 production increases: increase membrane effectors
CD40L and FasL
434
TCR activation and NF-kB, NFAT, AP-1 production increases: cytokines
IL-2, IFNg, IL-4
435
TCR activation and NF-kB, NFAT, AP-1 production increases: cytokine receptors
CD25 (IL-2Ra)
436
induction of anergy in mature T cells
HLA/Ag without costimulatory signals
437
IL-2
T cell proliferation, Treg survival
438
IL-2Rbgc
low affinity
439
IL-2Ra (CD25)
high affinity
440
B7 (APC) binding CD28 (T cells) induces
a chain addition to IL-2R to increase affinity
441
IL-4
IgE class switching
442
IL-5
IgA class switching, eosinophil activation
443
IL-17
proinflammatory
444
IL-22
neutrophil recruitment
445
IFNg
activates macrophages
446
Ag-specific T cells are arrested in lymph nodes by
CD69
447
CD69 binds
S1PR of lymph node
448
IFN-a/b promotes or inhibits CD69 membrane fusion to S1PR of lymph node?
promotes
449
S1P promotes or inhibits CD69 membrane fusion to S1PR of lymph node?
inhibits (sequesters S1PR)
450
time to Ag recognition by Ag-specific T cell arrested in lymph node
2 days
451
time to Ag-specific T cell activation in lymph node and response to Ag arrival
5 days
452
CD4 T cell + IFNg + IL-12
Th1
453
Th1 defends against
intracellular pathogens
454
Th1 secretes
TNFa, IFNg, IL-2 to activate classical macrophages, CTLs, and NK cells
455
CD4 T cell + IL-4
Th2
456
Th2 defends against
extracellular pathogens (helminths)
457
Th2 secretes
IL-4, IL-5, IL-13 to activate eosinophils, mast cells, and alternative macrophages
458
CD4 T cell + IL-1 + IL-6
Th17
459
T follicular helper (Tfh) cells defend against
extracellular pathogens by helping B cell development
460
Tfh cell activation occurs in
medullary area in lymph node
461
activated Tfh cells migrate to
edge of follicular zone in lymph node
462
activated Tfh cells increase expression of surface protein
CTLA-4 (makes APCs tolerant by binding B7)
463
activated Tfh cells secrete
IL-21 and either IFNg or IL-4
464
naïve B cell + LPS + IL-4
IgG and IgE
465
naïve B cell + LPS + TGFb
IgG and IgA
466
Treg cells activated by
TGFb and IL-2
467
activated Treg cells secrete
TGFb, IL-10, IL-4
468
CTLA-4 (Tregs) binds B7 (APCs) more avidly than
CD28 (T cells)
469
Th1 novel transcription factor
T-bet
470
activated classical (M1) macrophage secretes
IL-1, TNFa, IL-12
471
Th2 novel transcription factor
GATA-3
472
activated alternative (M2) macrophage secretes
TGFb and IL-10
473
activated Th17 cells secrete
IL-17 and IL-22
474
Th17 novel transcription factor
RORgt
475
will every effector T cell that enters an area be specific for Ag
no (selectins and integrins are nonspecific)
476
location of CD8 CTL activation
peripheral tissue
477
location of CD4 Th cell activation
lymph
478
CD8 CTLs release what onto surface of target cells
preformed lytic granule containing perforin and granzymes
479
CD8 CTLs and target cell interaction is stabilized by
ICAM-1 (target) binding LFA-1 (CTL)
480
CD8 CTLs induces apoptosis of target cell by
CD95/Fas (target) binding FasL (CTL)
481
NK cell killing enhanced by
IL-12 and IFN-a/b
482
NK cell killing inhibited by
HLA-I
483
ADCC
Ab-dependent cell-mediated cellular cytotoxicity
484
ADCC associated Abs
IgG or IgE binds to target cell
485
ADCC associated killers
NK cells, macrophages, monocytes, neutrophils, eosinophils (granular cells)
486
T memory cells remain after contraction of immune response because they express increased levels of
Bcl-2
487
T memory cells require what cytokines for survival
IL-7 and IL-15
488
regulatory receptors of adaptive immunity
CTLA-4 and PD-1
489
CTLA-4 (activated T cells)
binds B7 on APCs and induces anergy (tolerance)
490
PD-1 (T cells, B cells, myeloid cells)
binds PDL on APCs, tumor cells
491
T cell exhaustion occurs
during chronic infection, when CTLA-4 and PD-1 induced
492
mycobacteria evasion mechanism
survive within phagosome
493
HSV and CMV evasion mechanisms
inhibition of Ag presentation
494
EBV evasion mechanisms
inhibition of Ag presentation, secretion of IL-10
495
pox virus evasion mechanisms
block cytokine activation of effector cells
496
T cell surface molecules
TCR, CD4 or CD8, CD3, CD28, CTLA-4, PD-1, L-selectin, LFA-1, CCR7, CD40L
497
B cell surface molecules
BCR, co-BCR (CD19, CD21), HLA-II, CD40, B7, CD20, ICAM-1, CXCR5
498
mature naïve BCR
IgM, IgD, Iga and Igb)
499
B1 cells located
mucosa, limited Ag specificity, T-independently activated
500
B2 cells are divided into
follicular and marginal
501
follicular B cells located
primary and secondary lymph, T-dependently activated
502
marginal B cells located
spleen, recognize blood born polysaccharide Ags, T-independently activated
503
activation of mature naïve B cell in circulation prompts travel to
secondary lymphoid tissue (SLT) where they enter and travel to primary follicle (lymph node)
504
FDCs
B cell survival signals
505
first signal for B cell activation (T-dependent or T-independent)
crosslinking of 2 or more BCR by Ag
506
first signal for B cell activation (T-dependent or T-independent) stimulates secretion of
IgM
507
first signal for B cell activation (T-dependent or T-independent) signaling occurs through
Iga and Igb, CD21/CR2, CD19 cytoplasmic tails and involves Syk-B cell phosphorylation
508
compared to Ag bound with C3d, unbound Ag is
less immunogenic
509
first signal for B cell activation (T-dependent or T-independent) results in synthesis of
transcription factors Myc, NFAT, NF-kB, AP-1
510
after the first signal and before the second signal during T-dependent B cell activation, B cells increase CCR7 and migrate to
edge of follicular zone then enter T cell zone
511
CXCR5
how T cells locate primary follicles
512
T-independent second signal for B cell activation
mitogenic stimulation of B cell by Tl-1 antigen (TLRs recognizing PAMPs)
513
T-dependent second signal for B cell activation
co-stimulation between Th cell (CD40L) and B cell (CD40)
514
what cells are found in the germinal centers
activated B cells, Tfh cells, follicular DCs
515
Tfh in the germinal center secrete
IL-21, IFNg, IL-4
516
IL-21 secreted by Tfh cells facilitates
B cell differentiation to plasmablasts
517
Tfh cell cytokines induce
H chain class switching and affinity maturation
518
Tfh cell cytokines H chain class switching and affinity maturation by increasing expression of
activation-induced deaminase (AID)
519
AID
converts C's to Us by deamination, allowing AP endonuclease to create double strand breaks
520
Tfh cell surface molecules
CD4, low levels of CD25 (IL-2Ra), ICOS
521
in the T cell zone, Tfh cells and activated B cells interact by
ICOS (Tfh cell) binds ICOS-L (activated B cell)
522
after ICOS-ICOSL interaction occurs, activated B cell and Tfh cell migrate back to
follicular area and establish germinal centers
523
B cells producing highest affinity Abs are selected for survival through
FDC and Tfh interactions
524
what organelle is enlarged in plasma cells
ER
525
plasma cell surface molecules
high CD27, low CD19, CD20, HLA-II
526
do T-dependently activated or T-independently activated plasma cells live longer
T-dependently activated plasma cells live longer
527
affinity and isotype of T-independently activated plasma cells
mainly IgM, low-affinity
528
affinity and isotype of T-dependently activated plasma cells
isotype-switched, high-affinity
529
plasma cells are active during
primary response
530
memory cells are active during
secondary response
531
B memory cells remain after contraction of immune response because they express increased levels of
Bcl-2
532
B memory cell surface molecules
CD27, CD45R(O)
533
primary response lag after immunization
5-10 days
534
primary response Ab class
IgM > IgG
535
primary response Ab affinity
low (no affinity maturation)
536
secondary response lag after immunization
1-3 days
537
secondary response Ab class
increased IgG, and under certain circumstances, IgA or IgE
538
secondary response Ab affinity
high (affinity maturation)
539
most important cell for Ab production during humoral active immune response
plasma cells
540
plasma cell location
lymph
541
effector function of Abs mediated by what region of molecule
Fc
542
what are the five effector functions of Abs
neutralization, opsonization, ADCC, inflammation, CS activation, lysis (NO, ADCC, CSAL)
543
CD32/FcgRIIb
high affinity, B cells and sentinel cells, Ab feedback and attenuation of inflammation
544
Ab feedback
negative feedback for IgG only
545
Ab feedback: BCR signaling leads to formation of
PIP3
546
Ab feedback: Ab/IgG complex binds CD32/FcgRIIb which converts
PIP3 to PIP2
547
CD16/FcgRIIIa
high affinity, NK cells, ADCC
548
CD64/FcgRI
low affinity, phagocytes, activates phagocytosis
549
FceRI
low affinity, granulocytes, activates degranulation
550
what classes of Abs neutralize
all classes of Abs neutralize
551
what effector function of Abs sterically hinders microbes and toxins
neutralization
552
what effector function of Abs allows for clearance of immune complexes (ICs)
opsonization
553
erythrocyte CD64/FcgRI binds
circulating ICs then transports to liver and spleen where organ resident phagocytes remove IC from surface
554
purpose of IVIG therapy in autoimmune disease
provide passive immunity while engaging inhibitory FcR on B cells (IgG negative feedback)
555
anti-venom is an example of
passive immunization
556
natural exposure and vaccines are examples of
active immunization
557
does passive or active create immunologic memory
active
558
pros and cons of passive immunity
immediate but transient
559
pros and cons of active immunity
delayed but lasting
560
tetanus and rabies immunizations are examples of
combined passive-active immunization
561
influenza and HIV evasion of humoral immunity
antigenic variation
562
Neisseria gonorrhea evasion of humoral immunity
inhibition of complement activation
563
Streptococcus evasion of humoral immunity
hyaluronic acid capsule blocking T cell CD44 binding, Ab binding, and phagocytosis
564
hyperplasia of germinal centers suggests
normal B cell development
565
absence of secondary follicles and germinal centers suggests
abnormal B cell development
566
challenge of previous vaccine tests ability to elicit
secondary immune response
567
challenge of novel vaccine tests ability to elicit
primary immune response
568
most important Ig for pyogenic bacterial defense
IgG
569
Cyclosporin A inhibits
CD40L
570
Tuberculoid leprosy
Th1 favored, low infectivity, granulomas and local inflammation, peripheral nerve damage
571
Lepromatous leprosy
Th2 favored, high infectivity, disseminated infection
572
screen humoral immunity for
recurrent sinopulmonary bacterial infections
573
screen cellular immunity for
recurrent viral and/or fungal infection
574
screen phagocytes for
recurrent skin abscesses and/or fungal infections
575
screen complement for
bacteremia or meningitis with encapsulated bacteria
576
Diff CBC screens for
T cell, B cell, T/B cell defects
577
DTH skin test screens for
T cell defects (negative = impaired T cell response)
578
serum Ig screens for
humoral immunodeficiency
579
total hemolytic complement assay screens for
complement deficiency
580
nitroblue tetrazolium test screens for
phagocytic disorder
581
selective T cell immunodeficiencies
common gamma chain, IL-7R alpha chain, BLS II, MHC class I, CD3, DiGeorge syndrome
582
selective B cell immunodeficiencies
BTK agammaglobulinemia, agammaglobulinemia, IgA, IgG subclass, HIGM syndrome, transient hyper-IgM
583
severe combined immunodeficiencies (SCIDs)
ADA, PNP, artemis, RAG1/RAG2, Jak3
584
ADA immunophenotype
T- B- NK-
585
ADA Ab panel
IgM- IgG- IgA-
586
SCID infections
severe opportunistic
587
SCID vaccination
no live vaccines
588
PNP immunophenotype
T- B- NK-/+
589
PNP Ab panel
often normal
590
artemis immunophenotype
T- B- NK+
591
artemis Ab panel
some mutations can be low
592
SCID inheritance
autosomal
593
RAG1/RAG2 immunophenotype
T- B- NK+
594
RAG1/RAG2 Ab panel
IgM- IgG- IgA-
595
Jak3 immunophenotype
T- B+ NK-
596
Jak3 Ab panel
IgM+ IgG- IgA-
597
BTK agammaglobulinemia immunophenotype
T+ B- NK+
598
BTK agammaglobulinemia Ab panel
IgM- IgG- IgA-
599
BTK agammaglobulinemia inheritance
X-linked
600
BTK agammaglobulinemia infections
recurrent bacterial
601
BTK agammaglobulinemia vaccination
no live vaccines
602
agammaglobulinemia immunophenotype
T+ B- NK+
603
agammaglobulinemia Ab panel
IgM- IgG- IgA-
604
agammaglobulinemia inheritance
autosomal
605
agammaglobulinemia infections
recurrent bacterial
606
agammaglobulinemia vaccination
no live vaccines
607
IgA immunophenotype
T+ B+ NK+
608
IgA Ab panel
IgM+ IgG+ IgA-
609
IgA inheritance
autosomal higher in male
610
IgA infections
mostly asymptomatic
611
IgA vaccinations
no restrictions
612
IgG subclass immunophenotype
T+ B+ NK+
613
IgG subclass Ab panel
IgM+ IgG+ IgA+
614
IgG subclass inheritance
autosomal
615
IgG subclass infections
mostly asymptomatic
616
IgG subclass vaccination
no restrictions
617
HIGM immunophenotype
T+ B+ NK+
618
HIGM Ab panel
IgM+ IgG- IgA-
619
HIGM inheritance
X-linked and autosomal
620
HIGM infections
encapsulated opportunistic
621
transient HIGM immunophenotype
T+ B-/+ NK+
622
transient HIGM Ab panel
IgM+ IgG- IgA-
623
transient HIGM inheritance
N/A
624
transient HIGM infections
encapsulated opportunistic
625
transient HIGM vaccination
POLIO not recommended
626
HIGM vaccination
POLIO not recommended
627
common gamma chain immunophenotype
T- B+ NK-
628
common gamma chain Ab panel
IgM+ IgG- IgA-
629
common gamma chain inheritance
X-linked
630
common gamma chain infections
severe opportunistic infections
631
common gamma chain vaccination
no live vaccines
632
IL-7Ra chain immunophenotype
T- B+ NK+
633
IL-7Ra chain Ab panel
IgM+ IgG- IgA-
634
IL-7Ra chain inheritance
autosomal recessive
635
IL-7Ra chain infections
severe opportunistic
636
IL-7Ra chain vaccination
no live vaccines
637
BLS II immunophenotype
CD4 lymphopenia
638
BLS II Ab panel
hypogammaglobulinemia
639
BLS II inheritance
autosomal recessive
640
BLS II infections
severe opportunistic
641
BLS II vaccinations
no live vaccines
642
MHC class I immunophenotype
CD8 lymphopenia, functional NK deficiency
643
MHC class I Ab panel
IgM+ IgG+ IgA+
644
MHC class I inheritance
autosomal recessive
645
MHC class I infections
recurrent viral
646
MHC class I vaccination
no restrictions
647
CD3 immunophenotype
T- B+ NK+
648
CD3 Ab panel
IgM+ IgG- IgA-
649
CD3 inheritance
autosomal recessive
650
CD3 infections
recurrent viral
651
CD3 vaccination
no live vaccines
652
DiGeorge syndrome immunophenotype
T- B+ NK+
653
DiGeorge syndrome Ab panel
usually normal
654
DiGeorge syndrome inheritance
autosomal dominant
655
DiGeorge syndrome infections
recurrent viral
656
DiGeorge syndrome vaccination
no restrictions
657
adenosine deaminase (ADA)
deoxyadenosine accumulation
658
purine nucleoside phosphorylase (PNP)
dGTP accumulation
659
artemis
VDJ recombinase, repairs double strand breaks
660
artemis red flags
radiosensitivity, lymphoma
661
RAG1/RAG2
modulate initiation of VDJ recombinase
662
Omenn syndrome
partial functioning RAG1/RAG2, eosinophilia and high IgE
663
BTK
rearranges Ig H chain
664
IgA red flags
non-IgE mediated anaphylaxis in response to IVIG
665
DiGeorge microdeletion of
22q11.2 region
666
DiGeorge red flags
cardiac anomalies, hypocalcemia, hypoplastic thymus
667
live viral vaccine CD8 T cell cut off
>300 cells/mm3
668
HIGM
impaired class switching
669
transient hypogammaglobulinemia of infancy immunophenotype
T+ B+ NK+
670
transient hypogammaglobulinemia of infancy Ab panel
hypogammaglobulinemia, IgM low or normal
671
common variable immune deficiency (CVID) immunophenotype
T+ B-/+ NK+
672
common variable immune deficiency (CVID) Ab panel
hypogammaglobulinema, IgM low or nomal
673
transient hypogammaglobulinemia of infancy age range
resolves 2-4 years of age
674
common variable immune deficiency (CVID) age range
diagnosed 20-30 years of age
675
common gamma chain receptor
IL-2Rg
676
B cells in common gamma chain deficiency
present but not functional since T cells are unable to proliferate
677
B cells in IL-7Ra chain deficiency
present but not functional since T cells are unable to proliferate
678
Th1 cell deficiency mutation
IL-12, IL-12R, IFNgR
679
Th1 cell deficiency cannot produce
IFNg
680
Th17 deficiency due to mutations in
IL-17, IL-17R, STAT1, STAT3, AIRE
681
Th17 deficiency red flags
atopic disease, chronic mucocutaneous candidiasis, recurrent Staphylococcus aureus
682
IPEX mutation
FOXP3
683
IPEX results in
loss of inhibition of Treg
684
ALPS mutation
Fas, FasL, caspase-8, caspase-10
685
ALPS results in
no DISC formation, resistance of effector T cell to apoptosis
686
WAS mutation
WASP
687
WAS immunophenotype
T- B+ NK-
688
WAS Ab panel
low IgM, normal IgG, high IgA and IgE
689
WAS inheritance
X-linked
690
classical NK cell deficiency (CNKD)
absence of NK cells
691
classical NK cell deficiency (CNKD) mutation
GATA2
692
functional NK cell deficiency (FNKD)
presence of defective NK cells
693
functional NK cell deficiency (FNKD) mutation
perforin
694
leukocyte adhesion deficiency (LAD) mutation
CD18
695
leukocyte adhesion deficiency (LAD) results in
defective migration of phagocytes into infected tissues
696
leukocyte adhesion deficiency (LAD) infections
encapsulated bacteria
697
chronic granulomatous disease (CGD) mutation
NADPH oxidase, phagocytes cannot produce superoxide
698
chronic granulomatous disease (CGD) results in
impaired killing of phagocytosed bacteria
699
chronic granulomatous disease (CGD) infections
catalase-positive organisms, granulomas
700
G6PD deficiency mutation
G6PD, defective respiratory burst
701
G6PD deficiency results in
impaired killing of phagocytosed bacteria
702
G6PD deficiency infections
chronic bacterial and fungal, anemia induced by certain medication, granulomas
703
myeloperoxidase deficiency mutation
myeloperoxidase, phagocytes cannot produce toxic oxygen species
704
myeloperoxidase deficiency results in
impaired killing of phagocytosed bacteria
705
myeloperoxidase deficiency infections
chronic bacterial and fungal
706
Chediak-Higashi syndrome mutation
cathepsin G and elastase, defect in vesicle fusion
707
Chediak-Higashi syndrome results in
impaired phagocytosis due to inability of endosomes to fuse lysosomes
708
Chediak-Higashi syndrome infections
recurrent pyogenic granulomas
709
granuloma
mass of immune cells at site of inflammation or infection
710
CGD inheritance
autosomal, more common in males
711
G6PD inheritance
X-linked
712
LAD red flags
neutrophilia, inability to form pus, delayed detachment of umbilical cord
713
Chediak-Higashi syndrome red flags
azurophilic giant cytoplasmic inclusions in blood cells, partial albinism, absent NK activity
714
CP: C1 and C4 deficiency associated with
SLE or RA
715
CP: C2 deficiency red flags
recurrent Streptococcus pneumoniae
716
C5-C9 deficiency red flags
recurrent Neisseria infections
717
absent C8 in presence of normal C3 and C4 suggests
C8 deficiency
718
absent C8 in presence of low C3 and C4 suggests
chronic complement consumption
719
AP: properdin, FB, FD deficiency red flags
Neisseria meningitis and other extracellular bacteria
720
AP: FH deficiency associated with
hemolytic uremic syndrome or glomerulonephritis
721
AP: C1-INH deficiency associated with
hereditary angioedema (HAE)
722
AP: C1-INH mutation
SERPING1 gene
723
AP: DAF deficiency associated with
paroxysmal nocturnal hemoglobinuria (PNH)
724
AP: DAF deficiency mutation
GPI anchor
725
most important GPI anchor proteins
CD55/DAF and CD59/MIRL
726
MyD88 deficiency results in
impaired signaling for all TLRs except TLR3
727
MyD88 infections
pyogenic pacteria
728
MyD88 red flags
afebrile, normal ESR/CRP, low IL-1, TNFa, IL-6
729
TLR3 deficiency inheritance
autosomal dominant
730
TLR3 deficiency results in
increased susceptibility to HSV encephalitis
731
development of central tolerance located
primary lymphoid organs
732
central tolerance is induced in
immature self-reactive lymphocytes
733
development of peripheral tolerance located
lymph nodes or submucosal tissue
734
peripheral tolerance is induced in
mature self-reactive lymphocytes
735
central tolerance results in
deletion by apoptosis, change of BCR specificity, development of Treg cells
736
peripheral tolerance results in
induction of anergy, deletion by apoptosis, suppression by Treg cells
737
positive selection deletes by apoptosis what kind of cells
no affinity towards self-Ag
738
negative selection deletes by apoptosis what kind of cells
strong affinity towards self-Ag
739
natural Treg cells are generated in the
thymus
740
what other cells can develop Treg phenotype outside the thymus
mature Th0 cells, differentiate into induced Treg (iTreg) cells
741
FOXP3 expression can be induced in naïve CD4 cells in vitro upon Ag recognition in the presence of
TGFb
742
naïve CD4 T cell + TGFb + IL-6 + retinoic acid
induces expression of RAR and RORgt leading to development of Th17 cell
743
naïve CD4 T cell + TGFb + IL-2
induces expression of FOXP3 leading to expression of iTreg
744
iTreg cells are produced in the
lymph nodes (LNs) and GI tract
745
TGFb, IL-10, IL-4 from Treg cells downregulates what in APCs
CD40, B7, IL-12
746
TGFb, IL-10, IL-4 from Treg cells increases expression of what in APCs
IL-10
747
cell with inadequate B7:CD28 costimulation undergoes
induction of anergy
748
anti-CTLA-4 and anti-PD-1 therapy enhances
antitumor immune response and tumor regression (inhibits suppression of T cell response)
749
T cell deletion by apoptosis occurs by what two pathways
mitochondrial (intrinsic), death receptor (extrinsic)
750
T cell deletion by apoptosis: mitochondrial (intrinsic) pathway involves
Bax, Bak, cytochrome c, caspase 9
751
T cell deletion by apoptosis: death receptor (extrinsic) pathway involves
Fas:FasL(T cell), TNF:TNFR(T cell), caspase 8
752
preB cells express what type of chain
rearranged Ig H chain
753
all B cells that contain what kind of chain underwent BCR editing
lambda Ig L chain
754
inhibitory receptor of B cell
CD22
755
role of CD22
attenuate BCR signaling
756
mechanism of CD22 attenuation of BCR signaling
phosphorylated by Lyn, recruits SHP-1 tyrosine phosphatase
757
commensal microbes
reside in intestinal and respiratory tracts and on the skin
758
anti-inflammatory activity of normal microflora mediated by
Treg and IL-10
759
GALT
gut associated lymphoid tissue
760
two broad mechanisms of autoimmunity
susceptibility genes and environmental triggers
761
AIRE gene expressed in
medullary thymic epithelial cells
762
AIRE genes responsible for
production of tissue restricted Ags (TRAs) used in central tolerance
763
AIRE deficiency results in
breakdown of T cell negative selection (cannot delete self-reactive T cells)
764
CR1 located
RBC
765
CR1 on RBCs binds
C3b of ICs
766
in spleen and liver, macrophages remove ICs from RBCs through interaction of
CR1:C3b and FcR:Fc (stronger synapse)
767
CTLA-4 KO mice have what problems
uncontrolled lymphocyte activation (massive LNs) and fatal multi-system lymphocytic infiltrates
768
CTLA-4 deficiency associated with
type I diabetes mellitus and Grave's disease
769
cell-intrinsic function of CTLA-4
block signal of APC to inhibit T cell activation
770
cell-extrinsic action of CTLA-4
reduced B7 costimulation of T cell to inhibit T cell activation
771
Treg + APC + CTLA-4:B7 + CD28:B7
cell-intrinsic T cell inhibition by CTLA-4
772
Treg + APC + CTLA-4:B7
cell-extrinsic T cell inhibition by CTLA-4
773
four ways autoimmunity is prevented
tolerance, deletion, inhibition, suppression
774
prevention of autoimmunity: tolerance
specific Ag (e.g BBB) cannot become activated
775
prevention of autoimmunity: deletion
T cell that express Fas/CD95 can receive signals from FasL and undergo apoptosis
776
prevention of autoimmunity: inhibition
CTLA-4/CD152 binds B7/CD80 on APC and inhibits costimulatory signal
777
prevention of autoimmunity: suppression
Treg inhibits through production of IL-10 and TGFb
778
examples of immune privileged sites
eye, brain, pregnant uterus, ovary, testis, adrenal cortex, hair follicles
779
most of autoimmune disease associated with what HLA
HLA-II
780
three ways environment results in autoimmunity
molecular mimicry, polyclonal (bystander) activation, release of previously sequestered Ag (DAMPs)
781
type I (immediate) hypersensitivity
mediated by IgE, results from actions of mast cell mediators
782
type II hypersensitivity
mediated Ab self-reacting with normal tissue, results from action of complement
783
type III hypersensitivity
mediated by circulating ICs that deposit in vessels, results from action of complement
784
type IV (delayed) hypersensitivity
mediated by T cells, results from action of inflammatory cytokines or killing of host cells
785
type I most often triggered by
environmental Ags
786
atopic disease
allergies
787
mast cell mediators: histamine
dilation of small vessels, vascular permeability
788
mast cell mediators: proteases
local tissue damage
789
mast cell mediators: prostaglandins
vascular dilation
790
mast cell mediators: leukotrienes
prolonged smooth muscle contraction
791
mast cell mediators: cytokines
induce local inflammation
792
why second exposure to allergen is more severe than first during type I hypersensitivity
plasma cells make IgE to allergen, IgE bound by RcRe/CD23 on mast cells
793
late-phase (2-24 hours after secondary exposure to allergen) mast cell response characterized by
inflammatory infiltrate rich in eosinophils, neutrophils, and T cells
794
asthma
local type I hypersensitivity reaction
795
asthma is the reversible bronchiole lumen obstruction caused by
action of mast that stimulate local airway inflammation and bronchospasm
796
anaphylaxis
systemic type I hypersensitivity reaction
797
positive allergen testing
redness and swelling within 20 to 30 minutes of exposure
798
allergen-specific immunotherapy (allergen-SIT)
only curative approach to allergic disease, administration of increasing doses of allergen
799
allergen-SIT
increase threshold for mast cell activation, generation of iTreg cells, production of greater proportion of IgG to distract allergen from IgE
800
type II hypersensitivity: IgG and IgM activate CP, resulting in
production of C3a and C5a for inflammation and neutrophil chemotaxis
801
type II hypersensitivity: phagocytosis induced by
FcRg or CR1 receptors on macrophages
802
type II hypersensitivity: ADCC induced by
FcRgIII on NK cells
803
Grave's disease
type II hypersensitivity, stimulate thyroid activity by Abs specific for TSH receptor, hyperthyroidism
804
Myasthenia gravis
type II hypersensitivity, inhibit acetylcholine signaling by Abs specific for AChR, muscle weakness and paralysis
805
hemolytic disease of the newborn: mother and fetus Rh phenotypes
related to type II hypersensitivity, mother Rh-negative, fetus Rh-positive
806
drug-induced immune hemolytic anemias (DIIHA)
related to type II hypersensitivity
807
DIIHA: penicillin-induced
hapten model, drug binds directly to RBC surface, hemolysis by complement or phagocytosis
808
DIIHA: quinidine-induced
IC formation model, ICs bind RBC surface through CR1, hemolysis by complement
809
DIIHA: methyldopa-induced
autoimmune model, methyldopa Ab cross-reacts with Rh Ag on RBC surface, hemolysis by phagocytosis
810
autoimmune hemolytic anemia
type II hypersensitivity, Rh and I blood group Ags on RBC surface, hemolysis by phagocytosis, anemia
811
autoimmune (idiopathic) thrombocytopenic purpura
type II hypersensitivity, gpIIb/IIIa integrin on RBC surface, hemolysis by phagocytosis, bleeding
812
Goodpasture's syndrome
type II hypersensitivity, complement targets non-collagenous basement membrane proteins of kidney glomeruli and lung, nephritis and lung hemorrhage
813
pemphigus vulgaris
type II hypersensitivity, epidermal cadherin, activation of proteases, skin vesicles (bullae)
814
pernicious anemia
type II hypersensitivity, gastric intrinsic factor, decreased absorption of B12
815
rheumatic fever
type II hypersensitivity, Abs produced against Streptococcal cell wall cross react with myosin, myocarditis and arthritis
816
systemic lupus erythematosus (SLE)
type III hypersensitivity, DNA and nucleoproteins, nephritis, arthritis, vasculitis
817
polyarteritis nodosa
type III hypersensitivity, often microbial Ags, vasculitis
818
post-streptococcal glomuronephritis
type III hypersensitivity, streptococcal cell wall Ag, nephritis
819
serum sickness (clinical and experimental)
type III hypersensitivity, various protein Ags, systemic vasculitis, nephritis, arthritis
820
arthus reaction (experimental)
type III hypersensitivity, SQ administration of protein Ag to previously immunized animal, local cutaneous vasculitis
821
how tissue injury occurs during type IV hypersensitivity
CD4 (Th1 and Th17) mediated inflammation, CD8 CTL mediated host cell killing
822
most important microbial trigger of type IV hypersensitivity
Mycobacterium tuberculosis
823
delayed type hypersensitivity (DTH)
type IV hypersensitivity related, mainly CD4 T cell mediated, develops 24-48 hours after Ag exposure
824
how humans may become sensitized to DTH reactions
previous TB infection or contact sensitization
825
purified protein derivative (PPD)
protein Ag of Mycobacterium tuberculosis used in DTH testing
826
allergic contact dermatitis (ACD)
type IV hypersensitivity related, results from DTH reactions
827
most common cause of ACD
metals (nickel and cobalt in costume jewelry, chromium in leather)
828
multiple sclerosis (MS)
type IV hypersensitivity, myelin proteins, sensory and motor dysfunction
829
rheumatoid arthritis (RA)
type IV hypersensitivity, unknown Ags in join, inflammation of synovium, erosion of cartilage and bone
830
type 1 diabetes mellitus (type I DM)
type IV hypersensitivity, pancreatic islet Ags, impaired glucose metabolism, vascular disease
831
inflammatory bowel disease (IBD, Chron's disease)
type IV hypersensitivity with microbial component, aberrant reaction to intestinal microflora, bowel wall inflammation, diarrhea, hemorrhage
832
contact sensitivity (poison ivy)
type IV hypersensitivity, modified skin proteins, DTH reaction in skin
833
chronic infection (TB)
type IV hypersensitivity with microbial component, chronic granulomatous inflammation
