Immunology Flashcards
1
Q
Positive selection location
A
thymic cortex
2
Q
Negative selection location
A
Thymic medulla
3
Q
MHC class II deficiency
A
/defect in development of CD4+ cells in the thymus. /no MHC class II so helper cells cannot be selected by positive selection mechanisms in the thymus but CD8 cytotoxic cells can be produced. /also known as type II bare lymphocyte syndrome.
4
Q
Positive selection mechanism
A
T cells expressing TCRs capable of binding self-MHC on cortical epithelial cells survive.
5
Q
Negative selection mechanism
A
T cells expressing TCRs with high affinity for self antigens undergo apoptosis. Tissue-restricted self-antigens are expressed in the thymus due to the action of autoimmune regulator (AIRE).
6
Q
Autoimmune polyendocrine syndrome-1
A
deficiency of negative selection.
7
Q
Lymph drainage of head and neck
A
cervical
8
Q
Mediastinal lymp nodes drain
A
trachea and esophagus
9
Q
Axillary lymph node drainage
A
Upper limb, breast, skin above umbilicus
10
Q
Celiac lymph node drainage
A
Liver + stomach + spleen + pancreas + upper duodenum
11
Q
Superior mesenteric lymph node drainage
A
lower duodenum + jejunum + ileum + colon to splenic flexure
12
Q
Inferior mesenteric lymph node drainage
A
Colon from splenic flexure to upper rectum
13
Q
Internal iliac drains
A
Lower rectum to anal canal (above pectinate line) + bladder + vagina (middle third) + cervix + prostate
14
Q
Para-aortic drains
A
testes + ovaries + kidneys + uterus
15
Q
Superficial inguinal node drains..
A
anal canal (below pectinate) + skin below umbilicus (except popliteal area) + scrotum + vulva.
16
Q
popliteal drains
A
dorsolateral foot + posterior calf
17
Q
thoracic duct drains into..
A
junction of left subclavian + internal jugular veins
18
Q
Function of medullary sinus of lymph node
A
Outside near capsule. Houses reticular cells and macrophages, which perform nonspecific filtration.
19
Q
Location of B-cells in lymph node
A
Outer cortex.
20
Q
lymph node follicle
A
Site of b-cell localization and proliferation
21
Q
Difference between primary follicles and secondary follicles.
A
Primary follicles are dense and dormant, secondary follicles are activated and have pale central germinal centers.
22
Q
Function of medulla of lymph node and composition
A
Consists of medullary cords and medullary sinuses.
23
Q
Medullary cords
A
Closely packed lymphocytes and plasma cells.
24
Q
medullary sinuses
A
Communicate with efferent lymphatics and contain reticular cells and macrophages.
25
Where are T cells located in lymph node?
paracortex
26
Paracortex
region between follicles and medulla. Contains high endothelial venules through which T and B cells enter from blood.
27
Sinusoids of spleen
Long, vascular channels in red pulp with fenestrated "barrel hoop" basement membrane.
28
Where are T cells found in the spleen?
periarteriolar lymphatic sheath (PALS) within the white pulp.
29
Where are B cells found in the spleen?
Follicles within the white pulp.
30
Marginal zone of spleen.
Zone between the red pulp and white pulp that contains macrophages and specialized B cells.
31
Marginal zone of spleen function
Where APCs capture blood-borne antigens for recognition by lymphocytes.
32
GBS encapsulated or nonecapsulated?
encapsulated
33
Mechanism for increased susceptibility to encapsulated organisms with splenic dysfunction
Decreased IgM --> decreased complement activation --> decreased C3b opsonization.
34
Postsplenectomy hematologic findings
1) Howell-Jolly bodies (nuclear remnants)
2) Target cells
3) Thrombocytosis (loss of sequestration and removal)
4) lymphocytosis (loss of sequestration).
35
Spleen follicle organization
Germinal center surrounded by mantle zone surrounded by marginal zone.
36
Thymus location
Anterosuperior mediastinum
37
Thymus organization
Cortex is dense with immature T cells; medulla is pale with mature T cells and Hassall corpuscles
38
Hassall corpuscles
Contain epithelial reticular cells
39
T cell and B cell origin
T cells = Thymus (mature in thymus, originate in bone marrow), B cells = Bone marrow.
40
Thymic hypertrophy seen in...
MG
41
Innate immunity components
Neutrophils, macrophages, monocytes, dendritic cells, NK cells (lymphoid origin), complement.
42
Mechanism of innate immunity
Germline encoded
43
What physical barriers does innate immunity have?
epithelial tight junctions + mucus
44
Proteins secreted by innate immunity
lysozyme, complement, CRP, defensins.
45
Key features of pathogen recognition in innate immunity
Toll-like receptors (TLRs).
46
TLRs
Pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs) (eg LPs, flagellin, nucleic acids (viruses))
47
Components of adapative immunity
T cells, B cells, circulating antibodies
48
MHC 1 loci
HLA-A, HLA-B, HLA-C (all have 1 letter)
49
MHC 1 expression
Expressed on all nucleated cells. Not expressed on RBCs.
50
MHC I vs. MHC II function
MHC 1 present endogenously synthesized antigens (eg viral or cytosolic proteins) to CD8+ T cells. MHC II prsent exogenously synthesized antigens (eg bacterial proteins to CD4+ helper T cells).
51
protein associated with MHC 1
Beta2-microglobulin
52
Antigen loading in MHC 1
Antigen peptides loaded onto MHC I in RER after delivery via TAP (transporter associated with antigen processing).
53
MHC II loci
HLA-DP, HLA-DQ, HLA-DR (all have 2 letters)
54
MHC II expression
Expressed on APCs
55
protein associated with MHC II
Invariant chain
56
Mechanism of MHC II
Antigen loaded following release of invariant chain in an acidified endosome.
57
HLA A3
hemochromatosis
58
Addison disease HLA association
B8
59
MG HLA association
B8
60
MS HLA association
DR2
61
RA HLA association
DR4
62
Addison's HLA association
DR3 + DR4
63
Hashimoto's HLA association
DR5
64
DM1 HLA association
DR3 + DR4
65
MS HLA association
DR2
66
Goodpasture's HLA association
DR2
67
SLE HLA association
DR2 + DR3
68
Pernicious anemia HLA association
DR5
69
Hay fever HLA association
DR2
70
Graves HLA association
DR3
71
NK cell mechanism
Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells
72
What enhances NK cell activity?
IL-2 + IL-12 + IFN-alpha + IFN-beta
73
What induces NK cells?
Exposure to a nonspecific activation signal on target cell and/or to an absence of class I MHC on target cell surface.
74
NK cell other mechanism
antibody-dependent cell mediated cytotoxicity
75
antibody-dependent cell mediated cytotoxicity mechanism
CD16 binds Fc region of bound Ig, activating NK cell
76
Process of B cell antigen specificity
somatic hypermutation
77
CD4+ vs. CD8+ cells
CD4 help b cells make antibodies and produce cytokines to recruit phagocytes and activate other leukocytes. CD8 directly kill virus-infected cells.
78
Where are mature and immature T cells found?
immature in cortex, mature in medulla.
79
What activates Th1 cells?
IL-12
80
What activates Th2 cells?
IL-4
81
What activates Th17 cells?
TGF-beta + IL-6
82
What are cytotoxic T cells activated by?
Th1 cells
83
What induces differentiation of Th1 cells?
IFN-gamma and IL-12
84
What inhibits TH1 cells?
IL-4 + IL-10 (from Th2 cell)
85
What do Th2 cells secrete?
IL-4, IL-5, IL-10, IL-13
86
Th2 cell function
Recruit eosinophils for parasite defense and promote IgE production by B cells
87
What induces differentiation of Th2 cells?
IL-4
88
What inhibits Th2 cells?
IFN-gamma from Th1 cells
89
macrophage-lymphocyte interaction mechanism
Macrophages and other APCs release IL-12, which stimulates T cells to differentiate into Th1 cells. Th1 cells release IFN-gamma to stimulate macrophages.
90
Cytotoxic T cell mechanism
1) kill virus-infected, neopalstic, and donor graft cells by inducing apoptosis.
2) release cytotoxic granules containing preformed proteins (eg perforin, granzyme B)
91
Regulatory T cell mechanism
Maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions.
92
Regulatory T cell markers
CD3, CD4, CD25, FOXP3
93
What do activated regulatory T cells produce?
anti-inflammatory cytokines (IL-10 + TGF-beta)
94
APCs
B cells + macrophages + dendritic cells
95
Caveat about T and B cell activation
Two signals are required for T-cell activation, B-cell activation, and class switching.
96
Naive T-cell activation
Dendritic cell samples and processes antigen --> dendritic cell migrates to draining lymph node --> T-cell activation (signal 1): antigen is presented on MHC II and recognized by TCR on Th (CD4+) cell. Endogenous antigen is presented on MHC I to Tc (CD8+) cell --> Proliferation and survival (signal 2): costimulatory signal via interaction of B7 proteins (CD80/86) and CD28 --> Th cell activates and produces cytokines. Tc cell activates and is able to recognize and kill virus-infected cell.
97
B-cell activation and class switching mechanism
1. Th-cell activation.
2. B-cell receptor-mediated endocytosis; foreign antigen is presented on MHC II and recognized by TCR on Th cell.
3. CD40 receptor on B cell binds CD40 ligand (CD40L) on Th cell.
4. Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates and undergoes class switching, affinity maturation, and antibody production.
98
Fab
region of antibody containing variable/hypervariable regions.
99
What fixes comploment
Fc region of IgM and IgG
100
Idiotype
unique antigen-binding pocket; only 1 antigenic specificity expressed per B cell.
101
carbohydrate side chains
Expressed on Fc region
102
What determines isotype (IgM, IgD, etc)?
Fc region
103
neutralization
Antibody binding and preventing bacterial adherence.
104
VJ
light-chain genes
105
V(D)J
heavy-chain genes
106
How is antibody diversity generated?
1) Random recombination of VJ (light-chain) or V(D)J (heavy-chain) genes.
2) random addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase (TdT)
3) Random combination of heavy chains with light chains
107
How is antibody specificity achieved?
1) Somatic hypermutation and affinity maturation (variable region)
2) Isotype switching (constant region)
108
Affinity maturation mechanism
Process by which Th cell-activated B cells produce antibodies with increased affinity for antigen. With repeated exposures to the same antigen, host produces antibodies of successively greater affinities.
109
Immunoglobulins expressed on mature, naive B cells prior to activation...
IgM and IgD
110
What mediates isotype switching?
CD40L and cytokines
111
Immunoglobulin responsible for neutralizing bacterial toxins and viruses
IgG
112
Main antibody in secondary (delayed) response to an antigen
IgG
113
Which immunoglobulins have J chains?
IgA and IgM
114
IgA in circulation
Exists as a monomer
115
How does IgA cross epithelial cells?
Transcytosis
116
IgA caveat
Most produced antibody overall, but has lower serum concentrations.
117
What contains IgA
Tears, saliva, mucus, and breast milk.
118
What is secretory component?
Portion of IgA that IgA picks up from epithelial cells, and which protects Fc portion from luminal proteases.
119
What is produced in the immediate response to an antigen?
IgM
120
IgM forms
Monomer on B cell, pentamer with J chain when secreted.
121
Why does IgM exist as a pentamer?
Pentameric form enables avid binding to antigen while humoral response evolves.
122
IgD
Unclear function. Found on surface of many B cells and in serum.
123
What immunoglobulin has the lowest concentration in serum?
IgE
124
Thymus-independent antigens
Antigens lacking a peptide component. Thus, they can't be presented by MHC to T cells and are weakly immunogenic.
125
Example of thymus-independent antigen
LPS
126
Critical function of CD40L
Class-switching. Expressed on helper T cells
127
What activates acute-phase reactants?
IL-6
128
What produces acute-phase reactants
liver
129
CRP function
Opsonin; fixes complement and facilitates phagocytosis
130
CRP clinical significance.
Sign of ONGOING inflammation.
131
Function of ferritin
Binds and sequesters iron to inhibit microbial iron scavenging.
132
Functions of fibrinogen
1) coagulation factor
2) promotes endothelial repair
3) correlates with ESR.
133
Function of hepcidin
1) decreases iron absorption (by degrading ferroportin)
2) decreased iron release (from macrophages)
*
134
anemia of chronic disease mechanism
Increased hepcidin due to chronic inflammation.
135
Serum amyloid A
acute phase reactant
136
Transferrin mechanism
Internalized by macrophages to sequester iron.
137
Why is albumin downregulated with inflammation?
Reduction conserves amino acids for positive reactants.
138
MAC target
gram negative bacteria
139
What activates classic complement pathway?
IgG or IgM
140
What activates alternative complement pathway?
Microbe surface molecules
141
What activates Lectin complement pathway?
Mannose or other sugars on microbe surface
142
complement proteins involved in anaphylaxis
C3a, C4a, C5a
143
MAC components
C5b-9
144
C3b functions
1) opsonin
| 2) clears immune complexes
145
Primary opsonins in bacterial defence
C3b and IgG
146
What prevents complement activation of self cells?
1) decay-accelerating factor (DAF, aka CD55)
| 2) C1 esterase inhibitor
147
C1 esterase inhibitor deficiency mechanism
unregulated activation of kallikrein leads to increased bradykinin
148
DAF deficiency
Causes complement-mediated lysis of RBCs and PNH
149
Other name for IL-1
Osteoclast-activating factor
150
Il-1 functions
1) causes fever, acute inflammation
2) activates endothelium to express adhesion molecules
3) induces chemokine secretion to recruit WBCs
151
IL-6 functions
1) fever
| 2) stimulates production of acute-phase proteins
152
IL-12 functions
1) Induces differentiation of T cells into Th1 cells
| 2) activates NK cells
153
TNF-alpha functions
1) sepsis
2) activates endothelium
3) causes WBC recruitment
4) vascular leak
154
Cytokines secreted by macrophages
1,6,8,12,TNF-alpha
155
cytokines secreted by all T cells
IL-2 and IL-3
156
IL-2 functions
Stimulates growth of helper, cytotoxic, and regulatory T cells, and NK cells
157
IL-3 functions
- Supports growth and differentiation of bone marrow stem cells.
- Functions like GM-CSF
158
What secretes interferon-gamma
NK cells and Th1 cells in response to Il-12 from macrophages
159
Interferon-gamma functions
1) stimulates macrophages to kill pathogens
2) inhibits differentiation of Th2 cells
3) activates NK cells to kill virus-infected cells.
4) Increases MHC expression and antigen presentation by all cells.
160
cytokines secreted by Th2 cells
Il-4,5, and 10
161
IL-4 functions
1) induces differentiation of T cells into Th2 cells
2) promotes growth of B cells
3) enhances class switching to IgE
162
IL-5 functions
1) promotes growth and differentiation of B cells
2) enhances class switching to IgA
3) stimulates growth and differentiation of eosinophils
163
IL-10 functions
1) attenuates inflammatory response
2) decreases expression of MHC class II and Th1 cytokines
3) inhibits activated macrophages and dendritic cells
164
What is responsible for attenuating the immune response?
TGF-beta and IL-10
165
NADPH functions
Creation AND neutralization of ROS.
166
NADPH oxidase mechanism
Utilizes NADPH to generate oxygen anions
167
Lactoferrin
Protein found in secretory fluids and neutrophils that inhibits microbial growth via iron chelation.
168
Pyocyanin
enzyme in Pseudomonas that generates ROS to kill competing microbes
169
Interferons
Glycoproteins synthesized by virus-infected cells that act locally on uninfected cells, priming them for viral defense by helping to selectively degrade viral nucleic acid and protein.
170
Proteins found on T cells
1) TCR
2) CD3
3) CD28
4) CXCR4/CCR5
171
CD3 function
Associated with TCR for signal transduction.
172
CD28 function
Binds B7 on APC.
173
Regulatory T cell markers
CD4, CD25
174
B cell markers
1) Ig
2) CD19,20,21,40
3) MHC II
4) B7
175
Ig function
Protein expressed on B cells that binds antigen.
176
Proteins expressed on macrophages
1) CD14
2) CD40
3) CCR5
4) mHC II
5) B7 (CD80/86)
6) Fc and C3b receptors
177
CD14 function
receptor for PAMPs
178
NK cell markers
1) CD16
| 2) CD56 (unique marker for NK)
179
CD16 on NK cells functions
Binds Fc of IgG
180
Costimulatory signal
T and B cells need 2 signals to become activated. This is a safety mechanism of self-tolerance.
181
Superantigen mechanism
Cross-link Beta region of T-cell receptor to MHC class II on APCs. Can activate any CD4+ T cell --> massive cytokine release.
182
Endotoxins/LPS mechanism
Directly stimulate macrophages by binding to endotoxin receptor TLR4/CD14. No Th cells involved.
183
bacterial examples of antigenic variation
1) salmonella
2) borrelia recurrentis
3) N gonorrhoeae
184
viral examples of antigenic variation
1) influenza
2) HIV
3) HCV
185
parisitic examples of antigenic variation
trypanosomes
186
half-life of antibodies
3 weeks
187
When are patients given preformed antibodies (which bugs?)?
"To Be Healed Very Rapidly"
| Tetanus, Botulinium, HBV, Varicella, Rabies
188
When are combined passive and active immunizations needed?
Hep B + rabies exposure
189
Only live attenuated vaccine given to HIV patients
MMR
190
Live attenuated vaccine mechanism
organism loses its pathogenicity but retains capacity for transient growth within inoculated host.
191
Live attenuated vaccine pros/cons
Pro: induces strong, often lifelong immunity.
Con: can revert to virulent form.
192
hep A vaccine: live or killed?
killed
193
polio (salk) vaccine: live or killed?
killed
194
BCG: vaccine: live or killed?
live
195
varicella vaccine: live or killed?
live
196
yellow fever vaccine: live or killed?
live
197
measles vaccine: live or killed?
live
198
Rabies vaccine: live or killed?
killed
199
influenza injection vaccine: live or killed?
killed
200
mumps vaccine: live or killed?
live
201
rubella vaccine: live or killed?
live
202
polio (sabin) vaccine: live or killed?
live
203
site of action of histamine
postcapillary venules
204
Type I hypersensitivity mechanism and delayed response.
1) Preformed antibodies on mast cells or basophil (IgE) are cross-linked with free antigens.
2) Delayed response follows due to production of archidonic acid metabolites (eg, leukotrienes).
205
Type II mechanisms
1) opsonization and phagocytosis
2) Complement- and Fc receptor-mediated inflammation
3) Antibody-mediated cellular dysfunction
206
Direct Coombs test
Detects antibodies that have adhered to patient's RBCs (eg test Rh+ infant of an Rh- mother)
207
Indirect coombs test
Detects serum antibodies that can adhered to other RBCs (test an Rh negative woman for Rh positive antibodies)
208
Acute hemolytic transfusion reaction hypersensitivity type
Type II
209
AIHA hypersensitivity type
Type II
210
Type III hypersensitivity mechanism
Immune complexes activate complement, which attracts neutrophils; neutrophils release lysosomal enzymes.
211
Polyarteritis nodosa hypersensitivity type
Type III
212
Serum sickness mechanism
Antibodies to foreign proteins are produced. Immune complexes form and are deposited in membranes, where they fix complement, leading to tissue damage. Usually due to drugs acting as haptens.
213
serum sickness presentation
Fever + urticaria + arthralgia + proteinuria + lymphadenopathy
214
test for arthus reaction
immunofluorescent staining
215
Arthus reaction mechanism
Local subacute antibody-mediated. Intradermal injection of antigen into presensitized (already has circulating IgG) individual leads to immune complex formation in skin.
216
Arthus reaction presentation
edema + necrosis + complement activation.
217
Type IV mechanism
1) Sensitized T cells encounter antigen and release cytokines, leading to macrophage activation.
2) Response does not involve antibodies.
218
Type IV caveat
Not transferable by serum since cell mediated.
219
Transplant rejections hypersensitivity type
Type IV
220
Febrile nonhemolytic transfusion reaction mechanism
Type II hypersensitivity reaction. Host antibodies against donor HLA antigens and WBCs
221
Febrile nonhemolytic transfusion reaction presentation
Fever + headaches + chills + flushing
222
Acute hemolytic transfusion reaction mechanism
Type II hypersensitivity reaction. Intravascular hemolysis (ABO blood group incompatibility) or extravascular hemolysis (host antibody reaction against foreign antigen on donor RBCs).
223
Acute hemolytic transfusion reaction presentation
Fever + hypotension + tachypnea + tachycardia + flank pain + hemoglobinuria + jaundice (extravascular)
224
hemoglobinuria
intravascular hemolysis
225
Intravascular hemolysis
breakdown of RBCs in blood vessels
226
extravascular hemolysis example
host antibody reaction against foreign antigen on donor RBCs
227
drug-induced lupus antibody
anti-histone
228
autoantibodies in polymyositis, dermatomyositis
Anti-Jo-1 + anti-SRP + anti-Mi-2
229
primary membranous nephropathy autoantibody
antiphospholipase A2 receptor
230
scleroderma autoantibody
Anti-Scl-70 (anti-DNA topoisomerase I)
231
Autoimmune hepatitis type I autoantibody
anti-smooth muscle
232
anti-SSA
anti-Ro
233
anti-SSB
anti-La
234
celiac disease autoantibodies
IgA anti-endomysial + IgA anti-tissue transglutaminase
235
p-ANCA also known as
MPO-ANCA
236
c-ANCA also known as
PR3-ANCA
237
Other impt findings in bruton's
Absenct/scanty lymph nodes and tonsils
238
Bruton's gene mutation
BTK (tyrosine kinase)
239
Bruton's presentation
Recurrent bacterial and enteroviral infections after 6 months (after maternal IgG declines).
240
Most common primary immunodeficiency
Selective IgA deficiency
241
CVD etiology
defect in B-cell differentiation
242
term for cardiac defects in DiGeorge
Conotruncal abnormalities
243
How do you test for 22q11 deletion?
FISH
244
Immunodeficiency that prevents after adiminstration of BCG vaccine...
IL-12 receptor deficiency
245
IL-12 receptor deficiency etiology
decreased Th1 response
246
Labs in IL-12 receptor deficiency
decreased IFN-gamma
247
hyper-IgE syndrome etiology
Deficiency of Th17 cells due to STAT3 mutation, leading to impaired recruitment of neutrophils to sites of infection.
248
labs in hyper-IgE
Increased IgE + decreased IFN-gamma
249
hyper-IgE presentation
Coarse facies, cold (noninflammed) staphylococcal abscesses, retained primary teeth, eczema.
250
SCIDs etiology
either
1) Defective IL-2R gamma chain (x-linked)
OR
2) adenosine deaminase deficiency (AR)
251
Findings in SCIDS
1) Decreased T-cell receptor excision circles (TRECs)
2) absence of thymic shadow on CXR
3) absence of germinal centers
4) absence T cells on flow cytometry.
252
Findings in ataxia-telangiectasia
1) increased AFP
2) decreased IgA, IgG, and IgE
3) lymphopenia
4) cerebellar atrophy
253
Hyper-IgM inheritance
X-linked recessive
254
pathogens in Hyper-IgM
pneumocystis + cryptosporidium + CMV
255
gene mutation in Wiskott-Aldrich syndrome
WAS gene
256
Wiskott-Aldrich syndrome etiology
T cells unable to reorganize actin cytoskeleton.
257
lab findings in Wiskott-ALdrich
- decreased to normal IgG, IgM
- Increased IgE, IgA
- fewer and smaller platelets
258
Wiskott-aldrich association
Increasedd risk of autoimmune disease and malignancy.
259
Chediak-Higashi defect and etiology
- Defect in lysosomal trafficking regulator gene (LYST).
| - Microtubule dysfunction in phagosome-lysosome fusion.
260
Chediak higashi presentation
1) Recurrent pyogenic infections by staphylococci and streptococci.
2) Partial albinism
3) peripheral neuropathy
4) progressive neurodegeneration
5) infiltrative lymphohistiocytosis.
261
Findings in Chediak Higashi
1) Giant granules in granulocytes and platelets
2) pancytopenia
3) mild coagulation defects
262
another name for flow cytometry
dihyrorhodamine test
263
Catalase positive organisms
```
Nocardia
Pseudomonas
Listeria
Aspergillus
Candida
E coli
Staphylococci
Serratia
B cepacia
H pylori
```
264
Increased risk for... with deficiency in early complement
Encapsulated species.
265
T cell deficiency leads to increased risk of...
sepsis
266
bacterial infections with decreased granulocytes (neutropenia)
```
Staphylococcus
Burkholderia
Pseudomonas
Serratia
Nocardia
```
267
viral infections in B cell deficiency
Enteroviral encephalitis
| Poliovirus (live vaccine contraindicated)
268
Fungal infections in granulocyte deficiency (neutropenia)
Systemic candida
| Aspergillus
269
granulocytes
cells containing granules. Basophils, eosinophils, neutrophils.
270
Syngeneic graft (isograft)
Graft from identical twin or clone
271
Hyperacute graft rejection onset
within minutes
272
Hyperacute graft rejection pathogenesis
Pre-existing recipient antibodies react to donor antigen, activating complement.
273
Hyperacute graft rejection features
Widespread thrombosis of graft vessels --> ischemia/necrosis.
274
Acute graft rejection timeframe
Weeks to months
275
Acute graft rejection pathogenesis
Cellular: CD8+ T cells activated against donor MHcs (type IV
Humoral: similar to hyperacute, except antibodies develop after transplant.
276
Acute graft rejection features
Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
277
Chronic graft rejection timeframe
Months to years
278
Chronic graft rejection pathogenesis
CD4+ T cells respond to recipient APCs presenting donor peptides, including allogeneic MHC.
Both cellular and humoral components (type II and IV)
279
Chronic graft rejection features
Recipient T cells react and secrete cytokines --> proliferation of vascular smooth muscle + parenchymal atrophy + interstitial fibrosis + ateriosclerosis.
280
Lung chronic rejection disease
bronchiolitis obliterans
281
heart chronic rejection disease
accelerated atherosclerosis
282
kidney chronic rejection
chronic graft nephropathy
283
liver chronic rejection disease
vanishing bile duct syndrome
284
GVHD pathogenesis
Grafted immunocompetent T cells proliferate in immnocompromised host and reject host cells, leading to severe organ dysfunction.
285
When does GVHD usually occur?
Bone marrow and liver transplants (rich in lymphocytes)
286
When can GVHD be beneficial?
Potentially beneficial in bone marrow transplant for leukemia (graft-versus-tumor effect).
287
Cyclosporine uses
1) transplant rejection prophylaxis
2) psoriasis
3) RA
288
cyclosporine mechanism
Calcineurin inhibitors; binds CYCLOphilin.
| Blocks T-cell activation by preventing IL-2 transcription.
289
cyclosporine toxicity
nephrotoxic + HTN + hyperlipidemia + neurotoxicity + gingival hyperplasia + hirsitusm
290
Tacrolimus MOA
- Calcineuron inhibitor; binds FK506 binding protein FKBP.
| - Blocks T-cell activation by preventing IL-2 transcription.
291
Tacrolimus SE's
Increased risk of diabetes + neurotoxicity + highly nephrotoxic.
292
Sirolimus aka
Rapamycin
293
Sirolimus MOA
mTOR inhibitor; binds FKBP. Blocks T-cell activation and B-cell differentiation by preventing response to IL-2.
294
Sirolimus toxicity
Pancytopenia + insulin resistance + hyperlipidemia.
295
daclizumab, basiliximab SE's
Edema + HTN + tremor
296
Azathioprine MOA
antimetabolite precursor of 6-mercaptopurine.
| - Inhibits lymphocyte proliferation by blocking nucletoide synthesis.
297
Azathioprine uses
1) Transplant rejection prophylaxis
2) RA
3) Crohn's
4) glomerulonephritis
5) other autoimmune conditions
298
azathioprine SE's
leukopenia + anemia + thrombocytopenia
299
azathioprine contraindication
Allopurinol.
300
Other use for mycophenolate mofetil
lupus nephritis
301
mycophenolate mofetil association
Invasive CMV infection
302
mycophenolate mofetil SE's
GI upset + pancytopenia + HTN + hyperglycemia. Less nephrotoxic and neurotoxic.
303
corticosteroid immunosuppression mechanism
1) Inhibit NF-kB.
2) Suppress both B- and T-cell function by decreasing transcription of many cytokines.
3) Induce apoptosis of T lymphocytes.
304
Calcineurin action
NFAT-P--> NFAT, which is a TF
305
aldesleukin
IL-2
306
aldesleukin clinical uses
RCC + metastatic melanoma
307
Filgrastim
G-CSF
308
Sargramostim
GM-CSF
309
IFN-alpha uses
Chronic hep B and C, Kaposi sarcoma, malignant melanoma
310
Romiplostim, etrombopag
Thrombopoietin receptor agonists
311
Oprelvekin
IL-11
312
alemtuzumab clinical use
CLL + MS
313
bevacizumab clinical uses
CRC + RCC + mac degen
314
cetuximab target
EGFR
315
cetuximab uses
Stage IV CRC + head and neck cancer
316
Rituximab target
CD20
317
Rituximab uses
B-cell non-Hodgkin lymphoma + CLL + RA + ITP
318
certolizumab target
soluble TNF-alpha
319
etanercept MOA
decoy TNF-alpha receptor. NOT a monoclonal antibody.
320
Eculizumab clinical use
Paroxysmal nocturnal hemoglobinuria
321
Alpha4-integrin mechanism
WBC adhesion
322
abciximab target
IIb/IIIa
323
denosumab mechanism
inhibits osteoclast maturation
324
omalizumab target
IgE
325
palivizumab target
RSV F protein
326
monocytes
differentiate into macrophages, dendritic cells, and foam cells
