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Answer these questions, should be brief and to the point, and also show me diagrams where necessary

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tuberculin skin test AND hypersensitivity

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CDC tuberculin skin test interpretation 5 10 15 mm BCG vaccination

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https://www.cdc.gov/tb/hcp/testing-diagnosis/tuberculin-skin…

4A. Types of serological tests

A. Primary serological tests
Detect the initial binding between antigen and antibody. The reaction is not visible and needs a label/instrument.
Examples: ELISA, radioimmunoassay (RIA).

B. Secondary serological tests
Detect visible effects of antigen-antibody binding such as clumping or precipitate formation.
Examples: agglutination test, precipitation/immunodiffusion test.

C. Tertiary serological tests
Detect the biological effects produced by antigen-antibody reactions in cells or living systems.
Examples: complement fixation test, neutralization test.

4B. Agglutination vs precipitation

Feature	Agglutination	Precipitation
Antigen	Particulate/insoluble, e.g. cells, bacteria, latex particles	Soluble antigen
Visible result	Clumping of particles	Insoluble precipitate or precipitin line/ring
Example	Widal test, latex RF test	Ouchterlony test, radial immunodiffusion

4C. Principle of radial immunodiffusion (RID)

Antigen placed in a well diffuses radially into agar containing specific antibody. At the zone of equivalence, a precipitin ring forms. The square of ring diameter is proportional to antigen concentration.

 Agar containing antibody

       ┌───────────────┐
       │    ○○○○○      │  ← precipitin ring
       │   ○  Ag ○     │
       │    ○○○○○      │
       └───────────────┘

More antigen → larger ring diameter

Medical Microbiology 9e, p. 49.

4D. Principle of immunochromatography

A liquid sample moves along a membrane by capillary action. If target antigen or antibody is present, it binds labelled reagent and is captured at the test line, producing a visible coloured line. The control line confirms that the test worked.

Sample → [Conjugate pad] → [Test line] → [Control line] → Absorbent pad
                         target + label       test valid

Example: pregnancy test, rapid malaria antigen test, rapid COVID-19 antigen test.

4E. Ouchterlony double immunodiffusion patterns

Drawing	Pattern	Interpretation
`text Ag1 Ag2 \ / \_____/ Ab`	Identity	Ag1 and Ag2 have identical antigenic determinants. Lines fuse smoothly.
`text Ag1 Ag2 \ / \_____/ \ spur Ab`	Partial identity	Antigens share some determinants, but one antigen has additional determinants. Spur points toward the simpler antigen.
`text Ag1 Ag2 \ / \ X / Ab`	Non-identity	Antigens are unrelated and share no determinants. Lines cross.

Antigen and antibody diffuse toward each other and form a visible precipitin line at equivalence. Medical Microbiology 9e, p. 49.

5A. Types of hypersensitivity reactions

Type	Common name	Main immune component	Antigen location	Main mediators
I	Immediate/anaphylactic	IgE, mast cells, basophils	Soluble allergen	Histamine, leukotrienes, prostaglandins
II	Antibody-mediated cytotoxic	IgG or IgM	Cell surface or extracellular matrix	Complement, opsonization, ADCC
III	Immune-complex	IgG/IgM immune complexes	Soluble antigen complexes deposited in tissues	Complement, neutrophils
IV	Delayed-type/cell-mediated	T lymphocytes, macrophages	Tissue or cell-associated antigen	Cytokines, e.g. IFN-γ; cytotoxic T cells

5B. Mechanism and examples

Type	Underlying mechanism	Examples
I	Allergen cross-links IgE on mast cells, causing rapid mediator release.	Anaphylaxis; allergic rhinitis/asthma
II	IgG/IgM binds cells or tissue, activating complement or promoting phagocytosis/ADCC.	Mismatched blood transfusion; hemolytic disease of the newborn
III	Antigen-antibody complexes deposit in tissues, activate complement, and recruit neutrophils.	Serum sickness; SLE
IV	Sensitized T cells release cytokines or directly kill target cells; reaction occurs after 48-72 h.	Contact dermatitis; Mantoux test

5C. Two phases of Type I hypersensitivity

Sensitization phase: First exposure to allergen causes Th2-mediated IgE production. IgE attaches to mast cells/basophils.
Effector phase: On re-exposure, allergen cross-links mast-cell-bound IgE, causing an immediate reaction and a late inflammatory reaction.

First exposure: Allergen → IgE production → IgE binds mast cell
Re-exposure:    Allergen + IgE-coated mast cell → mediator release

5D. Mantoux test: principle and clinical importance

Principle: Intradermal PPD is injected. In a person previously sensitized to Mycobacterium tuberculosis, memory T cells cause a Type IV delayed hypersensitivity reaction, producing induration after 48-72 hours.

Clinical importance: Used to detect TB infection, especially latent TB. Measure induration only, not redness. It cannot by itself distinguish latent from active TB. CDC testing guidance explains that interpretation depends on risk category.

5E. Causes of false-negative PPD test

Very recent TB infection, before immune sensitization
Severe or overwhelming TB disease
HIV infection or other immunosuppression
Corticosteroids, chemotherapy, or TNF-α inhibitors
Malnutrition
Very young age or advanced age
Recent live-virus vaccination
Incorrect administration, storage, or reading of test

5F. Causes of false-positive PPD test

Previous BCG vaccination
Infection with non-tuberculous mycobacteria
Incorrect measurement or interpretation
Technical/administration error

5H. Mantoux test interpretation

Induration	Interpretation
<5 mm	Usually negative
≥5 mm	Positive in high-risk people: HIV, recent TB contact, transplant recipients, significant immunosuppression, or chest X-ray evidence of old TB
≥10 mm	Positive in moderate-risk persons: recent immigrants from high-TB countries, healthcare/laboratory workers, people in congregate settings, diabetes, chronic kidney disease, children <5 years
≥15 mm	Positive in persons with no known TB risk factors

These thresholds are based on induration, not erythema. CDC criteria

5I. Case: 25-year-old immigrant, previous BCG, PPD = 12 mm

Interpretation: Positive PPD, because an immigrant from a high-TB-prevalence country has a positive threshold of ≥10 mm.

Action: Refer for evaluation to exclude active TB, including symptom review and chest radiograph. An IGRA blood test is preferred in BCG-vaccinated people because BCG can produce a false-positive PPD result. BCG history should not simply be used to dismiss this 12-mm result. CDC BCG guidance supports using IGRA in BCG-vaccinated people.

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