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Block 4 Flashcards

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1
Q

When is immunosuppression necessary?

A

When immune system is contributing to human disease such as:

Organ transplant
Autoimmune disorders
Hematological malignancy
Allergic conditions

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2
Q

What are the Tx for organ graft rejection due to acute cellular rejection?

A

High dose steroids

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3
Q

What are the Tx for organ graft rejection due to rejection refractory from steroid treatment?

A
  1. Anti-thymocyte globulin

2. Alemtuzumab (anti-CD52)

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4
Q

Anti-thymocyte globulin is used when steroids dont work for organ graft rejection. What is its purpose?

A

T cell depletion

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5
Q

Alemtuzumab is used when steroids dont work for organ graft rejection. What is its purpose?

A

Lymphocyte depletion

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6
Q

What are the Tx for organ graft rejection due to acute humoral rejection?

A
  1. Plasmapheresis
  2. IVIG
  3. Rituximab
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7
Q

Type II
Type III
Type IV

Which one is cell mediated immunity?

A

Type IV

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8
Q

Type II
Type III
Type IV

Which one is AB forming immune complex?

A

Type III

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9
Q

Type II
Type III
Type IV

Which one is AB against cell surface?

A

Type II

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10
Q

What are the main functions of glucocorticoids on immune cells?

A
  1. Inhibits leukocyte traffic and their access to site of inflammation
  2. Interferes with leukocytes, fibroblasts, and endothelial cells
  3. Suppress the production and action of factors involved in inflammatory process
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11
Q

How do glucocorticoids affect the functions of leukocytes, fibroblasts, and endothelial cells?

A
  1. Decreases MHC II and Fc receptors

2. Affects endothelial cells by decreased vessel permeability

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12
Q

What are some short-term side effects of glucocorticoids?

A
  1. Increases appetite and weight
  2. Insomnia
  3. Edema
  4. Mood changes
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13
Q

What are some long-term side effects of glucocorticoids?

A
  1. Diabetes, HTN, Osteoporosis
  2. Muscle problems
  3. Bruising
  4. Infection
  5. Eye issues
  6. Growth retardation in children
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14
Q

If you stop taking glucocorticoids, why should you taper off?

A

Body reduces the production of natural steroids

If suddenly stopped, you will feel like crap

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15
Q

What is the dosing regimen for glucocorticoids?

A
  1. Low = ≤ 7.5mg
  2. Medium = 7.5 - 30mg
  3. High = 30 = 100mg
  4. Very high = ≥100mg
  5. Pulse = ≥250mg (for a few days max)
  6. Alternate = higher doses every other day
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16
Q

What are the calcineurin inhibitors?

A

Cyclosporine

Tacrolimus

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17
Q

Of the calcineurin inhibitors, what formulations do they come in?

A

Cyclosporine - oral

Tacrolimus - oral and topical

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18
Q

Calcineurin inhibitor MOA?

A

Dampen production of proinflammatory mediators by T cells, specifically IL-2

or

Binds to FK506 Binding protein which binds to calcineurin, then inactivates that. Regulatory proteins are unable to translocate into nucleus which reduces transcription of proinflammatory genes

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19
Q

What do calcineurin inhibitors do to cytokine production?

A

Down regulates them, but does not turn it off completely

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20
Q

Why doesnt cyclosporine come in as a topical therapy?

A

Too large to penetrate skin

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21
Q

AE of cyclosporine?

A

HTN, hyperkalemia, hypomagnesemia, hyperlipidemia

Reduced filtration rate and rise in SCr

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22
Q

AE of tacrolimus?

A

Similar w/ cyclosporine

Glucose intolerance and DM

Negative effect on pancreatic islet beta cells

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23
Q

Which immunosuppressant is inactive until metabolized by the liver?

A

Azathioprine

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24
Q

Azathioprine MOA?

A

Purine analogue that is incorporated into DNA and interferes with synthesis of DNA

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25
Azathioprine decreases proliferation of (B/T) cells
Both
26
When are calcineurin inhibitors used?
Solid organ transplants or immunological diseases
27
When is Azathioprine used?
Prevent/treat graft rejection or to treat systemic autoimmune conditions
28
Azathioprine and NK cells?
Function is suppressed w/o change in cell number
29
Azathioprine AE?
Generally well tolerated, but has minor GI issues Susceptible to opportunistic infections and malignancy Due to bone marrow suppression, leukopenia, thrombocytopenia, and anemia could happen Hepatotoxicity and Pancreatitis
30
Which immunosuppressant is produced by Streptomyces hygroscopicus?
Sirolimus
31
How is Sirolimus produced?
Via Streptomyces hygoscopicus
32
What advantage does Sirolimus have over calcineurin inhibitors?
Reduced renal toxicity
33
Sirolimus MOA?
Inhibits T cell activation of IL-2 and T cell growth factors, also binds to mTOR and FKBP-12
34
When is Sirolimus used?
Prophylaxis of organ transplant rejection
35
Methotrexate is an analogue of what? What is special about this?
Folic acid; inhibits purine and pyrimidine synthesis which suppresses cellular proliferation
36
Methotrexate MOA?
Besides affecting purine and pyrimidine, it also impairs monocyte and lymphocyte function reducing synthesis of ROS
37
Methotrexate AE?
Efficacy is lost due to caffeine | Hepatotoxicity
38
Which immunosuppressant is a prodrug?
Mycophenolate which is hydrolyzed to MFA
39
MFA MOA?
Selective, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase
40
Which immunosuppressant is contraindicated for pregnancy?
MFA
41
MFA AE?
GI issues Hematologic Increased risk of infection
42
Which immunosuppressant causes a rise in SCr and reduced glomerular filtration rate?
Cyclosporine and Tacrolimus
43
Which immunosuppressant causes glucose intolerance?
Tacrolimus
44
Which immunosuppressant releases adenosine which can reduce neutrophil accumulation ?
Methotrexate
45
What ia a biologic drug?
Product that is produced from a living organism or contains components of living organism
46
How is anti-thymocyte antibody generated?
Repeated injection of human thymocyte into rabbits (rATG) or horses (Atgam)
47
What is an example of a polyclonal antibody?
Anti-thymocyte antibody
48
Anti-thymocyte antibody MOA?
ATG contains cytoxic AB that binds to many T cell co-receptors and HLA I and II molecules Depletes T cells by direct measures (complement and cell-mediated) Block lymphocyte function by bind to cell surface molecules
49
What are the TNF inhibitors available?
ICAGE ``` Infliximab Certolizumab Adalimumab Golimumab Enterocept ```
50
Which monoclonal binds to CD25?
Daclizumab and Basiliximab
51
What is administered with Daclizumab or Basiliximab?
Cyclosporine and corticosteroids
52
Abatacept is approved to treat what?
Rheumatoid arthritis
53
Which monoclonal is a soluble protein consisting of CTLA-4 fused to Fc portion of IgG1?
Abatacept
54
Which monoclonal is a soluble form of B-lymphocyte stimulator (BLyS or BAFF)
Belimumab
55
Belimumab is approved to treat what?
SLE
56
Alemtuzumab is approved to treat what?
Chronic lymphocytic leukemia
57
Which monoclonal binds to CD52?
Alemtuzumab
58
Which monoclonal binds to CD20?
Rituximab
59
Lysis is mediated by what via Alemtuzumab?
AB-dependent
60
Lysis is mediated by what via Rituximab?
Complement, ADCC, induction of apoptosis
61
What are some side effects for Alemtuzumab?
Hemolytic anemia
62
What are some side effects for Rituximab?
Neutropenia
63
Daclizumab and Basiliximab is used to treat what?
Prevent organ transplant rejection
64
What are the main causes of anaphylaxis in a healthcare setting?
Latex Rx Biologics
65
What are the main prevention techniques of anaphylaxis in a healthcare setting?
Skin-prick test Food/Rx challenges Immunotherapy/desensitization
66
How many allergens have been identified in latex?
14
67
Who are the at-risk population groups for latex allergy?
1. Kids w/ spina bifida 2. Atopic individuals 3. Level of exposure 4. Ppl allergic to tropical fruits
68
What are the main Rx that cause anaphylaxis?
1. ABx 2. Neuromuscular blocking agents 3. NSAIDs 4. Local anesthetics 5. Opiates
69
Anesthetics and anaphylaxis, why is it difficult to isolate cause?
Exposed to many agents during anesthesia
70
What are the parts of vaccinations that cause anaphylaxis?
1. Antigen 2. Adjuvant 3. Additive/Excipient 4. Latex stopper on vial 5. Eggs (ovalbumim)
71
Although they have lack of evidence to prevent hypersensitivity, what Rx are typically given prior to transfusion?
APAP and Benadryl
72
What is radiocontrast media used for?
Diagnosis and Tx vascular diagnosis
73
To help prevent radiocontrast reactions, what is typically given immediately prior to the test? What is used as a protective agent?
H1 antihistamines Glucocorticoids in 2 doses (6 and 2 hrs prior to administration)
74
Which vaccines are cultured on hen's eggs?
Yellow fever MMR (considered safe w/ egg allergy) Influenza
75
Prophylactic regimens like APAP, antihistamines, glucocorticoids are based on what for preventing anaphylaxis?
Based on clinical experience rather than objective evidense
76
What are the basic steps of the HIV life cycle?
``` Attachment Fusion Uncoating Reverse transcription Integration ```
77
What exactly is connected when HIV sees a cell?
gp120 + CD4 molecule | w/ CCR5 or CXCR4 coreceptors
78
What is the clinical progression of HIV?
Time 0 to 6 weeks = CD4 count goes down and viremia goes up Time 6 to 12 weeks = CD4 goes up a little and viremia drastically goes down Time 1 to 7 yrs = CD4 gradually goes down and viremia stays steady Year 8 to 11 = viremia rises and constitutional symptoms appear, then opportunistic diseases, then death
79
Inflammation is characterized by transient local (vasoconstriction/vasodilation)
Vasodilation
80
Inflammation is characterized by (increased/decreased) capillary permeability
increased
81
What is a fever?
Body temperature greater than 100 F or 37.8 C (orally)
82
What is the mechanism behind fever?
Increase pyrogens which stimulate PGE2 production. Affects hypothalamus to increase core body temperature
83
What are the main types of pain?
1. Nociceptive | 2. Neuropathic
84
What is the mechanism behind nociceptive pain?
Stimulates nerve fibers via thermal or mechanical inflammation Can be broken down to visceral, deep somatic, or superficial pain
85
What is the mechanism behind neuropathic pain?
Damage to part of the nervous system
86
What are the mediators for nociceptive pain?
Cytokines Bradykinin Leukotriene Prostaglandins
87
How can you reverse the effects of nociceptive pain?
NSAIDs
88
What are some functions of prostaglandins?
Promote inflammation (which results in pain and fever) Support blood clotting function of platelets Protect lining of stomach from effects of acid
89
What produces prostaglandins?
Cyclooxygenase 1 and 2
90
Which COX enzyme supports blood clotting function and protects lining of stomach?
COX-1
91
What specifically do NSAIDs do with prostaglandins?
Block COX enzymes and reduce prostaglandin production
92
Who should avoid NSAIDs to prevent Reye's Syndrome?
Giving aspirin to kids w/ chickenpox or the flu.
93
What is Reye's Syndrome?
Disease of the liver
94
What AE are linked with NSAIDs?
Except aspirin, increase of heart attack, storke With aspirin, stomach ulcers, kidney failure, swelling of arms and legs
95
Why is aspirin inferior to ibuprofen when treating acute pain?
Potential GI bleed
96
Which NSAID is effective in treating tension headaches and migraines?
Aspirin
97
What are some advantages of aspirin vs other NSAIDs?
Tx tension headaches and migraines Anti-platelet activity May help prevent heart attacks in high risk patients
98
Aspirin MOA?
Irreversibly inhibits COX-1 and modifies COX-2
99
Which enzyme does aspirin modify?
COX-2; converts it to prostaglandin-forming to lipoxygenase-like enzyme Able to metabolize polyunsaturated fatty acids to hydroperoxy products (has anti-inflammatory properties)
100
Celecoxib MOA?
COX-2 inhibitor
101
What is different about celecoxib vs other NSAIDs?
Specific to COX-2 Causes less inflammation to stomach and intestines and does NOT interfere with clotting of blood
102
What Rx increases concentration of celecoxib in the body?
Fluconazole
103
In rheumatoid arthritis, what invades the cartilage and bone surface?
Pannus
104
(Men/Women) are more likely to get rheumatoid arthritis
Women (by 3x)
105
What diseases or infections are risk factors for rheumatoid arthritis?
Epstein Barr virus E. coli Periodontal disease Smoking
106
Type IV reactions for allow Th1 cells to active _______ while leads to the production of inflammatory cytokines such as ____________________
Macrophages TNF-alpha IL-6 IL-1Beta
107
Which type of mechanism is mediated via rheumatoid arthritis?
Type III and IV
108
Which immunoglobulin interacts with Fc of IgG in rheumatoid arthritis?
IgM (rheumatoid factor)
109
IgM-IgG complex is associated with what immune disease?
Rheumatoid arthritis
110
What is a useful diagnostic reference for patients with early arthritis and could be an indication of rheumatoid arthritis?
Anti-citrullinated protein antibodies (ACPAs)
111
Which amino acid is changed to a polar and neutral citrullin due to citrullination?
Arginine
112
Clinical presentation of rheumatoid arthritis states that joint pain and stiffness lasts more than _________
6 weeks
113
What are some factors used to assess patients with joint disease?
Pattern (mono-1, oligo-≤4, poly-≥5) Extra-articular disease
114
What is raynaud's phenomenon?
Fingers become white due to lack of blood flow, then blue as vessels dilate then to red and flow returns
115
In rheumatoid arthritis, ____ cells activate macrophages which leads to production of inflammatory cytokines such as TNF-alpha, IL-6, and IL-1Beta
Th1
116
Match please! Abatacept Rituximab Tocilizumab Anti-CD20 Anti-IL6 CTLA-4
Abatacept - CTLA-4 Rituximab - Anti CD20 Tocilizumab - Anti-IL6 All three can be used to treat Rheumatoid arthritis, but dont block TNF-alpha
117
What is a synthetic small molecule similar to DMARDS that can be used to treat rheumatoid arthritis?
Tofacitinib
118
Abatacept is a soluble protein consisting of CTLA-4 fused to Fc portion of _____
IgG1
119
Do all rheumatoid arthritis patients produce rheumatoid factor?
No but if it is present it is associated with increased severity.
120
If rheumatoid factor is found in patients, is it present in other diseases besides rheumatoid arthritis?
Yes
121
Rheumatoid arthritis is just cell mediated?
No, also humoral (antibody) mediated
122
How do you treat the flares from rheumatoid arthritis?
NSAIDs and corticosteroids
123
What causes IBD?
Idiopathic (unknown)
124
Crohn's Disease vs Ulcerative colitis Which one is confined to colon and rectum?
Ulcerative colitis
125
Ulcerative colitis is confined to what region?
Colon and rectum
126
Crohn's Disease vs Ulcerative colitis Which one is transmural (across the entire wall) of GI tract?
Crohn's Disease
127
Crohn's Disease is confined to what region?
Transmural and can occur in any part of the GI tract
128
IBD is confirmed by what?
Colonoscopy
129
Crohn's Disease vs Ulcerative colitis Which one is Th1 mediated?
Crohn's Disease
130
Crohn's Disease vs Ulcerative colitis Which one is Th2 mediated?
Ulcerative colitis
131
Crohn's Disease vs Ulcerative colitis Which one is has higher TNF-alpha?
Both are increased
132
Crohn's Disease is ____ mediated
Th1
133
Ulcerative colitis is ____ mediated
Th2
134
Smoking protects against (Crohn's Disease/Ulcerative colitis)
Protects w/ UC Increases incidence w/ CD
135
Which Rx can trigger CD or UC?
NSAIDs
136
Crohn's Disease presents with pain in where?
Right lower quadrant pain
137
What are some nutritional support items for Crohn's Disease or Ulcerative colitis?
Folic acid and B12
138
As colectomy is for _______, intestinal resection is for _______
Colectomy - ulcerative colitis Intestinal resection - Crohns
139
What are some pharmacologic Tx for flare on Crohn's disease or ulcerative colitis?
Glucocorticoids
140
What are some pharmacologic Tx for flares and maintenance for Crohn's or ulcerative colitis?
* Aminosalicylates * Immune suppressants * Biologics (anti-TNFalpha, anti-leukocyte adhesion) * Antimicrobials
141
What are some ways to treat the symptoms of Crohn's or ulcerative colitis?
Diarrhea - imodium, dicyclomine NSAIDs for arthritic symptoms (w/ risk of ulceration) Pain - opiate dependency risk
142
Besides Th1, what else is mediated by Crohn's Disease?
IL-12 and Th17
143
Besides Th2, what else is mediated by ulcerative colitis?
IL-13 (mucosal)
144
What are the maintenance Rx for rheumatoid arthritis?
DMARDS Tofacitinib Biologics

Immunology (4 decks)

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