19. IMMUNOLOGY
1. List the four classic types of hypersensitivity reactions.
• Anaphylactic (type I) • Immune complex-mediated (type III)
• Cytotoxic (type II) • Cell-mediated/delayed (type IV)
2. What causes type I hypersensitivity? Give the classic clinical examples.
Type I (anaphylactic) hypersensitivity is due to preformed IgE antibodies that cause release
of vasoactive amines (e.g.. histamine, leukotrienes) from mast cells and basophils. Examples are
anaphylaxis, atopy, hay fever, urticaria, allergic rhinitis, and some forms of asthma. Anaphylaxis
may be due to bee stings, food allergy (especially peanuts and shellfish), medications (especially
penicillins and sulfa drugs), or rubber glove allergy.
3. Describe the clinical findings with chronic type I hypersensitivity.
Look for eosinophilia, elevated IgE levels, positive family history, and seasonal exacerba-
tions. Patients also may have allergic "shiners" (bilateral infraorbital edema), and a transverse
nasal crease (due to frequent nose rubbing). Pale, bluish, edematous nasal turbinates with many
eosinophils in clear, watery nasal secretions are also classic.
4. What medication should be avoided in patients with nasal polyps?
Do not give aspirin, which may precipitate a severe asthma attack.
5. How do you recognize and treat true anaphylaxis?
Look for the classic triggers mentioned above just before the patient becomes agitated and
flushed and develops itching (urticaria), facial swelling (angioedema), and difficulty in breath-
ing. Symptoms tend to develop rapidly and dramatically.
Treat immediately by securing the airway (laryngeal edema may prevent intubation, in which
case do a cricothyrotomy, if needed) and give subcutaneous epinephrine. Antihistamines are only
useful for cutaneous reactions and itching, not for more severe reactions. Use corticosteroids only
if the initial treatment options are not available (not a first-line agent).
6. What usually causes hereditary angioedema?
A deficiency of Cl esterase inhibitor (complement) is the usual cause of hereditary
angioedema. Patients have diffuse swelling of lips, eyelids, and possibly the airway, unrelated to
allergen exposure. The disease is autosomal dominant; look for a positive family history. C4 com-
plement levels are low. Acute treatment is the same as for anaphylaxis. Androgens are used for
long-term treatment because they increase liver production of Cl esterase inhibitor.
7. What type of testing can identify an allergen if it is not obvious?
Skin or patch testing.
8. What causes type II hypersensitivity? List some classic clinical examples.
Type II (cytotoxic) hypersensitivity is due to preformed IgG and IgM antibodies that react
with the antigen and cause secondary inflammation. Examples include the following:
• Autoimmune hemolytic anemia (classically caused by methyldopa, penicillins, or sulfa
drugs) or other cytopenias caused by antibodies (e.g., idiopathic thrombocytopenic pur-
pura)
• Transfusion reactions
• Erythroblastosis fetalis (Rh incompatibility)
112
immunology 113
Patch testing. A battery of common 1 I |
and suspected allergens isapplied to
the back for 48 hours. The skin is then
examined at 96 hours. Irritant reac-
tions disappear, allergic ones do not.
Two positives are present. (From du
Vivier A: Atlas of Clinical Dermatol-
ogy, 3rd ed. New York, Churchill Liv-
ingstone, 2002, p 65, with permission.)
• Goodpasture's syndrome (watch for linear immunofluorescence on kidney biopsy)
• Myasthenia gravis
• Graves' disease
• Pernicious anemia
• Pemphigus vulgaris
• Hyperacute transplant rejection (as soon as the anastomosis is made at transplant surgery,
the transplanted organ deteriorates in front of the surgeon's eyes).
9. What lab test is usually positive with a type II hypersensitivity that causes anemia?
Coombs' test (usually the direct Coombs' test).
10. What causes type III hypersensitivity? List some classic clinical examples.
Type III (immune complex-mediated) hypersensitivity is due to antigen-antibody complexes
that usually are deposited in vessels and cause an inflammatory response. Examples include
serum sickness, lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa, cryoglobuline-
mia, and certain types of glomerulonephritis (e.g., from chronic hepatitis).
11. What causes type IV hypersensitivity? How is it related to tuberculosis testing?
Type IV (cell-mediated/delayed) hypersensitivity is due to sensitized T lymphocytes that
release inflammatory mediators. The tuberculosis skin test (purified protein derivative [PPD])
exploits this immune system reaction. Other examples include contact dermatitis (especially
poison ivy, nickel earrings, cosmetics, and medications), chronic transplant rejection, and granu-
lomas (e.g., sarcoidosis).
12. What sexually transmitted infectious disease should be in the back of your mind when
a patient presents with a sore throat and mononucleosis-like syndrome?
Human immunodeficiency virus (HIV) infection, because initial seroconversion may present
as a mononucleosis-like syndrome (e.g., fever, malaise, pharyngitis, rash, lymphadenopathy).
13. How is HIV diagnosed? How long after exposure does the HIV test become positive?
Diagnosis is made with the enzyme-linked immunosorbent assay (ELISA), which, if posi-
tive, should be confirmed with a Western blot test. All of these tests should be done before you
tell the patient anything. It takes at least 1 month for antibodies to develop. Therefore, if a patient
wants testing because of recent risk-taking behavior, you should retest the patient in 6 months if
the initial test is negative.
14. What is the reason for doing "control" tests when a PPD tuberculosis test is done in
HIV-positive patients?
Though now more controversial, control tests make sure that a negative PPD result is mean-
ingful. If a patient is anergic or fails to mount an immune response, a negative PPD means little.
If the control skin tests (usually candidal infection and mumps, to which everyone in the U.S. is
114 Immunology
exposed ) give positive results (which are normal in healthy people) and the PPD gives a nega-
tive result, you should feel more comfortable in saying that the patient probably does not have
tuberculosis (although the PPD test is not 100% sensitive).
15. How do you recognize Pneumocystis carinii pneumonia (PCP)?
For the Step 2 exam, think of PCP first in any patient with HIV and pneumonia, even though
community-acquired pneumonia is more common even in patients with AIDS. Look for severe
hypoxia with normal radiographs or diffuse, bilateral interstitial infiltrates (see figure). Patients
usually have a dry, nonproductive cough. PCP may be detected with silver stains (Wright-
Giemsa, Giemsa, or methenamine silver) applied to induced sputum; if not, you can use bron-
choscopy with bronchoalveolar lav age and brush biopsy to make the diagnosis. High levels of
lactate dehydrogenase are suspicious in the appropriate setting. PCP is now usually treated pre-
sumptively, with diagnostic testing reserved for those in whom the diagnosis is unclear or initial
treatment fails.
Pneumocystis carinii pneumonia in a patient with AIDS.
Extensive, predominantly central, interstitial opacities are
present bilaterally, right greater than left. (From Hoffbrand
AV, Pettit IE: Color Atlast of Clinical hematology, 3rd ed. St.
Louis, Mosby, 2000, p 136, with permission.)
16. What is the most common primary immunodeficiency? How do you recognize it?
IgA deficiency, which causes recurrent respiratory and gastrointestinal infections. IgA levels
are always low, and levels of IgG subclass 2 may be low. Do not give immunoglobulins, which
may cause anaphylaxis due to development of anti-IgA antibodies. Alternatively, if any patient
develops anaphylaxis after immunoglobulin exposure, you should think of IgA deficiency.
17. How do you recognize Bruton's agammaglobulinemia?
Bruton's agammaglobulinemia (X-linked agammaglobulinemia) is an X-linked recessive
disorder with low or absent B cells that affects males. Infections begin after 6 months when
maternal antibodies disappear. Look for recurrent lung or sinus infections with Streptococcus and
Hemophilus species.
18. What causes DiGeorge's syndrome? How do you recognize it?
DiGeorge's syndrome is caused by hypoplasia of the third and fourth pharyngeal pouches.
Look for hypocalcemia and tetany (from hypocalcemia due to absent parathyroid glands) in the
first 24-48 hours of life. The thymus also may be absent or hypoplastic, and congenital heart
defects and typical facies often are present.
19. What is the classic cause of severe combined immunodeficiency? How does it present?
Severe combined immunodeficiency may be autosomal recessive or X-linked. The classic
cause is adenosine deaminase deficiency (autosomal recessive). Patients have B- and T-cell
defects and severe infections in the first few months of life. Other symptoms include cutaneous
anergy and absent or dysplastic thymus and lymph nodes.
Immunology 115
20. What triad indicates the diagnosis of Wiskott-Aldrich syndrome?
Wiskott-Aldrich deficiency is an X-linked recessive disorder that affects males. The classic
triad consists of eczema, thrombocytopenia (look for bleeding), and recurrent infections (usually
respiratory).
21. How do you recognize Chediak-Higashi syndrome?
Chediak-Higashi syndrome is usually an autosomal recessive disorder characterized by giant
granules in neutrophils, infections, and often oculocutaneous albinism. It is caused by a defect in
microtubule polymerization.
22. Describe the pathophysiology of chronic granulomatous disease.
Chronic granulomatous disease is usually an X-linked recessive disorder that affects males.
Because of a defect in the activity of reduced nicotinamide adenine dinucleotide phosphate
(NADPH) oxidase, patients have recurrent infections with catalase-positive organisms (e.g.,
Staphylococcus aureus, Pseudomonas species). Diagnosis is clinched if the question mentions
deficient nitroblue tetrazolium dye reduction by granulocytes. This test measures the respiratory
burst, which patients with chronic granulomatous disease lack.
23. Cover the right-hand column, and answer the questions about HIVmanagement on the
left.
QUESTION ANSWER
After HIV diagnosis, how often do you check the CD4 Every 6 months
count?
When do you start antiretroviral therapy? When the CD4 count is < 500/mm 3
(or sooner)
When do you start PCP prophylaxis? When the CD4 count is < 200/mm 3
What is the drug of choice for PCP prophylaxis? Trimethoprim-sulfamethoxazole
(Bactrim)
What other agents are used in patients with allergy or Dapsone and pentamidine
intolerance to Bactrim?
When should you start Mycobacterium avium complex When the CD4 count is < 100/mm 3
(MAC) prophylaxis?
What drugs are used for MAC prophylaxis? Clarithromycin, azithromycin,
or rifabutin
True or false: Once the CD4 is < 200/mm 3, the patient isTrue
automatically considered to have AIDS (even without
opportunistic infections).
True or false: Give the measles-mumps-rubella vaccine. True (only live vaccine that is
given)
True or false: Do not give annual influenza vaccines. False (give every year)
True or false: PPD testing should be done annually. True
True or false: Oral polio vaccine should be given to patientsFalse (use inactive polio vaccine
and their contacts. injection)
The risk of which cancer is increased on skin and in theKaposi's sarcoma
mouth?
The risk of which type of blood cell cancer is increased?Non-Hodgkin's lymphoma
(usually primary B-cell lym-
phomas of CNS)
What do positive India ink preparations of the cerebrospinalCryptococcus neoformans
fluid mean? meningitis
What do ring-enhancing lesions in the brain on CT or MR Toxoplasmosis, cysticercosis/
scans usually mean? Taenia solium, or lymphoma
True or false: HIV may cause thrombocytopenia. True
116 Immunology
QUESTION ANSWER
True or false: Give pneumococcal and hepatitis vaccines.True
True or false: HIV can cause dementia. True
True or false: HIV protects against peripheral neuropathies.False (HIV can cause them)
True or false: HIV mothers may breast-feed their infants.False (breast milk transmits HIV)
First-choice agent for cytomegalovirus retinitis. Ganciclovir/valganciclovir
Second-choice agents for cytomegalovirus retinitis. Foscarnet or cidofovir
True or false: Pregnant patients should take zidovudine (AZT)True.
True or false: Infants born to HIV-positive mothers shouldTrue (for the first 6 weeks after
take AZT. delivery)
True or false: Cesarean section increases maternal HIV False (it may decrease transmission
transmission. to child)
Most likely cause of pneumonia in HIV patient Streptococcus pneumoniae
Most likely cause of opportunistic pneumonia in HIV patienPneumocystist carinii
Stain used on sputum to detect PCP Silver (Wright-Giemsa or Giemsa)
Two pathogens that cause chronic diarrhea only in AIDS. Cryptosporidium and Isospora spp.
True or false: Herpes-zoster infection in young adults =True (suggests immunodeficiency)
possible HIVinfection.
True or false: Thrush in young adults may mean HIV True (also assocated with diabetes,
infection leukemia, and steroids)
True or false: A positive HIV antibody test in a newborn iTruse (maternal antibodies in the
unreliable neonate can give a false-positive
result for the first 6 months)
24. Complement deficiencies of C5 through C9 cause recurrent infections with which genus
of bacteria?
Neisseria spp.
25. Define chronic mucocutaneous candidiasis.
Chronic mucocutaneous candidiasis is a cellular immunodeficiency specific for candidal
infection. Patients have thrush and candidal infections of the scalp, skin, and nails as well as
anergy to Candida sp. with skin testing. Often it is associated with hypothyroidism. The rest of
the immune function is intact; no other types of infections are present.
26. Give the classic description of hyper-IgE syndrome (Job-Buckley syndrome).
Patients with hyper-IgE syndrome have recurrent staphylococcal infections (especially of the
skin) and have extremely high IgE levels. They also commonly have fair skin, red hair, and
eczema.
