Immune-System Diseases

Hypersensitivity Reactions (Gell And Coombs)

The four-type classification is one of the highest-yield immunology topics on the MLS exam. Memorize the mediator and timing of each.

A common trap: the PPD (tuberculin) skin test is type IV (delayed, T-cell), read at 48-72 hours, while anaphylaxis is type I (immediate, IgE). The presence of antibody distinguishes I-III from the antibody-free type IV.

Autoimmune Diseases And Their Marker Antibodies

When autoimmunity breaks self-tolerance, the resulting autoantibody pattern names the disease. The exam expects you to match each antibody to its condition.

Worked example: A young woman has a positive ANA with a homogeneous immunofluorescence pattern, plus a positive anti-dsDNA and a malar rash. The combination of a sensitive ANA confirmed by the highly specific anti-dsDNA points to SLE; anti-dsDNA titers also correlate with disease activity and lupus nephritis.

ANA Patterns

When ANA is detected by indirect immunofluorescence on HEp-2 cells, the staining pattern suggests the underlying antibody:

• Homogeneous (diffuse): anti-dsDNA, anti-histone → SLE, drug-induced lupus.
• Speckled: anti-Sm, anti-RNP, anti-SS-A/SS-B → mixed connective tissue disease, Sjögren.
• Nucleolar: anti-Scl-70 → scleroderma.
• Centromere: anti-centromere → CREST.
• Rim/peripheral: anti-dsDNA → SLE (high specificity).

ANA is highly sensitive for SLE (a negative result largely rules it out) but not specific, so a positive ANA must be confirmed by the disease-specific antibodies above.

Immunodeficiency Disorders

Primary (congenital) immunodeficiencies are intrinsic defects:

• DiGeorge syndrome: thymic aplasia → absent T cells (cellular immunity); associated hypocalcemia and cardiac defects.
• Bruton agammaglobulinemia: X-linked, absent B cells → no antibody.
• Severe combined immunodeficiency (SCID): both T- and B-cell function absent; "bubble boy" disease.
• Selective IgA deficiency: the most common primary immunodeficiency; recurrent mucosal infections and a risk of anaphylactic transfusion reactions to IgA in blood products.
• Chronic granulomatous disease: phagocyte defect (failed oxidative burst), diagnosed historically by the nitroblue tetrazolium (NBT) test.

Secondary (acquired) immunodeficiency is far more common. HIV is the leading global cause; the virus infects CD4+ T cells, progressively depleting them. An AIDS diagnosis is associated with a CD4 count below 200 cells/µL and an inverted CD4:CD8 ratio (<1). Other secondary causes include malignancy, chemotherapy, corticosteroids, malnutrition, and protein loss.

High-Yield Traps

• Rheumatoid factor is an IgM antibody directed against the Fc of IgG — it can also be positive in Sjögren and chronic infections, so anti-CCP is the more specific RA marker.
• ANA is the screen, not the confirmation, for SLE; do not call a disease based on ANA alone.
• A transfusion reaction and hemolytic disease of the newborn are type II (cytotoxic), not type III.
• IgA-deficient patients can have anaphylactic reactions to plasma-containing products; they need washed or IgA-deficient components.

Mechanisms Of Autoimmunity And Tolerance

The immune system normally maintains self-tolerance by deleting or inactivating lymphocytes that react to self (central tolerance in the thymus and bone marrow, peripheral tolerance in the tissues). Autoimmune disease arises when tolerance breaks down. Tested mechanisms include molecular mimicry (a microbial antigen resembles a self antigen, so anti-microbial antibody cross-reacts with host tissue — as in rheumatic fever after group A streptococcal infection), release of sequestered self-antigens, and loss of regulatory T-cell control.

Autoimmune diseases can be organ-specific (Hashimoto thyroiditis, type 1 diabetes, Graves disease) or systemic (SLE, rheumatoid arthritis), and the exam expects you to place each disease on this spectrum.

Worked example: A child develops carditis and migratory arthritis weeks after a sore throat, with a high anti-streptolysin O (ASO) titer. The streptococcal antigen mimicked cardiac and joint tissue, so cross-reacting antibody now attacks self — a molecular-mimicry mechanism producing rheumatic fever.

Allergy And The Atopic Response

Type I hypersensitivity deserves its own focus because allergy testing appears in the immunology domain. On first exposure, an allergen drives IgE production; that IgE binds Fc receptors on mast cells and basophils (sensitization). On re-exposure, the allergen cross-links surface IgE, triggering degranulation and release of histamine, leukotrienes, and prostaglandins. Clinical results range from localized hay fever and urticaria to systemic anaphylaxis.

Laboratory clues to atopy and allergy include:

• Elevated total IgE and eosinophilia on the differential.
• Allergen-specific IgE testing (formerly RAST, now fluorescent or chemiluminescent immunoassay) to identify the offending allergen.
• Tryptase, a mast-cell enzyme, rising transiently after anaphylaxis.

A frequent trap is confusing the immediate IgE-mediated reaction (type I) with the delayed T-cell reaction of contact dermatitis (type IV); the timing — minutes versus 48-72 hours — and the presence or absence of antibody distinguish them. Severe combined immunodeficiency, by contrast, removes both antibody and T-cell defenses and presents in infancy with overwhelming infections.