Immunology/Allergy Flashcards
1
Q
What is an antigen?
A
Any molecule that can be specifically recognized by the specific immune system
2
Q
What is an antibody?
A
Specific Ig produced by a specific B cell that recognizes and binds to specific antigens that are recognized as non-self
3
Q
Where does the thymus develop from?
A
Third and fourth pharyngeal pouches
4
Q
How is the thymus critical for the immune system?
A
Critical for major histocompatibility complex restriction (MHC) which is imposed on lymphoid precursors arising form the yolk sac, fetal liver, and bone marrow
5
Q
Where do T-cells develop?
A
Thymus
6
Q
What are the members of the secondary lymphoid system?
A
Waldeyer ring, lymph nodes, spleen, mucosa-associated lymphoid tissue
7
Q
Where are B-cells primarily found in the lymph node?
A
Cortex and medulla
8
Q
Where are T-cells primarily found in the lymph node?
A
Paracortex and medulla
9
Q
What kind of Ig is produced by MALT?
A
Secretory IgA
10
Q
CD2 and CD3 differentiate what types of cells?
A
All T-cells
11
Q
Which types of T-cells have CD4?
A
Helper T-cells
12
Q
What are helper T-cells responsible for?
A
Augmenting the interactions between T-T, T-B, and T-macrophage cells
13
Q
Allergic inflammation is characterized by a TH1 or a TH2 response?
A
TH2
14
Q
What do TH1 cells produce?
A
IL-2 and IFN-gamma
15
Q
Do TH1 cells stimulate or inhibit B-cells?
A
Inhibit
16
Q
What do TH2 cells produce?
A
IL-4, 5, 6, and 10
17
Q
Do TH2 cells stimulate or inhibit B-cells?
A
Stimulate
18
Q
CD8 T-cells function by doing what?
A
Specific killing of target cells, inhibit the response of B-cells and other T-cells
19
Q
Which MHCs are associated with helper T-cells?
A
MHC II
20
Q
What MHCs are associated with cytotoxic T-cells?
A
MHC I
21
Q
In order for proper antigen recognition, what must an antigen be presented with?
A
MHC on the antigen-presenting cell
22
Q
What induces proliferation of both T- and B-cells?
A
IL-1
23
Q
What type of MHC is on the surface of B-cells?
A
MHC Class II
24
Q
Which CD molecules are on B-cells?
A
CD 19, 20, 22
25
What is the purpose of NK cells?
Eliminate cells that become spontaneously malignant or are infected with virus
26
What type of receptors are on NK cells?
IgG receptors
27
Which CD molecules are on NK cells?
CD 16, 56
28
What is the principle function of the MHC?
Bind fragments of foreign protein to form complexes recognized by T-cells
29
How are endogenous antigens processed?
Pass through rough endoplasmic reticulum and are associated with MHC Class I molecules
30
How are exogenous antigens processed?
Hydrolyzed and associated with MHC Class II molecules
31
Where are MHC Class I molecules found?
On nearly all nucleated cells
32
Where are MHC Class II molecules found?
B-cells, macrophages of dendritic cells, endothelial cells
33
Which cells are responsible for producing IFN-alpha?
Leukocytes
34
How does IFN-alpha work?
Decreases viral replication and increases cell membrane proteins
35
Which cells produce IFN-beta?
Fibroblasts and epithelial cells
36
What are the functions of IFN-beta?
Decreases viral replication and increases cell membrane proteins
37
Which cells produce IFN-gamma?
Activated T-cells and NK cells
38
What are the functions of IFN-gamma?
Increases expression of cell membrane antigens, including Class I and II HLA and Fc receptors; potent activator of eosinophils
39
Clinically significant allergen-induced reactions are mediated by what?
IgE
40
What causes the immediate allergic reaction?
Release of mast cell mediators and proteases
41
When does the late phase of an allergic reaction begin?
Three to four hours after the immediate response
42
What is the significance of the IgE-mediated late phase response?
Thought to play a role in the triggering of allergic diseases such as asthma, atopic dermatitis, and allergic rhinitis
43
What cytokines are usually released after IgE cross-linking?
IL1, IL3, IL4, IL5, IL6, GM-CSF, and TNF-alpha
44
How does IL-4 affect T-cell proliferation?
Induces differentiation into a TH2 phenotype
45
How does IL-4 affect B-cells?
Enhances B-cell growth and antigen presentation of B-cells
46
What is the role of IL-13 in the allergic response?
Has IL-4 like activities on B-cells and monocyts and induces IgE isotype switching
47
What is the primary role of IL-5 in the allergic response?
* Promotes differentiation of eosinophils
* Chemotactic factor
* Activates mature eosinophils
* Reduces apoptosis
48
What cells act as antigen-presenting cells?
* Macrophages
* Endothelial cells
* Dendritic cells found in the:
* Skin & mucosa
* Lymph node
* Spleen
* Thymus
* Glia
* Activated B-cells
49
What major cytokine is released by macrophages after antigen exposure?
IL-1, which stimulates precursor TH cell to develop into a mature TH
50
What is a Type I Gell & Coombs allergic reaction?
Occurs after cross-linking of IgE on mast cells leading to degranulation. Memory cells exposued to the allergen produce more IgE
51
What is a Type II Gell & Coombs allergic reaction?
* First exposure-allergen induces a B-cell response with production of allergen
* Second exposure-antibodies bind to cell surfaces expressing the allergen
* Complement is activated and cell is lysed
* The attached antibodies act as an opsonin and phagocytic cells are attracted
* Damage is tissue-specific
* Unclear if Type II reactions produce allergic symptoms
52
What is a Type III Gell & Coombs allergic reaction?
* First exposure-allergen induces a B-cell response with production of antibodies
* Second exposure-allergen circulating in the blood binds to the antibody to create an immune complex
* When large quantities accumulate, they cannot be easily removed by the reticuloendothelial system
* Complexes attached to small vessel endothelium and initiate a inflammatory response through complement activation
53
What is a Type IV Gell & Coombs allergic reaction?
* First exposure-allergen sensitizes T cells
* Second exposure-allergen is detected on a target cell surface
* Previously sensitized T-cells lyse the target cell
* Inflammatory response initiated
54
What intracellular signalling pathway is used by mast cells for release of mediators?
cAMP/cGMP and calcium
55
What is the major precursor to both prostaglandins and leukotrienes?
Arachadonic acid
56
During metabolism of arachadonic acid, which pathway leads to production of leukotrienes?
Lipoxygenase
57
During metabolism of arachadonic acid, which pathway leads to production of prostaglandins?
Cyclo-oxygenase
58
What are the four major effects of histamine?
1. Vasodilation
2. Increased capillary permeability
3. Bronchoconstriction
4. Tissue edema
59
Where are type 1 histamine receptors located?
Smooth muscle of vessels, bronchi, goblet cells, and GI mucosa
60
Where are type 2 histamine receptors located?
Suppressor T-cells, basophils, mast cells, neutrophils, gastric cells
61
What is the role of heparin in an allergic response?
Released by mast cells and causes histamine suppression, increased phagocytosis, and anticoagulation
62
What is the role of leukotrienes in the allergic response?
Vasoactive, chemotaxis, bronchoconstriction
63
What is the role of prostaglandins in the allergic response?
Bronchoconstriction, platelet aggregation, vasodilation
64
What are Dennie's lines?
Fine horizontal lines in the lower eyelids
65
What are ocular clinical signs of allergies?
* Allergic shiners
* Dennie's lines
* Conjunctivitis
* Lymphoid aggregates on the palpebral conjunctiva
66
What are nasal clinical signs of allergies?
* Itching
* Allergic salute
* Facial grimace
* Nasal obstruction
* Sneezing
67
What are oral clinical signs of allergies?
* Chronic mouth breathing secondary to nasal airway obstruction
* Nocturnal tooth grinding
68
What are pharyngeal clinical signs of allergies?
* Dry, irritated, sore throat
* Repeated throat clearing
* Cobblestoning
69
What are airway clinical signs of allergies?
* Hoarseness
* Asthma
* Wet cough, especially with mold allergy
70
What is house dust composed of?
Mites, cockroach, cotton particles, human scales
71
What is the major allergenic component from dust mites?
Feces
72
What is it that makes cats allergenic?
Fel D1 antigen produced in sebaceous glands and shed on skin scales
73
What are the primary molds that cause allergic symptoms?
Aspergillus, Penicillium, Alternaria, Cephalosporium
74
What is the first screening tool used for allergy testing?
Epicutaneous prick testing
75
How is skin prick testing performed?
Antigen is inserted into the skin via a sterile #26 gauge needle
76
What are the positive and negative controls used in skin prick testing?
* Positive-histamine
* Negative-glyercine
77
What are the advantages to skin prick testing?
* Rapid
* Better correlation with intradermal tests
* Relatively safe
78
What are the disadvantages to skin prick testing?
* Qualitative measure of allergy only (yes vs. no)
* Will miss low degree of allergy (increased false negatives)
* Grading of skin test is subjective
79
What is the Patterson System for scoring skin prick testing?
* Negative-no reaction or no different from control
* One plus-erythema smaller than a nickel in diameter
* Two plus-erythema larger than a nickel in diamter with no wheel
* Three plus-wheal with surrounding erythema
* Four plus-Wheal with pseudopods and surrounding erythema
80
How many dilutions are made for intradermal dilution titration?
6 dilutions that are fivefold diluted compared to the previous
81
Does dilution #1 have a higher or lower concentration of allergen than dilution #6 for IDT?
Higher
82
What is standard concentration of the allergen concentrate?
1:20
83
What is the concentration of dilution #1 for IDT?
1:100
84
When doing IDT, which dilution is injected first?
#6
85
How much dilution is injected at a time during IDT?
0.01 ML, which produces a 4 mm wheal that enlarges (without reaction) to a 5 mm wheal
86
What defines a postive, allergic response during SDET?
2 mm of wheal enlargement beyond the size of the original 5 mm wheal
87
What is the endpoint in SDET?
The first dilution which yields a wheal at least 2 mm larger than the predecing negative wheal, and which is followed by a wheal at next stronger dilution that is at least 2 mm larger still
88
What are the advantages of SDET?
* Quantitative and qualitative measure
* Highly reproducible
* Very sensitive
* Safe
89
What are the disadvantages of SDET?
* Time-consuming
* Possible false positives in low degree of allergy
* More office supplies needed
90
How long should a patient be off of antihistamines before allergy testing?
36 hours
91
How long should a patient be off tricyclic antidepressants before skin testing?
2-4 days
92
What is the concern with patients being on Beta-blockers when doing allergy testing?
If the patient develops an anaphylactic response, you don't want the beta-adrenergic receptors blocked and hamper the use of epinephrine
93
What does RAST stand for?
RadioAllergoSorbent Test
94
What is the purpose of RAST testing?
Measure the serum level of allergen-specific IgE
95
How does RAST work?
* A paper disc with antigen on the surface is placed in a test tube and patient serum is added
* Allergen-specific IgE binds to the antigen on the disc
* Radiolabeled anti-IgE antibody is added and binds to the patient IgE
* Amount of bound radiolabel is then measured
96
What are the advantages of RAST testing?
* Eliminates variability of the skin response
* Eliminates drug effects
* More specific than skin testing
* Can be used to determine starting doses for immunotherapy
* Safe for patients on beta-blockers
97
What are the disadvantages of RAST testing?
* More expensive
* Requires specialized lab equipment and technician training
* May be less sensitive than skin testing
98
What are indications for in vitro allergy testing?
* Patients not responding to environmental control and medical management
* Sytmptomatic patients with conditions in which in vivo skin testing is contraindicated
* Patients doing poorly on immunotherapy
* Diagnosis of IgE-mediated food sensitivity
99
What are examples of first generation antihistamines?
Benadryl, Chlortrimeton, Phergan, Atarax, Vistaril
100
What are examples of second-generation antihistamines?
Claritin, Zyrtec, Allegra
101
Why are first generation antihistamines more sedating than second generation ones?
They are lipophilic and able to more easily cross the blood brain barrier
102
What is the disadvantage of systemic decongestants?
Alpha-adrenergic effects which can lead to hypertension, decreased appetite, tachycardia & palpitations
103
What is the complication associated with long-term nasal decongestant use?
Rhinitis medicamentosa
104
Nasal steroid sprays are considered first-line therapy for what conditions?
* Allergic rhinitis
* Non-allergic rhinitis
* Rhinitis medicamentosa
* Nasal polyps
105
Do systemic corticosteroids have increased efficacy compared to nasal corticosteroids for treatment of allergic rhinitis?
Efficacy is equivalent
106
What is the reason for immunotherapy?
Leads to reduction in mediator release, antigen-induced eosinophil migration, and clinical symptoms from both immediate and late phase reactions
107
What are the immunologic effects of immunotherapy?
* Rise in serum IgG blocking antibody levels
* Suppresion of annual season rise in IgE followed by a decline in the level of specific IgE over the course of immunotherapy
* Increase in IgA and IgG levels in nasal secretions
108
What are the starting doses for immunotherapy?
* 0.05 mL of the endpoint dilution from SDET (dilution that produced the first positive reaction)
* 0.05 mL of endpoint minus 1 or minus 2 for safety based on RAST
109
How are immunotherapy doses escalated?
* Generally, increasing by 0.05 mL each week is safe
* Increasing by 0.10 mL each week may be used for weaker dilutions if well tolerated
* Increasing by 0.20 mL each week may be used for weaker dilutions if shots are given outside of the blooming season
110
How is the maintenance dose decided for immunotherapy?
* Plateau of clinical improvement
* Control of symptoms for at least one week
* Local reaction of 2 to 3 cm that lasts for more than 48 hours
111
When can dosing intervals be lengthened from weekly to every 2 or 3 weeks?
After the first full year of well-controlled symptoms
112
When can immunotherapy be stopped?
After 3 to 5 years of maintenance
113
What are contraindications to immunotherapy?
* Nonimmune mechanism for symptoms
* IgE-mediated mechanism
* Mild symptoms easily controlled by conservative therapy
* Easily avoidable allergen
* Atopic dermatitis
* GI food allergies
* Noncompliant patients
* Patients taking beta-blockers
* Infants and children under 2
* IgE-mediated drug and chemical sensitivity
114
What are the complications of immunotherapy?
* Local reactions-erythema larger than 3 cm with induration and lasting more than 24 hours
* Worsening of allergic symptoms after a shot
* Urticaria or angioedema
* Anaphylactic shock
115
What are the two major types of food allergy?
Cyclic & non-cyclic
116
What are the vast majority of food allergies?
* Cyclic
* 60-95% of cases
* Symptoms not apparent for 4-48 hours
* Mostly IgG-mediated, immune complex
117
What defines non-cyclic food allergies?
* 5 to 40% of cases
* Severity is fixed
* Does not depend on dose or frequency of ingestion
* Onset within minutes
* IgE mediated
118
How is cyclic food allergy diagnosed?
* History-combined with 1 week food diary
* Oral challenge
* 4 days of not eating suspect food, evaluate for symptoms after a large amount is eaten
* Prick testing
* Many false positives and false negatives
* Cyclic food allergy is not IgE mediated
* Provocation (neutralization)
* Allergen given sublingually, subcutaneously, or subdermally
* Watch for onset of symptoms or pattern of skin test reactions
119
How does one treat cyclic food allergy?
* Elimination of food
* Omission for 3 month interals with challenge test feedings for tolerance
* Omission of the food until tolerance develops will then usually allow gradual reintroduction into the diet
120
What organisms are usually associated with allergic fungal sinusitis?
Aspergillus, Bipoaris, Alternaria, Curvularia
121
Name four radiographic features of allergic fungal sinusitis
* Hypercalcified speckling of sinus opacity
* Thickening of sinus walls
* Bone erosion
* Expansion of sinus volumes
122
What are the histopathologic features of allergic fungal sinusitis?
* Allergic mucin with eosinophils
* Charcot-Leyden crystals
* Fungal hyphae
123
What is the major treatment of allergic fungal sinusitis?
Endoscopic drainage
124
What are the major laryngeal manifestations of SLE?
* Thickening of the vocal folds, hoarseness
* Perichondritis/chondritis; loss of laryngeal cartilage support
* Cricothyroid joint arthritis with airway obstruction
125
What are the major nasal manifestations of SLE?
* Butterfly rash over nose and cheeks
* Nasal septal ulcers
* Nasal septal perforation
126
What are the major oral cavity manifestations of SLE?
* Superficial ulcers with surrounding erythema
* Petechiae and hemorrhagic bullae if thrombocytopenia develops
127
What is the difference between primary and secondary Sjogren's syndrome?
Secondary Sjogren's is exocrine gland dysfunction in conjunction with other autoimmune conditions
128
What are the primary manifestations of Sjogren's syndrome?
* Keratoconjunctivitis sicca
* Xerostomia
* Difficulty swallowing
* Dental caries
* Myositis
129
What are the key laboratory markers for Sjogren's syndrome?
* ANA
* anti-SSA
* anti-SSB
* RF
130
What are the key histopathologic findings for Sjogren's syndrome?
Aggregates of lymphoid proliferation around minor salivary gland remants from the lower lip
131
What are the major ENT manifestations of Rheumatoid arthritis?
* TMJ arthritis
* Cricoarytenoid joint arthritis
* Vocal fold thickening
* Cervical spine subluxation
* Synovitis of the ossicular chain which leads to erosion rather than fixation
