Immuno/Path Flashcards
1
Q
What is central tolerance?
A
elimination of self reactive T and B cells during development in thymus or bone marrow
2
Q
What is peripheral tolerance?
A
after the lymphocyte has left bone marrow or thymus and encounters self antigen
3
Q
What are the mechanisms of T cell central tolerance?
A
if they react they will undergo apoptosis (negative selection) or become Treg cells
4
Q
What is the significance of AIRE?
A
transcription factor that regulates expression of peripheral proteins in the thymus-allows T cells to see peripheral antigens within the thymus
5
Q
What are the possible outcomes of central tolerance for a T cell?
A
positive selection-recognize MHC
negative selection-too much recognition
apoptosis-no recognition
6
Q
What happens when AIRE is defective?
A
APS-T cells that interact escape into circulation
presents with musculocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency
7
Q
What are Treg cells?
A
most are CD4 T cells
inhibit activation of CD4 and CD8 T cells by producing IL-10 and CTLA-4
8
Q
What do Treg cells express?
A
CD25
transcription factor Foxp3
9
Q
What results from mutations to Foxp3?
A
IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X linked syndrome)
10
Q
What can happen in peripheral T cell tolerance?
A
anergy-functional unresponsiveness
deletion through apoptosis
suppression by Treg cells
11
Q
How does anergy happen?
A
lack of costimulation (problem in second signal of B7 and CD28)
inhibitory receptors-CTLA4
12
Q
Where is CTLA4 expressed?
A
always on Treg cells
on cytotoxic T cells after activation-off switch
13
Q
How can a self reactive T cell undergo apoptosis?
A
poor costimulation can cause leak of mitochondrial proteins-cytochrome c to activate caspases
Fas/FasL interaction
14
Q
How do Treg cells inhibit activation of T cells?
A
Tregs grow in response to IL2
Tregs produce IL-10, TGF beta, express CTLA-4, and consume IL2 so it is unavailable for effector T cells
15
Q
What can happen in B cell central tolerance?
A
edit receptors-efficient
apoptosis
16
Q
How does B cell receptor editing occur?
A
reactivate RAG genes
resume light chain recombination, same heavy chain is expressed
strictly a B cell phenomenon
17
Q
How do B cells become anergic in the peripheral tissues?
A
no interaction between CD40 and CD40L
18
Q
How do we tolerate commensal microbes?
A
physical barrier
Treg cells
CD103+ DC promote Treg cells fr sampling
IL-10 secretion
19
Q
How does a mother tolerate the fetus?
A
placental barrier
Treg cells
exclusion of inflammatory cells from uterus
poor antigen presentation in uterus
20
Q
What HLA is associated with MS?
A
DR2
21
Q
What HLA is associated with lupus?
A
DR2/DR3
22
Q
What HLA is associated with T1DM?
A
DR3/DR4
23
Q
What HLA is associated with rheumatoid arthritis?
A
DR4
24
Q
What HLA is associated with anklosing spondylitis?
A
B27 (Reiters also-can’t pee, can’t see, can’t climb a tree)
25
What is NOD2 associated with?
Chrons
26
What are defects in C2, C4 associated with?
SLE
27
What are defects in FAS associated with?
ALPS
28
What are the environmental factors that can trigger autoimmune syndromes?
```
infection
drugs
stress
chemicals
diet
hormones
```
29
How does infection promote autoimmunity?
molecular mimicry
release of sequestered antigens
bystander activation
30
What is molecular mimicry?
microbes may carry elements similar in structure to self antigens
activated B and T cells cross react to self
31
What is bystander activation?
infection causes nonspecific activation of surrounding lymphocytes (self reactive T cells that have not gone through peripheral tolerance are activated)
32
How does ankylosing spondylitis present?
young man with sacroiliac inflammation
| axial spine-fusion of vertebra
33
How does SLE present?
usually in women
autoantibodies and immune complexes (type III hypersensitivity) deposit in tissues
ANA-antinuclear antibody (sensitive not specific)
34
How does rheumatoid arthritis present?
rheumatoid factor positive
| DIPS are not swollen but PIPs and MCPs are
35
How does myasthenia gravis present?
autoantibody to acetylcholine receptor
| eyelid drooping that gets worse with exertion
36
How does Graves disease present?
prominent eyes, hyperthyroidism
| elevated T4, low TSH
37
How does scleroderma present?
heartburn and tight skin on face and hands
T cell stimulated collagen synthesis
CREST syndrome (calcinosis, raynauds, esophageal dysfunction, sclerodactylyl, telangiectasia)
38
How does MS present?
urinary incontinence, sensory loss, blurry vision
MRI with multiple lesions
demyelination of brain and spinal cord
39
How does T1DM present?
increased thirst and urination
| autoreactive CD8 cells destroy pancreatic Beta cells resulting in inability to produce insulin
40
What are the possible therapies for autoimmune diseases?
steroid-prednisone
antimetabolities-methotrexate
monoclonal antibodies-adalimumab (TNF inhibiting antibody)
41
What is the difference between fibrosis and repair/regneration?
Fibrosis occurs after persistent tissue damage
42
What occurs in labile tissue?
constant active self renewal
43
What occurs in stable tissue?
low level of renewal but has capacity to replace
44
What occurs in permanent tissue?
no capacity to replace cells
45
What role do macrophages play in repair?
secrete VEGF, FGF-2, PDGF for angiogenesis
chemotaxis for fibroblasts through PDGF, TGF beta, TNF, IL-1, KGF-7
deposition and remodeling of ECM through collagenase, MMPs, OPN, TNF, PDGF, TGF beta
46
What is the function of epidermal growth factor?
mitogenic for keratinocytes and fibroblasts; stimulates formation of granulation tissue
47
What is the function of TGF alpha?
stimulates proliferation of hepatocytes and other epithelial cells
48
What is the function of VEGF?
increases vascular permeability; stimulates endothelial cell proliferation
49
What is the function of PDGF?
chemotactic for neutrophils, macrophages, fibroblasts and smooth muscle cells; activates proliferation of fibroblasts, endothelial cells
50
What is the function of TGF-beta?
chemotactic for leukocytes and fibroblasts; suppresses acute inflammation
51
What are the steps in scar formation?
inflammation
formulation of granulation tissue
ECM deposition and remodeling
52
How does collagen differ in granulation tissue and a mature scar?
Type III in granulation
| Type I in mature scar
53
How does first intention differ from second intention?
Minimal damage in first intention (edges of skin together vs gaping hole in second intention)
54
When does collagen deposition start?
3-5 days
55
What is responsible for wound contraction?
myofibroblasts
56
What systemic factors influence wound healing?
vitamin C deficiency
poor perfusion-atherosclerosis
glucocorticoids (inhibit TGF-beta)-->can be prescribed to decrease collagen deposition
57
What is the most important growth factor in fibrosis?
TGF beta
| fibroblast migration and proliferation, angiogenesis and increased collagen and fibronectin production
58
What local factors can influence wound healing?
infections
mechanical factors-increased local pressure
size, location and type of wound
59
What causes a keloid?
excessive collagen formation
60
What is dehiscence?
inadequate granulation tissue
| leads to ruptures of wound, common after abdominal surgery
61
What happens in excessive contraction?
contraction of skin
| common in palms, soles, thorax in burn patients
62
What happens in exuberant granulation?
more granulation tissue than needed
63
What are desmoids?
fibrous overgrowths of dermal and subcutaenous connective tissue
64
What are immunodeficiencies impair maturation?
SCID
X linked agammaglobulinemia
DiGeorge
65
What immunodefieicines impair activation and function?
X linked hyper IgM syndrome
common varaible immunodeficiency
bare lymphocyte syndrome
66
What immunodeficiencies are defects in innate immunity?
chronic granulomatous disease
leukocyte adhesion deficiency
complement deficiencies
Chediak-Higashi syndrome
67
What are lymphocyte abnormalities associated with other diseases?
Wiskott Aldrich syndrome
| Ataxia-telangiectawsia
68
Histologically where will T and B cell deficiencies be seen?
T-paracortex
| B-germinal centers
69
What are characteristics of all immunodeficiencies?
increased susceptibility to newly acquired infections
reactivation of latent infections
increased incidence of cancers
70
What is the definition of SCID?
Decreased T cell
71
What is the mechanism of defect in X linked SCID?
mutation in gamma common chain; no IL-7 for maturation of T cells; no IL-15 for NK cells
72
What are some causes of autosomal recessive SCID?
IL-7R signaling, defect in RAG genes, missing JAK3
73
What does the common gamma chain act as a signal receptor for?
IL2, 4, 7, 9, 11, 15, 21
74
What is the most common AR SCID?
ADA deficiency
| leads to accumulation of dATP
75
What accumulates in PNP deficiency?
dGTP
76
How can SCID be treated?
stem cell transplant
| gene therapy-most successful against ADA deficiency
77
What virus is now used as a viral vector for gene therapy? What are the dangers?
lentivirus
| fear of inserting near oncogene and activating cancer
78
What happens in Bruton's agammaglobulinemia?
```
mutation in Bruton tyrosine kinase
inability of preB cells to develop into mature B cells
usually diagnosed at 6 months
absence of Ig classes
treated with gamma globulin injections
no CD19 B cells in peripheral blood
```
79
What causes DiGeorge syndrome?
dysmorphogenesis of third and fourth pharyngeal pouches
aplasia of thymus and parathyroid, facial and heart abnormalities
present with neonatal tetany
22q11 deletion
associated with schizophrenia and bipolar disorder
80
What happens in X-linked hyper IgM syndrome?
mutation in CD40L
absence of CD40L on T cells-no class switching
high levels of IgM
81
What happens in IgA deficiency?
most common
no IgA secreting plasma cells-low IgA
can be asymptomatic or have recurrent infections and diarrhea
82
What happens in common variable immunodeficiency?
failure of B cells to mature into plasma cells
low serum IgA and IgG, normal IgM
respiratory and GI infections with pyogenic bacteria
83
What is the triad associated with Wiskott Aldrich syndrome?
thromocytopenia
eczema
recurrent bacterial infections
84
How does ataxia telangiectasia present?
neuro-staggering
abnormal dilation of vaculature
defects for T and B cells
low IgA and IgG
85
What happens in leukocyte adhesion deficiency?
defect in adhesion (selectin ligand or beta chain of integrin)
poor recruitment
infections without pus formation
86
What happens in Chediak-Higashi syndrome?
giant cytoplasmic granules (defect in cytoskeleton so lysosomes and phagosomes cannot fuse)
cannot kill bacteria
87
What happens in chronic granulomatous disease?
defective production of ROI
| test with nitroblue tetrazolium test
88
What does the nitroblue tetrazolium test demonstrate?
respiratory burst
89
What do complement deficiencies present with?
C1/C3-infections with encapsulated organisms
C2/C4-SLE
C5-C9-Neisseria
90
What is hereditary angioedema?
deficiency in C1 inhibitor
| results in excessive C4 and C2 activation and localized edema
91
What is paroxysmal nocturnal hemoglobulinemia?
Deficiency in DAF
host cells not protected from complement activation
intravascular hemolysis-occurs at night as pH drops
92
What can cause secondary immunodeficiencies besides AIDS?
protein calorie malnutrition
cancer-bone marrow tumors
measles-infect lymphocytes
herpes can secrete proteins like IL10
Trypanosoma cruzi-reduced IL2 receptors
absence of spleen-increased susceptibility to encapsulated bacteria
drugs-immunosupprssive, anti-inflammatory
93
What is physiologic hypogammaglobulinema?
neonate protection from IgG because development of Th1 and CD8 T cell responses are delayed
94
What is transient hypogammaglobulinemia of infancy?
prolongation of physiologic hypogammaglobulinemia
may take 2-4 years
2 standard deviations below IgG
95
What is immunosenescence?
impaired ability to respond to new antigens in the elderly
unsustained memory response
results-increased infection, cancer, autoimmune diseases
96
What are the possible laboratory tests for diagnosing immunodeficiencies?
```
lymphocyte counts and morphology
flow cytometry
serum protein electrophoresis
Ig levels
antibody response to immunization
DTH skin testing
T cell proliferation assays
cytokine assays
```
97
What are some examples of tumor antigens?
products of mutated oncogenes or tumor suppressor genes
mutated forms of cellular genes
normal proteins over expressed in tumor cells
products of oncogenic viruses
oncofetal antigens-fetal development proteins
glycolipids and glycoproteins
98
What are examples of mutated forms of cellular genes?
BCR/ABL
RAS
mutated p53
99
What are examples of cellular proteins that undergo abnormal expression?
proteins expressed in gametes and trophoblasts
| Her2/Neu
100
What are examples of antigens expressed from oncogenic viruses?
E6 and E7 of HPV in cervical carcinomas
| EBNA-1 of EBV
101
What are examples of oncofetal antigens?
CEA-carcinoembryonic antigen
| alpha-fetoprotein
102
What are some altered glycoproteins?
gangliosides expressed in high levels in neuroblastomas, melanomas, and sarcomas
103
What are some tissue specific antigens?
PSA-prostate specific antigen
| CD20 on B cell lymphomas
104
What is the innate anti-tumor immunity?
NK cells-kill tumors that decrease expression of MHC I if activated by NK cells
Macrophages-M1 kill tumor cells (IFN gamma necessary)
M2 may contribute to tumor progression
105
What is the adaptive anti-tumor immunity?
CD8 cells-surveillance, require cross priming by DC
106
What is cross priming?
Activation of naive CD8 T cells by APCs that acquire antigens from another cell
107
How do tumors evade the immune system?
intrinsic mechanisms
extrinsic mechanisms
myeloid-derived suppressor cells
108
What are the extrinsic methods to suppress the immune system?
TAM=promote tumor growth
M2 impair T cell activation
Treg may suppress T cell responses to tumors
109
What are the intrinsic methods to evade the immune system?
tumors lose expression of immunogenic antigens
inaccessible to immune system-expressing glycocalyx to mask immune epitopes
TGF beta and PDL1 inhibit immune system
FasL to stimulate WBC apoptosis
110
How do myeloid derived cells suppress the immune system?
Immature cells leave bone marrow and induce development of Tregs, skew T helper towards Th2, and dampen chronic inflammation
111
What are the different types of tumor vaccines?
```
killed tumor vaccine
purified tumor antigens
dendritic cell vaccines
cytokine and costimulator enhanced vaccines
DNA vaccines
viral vectors
```
112
How are dendritic cell vaccines made?
pulsed with Ag and then transfect DC with Ag genes
113
What is adoptive cellular therapy?
reinfuse IL-2 activated host PBMCs
114
What are lymphokine-activated killer cells?
NK cells that are expanded and gain enhanced tumor killing activity by in vitro culture with IL2
115
What are tumor infiltrating lymphocytes?
lymphocytes expanded in vitro culture with tumor cells and IL-2 enriched
116
What are some monoclonal antibodies?
Anti-Her2Neu
| Anti-CD20
117
How does the immune system contribute to tumor growth?
chronic inflammation-risk factor for tumors
| TAMs (tumor associated macrophages) can produce VEGF, MMP, and growth factors to help tumors grow
118
Why do we vaccinate?
protection
stronger and faster immune response through memory immune response
decrease the number of susceptible hosts-herd immunity
119
What are properties of a good candidate for vaccine development?
organism causes significant illness
only one serotype
antibody blocks infection or systemic spread
organism does not have strong oncogenic potential
vaccine is heat stable
120
What is passive immunization?
transferred to naive individual from another individual already immune to an infection
- transplacental transfer of maternal IgG to fetus
- IgA in breast milk
121
What are the advantages of passive immunization?
prevent disease after known exposure
ameliorate symptoms of ongoing disease
protect immunodeficient individuals
block bacterial toxins and prevent the disease they cause
122
What are the different types of globulin?
human serum-pooled plasma
hyperimmune globulins-high titers of antibody
available for HBIG, CMVIG, VZIG, RSVIG
123
What is active immunization?
immune response is stimulated due to challenge (natural immunization or vaccines)
124
How does the immune system respond to protein antigens?
B cells making immunoglobulin
| longer lived in germinal centers
125
How does the immune system respond to polysaccharide antigens?
do not activate germinal cells
| Ig for just a little bit
126
What is the advantage of T dependent response?
isotype switching
high affinity antibodies
long-lived plasma cells
127
How do the primary and secondary responses differ?
primary-IgM>IgG; lower affinity
| secondary-IgG; higher affinity
128
What are the different types of vaccines?
inactivated-toxoid, subunit, conjugate vaccines
live, attenuated vaccines
DNA vaccines
recombinant vector vaccines
129
What are the advantages of inactivated vaccines?
antibody response without risk of infection
| induce immunity but may cause recurrent infection or have oncogenic potential
130
How are inactivated vaccines produced?
heat or chemical inactivation of bacteria, bacterial toxins, or viruses
can be produced by purification or synthesis of the components or subunits of the infectious agents
131
What are adjuvants?
administered with inactivated vaccines
boost immunogenicity by enhancing uptake by or stimulating dendritic cells and macrophages
some stimulate TLR to activate APC
132
What is the most common adjuvant?
alum
| others-MF59, MPL, emulsions, liposomes, molecular cages for antigen, polymeric surfactants
133
What are the major types of inactivated bacterial vaccines?
toxoid
inactivated (killed) bacteria
capsule or protein subunits of bacteria-includes polysaccharide capsule subunits
134
What are examples of inactivated viral vaccines?
polio, Hep A, influenza, rabies
| Salk poli-prepared with formaldehyde inactivation
135
What do subunit vaccines consist of?
bacterial or viral components
surface structures of bacteria and viral attachment proteins
T cell antigens may also be included
136
How are toxoid vaccines made?
inactivated with formalin
cannot cause disease and no possibility of reversion to virulence or spread
stable
137
What are conjugate vaccines?
used when polysaccharide of capsule is linked to a protein carrier (typically diptheria, neisseria)
138
What are the disadvantages of inactivated vaccines?
```
immunity is not lifelong
immunity may only be humoral
no local IgA response
booster required
larger dose necessary
```
139
How are live vaccines prepared?
avirulent or attenuated
especially useful for protection against infections caused by enveloped viruses that require T-cell immune responses for resolution of the infection
140
How are live viral vaccines prepared?
attenuated by growth in embryonated eggs at nonphysiologic temperatures and away from selective pressures of the host immune response
mutants that grow poorly at human temp, cannot escape immune control, may replicate at benign site but not disseminate
141
What are the disadvantages of live vaccines?
may be dangerous to immunosuppressed people or pregnant women
may revert to virulent viral form
viability of vaccine must be maintained
142
What are DNA and recombinant vector vaccines?
DNA attempted vaccine against West Nile Virus
recombinant-similar to DNA but use attenuated virus to introduce microbial DNA to cells in body (vector refers to virus or bacterium as carrier)
143
Why are steroids slow acting?
act on transcription factors
144
When is cortisol highest? When is aldosterone highest?
cortisol-morning
| aldo-constant throughout the day
145
What are the properties of glucocorticoids?
metabolism of fats and glucose
negative calcium balance
hypertension and polycythemia
bone resportion
146
What makes glucocorticoids anti-inflammatory?
increase lipocortin levels which inhibits phospholipase A2
| reduces NF kappa B levels (reduces proteolytic enzymes, reduces vasoactive cytokines, reduces COX2 and NOS)
147
What modulates mineralocorticoid release and what does it do?
release modulated by renin angiotensin system
| regulate sodium, water and potassium (promotes K excretion, enhances sodium and water reabsorption)
148
What is the MOA of aminoglutethimide?
```
inhibits CYP11A1 (reduces all corticosteroids)
need fludrocortisones to replace mineralocorticoids
```
149
What are the drug interactions for aminoglutethimide?
increased metabolism of warfarin, theophyline, and digitoxin
150
What is the MOA of ketoconazole?
inhibit CYP17 (inhibit glucocorticoid and androgen) and CYP11A1 (all steroidogenesis)
151
What are the drug interactions for ketoconazole?
increase P-gp substrates
| cardiac arrhythmias from ergot derivatives, cisapride, or triazolam
152
What is the MOA of metyrapone?
selective inhibitor of CYP11B1 (mores selective for cortisol)
153
What are the side effects of metyrapone?
hirsuitism from increased androgens
154
What is the MOA for etomidate?
anesthetic drug that blocks 11-beta-hydroxylation
155
What is the MOA of mitotane?
inhibits CYP11B1 and CYP11A1
| pharmacological ablation
156
What is the MOA of mifepristone?
block glucocorticoid receptors from being released from chaperone proteins
also abortion pill
157
What are the side effects of mifepristone?
vaginal bleeding, abdominal pain
158
What is the common defect in CAH? What is the clinical manifestation?
CYP21 most common
| pseudohermaphroditism in females and precocious puberty in males
159
Why are glucocorticoids given every other day when in remission?
reduces suppression of HPA axis
160
What can occur from treatment of asthma with glucocorticoids?
oral candidiasis
161
What is fludrocotrisone used for?
aldo replacement only
162
When are betamethasone and dexamethasone used?
immature lungs
| most potent
163
How are the drugs transported?
bound to protein (CBG and albumin)
164
What is the difference in the distribution of HSD?
HSD1 activates in gluco tissues
| HSD2 inactivates in mineralocorticoid tissues
165
How are corticoids eliminated?
conjugation with glucoronides (first pass varies)
| renal excretion
166
What are the withdrawal effects?
looks like Addisons
| HPA suppression
167
What are the side effects?
looks like Cushings
| dose and time dependent
168
What are the contraindications?
children
immunosuppression
mask viral infections-cannot give live vaccines
be careful with CHF, HTN, osteoprosis, diabetic, psychotic
169
What are the drug interactions?
```
estrogen increases (induces CYP3A4)
barbituates, carbamazepine, phenytoin promote corticosteroid metabolism
```
170
What are the products of dihomo-gamma-linolenic acid?
PGE1, PGI1, TXA1
171
What is the main pathway for arachidonic acid byproducts?
liver from linoleic acid
main-phospholipase A2
secondary-PLC
172
What are the products of eicosapentaneoic acid?
PGE3, PGI3, TXA3
173
What are the steps of the cyclo-oxygenase pathway?
hydration
| oxidation of 15-hydroxyl to ketone by 15-OH dehydrogenase
174
Where is COX1 found?
endothelial cells, stomach, kidney
| constitutive form
175
Where is COX2 found?
elevated by inflammation
| constitutive in brain and kidney
176
What are the actions of prostacyclin PGI2?
```
vasodilator
inhibit platelet aggregation
bronchodilator
inhibits gastric acid secretion
increase GFR, stimulates renin
relax uterine muscles
induces pain
```
177
What are the actions of prostaglandin PGE2?
```
vasodilator
inhibit platelet aggregation (high levels)
increase GFR, stimulates renin
relax uterine at high
induces pain
induces fever
```
178
What are the actions of thromboxane TXA2?
```
synthesized by platelets, lung, and kidney
vasoconstrictor
platelet aggregation
constrict airway
intrarenal constriction
uterine contraction
```
179
What are the actions of PGFalpha2?
vasoconstrictor
contracts airway
contracts uterine muscle
eyes-decrease intraocular pressure
180
What is misoprostol?
PGE1 analog
given for NSAID therapy to reduce ulcers
can induce labor in pregnant women
181
What is latnoprost?
PGF2 alpha analog
| opthalmic-decrease intraocular pressure
182
What is alprostadil?
PGE1 analog
| temporarily maintains PDA in newborns
183
What are 5HPETE and LTB4?
chemotactic agents for PMN leukocytes, eosinophils, monocytes
184
What is zafirlukast?
LTD4 receptor antagonist
inhibits bronchoconstriction
prophylaxis
more side effects (inhibits 3A4, food decreases bioavailability, older kids)
185
What is montelukast?
LTD4 receptor antagonist
inhibits bronchoconstriction
side effect-headache
can be used for anyone over 1
186
What is Zileuton?
inhibitor of 5-lipoxygenase (decrease all LT synthesis)
must monitor liver
drug interactions-theophylline, warfarin, propanolol
contraindicated in liver disease, ergot alkaloids
187
What are the side effects of NSAIDs?
increased GI ulcer
increased bleeding risk
fluid retention
cross sensitivity with aspirin
188
What is the MOA of aspirin?
irreversible inhibitor of cyclo-oxygenase
| acetylates ser530 in cox1 and ser516 in cox2
189
What are the uses of aspirin?
analgesic local and brain but does not interact with opioid receptor
therapeutic limits for arthritis
190
What is salicyclism?
intoxication characterized by tinnitis
191
What are the propionic acid derivatives? What are the drug interactions?
ibuprofen and naproxen (better anti-inflammatory)
| ACE inhibitors and antacids
192
What is the heteroarylacetic acid prep? What is it used for?
ketorolac
| used for cataract surgery-good for those with morphine habits
193
What is the phenylacetic acid prep? What is it used for?
diclofenac
opthalmic post cataract surgery
not during pregnancy
194
What is the indole derivative?
indomethacin
can treat gouty arthritis
and close PDA
195
What are the side effects and contraindications for indomethacin?
displaces bilirubin from albumin and decreases urine output
| do not give during hyperbilirubinemia and renal failure
196
What are the coxibs?
COX2 inhibitors
low GI pain
for RA and ankylosing spondylitis
monitor fluco
197
What is true of NSAIDs and pregnancy?
inhibit uterine motility-PGE, PGF
induce bleeding in last trimester
premature closing of ductus arteriosus
198
What NSAID has the highest risk of acute renal failure?
indomethacin
199
What are the net effects of NSAIDs on the kidney?
hyperkalemia
| fluid retention
200
What are the advantages of acetaminophen?
```
for people sensitive to aspiring
weak anti-inflammatory
less GI upset
drug interaction with alcohol
hepatic toxicity and renal toxicity
```
201
What is the MOA for gold salts?
inhibition of function and maturation of T cells
decreased levels of rheumatoid factor
inhibits phagocytosis in macrophages
202
What are the side effects?
chrysiasis (gray skin) and mucosal lesion
anemia and thrombocytopenia
anaphylactic reaction to injection
203
What are the contraindications for gold salts?
renal disease
lupus
eczema
204
What is the mechanism of type I reaction?
release of mediators from IgE sensitized mast cells
205
What happens in sensitization?
antigen activation of Th2 cells and stimulation of IgE class switching in B cells (IL4 mediated), IgE to mast cells
206
What causes the immediate hypersensitivity?
vasoactive amines
207
What causes the late phase reaction?
Il-5 from mast cells and Th2 recruit and activate eosinophils
eosinophils release additional mediators
208
What are the clinical examples of type I hypersensitivity?
hay fever
food allergies
bronchial asthma
anaphylaxis-food or bee sting
209
What is a common sign of possible progression to allergies?
atopic dermatitis
210
How can type I hypersensitivity be tested?
skin tests-observe wheal and flare
allergen specific IgE levels-plate with allergen and labeled anti-E added (for young and dermatographia)
total IgE levels-immunodeficient
211
What is immunotherapy?
inject subcutaneously
| rise in serum IgG leading to suppression of IgE (changing relative ratio between the two)
212
What are the characteristics of type II hypersensitivity?
involves IgM or IgG antibodies
| involves antigen on surface of cell in circulation or in tissue
213
What is antibody dependent cellular cytotoxicity?
IgG antibodies serve as bridge to link target cells to effector cells
214
What are examples of type II hypersensitivity?
```
transfusion reaction
hemolytic disease of newborn
Goodpastures-antiBM
autoimmune hemolytic anemia-antiRBC
pemphigus vulgaris-antiEcadherin
rheumatic fever-antiM
pernicious anemia-antiIF (decreased B12 absorption
myasthenia-antiAchR
graves-antiTSHR
```
215
What is hemolytic disease of newborns?
second pregnancy of RhD- woman and RhD+ baby
| treat with rhogam
216
How is Goodpasture's disease treated?
plasmapheresis and immunosuppressant drugs
217
What is the staining pattern for type II hypersensitivity?
linear
218
What are the tests for type II hypersensitivity?
direct-antibodies on surface of RBC (hemolytic disease of newborn, autoimmune hemolytic anemia, transfusion reaction)
indirect-measure anti RBC abs in serum
219
What are the characteristics for type III hypersensitivity?
immune complexes deposit in tissue
IgM or IgG that react with soluble antigens
complement activated-leading to tissue damage
microthrombus
220
Where are the favored sites for type III hypersensitivity?
```
kidneys
joints
small vessels
heart
skin
mostly small IC in ab excess
```
221
What are the examples of type III hypersensitivity?
```
serum sickness
rheumatoid arthritis (IgM on Fc to IgG)
systemic lupus
post-streptococcal GN
polyarteritis nodosum-hepB antigen
drug interactions-penicillins
```
222
What is the staining characteristic of type III hypersensitivity?
lumpy bump
223
What are the pathologic lesions for type III hypersensitivity?
vessels-vasculitis
kidney-glomerulonephritis
joints-arthritis
224
What is the arthus reaction?
skin test for type III
antigen intradermally in presence of preformed ab
skin reaction-peaks at 4-10 hours, necrosis around
225
How can type III be diagnosed?
measure complement
decrease with active deposition of immune complexes
direct-tissue biopsy
226
What are the characteristics of type IV hypersensitivity?
cell mediated-initiated by antigen specific Th1 cells
delay in time for reaction to develop
recruitment of macrophages and extensive damage
cytokines-IFN gamma and TNF alpha
227
What are teh clinical examples of type IV sensitivity?
contact dermatitis
haptens-nickel or chromate
tuberculosis
multiple sclerosis and T1DM-autoimmune
228
What is the DTH skin test?
assess immunologic memory of specific antigens
injected intradermally-peaks at 48-72 hrs
positive when sensitized
PPD, candida, tetanus diptheria
229
What is the patch test?
assess reactivity to contact antigens
| sensitizing on skin and covered with dressing
230
What are the advantages to the TB from blood test?
interferon gamma release assays
| single visit and prior BCG does not cause false positive
231
What is granulomatous hypersensitivity?
```
form of DTH
epithelioid cells and multineuclated giant cells
IL-12/APC drive Th1
TGF beta to increase fibrosis
central zone of necorsis
```
232
What is anergy?
inability to react to a battery of common skin tests
| associated with AIDS, RA, Hodgkin lymphoma, CLL, sarcoidosis, influenza, mumps, measles, TB, leprosy
233
What is allograft?
different member of same species
234
What is autograft?
one part of body to another
235
What is isograft?
genetically identical individuals
236
What is xenograft?
member of different species
237
What genes contribute to rejection?
MHC and HLA
238
What is the direct graft response?
T cells recognize allogenic MHC molecules on graft
| displayed by donor dendritic cells in graft, processed and presented by host dendritic cells to activate T cells
239
What is the indirect graft response?
graft cells are ingested by recipient dendritic cells, donor allogens are presented by self MHC molecules on recipient APCs
240
What happens in hyperacute rejection?
```
happens within minutes
antibody-antigen reaction
target Ags on endothelium
thrombotic occlusion of capillaries
fibrinoid occlusion of arterial walls, kidney cortex get infarction with necrosis
```
241
What happens in acute rejection?
humoral and cellular mechanisms
242
What happens in humoral acute rejection?
mediated by antidonor antibodies, intima thickening if proliferative, necrosis and polyps if necrotizing vasculitis
243
What happens in cellular acute rejection?
extensive mononuclear infiltrate
| CD8 cells invade and damage vascular endothelium
244
What happens in chronic rejection?
slow rise in creatinine
intimal fibosis and interstitial fibrosis
glomerular-duplication of basement membrane
245
Where and when does GVHD happen?
bone marrow transplant
| target organs are skin, liver, and intestine
246
What happens in GVHD?
effector donor T cells enter tissues and cause destruction after being activate in 2nd lymph organs
247
How can rejection be minimized?
ABO blood typing
| HLA typing
248
What are the limitations to immunopharmacology therapy?
increased risk of infection
| increased risk of lymphomas and related cancer
249
What is the MOA of cylcosporine?
calcineurin inhibitor by binding to cyclophilin (NFAT remains phosphorylated, decrease in IL2 synthesis)
250
What are the toxicities of cyclosporine?
nephrotoxicity
hypertension
hepatotoxicity
251
What is the MOA for tacrolimus?
calcineurin inhibitor by binding to FK506
| more potent than cyclosporine
252
What are the toxicities of tacrolimus?
nephrotoxicity
| neurotoxicity
253
What is the MOA for sirolimus and everolimus?
binds FKBP and inhibits mTOR
| blocks T cell at G1 to S transition
254
What are the toxicities associated with sirolimus and everolimus?
hyperlipidemia
| delayed wound healing
255
What is the MOA for azathioprine?
converted to 6MP and blocks de novo synthesis of purines (selective for lymphocytes due to lack of salvage pathway)
256
What are the toxicities and drug interactions for azathioprine?
bone marrow suppression
| allopurinol inhibits xanthine oxidase
257
What is the MOA for mycophenolate mofetil?
inhibitor of IMPDH (inosine monophosphate dehydrogenase)
| inhibits guanine synthesis
258
What are the toxicities and drug interactions for mycophenolate mofetil?
GI effects
| antacids decrease absorption
259
What is antithymocyte globulin?
ATGAM-polyclonal antibody to T lymphocytes
260
What are the toxicities for ATGAM?
serum sickness, nephritis, chills, fever and rashes
261
What is basiliximab?
chimeric anti CD25 antibody that binds alpha subunit of IL2 on T cells
given prior to surgery to prevent rejection
262
What is alemtuzumab?
humanized anti-CD52 antibody
| induces cytolysis upon binding lymphocytes, monocytes, macrophages and NK cells
263
What is tocilizumab?
humanized anti-IL6
264
What is the MOA for efalizumab?
binds CDIIa on LFA1 (withdrawn)
265
What is rituximab?
chimeric anti CD20 antibody against B lymphocytes to cause apoptosis
266
What is etanercept?
decoy TNF alpha receptor
267
What are the anti TNF drugs?
infliximab
certolizumab
adalimumab
golimumab
268
What are abatacept and belatecept?
CTLA4Ig
| binds CD80 and CD86 (B7) on APC to prevent binding to CD28 (inhibits costim)
269
What are immunostimulants?
treat immunodeficiency through cellular or humoral immunity
270
What can natural adjuvant be used for?
immune globulin to prevent measles, hep A, and tetanus
271
What is the BCG vaccine?
mycobacterium bovis with muramyl dipeptide to stimulate NK and T cells
treat bladder cancer
can cause hypersensitivity and shock
272
What is levamisole?
antihelminic agent that inhibits T suppressor cells
273
What is isoprinosine?
NK cell cytotoxicity increases and activity of T cells
274
What is thalidomide?
for ENL, multiple myeloma
reduces TNF levels in ENL
contraindicated in women who are pregnant
275
What is IFN alpha used for?
macrophages, T lymph, NK cell activation
treat cancers, hep B and hep C
can cuase flu like symptoms
276
What is IL-2 used for?
activates cellular immunity
indicated for metastatic melanoma, renal carcinoma, aids
can lead to hypotension and cardiovascular toxicity
277
What is GCSF?
increases number of granulocytes and monocytes
| used to reduce neutropenia
278
What is the MOA of muromonab?
internalization of T cell receptor
| adverse-cytokine release syndrome, CNS toxicity, anaphylactic reactions
