3.3 about 38 minDeep Learning viewL3 p.15–27

Hypersensitivity reactions

Hypersensitivity is a normal immune mechanism doing harm. Read every case in the same order: what triggered it, where the antigen sits, which effector did the damage, what injury resulted, and which clue in the case proves it.

One method for four types

L3 p.15

The four Gell–Coombs types are remembered as ABCD: Anaphylactic and Atopic (type I), antiBody-mediated (type II), immune Complex (type III) and Delayed, cell-mediated (type IV). Types I–III are all made by antibody; type IV is made by T cells. The names are less useful than the questions behind them, so the chapter reads every case the same way.

Teaching schematic

Type I · Immediate

Target: Free antigen meeting IgE on mast cells
Effector: Histamine, tryptase, lipid mediators
Injury: Leak, bronchospasm, itch
Clue: Minutes; wheal; tryptase

Type II · Antibody

Target: Antigen fixed on a cell or matrix
Effector: IgG/IgM + complement, phagocytes, NK; or a receptor
Injury: Lysis, removal, inflammation, receptor on/off
Clue: Coombs+; linear IF

Type III · Immune complex

Target: Complexes formed in blood
Effector: Deposition, complement, neutrophils
Injury: Vasculitis, GN, arthritis
Clue: Granular IF; low C3/C4

Type IV · Delayed

Target: Peptide on MHC (no antibody)
Effector: Th1 → macrophages; CD8 killing
Injury: Induration, granuloma, cell death
Clue: 48–72 h; lymphocytes

Each type as trigger → target → effector → injury → case clue. Types I–III use antibody; only type IV is made by T cells.L3 p.15–26

Trigger → target → effector → injury → case clueL3 p.15–26

Type	Target	Effector	Injury	Case clue
I	Free (soluble) antigen meeting IgE already on mast cells	Mast-cell and basophil mediators; later eosinophils	Leak, smooth-muscle spasm, mucus, itch	Minutes after re-exposure; wheal and flare; raised tryptase or specific IgE
II	Antigen fixed on a cell surface or in matrix	IgG/IgM with complement, phagocytes or NK cells; or the antibody alters receptor function	Lysis, removal of coated cells, local inflammation, or a receptor switched on or off	Positive direct Coombs; linear immunofluorescence; antireceptor antibody
III	Antigen–antibody complexes formed in blood (or locally)	Deposited complexes fix complement; C5a and Fc receptors bring neutrophils	Vasculitis, glomerulonephritis, arthritis wherever complexes lodge	Granular immunofluorescence; low C3/C4; days to weeks after the antigen
IV	Peptide on MHC recognized by sensitized T cells (no antibody)	Th1/Th17 cytokines activating macrophages; CD8 cells killing	Induration, granulomas, vesicular dermatitis, cell death	Peaks 48–72 h; lymphocytes and macrophages; positive patch or tuberculin test

I
Target
Free (soluble) antigen meeting IgE already on mast cells
Effector
Mast-cell and basophil mediators; later eosinophils
Injury
Leak, smooth-muscle spasm, mucus, itch
Case clue
Minutes after re-exposure; wheal and flare; raised tryptase or specific IgE
II
Target
Antigen fixed on a cell surface or in matrix
Effector
IgG/IgM with complement, phagocytes or NK cells; or the antibody alters receptor function
Injury
Lysis, removal of coated cells, local inflammation, or a receptor switched on or off
Case clue
Positive direct Coombs; linear immunofluorescence; antireceptor antibody
III
Target
Antigen–antibody complexes formed in blood (or locally)
Effector
Deposited complexes fix complement; C5a and Fc receptors bring neutrophils
Injury
Vasculitis, glomerulonephritis, arthritis wherever complexes lodge
Case clue
Granular immunofluorescence; low C3/C4; days to weeks after the antigen
IV
Target
Peptide on MHC recognized by sensitized T cells (no antibody)
Effector
Th1/Th17 cytokines activating macrophages; CD8 cells killing
Injury
Induration, granulomas, vesicular dermatitis, cell death
Case clue
Peaks 48–72 h; lymphocytes and macrophages; positive patch or tuberculin test

Hypersensitivity case sorter

L3 p.15–27Ch. III cases p.3, 8Midterm sim. p.6–8

Practise the method on whole cases. For each vignette, decide first where the antigen is and what does the damage; only then are you asked for the type. After a correct answer, one clue in the case changes. Decide again: the mechanism moves, and you see exactly which clue moved it.

Centerpiece · Hypersensitivity case sorter

Hypersensitivity case sorter

Read the case, then decide where the antigen is and what does the damage. Only then choose the type. After a correct answer, one clue changes: decide again and watch the mechanism move.

Solved 0 of 9

1. Target + effector
2. Type
3. One clue changes
4. Type again

The case

A 24-year-old woman with a sore throat takes amoxicillin; she had a full course of penicillin two years ago without problems. Within 15 minutes of the first tablet she has generalized hives, wheezing and a blood pressure of 80/50 mm Hg; serum tryptase is raised.

What caused the reaction?

Step 1 · Where is the antigen, and what does the damage?

Target

Effector

Choose one target and one effector, then check.

The worked solution unlocks after your first attempt.

Type I: IgE and mast cells

L3 p.16–19

Type I hypersensitivity needs two meetings with the allergen. The first meeting sensitizes; the second elicits the reaction. Atopy, the inherited tendency to make IgE to harmless environmental antigens, runs strongly in families.

Sensitization. Dendritic cells carry the allergen (pollen, dust mite, food, drug) to lymph nodes. With IL-4 in the environment, naive CD4 cells become Th2 cells that make IL-4, IL-5 and IL-13. IL-4 (with CD40L) switches allergen-specific B cells to IgE; IL-5 raises and activates eosinophils. IgE binds the high-affinity receptor FcεRI on mast cells and basophils and waits there.
Re-exposure, early phase (minutes). The allergen cross-links two IgE molecules on the mast cell. The cell degranulates, releasing preformed histamine (vasodilation, leak, bronchoconstriction, itch), tryptase (a marker of mast-cell activation) and eosinophil chemotactic factor, and within minutes it makes leukotrienes C4/D4/E4, prostaglandin D2 and platelet-activating factor from membrane lipids.
Late phase (about 2–24 hours). Mast-cell cytokines (TNF, IL-4, IL-5, IL-13) and leukotrienes recruit eosinophils, neutrophils, basophils and Th2 cells. This cellular infiltrate prolongs swelling and, in the airway, causes the sustained obstruction and hyperreactivity of asthma.

L3 p.16–17, 19

Early and late phase comparedL3 p.16–17

	Early (immediate) phase	Late phase
Timing	Within minutes; fades in about an hour	Hours later (about 2–24 h), lasting a day or more
Main mediators	Histamine, tryptase, then leukotrienes, PGD₂, PAF	Cytokines and lipid mediators recruiting eosinophils, neutrophils, Th2 cells
What you see	Wheal and flare, sneezing, bronchospasm, hypotension	Persistent swelling, airway inflammation, mucus
Treatment logic	Epinephrine, antihistamines	Corticosteroids, leukotriene antagonists

Timing
Early (immediate) phase
Within minutes; fades in about an hour
Late phase
Hours later (about 2–24 h), lasting a day or more
Main mediators
Early (immediate) phase
Histamine, tryptase, then leukotrienes, PGD₂, PAF
Late phase
Cytokines and lipid mediators recruiting eosinophils, neutrophils, Th2 cells
What you see
Early (immediate) phase
Wheal and flare, sneezing, bronchospasm, hypotension
Late phase
Persistent swelling, airway inflammation, mucus
Treatment logic
Early (immediate) phase
Epinephrine, antihistamines
Late phase
Corticosteroids, leukotriene antagonists

Four clinical photographs: dark discoloration under the eye, a transverse nasal crease, cobblestone papillae on the everted upper eyelid, and raised urticarial wheals on the back. — Atopic signs from the lecture: **allergic shiners** (venous congestion under the eyes), the **nasal crease** from repeated upward rubbing in allergic rhinitis, **cobblestone** papillae of allergic conjunctivitis, and **hives** (urticaria): raised, itchy wheals from histamine-driven dermal edema.L3 p.18

The same mechanism looks different depending on where the allergen enters: the nose (allergic rhinitis), the conjunctiva, the skin (urticaria, angioedema), the bronchi (allergic asthma), the gut (food allergy) or the bloodstream, where mediator release is systemic. Anaphylaxis is the systemic form: vasodilation and leak cause shock, laryngeal edema and bronchospasm threaten the airway, and only intramuscular epinephrine reverses all three quickly.

Forearm skin-prick test with labelled sites; pale raised wheals at the histamine control and several allergen sites, none at the negative control. — **Skin-prick test.** A drop of each allergen is pricked into the epidermis. Where the patient's mast cells carry matching IgE, a histamine-driven **wheal and flare** appears within 15–20 minutes. Histamine is the positive control and saline the negative control.L3 p.19

Skin-prick (scratch) test: the standard first test; reads IgE on skin mast cells. Antihistamines must be stopped beforehand.
Allergen-specific serum IgE (the older RAST, now immunoassays): measures IgE against a named allergen without exposing the patient. Useful with extensive eczema or when antihistamines cannot be stopped.
Total serum IgE: raised in atopy, helminth infection and hyper-IgE syndrome; not specific for one allergen.
Serum tryptase: rises within about an hour of anaphylaxis; confirms mast-cell activation after the event.

L3 p.19

Core activity · The Missing Arrow

The Missing Arrow

Complete the causal chain. Place the missing step by dragging a card onto a gap, or tap a card and then tap the gap. Some gaps need an event; others need the mechanism that links one event to the next.

A child inhales grass pollen in spring for the first time, and again the next spring. Complete the chain to the itchy wheal on her skin-prick test.

One gap asks for the event that sensitizes the mast cell; another asks for the mechanism that sets it off on re-exposure.

Dendritic cells present pollen peptide to naive CD4 T cells
B cells switch to IgE against pollen
IgE circulates and binds the high-affinity Fc receptor
histamine dilates venules and opens endothelial junctions
Wheal and flare within 15–20 minutes; late-phase eosinophils hours later

Cards

Tap or drag a card. Placing a used card moves it.

Type II: antibody against a fixed antigen

L3 p.20–22

In type II reactions, IgG or IgM binds an antigen that is part of a cell surface or of extracellular matrix: a red-cell antigen, a platelet glycoprotein, collagen in a basement membrane, a hormone receptor. The antigen may be self (autoimmunity), foreign (a transfused red cell), or a drug sitting on a cell as a hapten. What happens next depends on the effector the antibody recruits.

Four ways an antibody on a cell causes diseaseL3 p.20, 22

Mechanism	How it works	Examples
Complement lysis	IgM (or IgG) fixes C1q; the membrane attack complex punctures the cell inside the vessel	ABO-incompatible transfusion (IgM anti-A/anti-B); cold autoimmune hemolysis
Opsonization and phagocytosis	IgG and C3b coat the cell; splenic and hepatic macrophages with Fc and C3b receptors eat it (extravascular)	Warm autoimmune hemolytic anemia; immune thrombocytopenia (ITP); hemolytic disease of the newborn (maternal IgG anti-D); penicillin bound to red cells
Inflammation and ADCC	Antibody on matrix or a cell activates complement (C5a draws neutrophils) or engages Fc receptors on neutrophils, macrophages and NK cells, which release enzymes and oxygen radicals or kill the coated cell	Goodpasture syndrome (type IV collagen of glomerular and alveolar basement membranes); acute rheumatic fever; pemphigus vulgaris; hyperacute rejection; NK killing of IgG-coated cells
Receptor dysfunction without injury	Antibody stimulates or blocks a receptor; the cell is not destroyed	Graves (stimulates the TSH receptor → hyperthyroidism); myasthenia gravis (blocks and removes the acetylcholine receptor → weakness); pernicious anemia (anti–intrinsic factor and anti-parietal-cell antibodies → B12 deficiency)

Complement lysis
How it works
IgM (or IgG) fixes C1q; the membrane attack complex punctures the cell inside the vessel
Examples
ABO-incompatible transfusion (IgM anti-A/anti-B); cold autoimmune hemolysis
Opsonization and phagocytosis
How it works
IgG and C3b coat the cell; splenic and hepatic macrophages with Fc and C3b receptors eat it (extravascular)
Examples
Warm autoimmune hemolytic anemia; immune thrombocytopenia (ITP); hemolytic disease of the newborn (maternal IgG anti-D); penicillin bound to red cells
Inflammation and ADCC
How it works
Antibody on matrix or a cell activates complement (C5a draws neutrophils) or engages Fc receptors on neutrophils, macrophages and NK cells, which release enzymes and oxygen radicals or kill the coated cell
Examples
Goodpasture syndrome (type IV collagen of glomerular and alveolar basement membranes); acute rheumatic fever; pemphigus vulgaris; hyperacute rejection; NK killing of IgG-coated cells
Receptor dysfunction without injury
How it works
Antibody stimulates or blocks a receptor; the cell is not destroyed
Examples
Graves (stimulates the TSH receptor → hyperthyroidism); myasthenia gravis (blocks and removes the acetylcholine receptor → weakness); pernicious anemia (anti–intrinsic factor and anti-parietal-cell antibodies → B12 deficiency)

The lecture adds two antibody-dependent killing mechanisms that do not need complement: NK cells kill IgG-coated virus-infected or tumor cells through their Fc receptors (antibody-dependent cell-mediated cytotoxicity), and eosinophils bind IgE on a tissue helminth and release major basic protein onto it.

Receptor antibodies: stimulate or block

Graves disease

IgG against the TSH receptor acts like TSH
Thyroid cells make excess T3/T4 and the gland grows
TSH falls (negative feedback) while the gland keeps working
Diffuse warm goiter, exophthalmos, pretibial myxedema

Myasthenia gravis

IgG against the acetylcholine receptor blocks it, cross-links it for removal and fixes complement at the end plate
Fewer receptors → smaller end-plate potentials
Fatigable weakness: ptosis, diplopia, worse at day's end
Associated with thymic hyperplasia or thymoma

L3 p.20, 22

Woman with marked bilateral proptosis and lid retraction and a fullness of the lower neck. — Graves disease from the simulation file: bilateral **exophthalmos** and a diffusely enlarged thyroid. The orbital fibroblasts also carry the TSH receptor, which is one reason the eyes are involved.Midterm sim. p.7

Teaching schematic

Direct Coombs (direct antiglobulin test)

Asks: is antibody or C3d already on the patient's red cells? Autoimmune hemolysis, a newborn with HDN, a hemolytic transfusion reaction, drug-induced hemolysis.

Indirect Coombs

Asks: does the patient's serum contain antibody against red-cell antigens? Antenatal anti-D screening, antibody screen and crossmatch before transfusion.

Direct Coombs: antibody already on the patient's red cells (autoimmune hemolysis, a newborn with HDN, a transfusion reaction). Indirect Coombs: antibody free in the serum that would bind red cells (antenatal anti-D screening, pre-transfusion antibody screen and crossmatch).L3 p.22

Type III: immune complexes

L3 p.23–25, 39

Antigen–antibody complexes form whenever antibody meets soluble antigen, and the mononuclear phagocyte system normally clears them. Complexes become harmful when they are made faster than they are cleared, which usually means a persistent antigen (a chronic infection, a drug, nuclear antigens in SLE) and complexes of small to intermediate size, formed in slight antigen excess. These escape clearance and lodge where blood is filtered under pressure: glomeruli, synovium, small vessels of the skin.

From complex to injury

Persistent soluble antigen + IgG
Complexes circulate
Deposit in glomeruli, joints, small vessels
Classical complement activated (C3, C4 consumed)
C5a and Fc receptors recruit neutrophils
Enzymes and radicals: vasculitis, glomerulonephritis, arthritis

L3 p.23

Because the injury is made by complement and neutrophils, three findings follow. Serum C3 and C4 fall while complement is consumed. Immunofluorescence shows IgG and C3 as granular, lumpy deposits wherever complexes settled. And small vessels may show fibrinoid necrosis, the bright pink smudge of plasma proteins and fibrin in a damaged wall (fibrinoid necrosis).

Systemic versus local: serum sickness and the Arthus reaction

Serum sickness (systemic)

Foreign serum or protein (antivenom, antithymocyte globulin, monoclonal antibodies), drugs (penicillin), chronic antigen (HBsAg)
Antibody appears after about a week; complexes form as it meets remaining antigen
1–2 weeks after exposure: fever, urticarial rash, arthralgia, painful lymphadenopathy, splenomegaly, proteinuria; low complement
Resolves when the antigen is cleared

Arthus reaction (local)

Antigen injected into the skin of someone who already has a high level of IgG against it (for example an extra tetanus booster)
Complexes form in the wall of small vessels at the injection site
Hours (about 4–10 h): painful swelling, hemorrhage, then necrosis and ulceration
Neutrophils, fibrinoid necrosis and thrombosis in local vessels

L3 p.24–25

Infant's back with widespread confluent pink urticarial plaques with paler centers. — **Serum sickness** in a child: a widespread urticarial rash. In the lecture's example it followed an injected foreign protein; the rash, fever and joint pain appear one to two weeks later, when complexes form.L3 p.24

Immune-complex diseases in this chapterL3 p.23–24, 36, 39

Disease	Antigen	Where complexes lodge	Clues
Poststreptococcal glomerulonephritis	Nephritogenic group A streptococcal antigens	Glomerular capillary wall: subepithelial humps on EM	Child, 1–3 weeks after pharyngitis; cola urine, periorbital edema, hypertension; low C3; raised ASO/anti-DNase B; granular IgG + C3
Lupus nephritis	DNA and nucleosomes (anti-dsDNA)	Glomeruli (mesangial, subendothelial, subepithelial), skin, joints, serosa	Granular 'full-house' IF (IgG, IgA, IgM, C1q, C3); low C3 and C4; anti-dsDNA (3.5)
IgA vasculitis (Henoch–Schönlein purpura)	IgA-containing complexes	Small vessels of skin, gut, glomerular mesangium	Child after an upper respiratory infection; palpable purpura on buttocks and legs with normal platelets; arthralgia, colicky abdominal pain, hematuria
Polyarteritis nodosa (HBV-associated)	Hepatitis B surface antigen	Medium-sized muscular arteries	Segmental fibrinoid necrosis, aneurysms, renal infarcts, mononeuritis; ANCA-negative; HBsAg positive
Serum sickness; Arthus reaction	Foreign protein, drug; injected antigen	Systemic small vessels and glomeruli; local dermal vessels	Timing (1–2 weeks vs hours)
Rheumatoid arthritis, reactive arthritis (as listed in the lecture)	Rheumatoid factor (IgM anti-IgG) complexes; bacterial antigens	Synovium	RA also has a large T-cell (type IV) component

Poststreptococcal glomerulonephritis
Antigen
Nephritogenic group A streptococcal antigens
Where complexes lodge
Glomerular capillary wall: subepithelial humps on EM
Clues
Child, 1–3 weeks after pharyngitis; cola urine, periorbital edema, hypertension; low C3; raised ASO/anti-DNase B; granular IgG + C3
Lupus nephritis
Antigen
DNA and nucleosomes (anti-dsDNA)
Where complexes lodge
Glomeruli (mesangial, subendothelial, subepithelial), skin, joints, serosa
Clues
Granular 'full-house' IF (IgG, IgA, IgM, C1q, C3); low C3 and C4; anti-dsDNA (3.5)
IgA vasculitis (Henoch–Schönlein purpura)
Antigen
IgA-containing complexes
Where complexes lodge
Small vessels of skin, gut, glomerular mesangium
Clues
Child after an upper respiratory infection; palpable purpura on buttocks and legs with normal platelets; arthralgia, colicky abdominal pain, hematuria
Polyarteritis nodosa (HBV-associated)
Antigen
Hepatitis B surface antigen
Where complexes lodge
Medium-sized muscular arteries
Clues
Segmental fibrinoid necrosis, aneurysms, renal infarcts, mononeuritis; ANCA-negative; HBsAg positive
Serum sickness; Arthus reaction
Antigen
Foreign protein, drug; injected antigen
Where complexes lodge
Systemic small vessels and glomeruli; local dermal vessels
Clues
Timing (1–2 weeks vs hours)
Rheumatoid arthritis, reactive arthritis (as listed in the lecture)
Antigen
Rheumatoid factor (IgM anti-IgG) complexes; bacterial antigens
Where complexes lodge
Synovium
Clues
RA also has a large T-cell (type IV) component

Six immunofluorescence panels of one glomerulus stained for IgM, IgG, IgA, C1q, C3 and C4, all showing coarse granular green deposits along capillary loops. — **Lupus nephritis**, immunofluorescence of one glomerulus for six proteins. Every stain is positive in a **granular** pattern along the capillary loops: IgG, IgM and IgA with the early classical components C1q and C4 and C3 (a 'full house'). Granular deposits plus consumed complement mean immune complexes.L3 p.39

Core activity · Almost Twins

Almost Twins

Two look-alikes side by side. Decide what they share, then pick the clue that separates them and say why it works.

Look-alike A

Anti-GBM (Goodpasture) disease

Glomerular capillary loop, immunofluorescence for IgG (schematic).

Hematuria, red-cell casts, rising creatinine
Smooth linear IgG along the basement membrane; antibody against type IV collagen fixed in the GBM
Serum C3 usually normal
May bleed into the lungs (alveolar basement membrane shares the antigen)

Step 1 · What they share

What do the two diseases share?

Select every feature that both show.

Core activity · The Missing Arrow

The Missing Arrow

A man with chronic hepatitis B makes antibody against the surface antigen that his liver keeps releasing. Complete the chain to the necrotizing arteritis.

HBsAg circulates for months; IgG anti-HBs is made
antigen and antibody combine in slight antigen excess
Fibrinoid necrosis of medium-sized arteries: polyarteritis nodosa

Cards

Tap or drag a card. Placing a used card moves it.

Necrotizing vasculitis: ANCA or immune complex?

L3 p.23–24Midterm sim. p.6–7

A biopsy that shows fibrinoid necrosis of a small artery tells you the vessel wall has been destroyed and plasma proteins have leaked into it. It does not tell you how. Two antibody mechanisms produce the same picture, and they are separated by the immunofluorescence, the complement level and the serology.

Small muscular artery whose wall is replaced by a bright pink, smudgy band of fibrinoid material, surrounded by a dense inflammatory infiltrate. — Simulation Q17: **fibrinoid necrosis** of a small muscular artery. The wall is replaced by bright pink fibrinoid material with inflammatory cells around it. The appearance is shared by immune-complex and ANCA-associated vasculitis.Midterm sim. p.7

Teaching schematic

Linear. Antibody bound evenly to an antigen fixed in the GBM (type IV collagen): Goodpasture. Serum C3 normal.

Granular. Deposited immune complexes: lumps of IgG and C3, humps on EM in PSGN, 'full house' in lupus. Serum C3 low.

Pauci-immune. Little or no immunoglobulin despite necrosis (pink) and a crescent (gray): ANCA vasculitis. Complement normal.

Immunofluorescence of a glomerular capillary loop separates three antibody mechanisms: linear (antibody against basement membrane, type II), granular (deposited complexes, type III) and pauci-immune (little or no immunoglobulin despite necrosis: ANCA).

ANCA-associated (pauci-immune)

IgG autoantibodies against neutrophil granule enzymes: myeloperoxidase (p-ANCA) or proteinase 3 (c-ANCA)
Cytokines (for example during an infection) prime neutrophils, which move MPO or PR3 to their surface; ANCA bind them and engage Fc receptors
Activated neutrophils degranulate and release radicals at the endothelium: necrotizing small-vessel vasculitis, crescentic glomerulonephritis
IF: few or no deposits; serum complement usually normal
p-ANCA: microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis

Immune-complex

Antibody meets a soluble antigen (HBsAg, streptococcal antigen, DNA) and complexes deposit in the wall
Complement is consumed; C5a and Fc receptors bring neutrophils
IF: granular IgG and C3; serum C3 and C4 low
Classic polyarteritis nodosa with HBV (ANCA-negative), lupus vasculitis, cryoglobulinemia, IgA vasculitis

L3 p.23–24

Source note

Simulation Q17: what the p-ANCA supports

The question shows fibrinoid necrosis of a small muscular artery with a positive p-ANCA, and asks which immune response explains it. Option (B) is missing in both the PDF and the Word file, and no key is supplied. The lecture lists polyarteritis nodosa among immune-complex diseases (L3 p.23–24), so (E) immune complex disease is the answer the question expects.

Read the clues, though: p-ANCA with necrotizing small-vessel vasculitis and hematuria fits an ANCA-associated vasculitis such as microscopic polyangiitis. There the injury is ANCA-driven neutrophil activation with pauci-immune immunofluorescence and normal complement; standard texts group it with antibody-mediated (type II) diseases. Classic polyarteritis nodosa is ANCA-negative. On an exam with these printed choices, choose E; in a patient, order immunofluorescence and complement levels to tell the two apart.

Midterm sim. p.6–7L3 p.23–24Ref.

Core activity · One Fact Changes

One Fact Changes

Answer a case and name the decisive clue. Then exactly one fact changes. Decide whether the answer moves, and why.

1 · The original case

A 50-year-old man has fever, weight loss, abdominal pain, bloody urine and red-purple palpable skin lesions. Skin biopsy shows fibrinoid necrosis of small arteries with neutrophils. p-ANCA (anti-myeloperoxidase) is strongly positive; immunofluorescence shows almost no immunoglobulin or complement; serum C3 and C4 are normal.

Which mechanism best explains the vasculitis?

Which fact decided it?

Type IV: T cells, delayed

L3 p.26–27

Type IV reactions involve no antibody. Sensitized T cells recognize peptide on MHC in the tissue and cause injury in one of two ways, and both take time because the T cells must be recruited and must make new proteins. Reactions therefore peak at 48–72 hours.

CD4 T-cell inflammation (delayed-type hypersensitivity)

Antigen on class II → memory Th1 (and Th17) cells
IFN-γ activates macrophages; TNF and chemokines bring more cells
Induration; with persistent antigen, granulomas
Tuberculin (PPD) reaction, tuberculosis, contact dermatitis

CD8 T-cell cytotoxicity

Antigen on class I of altered cells: virus-infected, tumor, donor graft
Perforin and granzymes, Fas ligand → apoptosis of the target
Tissue cells die without antibody
Viral hepatitis, type 1 diabetes, acute cellular rejection, graft-versus-host disease

L3 p.26

Allergic contact dermatitis shows both stages clearly. In the sensitization stage, a small reactive molecule (a hapten: urushiol from poison ivy, nickel, rubber-glove chemicals, formaldehyde, topical sulfonamides) binds skin proteins. Langerhans cells carry the modified protein to regional lymph nodes and present it, creating CD4 Th1 memory cells and CD8 effector memory cells. In the elicitation stage, re-exposure brings the hapten back; Langerhans cells present it to the circulating memory cells, which release cytokines or kill keratinocytes. Itching, redness, edema and vesicles of clear fluid appear exactly where the substance touched, 24–72 hours later.

Wrist with a red, scaly, slightly vesicular patch exactly under the metal buckle of a wristwatch strap. — **Nickel contact dermatitis** under a watch buckle: the eczematous patch matches the shape of the metal contact, the giveaway of a delayed hapten reaction.L3 p.27

Tuberculin (PPD) test: protein injected into the dermis; previously sensitized Th1 cells produce a firm induration read at 48–72 hours. The Candida skin test uses the same principle to check whether T-cell immunity works at all.
Tuberculosis: persistent mycobacterial antigen turns the same response into caseating granulomas (3.2).
Other delayed examples in the lecture: drug reaction with eosinophilia and systemic symptoms (DRESS) and graft-versus-host disease (3.4).
Diminished cell-mediated immunity makes the skin test smaller or negative (anergy): older adults, and people with AIDS whose CD4 cells are lost.

L3 p.26

Knowledge check · 3.3

Answer, read why, and try again whenever you like. Answers are kept in both study modes.

0 of 7 correct

Q1Poststreptococcal GN: type IIIL3 p.23Ch. III cases p.3
An 8-year-old boy has periorbital edema and throbbing headaches. His parents report a 'strep throat' 2 weeks ago. Urinalysis shows 3+ hematuria. A renal biopsy shows hypercellular glomeruli, and electron microscopy shows subepithelial 'humps'.
Which best explains the pathogenesis of the glomerulonephritis?
Q2Tuberculous granuloma: type IVL3 p.26Ch. III cases p.4L2 p.42–43
A 34-year-old woman has had fever, productive cough with blood-tinged sputum and 4 kg of weight loss for 6 weeks. Cervical lymph nodes are enlarged. Chest x-ray shows a 2.5-cm nodule in the right upper lobe; biopsy shows caseating granulomas with multinucleated giant cells.
Which mechanism underlies the pulmonary nodule?
Q3Contact dermatitis: type IVL3 p.26–27Midterm sim. p.6
A 20-year-old gardener has what he calls 'poison ivy'. His hands and forearms are red and covered with oozing blisters and crusts, two days after clearing weeds.
Which best describes the pathogenesis of these lesions?
Q4ANCA vs immune-complex vasculitisMidterm sim. p.6–7L3 p.23–24Ref.
A 50-year-old man has fever, weight loss, abdominal pain and bloody urine, with red-purple palpable lesions on his legs. A skin biopsy shows fibrinoid necrosis of small arteries with neutrophils. p-ANCA (anti-myeloperoxidase) is strongly positive. Immunofluorescence of the biopsy shows little or no immunoglobulin or complement, and serum C3 and C4 are normal.
Which immune mechanism best explains the necrotizing vasculitis?
Q5Graves: stimulating antireceptor antibodyL3 p.20, 22Midterm sim. p.7
A 53-year-old woman (shown) has weight loss, nervousness, sweating, tachycardia and exophthalmos. Her thyroid is diffusely enlarged and warm. TSH is low and T3 and T4 are markedly raised.
Case image
Which mechanism best explains her thyroid disease?
Q6ABO transfusion reaction: type IIL3 p.20Midterm sim. p.8
A 54-year-old woman needs a transfusion after a car accident. Five hours later she is febrile with severe back pain, and tests show intravascular hemolysis. Type A Rh⁺ blood had been given by mistake to this type B Rh⁺ patient.
Which best explains the intravascular hemolysis?
Q7Image: granular full-house IFL3 p.39
A 27-year-old woman has hematuria, red-cell casts and proteinuria. Her kidney biopsy immunofluorescence is shown: each panel is the same glomerulus stained for a different protein.
Lecture image
Which serum finding best fits this pattern, and why?

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