Immunology Flashcards
List the four classic types of hypersensitivity reactions.
- Anaphylactic (type I)
- Cytotoxic (type II)
- Immune complex-mediated (type III)
- Cell-mediated/delayed (type IV)
What causes type I hypersensitivity? Give the classic clinical examples.
preformed IgE antibodies that mediate 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 caused by bee stings, food allergy (especially peanuts and shellfish), medications (especially penicillins and sulfa drugs), or rubber glove allergy.
Describe the clinical findings with chronic type I hypersensitivity
Eosinophilia, elevated IgE levels, positive family history, and seasonal exacerbations
physical findings: allergic shiners (bilateral infraorbital edema); transverse nasal crease; Pale, bluish, edematous nasal turbinates with many eosinophils in clear, watery nasal secretions
What medication should be avoided in patients with nasal polyps and why?
Do not give aspirin, which may precipitate a severe asthma attack.
How do you recognize and treat true anaphylaxis?
patient becomes agitated and flushed and develops itching (urticaria), facial swelling (angioedema), and difficulty in breathing; symptoms develop rapidly and dramatically
Treat immediately by securing the airway (laryngeal edema may prevent intubation, in which case do a cricothyroidotomy, if needed) and give sub-cu epinephrine.
- Antihistamines are only useful for cutaneous reactions/itching, not for more severe reactions.
- Use corticosteroids only if the initial treatment options are not available (not a first-line agent).
What usually causes hereditary angioedema?
What is the inheritance pattern?
What do patients experience?
How do you diagnose and treat these patients?
C1 esterase inhibitor (complement) deficiency - AD inheritance (look for (+) family history); patients have diffuse swelling of the lips, eyelids, and possibly the airway, unrelated to allergen exposure.
C4 complement levels are low.
Acute treatment: same as for anaphylaxis (secure airway + sub-cu heparin)
Long-term treatment: Androgens - increase liver production of C1 esterase inhibitor
What type of testing can identify an allergen if it is not obvious?
Skin or patch testing
What causes type II hypersensitivity? List some classic clinical examples.
Type II (cytotoxic) hypersensitivity - 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 purpura).
- Transfusion reactions.
- Erythroblastosis fetalis (Rh incompatibility).
- Goodpasture 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).
What laboratory test is usually positive with a type II hypersensitivity that causes anemia?
Coombs test (usually the direct Coombs test).
What causes type III hypersensitivity? List some classic clinical examples.
antigen-antibody complexes that are usually deposited in vessels and cause an inflammatory response.
Examples include
- serum sickness
- lupus erythematosus
- rheumatoid arthritis
- polyarteritis nodosa
- cryoglobulinemia
- certain types of glomerulonephritis (e.g., from chronic hepatitis)
What causes type IV hypersensitivity? How is it related to tuberculosis testing?
sensitized T lymphocytes that release inflammatory mediators.
Examples: TB skin test (purified protein derivative/PPD), contact dermatitis (especially poison ivy, nickel earrings, cosmetics, and medications), chronic transplant rejection, and granulomas (e.g., sarcoidosis).
What STIs should be considered when a patient’s presenting symptoms include a sore throat and mononucleosis-like syndrome?
HIV infection because initial seroconversion may present as a mononucleosis-like syndrome (e.g., fever, malaise, pharyngitis, rash, lymphadenopathy).
How is HIV diagnosed? How long after exposure does the HIV test become positive?
diagnosed with ELISA, which if (+), is confirmed with a western blot
It takes 6 to 12 weeks for antibodies to develop in the majority of patients, so these tests will likely be negative if done prior to this. Since antibodies are present by 6 months in 95% of patients, patients should be retested in 6 months if the initial test is negative
Rapid tests are available, but predictive accuracy is low and therefore (+) tests require confirmatory testing with ELISA and Western blot. Negative test results are reliable unless the patient is in the window period of acute HIV infection.
Are “control” tests needed when a PPD tuberculosis test is done in HIV-positive patients?
No
How do you recognize Pneumocystis jiroveci pneumonia (PCP)?
What are some symptoms?
What are some findings that would indicate PCP? How do you cinch the diagnosis?
How is it treated?
For the Step 2 examination, think of PCP first in any patient with HIV and pneumonia, even though community-acquired pneumonia is more common even in patients with AIDS.
Symptoms: dry, nonproductive cough
Diagnosis:
- Look for severe hypoxia with normal radiographs or diffuse bilateral interstitial infiltrates
- PCP may be detected with silver stains (Wright-Giemsa, Giemsa, or methenamine silver) applied to induced sputum or bronchoscopy specimens
- High levels of lactate dehydrogenase are suspicious in the appropriate setting
Treatment: TMP-SMX with corticosteroids
What is the most common primary immunodeficiency?
How do you recognize it?
What should you avoid giving in these patients?
IgA deficiency - causes recurrent respiratory and GI infections.
Do not give Ig’s, which may cause anaphylaxis because of pre-formed anti-IgA antibodies. If any patient develops anaphylaxis after Ig exposure, you should think of IgA deficiency.
What is Bruton agammaglobulinemia?
What is the inheritance pattern?
How do you recognize it?
X-linked recessive disorder with low or absent B cells that affects males (B for boy); results in recurrent lung or sinus infections with Streptococcus and Haemophilus spp.
Infections begin after 6 months of age when maternal antibodies disappear.
What causes DiGeorge syndrome? How do you recognize it?
How is it diagnosed?
22q11 deletion -> failure to develop 3rd and 4th pharyngeal pouches –> absent thymus and parathyroids. Also results in
- congenital heart defects and typical facies are also present
- recurrent viral/fungal infections due to T cell deficincy
results in hypocalcemia and tetany in the first 24 hours of life
dx: decreased T cells, PTH, Ca2+. Absent thymic shadow on CXR., FISH 22q11 deletion
What is the classic cause of severe combined immunodeficiency (SCID)? How does it present?
may be autosomal recessive (IL-2R) or X-linked (ADA deficiency - more common)
Patients have B- and T-cell defects and severe infections (fungal, viral, bacterial, and protozoa) in the first few months of life, resulting in failure to thrive, chronic diarrhea, thrush.
Diagnosis: absent thymic shadow on CXR, LN biopsy
Treatment: bone marrow transplant
What triad indicates the diagnosis of Wiskott-Aldrich syndrome?
X-linked recessive mutation in WAS gene resulting in T cells that are unable to reorganize actin cytoskeleton; affects males
Results in WATER: Wiskott-Aldrich
- Thrombocytopenia (look for bleeding)
- Eczema
- Recurrent infections (usually respiratory)
How do you recognize Chediak-Higashi syndrome?
- autosomal recessive resulting in a defect in genes regulating lysosomal trafficking and microtubule dysfunction
- Presentation: recurrent infections by staph and strep, oculocutaneous albinism. peripheral neuropathy, progressive neurodegeneration
- Dx: giant granules in neutrophils and platelets
Describe the pathophysiology of chronic granulomatous disease (CGD).
Which organisms are they most susceptible to? 7
How to diagnose it?
X-linked recessive d/o; affects males
Defect of NADPH oxidase -> decrased ROS (e.g., superoxide) and absent respiratory burst in neutrophils -> recurrent infections with catalase (+) organisms (PLACESS):
- Pseudomonas
- Listeria
- Aspergillus
- Candida
- E. coli
- S. aureus
- Serratia
Diagnose with Nitroblue tetrazolium (NBT), which measures the resspiratory burst (which NBT patients lack). However, this test has fallen out of favor and now the preferred diagnostic test is Abnormal dihydrorhodamine (flow cytometry) test.
After HIV diagnosis, how often do you check the CD4 count?
Every 3-4 months. Every 6 months for patients who are adherent to therapy with sustained viral suppression and stable clinical status for more than 2-3 years.
When do you start antiretroviral therapy?
When the CD4 count is less than 350/mm3 or if there is a history of an AIDS-defining illness. Also should be initiated in pregnant women, in patients with HIV-associated nephropathy, and in patients with hepatitis B coinfection.
What are the AIDS-defining illnesses?
ß
When do you start PCP prophylaxis?
When the CD4 count is less than 200/mm3 or a history of oropharyngeal candidiasis
What is the drug of choice for PCP prophylaxis?
Trimethoprim-sulfamethoxazole (Bactrim)
What other agents are used in patients with allergy or intolerance to Bactrim?
Dapsone, aerosolized pentamidine, and atovaquone
When should you start Mycobacterium avium complex (MAC) prophylaxis?
When the CD4 count is less than 50/mm3
What drugs are used for MAC prophylaxis?
Clarithromycin or azithromycin (rifabutin is an alterative)
True or false: Once the CD4 count is
True
True or false: Give the measles-mumps-rubella vaccine.
True (CD4 count must be greater than 200/mm3)
True or false: Give the varicella vaccine.
True, if patient does not have evidence of immunity (CD4 count must be greater than 200/mm3)
True or false: Do not give annual influenza vaccines.
False (give every year to all HIV-infected patients)
True or false: Pneumococcal vaccine should be given.
True. It should be given to all HIV-infected patients, and revaccination every 5 years should be considered
True or false: Give hepatitis A vaccine.
True, if the patient has chronic liver disease or is at increased risk for hepatitis A infection
True or false: Give hepatitis B vaccine.
True
True or false: PPD testing should be done annually.
True, if the initial test is negative and the patient is high-risk
True or false: Oral polio vaccine should be given to patients who are at risk of exposure through travel or work.
False (use inactive polio vaccine injection)
The risk of which cancer is increased on skin and in the mouth?
Kaposi sarcoma
The risk of which type of blood cell cancer is increased?
Non-Hodgkin lymphoma (usually primary B-cell lymphomas of CNS)
What do positive India ink preparations of the cerebrospinal fluid mean?
Cryptococcus neoformans meningitis
What do ring-enhancing lesions in the brain on CT or MR scans usually mean?
Toxoplasmosis, cysticercosis/Taenia solium, or lymphoma
True or false: HIV may cause thrombocytopenia.
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-positive mothers may breast-feed their infants.
False (breast milk transmits HIV)
What is the first-choice agent for cytomegalovirus retinitis?
Valganciclovir
What are the second-choice agents for cytomegalovirus retinitis?
Ganciclovir, foscarnet, or cidofovir
True or false: Pregnant patients should receive anti-retroviral therapy.
True. Three-drug therapy is currently recommended (no different for the pregnant female; earlier administration is best)
True or false: Infants born to HIV-positive mothers should take zidovudine (ZDV).
True (for at least 6 weeks after delivery)
True or false: Cesarean section increases maternal HIV transmission.
False (it may decrease transmission to the infant)
What is the most likely cause of pneumonia in HIV-positive patient?
Streptococcus pneumoniae
What is the most likely cause of opportunistic pneumonia in HIV-positive patient?
Pneumocystis jiroveci
What is the stain used on sputum to detect PCP?
Silver (Wright-Giemsa or Giemsa)
What are the two pathogens that cause chronic diarrhea only in AIDS?
Cryptosporidium and Isospora spp.
True or false: Herpes-zoster infection in young adults = possible HIV infection.
True (suggests immunodeficiency)
True or false: Thrush in young adults may mean HIV infection.
True (also associated with diabetes, leukemia, and steroids)
True or false: A positive HIV antibody test in a newborn is unreliable.
True (maternal antibodies in the neonate can give a false-positive result for the first 6 months)
Complement deficiencies of C5 through C9 cause recurrent/increased susceptbility to infections with which genus of bacteria?
Neisseria species.
Define chronic mucocutaneous candidiasis.
What is this most offen associated with?
T cell dysfunction; many causes that result in non-invasive candida albicans infection of skin/mucous membranes, as well as anergy to Candida sp. with skin testing.
It is often associated with hypothyroidism.
The rest of the immune function is intact; no other types of infections are present.
Give the classic description of hyper-IgE syndrome (Job-Buckley syndrome).
Patients with hyper-IgE syndrome have impared recruitment of PMNs to sites of infection, resulting in recurrent stap infections (especially of the skin) and have extremely high IgE levels. They also commonly have fair skin, red hair, and eczema.
Mnemonic: FATED
- coarse Facies,
- cold (noninflamed) staphylococcal Abscesses
- retained primary Teeth
- high IgE, low IFNg
- Dermatologic problems (eczema)
