Hypersensitivity Flashcards
(113 cards)
1
Q
Innate immunity
A
Nonspecific, no memory, rapid response, inborn
Leukocytes, TLR, PAMP, iNKT
Skin/inflammatory response
2
Q
Acquired immunity
A
specific, has memory, slower to respond, 2 branches (cell mediated/humoral)
lymphocytes (b/t) , APC, cytokines, complement
3
Q
Cell mediated
A
T lymphocytes
antibodies are not involved
4
Q
Humoral
A
B lymphocytes, plasma cells, antibodies are involved
5
Q
Types of acquired immunity
A
Active vs passive
natural vs artificial
6
Q
Active, natural
acquired immunity
A
infection
7
Q
Active artificial
acquired immunity
A
Vaccination
- immunogens
- live virus
8
Q
Passive, natural
acquired immunity
A
maternal antibody transfer (IgG)
9
Q
passive, artificial
acquired immunity
A
Immunoglobulin plasma transfer
- tetanus Ig
- Rho-Gam
- ATGAM
- Thymoglobulin
10
Q
Immunomodulator
A
can cause both positive/negative fx
bacteria + its byproducts on immune system
11
Q
Immunostimulants
A
stimulates T cells and macrophages in immune deficiency
- isoprinosine
- bacillus calmette goerin
- levamisole
12
Q
Immunopotentiator
A
boosts a failing immune system
- IV immunoglobulin
- CMV immunoglobulin
13
Q
Immunoadjuvants
A
Given with antigen
- muramyl dipeptide (MDP)
14
Q
Immunosupressants
A
attenuate the immune response
- azathioprine
- glucocorticoids
- calcineurin inhibitors
- antilymphocyte globulin
for organ transplant
15
Q
Primary immunodeficiency
A
Congenital/genetic
- Severe combined immunodeficency aka SCID (tcell/bcell defect)
16
Q
Seconday immunodeficiency
acquired
A
Lifetime development, can be caused by other disease/environment
- Drug therapy, cancer, irradiation, malnutrition, old age, chronic disease
17
Q
3 main ways the immune system can fail
A
- Hypersensitivity
- Immunodeficiency
- Autoimmune disease
18
Q
Neutrophil count
A
2300-7700 cells/mm3
50-70% (60%)
19
Q
CD4+ count
A
70-110 (80) cells/mm3
38-46% (42)
20
Q
CD8+ count
A
50-90 (70) cells/mm3
31-40% (35%)
21
Q
WBC count
A
4500-11000 (7500) cells/mm3
100%
22
Q
Leukocytosis
A
high WBC
23
Q
Leukopenia
A
Low WBC
24
Q
Neutropenia
A
Low neutrophil
risk of opportunistic infection
25
Cluster Determination (CD)
specific sites on lymphocytes surfaces made of proteins/glycoprotein
Used to monitor disease states
Drug target
26
CD3
on all T lymphocytes
27
CD4
on helper T lymphocytes
TH1 or TH3
28
CD8
Cytotoxic/supressor T lymphocytes
29
CD20
B lymphoctes
30
CD25
Activated T lymphocytes
B lymphocytes
**IL2 receptor chain Tac**
31
CD56
Natural Killer Cell
32
Functional assessment of cell mediated immunity of T cells
skin test using common recall antigens:
candida, mumps, ppd, trichophyton
Tests for anergy (no response despite prev exposure)
33
Total immunoglobulins measure
Measures B cell function by serum protein (humoral response) electrophoresis w/ 5 fractions
(IgG, IgM, IgA, IgE, IgD)
Assess primary vs secondary immunodeficiency
34
IgM
Pentamer
Primary response
best at fixing complement in monomer form (B cell receptor)
Does not cross placenta
35
IgG
monomer
secondary response
80% in serum
heavy chain binds to phagocyte
crosses placenta/breast milk
neutralizes/opsonizes
36
IgA
dimer
respiratory secretory actions
37
IgE
Monomer
Allergy and parasitic activity (Type 1 hypersensitivity)
Binds to mast cells and basophils
38
IgD
monomer
B cell receptor, homeostasis
39
Source of cytokines
Soluble mediators secreted by various cells to aid in communication between cells
40
Types of cytokines
Proinflammatory
Regulatory
colony stimulating
41
Proinflammatory cytokines
IL-1
TNF
CSF
42
Regulatory cytokines
Interleukins 1,2,4,6
TNFa/b
43
IL1
From macrophages, fibroblasts, endothelial cells
Activates lymphocytes, hematopoetic growth factor, induces inflammation
44
IL2
From CD4 t cells (TH1)
Activates lymphocytes and NK cells
45
IL4
From CD4 T cells (TH2), mast cells, basophils, eosinophils
Activates macrophages, lymphocyte growth factor
Promotes IgE production and bone marrow precursor proliferation
46
IL6
From CD4 T cells (TH2), macrophages, mast cells, fibroblasts
Augments inflammation
Growth factors: lymphocytes and hematopoetic
47
TNF a
From macrophages, NK cells, Lymphocytes, mast cells
Activates cells to produce acute phase proteins (WBC, endothelial, lymph/liver cells)
48
TNF b
From T lymphocytes
Tumoricidal action
49
Hematopoetic growth factors
IL3 (multi-lineage)
EPO (RBC)
G-CSF
GM-CS
50
Interferon alpha
From monocytes/other
Antiviral effect: activates NK cells/macrophages, upregulates MHC 1
51
Interferon gamma
From T lymphoctes and NK cells
Activates NK cells/macrophages, upregulates MHC 1 & MHC 2
52
G CSF
Filgrastim
recombinant DNA
Increases neutrophil count
53
G CSF
Filgrastim
recombinant DNA
Increases neutrophil count
54
GM CSF
Sargramostim (Leukine)
DNA recombinant
dose dependent prod neutrophils and macrophages
55
Colony stimulating Factor indication
Chemo
bone marrow transplant
myelodysplastic syndrome
HIV
56
EPO
retacrit, darbepoetin alfa
Binds EPO receptor on erythroid CFU
Stimulates BFU-E and CFU in bone marrow to proliferate/differentiate into **mature RBC**
57
INF alpha
| drug
Peginterferon alfa
- 2a = pegasys; 2b=pegintron
- antiviral action, surpess cell cycle, induce apoptosis/anti-angiogenic actions,
immunomodulator, increases phagocytosis
For hepatitis C virus
58
INF beta
Peginterferon beta 1a (plegridy)
- INF b1a (Avonex/Refib); INF b1b (Betaseron)
For relapsing multiple sclerosis
59
G-CSF ADR
| Filgrastim (neupogen); Pegfilgrastim (neulasta)
Bone pain
N/V
marked leukocytosis (high WBC)
increased **uric acid**
hypersensitivity rxn
59
G-CSF ADR
| Filgrastim (neupogen); Pegfilgrastim (neulasta)
Bone pain
N/V
marked leukocytosis (high WBC)
increased **uric acid**
hypersensitivity rxn
60
GM-CSF ADR
| sargramostim (leukine)
Fever
Diarrhea
N/V
Malaise/weakness
headache/chills
rash
61
EPO ADR
HyPERtension
Fever
N/V
headache, rash, itching, joint aches, cough
62
Interferon a ADR
Bone pain
myalgia
Fever,fatigue
Neutropenia (low)
63
Monoclonal antibody classes (2)
1. unconjugated (naked)
2. immunoconjugates (tag toxin, chemo agent, or radioactive particle)
64
Therapeutic use of moab
Target:
- surface antigens --> cell death
- growth factor receptors --> stop proliferation
65
HAMA reaction
can increase CL of moab and reduce bidning to target (reduce therapeutic effect & cause hypersensitivty/infusion reaction)
Common with murine source
66
HAMA premedication
glucocorticoids
diphenhydramine
67
PolyAb
When the immune response to antigen is heterogenous. Plasma cells are sensitized to different epitopes and produce multiple different antibodies to the same antigen
1 antigen, many antibodies
68
PolyAb products
Gammagard S/D
gamunex
ocagam
| for immunodeficiency
69
Limitation of PolyAb
batch to batch varability because it's produced in different animals at different times
High chance of cross-reactivity due to recognition of multiple epitopes
70
IVIG
intravenous immunoglobulin = artificial passive immunity
A IV blood product containing at least 90% of pooled IgG antiboides harvested from at least 1000 patients (polyclonal formulation)
DO NOT INTERCHANGE IV and IM !!!
71
SLE treatment
pathology: B cells produce autoantibodies = organ damage
Belimumab (benlysta): targets B cell receptor to cause depletion; for lupus nephritis
72
RA treatment
Drugs will modify TNF-a, reduce inflammation
1. Etanercept (enbrel): soluble cytokine receptor drug
* fusion proteins bind to TNF-a in circulation, prevent binding to T cell target
2. Infliximab/adalimumab: chimeric mAb
* moab binds to circulating TNF-a, prevent interaction with lymphocytes/macrophages + inactivate laready bound TNF-a
73
Cytokine surface receptors
on target cell
74
Soluble cytokine receptors
endogenous, circulates in blood
75
TNF-a
endogenous mediator of inflammation
* increases tissue adhesion molecules
* stimulates pro-inflammatory cytokines (IL2,IL2,IL5,PG)
76
Exudate
High protein content
77
Transudate
Low protein content
78
Tetanus
AKA lockjaw, bacterial infection (clostridium tetani) , non-contagious
Characterized by muscle spasm and back muscle spasms (or opistotonos) which start in the jaw and progress to other body parts
79
Tetanus sx
Sx: fever, sweating, headaches, urinary retention, tachycardia, HTN, impaired swallowing
everyone should get vaccinated
Tetanus Ig for tx
80
Type 1 hypersensitivity cells
B lymphocytes/plasma cells/mast cells/IgE antibodies
81
Type 2 hypersensitivity cells
Macrophage/IgD> antibody/neutrophils/RBC
82
Type 3 hypersensitivity cells
IgG or IgM antibodies/basophils/lymphocytes/neutrophils/c3b
83
Type 3 hypersensitivity cells
IgG or IgM antibodies/basophils/lymphocytes/neutrophils/c3b
84
Type 4 hypersensitivity cells
T lymphocytes, cytokines, macrphages
| NO ANTIBODIES -- CELL MEDIATED
85
MAb limits
potential hypersensitivity reactions
unknown long term effect
limited production
antigenic modulation
86
Abciximab (ReoPro)
binds to GP2B3A to inhibit platelet aggregation
87
Muromonab-CD3
anti-CD3 antibody prevents or reverses allograft rejection
88
Muromonab-CD3
anti-CD3 antibody prevents or reverses allograft rejection
89
Liposomal conjugates (moab)
Amphotericin B
Doxorubicin
90
Alemtuzumab (Campath)
MoAB against CD52 surface antigen on mature lymphocytes (T cell> B cell), NK cells, macrophages, monocytes, eosinophils, male reproductive tract. FC domain activates complement → ab dependent cellular cytotoxicity (ADCC) → cell lysis
91
Basiliximab (simulect)
blocks CD25 to prevent activated T-lymphocyte proliferation (makes Il-2 resistant to stimulation)
92
Inflammation purpose
1. prevent antigen from invading body unchecked
2. Promotes healing and repair from antigen invasion
3. limits festering of antigen in body
93
inflammation characteristics
1. Nonspecific, not dependnent on antigen type
2. Depends on activity of cellular/chemical components
3. temperature, heat, redness, swelling, loss of function
94
Cells of acute inflammation
Primarily neutrophils
95
cells of chronic inflammation
lymphocytes and macrophages
granulomatous inflammmation (granulomas) form
96
Treatment of systemic inflammation
1. Fever
2. assess CBC with differential
- leukocytosis left shift
- increased immature WBC bands
- ANC calculation check neutrophil count
- Lymphangitis
- Lymphadenopathy
- Edema
- scar like tissue (fibrosis)
97
Type 1 hypersensitivity presentation
1. Reduced blood pressure after allergen exposure
2. Reduced end organ dysfuncion
2. Respiratory compromise/skin reaction/persistent GI sx
98
Type 1 Hypersensitivity mechanism
1. allergen exposure
- immunologic: IgE (food,med,insect bite,latex)
- non-immunologic (exercise, cold air/water, meds, etc)
2. sensitized B cells are activated and produce IgE antibodies. Second exposure = mast cell degranulation
3. Fatality greatest in first 30 min due to anaphylaxis, watch for late phase reactions
4. Mediators:
- primary: histamine, chemotactic factors
- secondary: leukotrienes, prostaglandin
99
Atopy
heightened immune response to common allergens -- asthma, allergic rhinitis
100
Type 2 hypersensitivity presentation
Cytotoxic IgG
Hemolytic anemia of newborn
-Rho negative mother's B cells make IgG antibodies against Rho positive fetus --> cross placenta and cause RBC lysis
Graves disease (hyperthyroid
- antibodies block TSH receptor on thyroid epithelial cells, constantly stimulate TH release even without TSH present
101
Type 3 hypersensitivity presentation
Immune complex mediated IgG
1. serum sickness (fever, rash, swollen joints/lymph, dermatitis
2. arthus reaction (local, not rotating insulin)
3. drug induced lupus (minimal organ involvement)
102
Drug Induced Lupus
| Type 3 hypersensitivity
Milder/rarer disease than idiopathic SLE
Sx: fever, malaise, myalgia
Occurance: slow acetylators, elevated ANA/SS-DNA/ESR
Drugs: hydralazine, procainamide, isoniazid, quinidine, TNFa inhibitors
103
Type 4 hypersensitivity presentation
Cell mediated (t cell); delayed HS that occurs a few days after exposure to an antigen
A. Tuberculosis PPD, contact dermatitis
B. chronic asthma/allergic rhinitis
C. contact dermatitis, SJS, TEN, maculopapular
D. Acute generalized Exanthematous Pustulosis
104
Type 4A
TH1 cell activation
Effector: macrophage activation
Antigen presented by cells or by T cell stimulation
| contact dermatiitis, TB PPD
105
Type 4B
TH2 cell activation
Effector: Eosinophils
Antigen presented by cells or by T cell stimulation
| chronic asthma/allergic rhinitis
106
Type 4C
Serious life threatening condition: macules rapidly spread and coalesce, leading to epidermal blistering, necrosis, and sloughing– of SKIN and in mucosa (eye, mouth, GI)
TEN more BSA affected than SJS
| SJS, TEN, contact dermatitis (again)
107
Type 4D
Soluble antigen presented by cells or direct T-cell stimulation
Effector: Neutrophils
Patho unclear, 90% drug association (less so bacterial/viral/parasitic)
Occurs up to 3 weeks after drug exposure
| AGEP
108
Contact dermatitis treatment
Drugs:
* Topical steroids (HC)
* Oral antihistamines
* Topical immunomodulators (tacrolimus)
* Systemic steroids (if sx do not subside in 7-14 days)
Homeopathic
* cold compress
* for oozing lesions: calamine lotion, colloidal oatmeal
* Mild soap, nonirritating, avoid dye/fragrance
* acoid known triggers, wash skin after exposure
109
Type 4 cell mediated disease manifestations
1. tuberculosis
2. leprosy
3. schistosomiasis
4. sarcoidosis
5. contact dermatitis
6. eczema
110
Type 1 hypersensitivity treatment
1. Give epinephrine every 15-20 minutes
* 1:1000 IM or SQ every 15-20 minutes
* If bronchospasm doesnt respond to epi, use nebulized albuterol in the ER
2. Oxygen therapy if needed (8-10L/min)
3. Treat late phase reactions using (histamine blockers)
* IV diphenhydramine 25-50mg
* h2 receptor blocker (cimetidine)
4. Reduce recurrent risk
* IV hydrocortisone 5mg/kg or 250mg
* OR PO prednisone 20mg -- taper usually needed
5. If hypotensive? -- give IV fluids isotonic or colloid replacement
111
SJS/TENs drug induced
SJS 50%; 95% SJS
* Sulfonamides (bactrim, sulfasalazine)
* Antibiotics (aminopenicillins, fluoroquinolones, cephalosporins)
* Anti-epileptics
* Miscellaneous (allopurinol)
112
AGEP is associated with:
drugs (90%)
