Immunology Flashcards
B cells vs T cells
B cells make immunoglobulins and are responsible for immunity against extracellular bacteria.
T cells are responsible for immunity against intracellular bacteria, viruses and fungi
Immunodeficiency disorders general
Congenital immunodeficiencies are rare and often present with chronic or recurrent infections (chronic thrush), unusual or opportunistic organisms, incomplete treatment response, or FTT
B cell deficiencies
Most common (50%). Typically present after 6 months of age with recurrent sinopulmonary, GI, and urinary tract infections with encapsulated organisms (H flu, strep pneumo, neisseria meningitides). Treat with IVIG (except for IgA deficiencies)
1) Bruton’s - can be confused with transient hypogammaglobulinemia of infancy (THI) as both are characterized by increased susceptibility at 6mo of age when trasplacental maternal IgG is no longer active. Low B cells in Bruton’s
2) CVID - older males and females (15-35) and less severe
3) IgA
T cell deficiencies
Tend to present earlier (1-3months) with opportunistic and low-grade fungal, viral and intracellular bacterial infections (mycobacteria).
Secondary B-cell dysfunction may also be seen
1) DiGeorge
Phagocyte deficiencies
Characterized by mucous membrane infections, abscesses and poor wound healing
Infections with catalase positive organisms (S aureus), fungi, and gram negative enteric organisms are common
1) CGD
2) LAD
3) Chediak-Higashi
4) Job’s
Complement deficiencies
Present in children with congenital asplenia or splenic dysfunction (sickle cell). Characterized by recurrent bacterial infections with encapsulated organisms.
1) C1 esterase deficiency (hereditary angioedema)
2) Terminal complement deficiency (C5-C9)
Combined disorders
1) Ataxia Telangiectasia
2) SCID
3) Wiskott-Aldrich Syndrome
Bruton’s Congenital Agammaglobulinemia
1) X linked recessive B cell deficiency found only in boys*
2) Symptoms begin after 6 months of age when maternal IgG is no longer active
3) Life threatening, characterized by encapsulated pseudomonas, strep pneumo, H flu infections after 6 months of age
4) Quantitative Ig levels. If low, conform with B and T cell subsets (B cells are absent, T is often high). Absent tonsils and other lymphoid tissue may provide a clue
5) Treat with ppx ABx and IVIG
Common Variable Immunodeficiency
1) Usually a combined B and T cell defect. All Ig levels are low (in the 20s and 30s). Normal B cell numbers; low plasma cells. Symptoms usually later in life (15-35years)
2) Increased pyogenic upper and lower respiratory infections. Increased risk of lymphoma and autoimmune disease
3) Quantitative Ig levels. Confirm with B and T cell subsets.
4) Treat with IVIG
IgA deficiency
1) Mild; most common immunodeficiency. Reduced IgA only
2) Usually ASx; patients may develop recurrent respiratory or GI infections (Giardia).
3) Anaphylactic transfusion rxn due to anti-IgA antibodies is a common presentation
4) Quantitative IgA levels; treat infections
5) DO NOT GIVE IVIG, as it can lead to production of anti-IgA antibodies
Thymic aplasia (DiGeorge)
1) Presents with tetany (secondary to hypocalcemia) in first days of life. CATCH-22 (Cardiac abnormalities, Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia, chromosome 22
2) Variable risk of infection. Greatly increased infections with viruses, fungi, and PCP. XR may show absent thymic shadow
3) Absolute lymphocyte count; mitogen stimulation response; delayed hypersensitivity skin testing
4) Treat with bone marrow transplant and IVIG for antibody deficiency. Give PCP ppx. Thymus transplant is an alternative
Ataxia telangiectasia
1) Progressive cerebellar ataxia and oculocutaneous telangiectasias. Caused by DNA repair defect
2) Increased incidence of malignancies, including non-Hodgkin’s lymphoma, leukemia, and gastric carcinoma
3) No specific tx, may require IVIG depending on severity of Ig deficiency
SCID
1) Severe lack of B and T cells due to defect in stem cell maturation and reduced adenosine deaminase. Referred to as “bubble boy disease” bc children are often confined to an isolated, sterile environment
2) Severe, frequent bacterial infections; chronic candidiasis; opportunistic organisms
3) Treat with bone marrow or stem cell transplant and IVIG for antibody deficiency. Requires PCP ppx
Wiskott-Aldrich
1) X linked recessive only in boys. Symptoms usually present at birth. Patients have high IgE and IgA. Low IgM and low platelets.
2) Classic presentation involves bleeding, eczema, and recurrent otitis media. WIPE - Wiskott Infections Purpura Eczema
3) Increased risk of atopic disorders, lymphoma/leukemia and infection from strep pneumo, staph aureus, and HfluB (encapsulated organisms)
4) Treatment is supportive (IVIG and ABx). Patients rarely survive to adulthood. Patients with severe infections may be treated with bone marrow transplant
CGD
1) X linked (two thirds) or autosomal recessive disease with deficient superoxide production by PMNs and macrophages
2) Anemia, lymphadenopathy, and hypergammaglobulinemia may be present
3) Chronic skin, LN, pulmonary, GI and urinary tract infections; osteomyelitis and hepatitis. Infecting organisms are catalase positive (Aureus, E Coli, Candida, Kleb, Pseudomonas, Aspergillus)
4) May have granulomas of the skin and GI/GU tracts
5) Absolute neutrophil count with neutrophil assays. The nitroblue tetrazolium test is diagnostic.
6) Treat with daily Bactrim; make judicious use ofABx during infections. IFN-gamma can reduce incidence of serious infection. Bone marrow transplant and gene therapy are new therapies
Leukocyte Adhesion Deficiency
1) Defect in chemotaxis of leukocytes
2) Recurrent skin, mucosal, and pulmonary infection. May present as omphalitis in the newborn period with delayed separation of the umbilical cords*
3) No pus with minimal inflammation in wounds (due to chemotaxis defect). High WBCs in blood. Bone marrow transplant is curative.
Chediak-Higashi
1) Auto recessive disorder that leads to defect in neutrophil chemotaxis/microtubule polymerization
2) The syndrome includes partial oculocutaneous albinism, peripheral neuropathy, and neutropenia
3) Increased incidence of overwhelming pyogenic infections with strep pyogenes, staph aureus, and pseudomonas
4) Look for giant granules in neutrophils
5) Bone marrow transplant is treatment of choice
Job’s Syndrome
1) A defect in neutrophil chemotaxis. FATED - coarse Facies, Abscesses (staph aureus), Teeth (retained primary), hyper IgE, Derm (severe eczema)
2) Recurrent staph aureus infections and abscesses
3) Treat with penicillinase-resistant antibiotics and IVIG
C1 esterase deficiency (hereditary angioedema)
1) Auto dominant* with recurrent episodes of angioedema lasting 2-72h and provoked by stress or trauma
2) Can lead to life threatening airway edema
3) Total hemolytic complement (CH50) to assess the quantity and function of complement. Purified C1 esterase and FFP can be used prior to surgery
Terminal complement deficiency (C5-C9)
1) Inability to form MAC
2) Recurrent Neisseria infections, meningococcal or gonococcal. Rarely, lupus or glomerulonephritis.
3) Meningococcal vaccine and appropriate ABx
Kawasaki Disease
Multisystemic acute vasculitis that primarily affects young children (80% are less than 5 years old), particularly those of Asian ancestry. Divided into acute, subacute and chronic phases.
Acute phase of Kawasaki
Lasts 1-2w and presents with following symptoms (fever plus 4 or more of below stuff required for dx)
1) Fever. Usually above 104 for at least 5d
2) Bilateral, nonexudative painless conjunctivitis sparing the limbus
3) Polymorphous rash (mostly truncal)
4) Cervical LAD (often painful and unilateral, with at least 1 node above 1.5cm)
5) Diffuse mucous membrane erythema (strawberry tongue); dry, red, chapped lips
6) Erythema of the palms and soles; indurative edema of the hands and feet; late desquamation of the fingertips (in subacute phase)
7) Other manifestations include sterile pyuria, gallbladder hydrops, hepatitis, arthritis
Subacute Kawasaki
Begins after abatement of fever and typically lasts an extra 2-3w.
Manifestations are thrombocytosis and high ESR.
Untreated kids may begin to develop coronary artery aneurysms (40%). All patients should be assessed by Echo at diagnosis
Chronic Kawasaki
Begins when all clinical symptoms have disappeared; lasts until ESR returns to baseline. Untreated children are at risk of aneurysmal expansion and MI.
Symptoms of Kawasaki shortcut
CRASH and BURN
Conjunctivitis Rash Adenopathy (unilateral) Strawberry tongue Hands and feet (red, swollen, flaky skin)
BURN (fever over 104 for 5 or more days)
Scarlet fever looks similar, but doesn’t have any lip or conjunctival involvement.
Tx of Kawasaki
1) High dose ASA (for inflammation and fever) and IVIG (to prevent aneurysm)
2) Low dose ASA is then continued usually for 6w. Kids who develop coronary artery aneurysms may require chronic anticoagulation with ASA or other antiplatelet meds
3) Corticosteroids may be used in IVIG-refractory cases, but routine use is not recommended
Juvenile Idiopathic Arthritis
An autoimmune disorder manifesting as arthritis with morning stiffness and gradual loss of motion that is present for at least 6w in patient under 16 years old. Formerly known as juvenile RA.
Dx of JIA
1) Pauciarticular (oligoarthritis): most common; involves 4 or fewer joints (usually weight bearing); usually ANA positive and RF negative. Involves young females. Uveitis is common and requires slit-lamp exam for eval. No systemic symptoms
2) Polyarthritis: Involves 5 or more joints. Symmetric. RF positivity is rare and indicated severe disease; younger children may be ANA positive with milder disease. Systemic symptoms rare
3) Systemic-onset (Still’s Disease): May present with recurrent high fever (usually above 102.2), HSM, and a salmon-colored macular rash; usually RF and ANA neg
Tx of JIA
1) NSAIDs and strengthening exercises
2) steroids (for carditis) and immunosuppressive meds (methotrexate, anti-TNF agents like etanercept) are second line
