PA8.1-6,PA9.1-2 | Immunopathology & Amyloidosis — Glossary

Secondary (reactive) systemic amyloidosis caused by deposition of serum amyloid-associated (SAA) protein fragments; complicates chronic inflammatory diseases such as rheumatoid arthritis, tuberculosis, and inflammatory bowel disease.

A minimally invasive biopsy technique for diagnosing systemic amyloidosis in which subcutaneous fat from the periumbilical region is aspirated and stained with Congo red; sensitivity ~80% for systemic disease.

T-cell-mediated graft injury occurring weeks to months post-transplant, characterised histologically by interstitial lymphocytic infiltrate and tubulitis (in kidney).

The antigen-specific, MHC-restricted immune response mediated by T and B lymphocytes that develops over days and generates long-lived immunological memory.

Late stage of HIV infection defined by CD4+ T-cell count < 200 cells/µL or the presence of an AIDS-defining illness (opportunistic infection or malignancy); distinguished from HIV infection, which precedes it by years.

Gene expressed in thymic epithelium that drives ectopic expression of peripheral tissue antigens, enabling deletion of potentially autoreactive T cells; mutations cause APECED syndrome.

Primary systemic amyloidosis caused by extracellular deposition of immunoglobulin light chains (κ or λ) derived from a clonal plasma cell population; associated with multiple myeloma and MGUS.

An abnormal extracellular deposit of insoluble fibrillar proteins sharing a β-pleated sheet secondary structure, resistant to physiological proteolysis and identified by apple-green birefringence on Congo red staining under polarised light.

A 40–42 amino acid fragment of amyloid precursor protein (APP) generated by sequential β- and γ-secretase cleavage; the principal component of senile plaques and amyloid angiopathy in Alzheimer disease and Down syndrome.

Heterogeneous group of autoantibodies directed against nuclear components; a sensitive screening test for SLE (>95% positive) but not specific.

Functional unresponsiveness of a T cell that has received TCR stimulation without co-stimulatory (CD28–B7) signals; a key peripheral tolerance mechanism.

Highly specific autoantibody for SLE; directed against double-stranded DNA; titre correlates with disease activity, particularly lupus nephritis.

Autoantibody against Smith antigen (snRNP core proteins); highly specific for SLE though less sensitive; named after patient Stephanie Smith.

A Type II mechanism in which IgG antibodies bound to target cell surfaces are recognised by Fc receptors on NK cells, triggering perforin/granzyme-mediated killing of the antibody-coated target.

Hypercoagulable state caused by anticardiolipin antibodies and lupus anticoagulant directed against phospholipid-binding proteins; presents with arterial/venous thrombosis and recurrent pregnancy loss.

Combination treatment for HIV using ≥ 3 drugs from ≥ 2 different mechanistic classes; prevents resistance through simultaneous multi-target blockade; goal is undetectable viral load, allowing CD4 recovery and prevention of AIDS.

A localised Type III hypersensitivity reaction at a site of antigen injection (e.g., vaccine booster) in a previously sensitized individual, manifesting as oedema and necrosis due to local immune complex deposition.

A familial predisposition to develop IgE-mediated (Type I) hypersensitivity reactions (asthma, allergic rhinitis, eczema, food allergy) resulting from a Th2-biased immune response to common environmental antigens.

Amyloidosis caused by deposition of transthyretin fibrils; occurs in a hereditary form (point mutations, e.g. Val30Met) presenting as peripheral neuropathy, and a wild-type (senile) form presenting predominantly as restrictive cardiomyopathy in elderly men.

Amyloidosis caused by accumulation of β2-microglobulin (MHC class I light chain) that is not adequately cleared by conventional haemodialysis membranes; presents as carpal tunnel syndrome and destructive arthropathy in long-term dialysis patients.

Activation of autoreactive T cells during an inflammatory response at a tissue site, triggered by co-stimulatory signals from activated APCs presenting self-antigens released by tissue damage.

Complement split product that covalently binds peritubular capillary endothelium; its presence on biopsy is a marker of antibody-mediated (humoral) rejection.

Class of immunosuppressants (ciclosporin, tacrolimus) that block calcineurin, preventing NFAT nuclear translocation and IL-2 gene transcription, thereby suppressing T-cell activation.

Chemokine receptor (C-C motif receptor 5) expressed on macrophages and memory CD4+ T cells; serves as co-receptor for M-tropic (R5) HIV strains; homozygous CCR5-Δ32 deletion confers near-complete HIV-1 resistance.

32-base-pair deletion in the CCR5 gene that prevents surface expression of the CCR5 co-receptor; homozygous carriers are nearly completely resistant to M-tropic (R5) HIV-1 infection; found in ~1% of Northern Europeans.

Deletion of self-reactive lymphocytes during maturation in the thymus (T cells) and bone marrow (B cells), mediated by apoptosis upon high-affinity self-antigen binding.

The reduction in serum complement proteins (especially C3 and C4) that occurs when complement is activated by immune complexes in Types II and III hypersensitivity; a low C3/C4 level in nephritis supports Type III (immune complex) disease.

Fall in C3, C4, and CH50 during active SLE due to continuous complement pathway activation by circulating immune complexes; a clinically useful marker of disease flares.

The pathognomonic apple-green optical phenomenon seen when amyloid-laden tissue stained with Congo red is viewed under crossed polarised light; caused by ordered alignment of dye molecules along β-pleated sheet fibrils.

Pre-transplant assay in which recipient serum is tested against donor lymphocytes; a positive result indicates pre-formed anti-donor antibodies → contraindication to transplantation.

Chemokine receptor (C-X-C motif receptor 4) expressed on naïve CD4+ T cells; serves as co-receptor for T-tropic (X4) HIV strains that typically emerge late in disease progression and are associated with rapid CD4 decline.

The Th1 CD4⁺ T-cell-mediated subtype of Type IV hypersensitivity characterised by IFN-γ secretion, macrophage activation, and inflammatory induration appearing 48–72 hours after antigen re-exposure.

SLE-like syndrome triggered by drugs (procainamide, hydralazine, isoniazid); characterised by anti-histone antibodies; generally spares kidneys and CNS; reversible on drug withdrawal.

The paradoxical finding of increased wall thickness on echocardiography combined with low-voltage QRS complexes on ECG; occurs in cardiac amyloidosis because amyloid-infiltrated myocardium is electrically inert, unlike hypertrophied muscle.

Progressive broadening of an autoimmune response to additional self-epitopes as tissue damage releases new self-antigens, driving disease chronicity and organ involvement.

The high-affinity IgE receptor expressed on mast cells and basophils; aggregation of FcεRI upon IgE cross-linking by multivalent antigen is the trigger for mast cell degranulation in Type I hypersensitivity.

The process by which pre-existing amyloid fibrils act as templates that recruit and orient soluble monomers, converting them into β-sheet configurations; responsible for the self-amplifying, accelerating nature of amyloid deposition.

The ineffective attempt by neutrophils to engulf immune complexes deposited on basement membranes; because the complexes are immobilised, lysosomal enzymes are released extracellularly, causing tissue necrosis in Type III reactions.

A four-type framework (Types I–IV) categorising hypersensitivity reactions by their effector mechanism: IgE/mast cell, IgG/IgM cytotoxic, immune complex, and T-cell–mediated.

A Type II hypersensitivity disease caused by IgG autoantibodies against the α3 chain of type IV collagen in the glomerular and alveolar basement membranes, producing rapidly progressive glomerulonephritis and pulmonary haemorrhage.

Outer glycoprotein subunit of the HIV envelope spike; binds CD4 on host cells and undergoes conformational change to engage chemokine co-receptors (CCR5 or CXCR4); primary target for neutralising antibodies and entry inhibitors.

Transmembrane glycoprotein subunit of the HIV envelope spike; mediates fusion of viral and host cell membranes after gp120 binds receptor and co-receptor; target for fusion inhibitor enfuvirtide.

A focal aggregate of activated (epithelioid) macrophages, often with multinucleate giant cells and a rim of lymphocytes, representing a persistent Type IV response to an incompletely cleared antigen such as Mycobacterium tuberculosis.

A Type II hypersensitivity disease in which IgG antibodies against the TSH receptor act as agonists, causing constitutive thyroid stimulation, diffuse goitre, and hyperthyroidism.

Condition in haematopoietic stem cell transplantation where donor T cells recognise and attack host tissues, primarily skin, liver, and gut.

Kaposi sarcoma-associated herpesvirus; a gamma-herpesvirus that infects endothelial cells and B cells; reactivates under immunosuppression to drive Kaposi sarcoma; encodes viral FLICE-inhibitory protein (vFLIP) to prevent apoptosis.

CNS complication of direct HIV infection of brain macrophages and microglia; manifests as progressive cognitive impairment, psychomotor slowing, and behavioural change; pathology shows microglial nodules and multinucleated giant cells.

Human MHC cell-surface glycoproteins classified as class I (A, B, C — on all nucleated cells) and class II (DR, DP, DQ — on professional APCs).

Graft destruction occurring within minutes to hours of transplantation due to pre-formed recipient antibodies that activate complement and trigger intravascular thrombosis.

An exaggerated or inappropriate immune response to an antigen that causes tissue damage or physiological dysfunction in the host rather than protection.

An antigen-antibody aggregate formed in circulation or in situ; intermediate-sized complexes in slight antigen excess are most pathogenic in Type III hypersensitivity owing to incomplete phagocytic clearance.

The immediate, non-specific, genetically encoded first line of host defence comprising physical barriers, phagocytes, NK cells, complement, and inflammatory mediators, with no immunological memory.

Class of ART drug (e.g., dolutegravir, raltegravir) that blocks HIV integrase from inserting proviral dsDNA into host chromosomes; highly effective, well-tolerated, and now a preferred component of first-line regimens.

A peptide co-secreted with insulin by pancreatic β-cells that forms amyloid deposits in the islets of Langerhans in type 2 diabetes mellitus; contributes to progressive β-cell loss.

Vascular malignancy of endothelial origin caused by HHV-8; the most common AIDS-defining malignancy; presents as violaceous skin/mucosal lesions; can involve viscera; histology shows spindle cells, slit-like vascular channels.

A macroscopic pattern of splenic amyloidosis in which deposits diffusely infiltrate the red pulp, producing a homogeneous, pale grey, lard-like cut surface; represents more advanced or diffuse disease.

A neutrophil that has phagocytosed an opsonised nuclear remnant (coated by anti-histone antibody); a historical SLE test, now superseded by ANA testing.

Non-infective sterile verrucous vegetations on cardiac valve leaflets (mitral most common) seen in SLE; can occur on either surface of the valve leaflet (unlike rheumatic fever).

Diffuse proliferative lupus nephritis; most severe class with >50% glomeruli affected, wire-loop lesions, and full-house immunofluorescence; highest risk of renal failure.

Disseminated opportunistic mycobacterial infection occurring at CD4 < 50 cells/µL; presents with fever, night sweats, weight loss, hepatosplenomegaly, and anaemia; treated with clarithromycin + ethambutol.

Abnormal enlargement of the tongue caused by amyloid infiltration of the tongue stroma; a hallmark clinical feature of systemic AL amyloidosis, distinguishable from muscular hypertrophy by its firm, rubbery consistency.

A tissue-resident granulated cell bearing high-affinity IgE receptors (FcεRI); cross-linking of surface IgE by antigen triggers degranulation releasing histamine and initiating the Type I hypersensitivity response.

Gene cluster on chromosome 6p21 encoding HLA glycoproteins that present peptide antigens to T lymphocytes; the human equivalent is the HLA system.

Cell-surface glycoprotein expressed on all nucleated cells that presents endogenous (intracellular) peptides to CD8⁺ cytotoxic T lymphocytes; encoded by HLA-A, -B, -C loci.

Cell-surface glycoprotein expressed on professional antigen-presenting cells (dendritic cells, macrophages, B cells) that presents exogenous peptides to CD4⁺ T helper cells; encoded by HLA-DR, -DP, -DQ loci.

Mechanism of tolerance breakdown where structural similarity between a microbial antigen and a self-antigen allows an anti-pathogen immune response to cross-react with self-tissue.

A Type II hypersensitivity disease in which IgG antibodies against nicotinic acetylcholine receptors at the neuromuscular junction cause receptor internalisation and complement-mediated degradation, leading to fatigable muscle weakness.

A clinical triad of heavy proteinuria (>3.5 g/day), hypoalbuminaemia, and oedema; the most common and most lethal renal manifestation of systemic amyloidosis, caused by amyloid obliterating glomerular filtration surfaces.

Core capsid protein of HIV; earliest laboratory marker of HIV infection, detectable 2–4 weeks post-infection before antibodies develop; detected by 4th-generation ELISA; useful for diagnosing acute HIV and neonatal infection.

The most common AIDS-defining opportunistic infection (CD4 < 200); caused by the fungus Pneumocystis jirovecii (formerly carinii); presents with bilateral interstitial infiltrates, dry cough, progressive hypoxia; treated with co-trimoxazole.

The existence of thousands of allelic variants at each HLA locus across the human population, enabling diverse peptide presentation but complicating transplant matching.

Failure of a polypeptide to attain or maintain its normal three-dimensional conformation; the fundamental event initiating amyloid fibril formation when misfolded intermediates adopt a β-sheet configuration that aggregates rather than being corrected by chaperones.

Double-stranded DNA copy of the HIV genome integrated into host cell chromosomes by viral integrase; replicates with every cell division; constitutes the permanent, irradicable viral reservoir that prevents cure.

Inflammatory programmed cell death triggered by caspase-1 activation via the inflammasome; the dominant mechanism of CD4+ T-cell bystander death in HIV infection, driven by cytosolic sensing of abortive viral DNA.

CD4+CD25+FOXP3+ T cells that suppress autoreactive lymphocytes via IL-10, TGF-β, and contact-dependent mechanisms; their deficiency predisposes to autoimmunity.

A pattern of heart failure caused by abnormally stiff ventricular walls that impairs diastolic filling; in amyloidosis, caused by interstitial amyloid deposits replacing normal myocardium and producing the ECG-echo mismatch pattern.

RNA virus that uses reverse transcriptase to copy its genome into DNA, which is then integrated into host cell chromatin as a provirus; examples include HIV-1, HIV-2, and HTLV-1.

Viral RNA-dependent DNA polymerase packaged in HIV virions; copies the single-stranded RNA genome into double-stranded DNA; lacks proofreading, generating ~1 error per replication cycle and driving genetic diversity.

A macroscopic pattern of splenic amyloidosis in which deposits are confined to the white pulp follicles, producing discrete translucent grey nodules resembling sago or tapioca pearls on cut section.

The normal immune state of unresponsiveness to self-antigens, maintained by central deletion in primary lymphoid organs and peripheral suppression mechanisms.

The clinically silent initial exposure phase in Type I hypersensitivity during which antigen-specific IgE is produced and bound to mast cell FcεRI receptors; no symptoms occur at this stage.

Symptomatic acute HIV infection (fever, lymphadenopathy, rash, sore throat) occurring 2–4 weeks after infection due to high-level viraemia and immune response; often misdiagnosed as infectious mononucleosis or viral flu.

A pentameric glycoprotein that binds all amyloid fibrils in a calcium-dependent manner; protects fibrils from proteolysis and is used as a radioligand in SAP scintigraphy to image whole-body amyloid burden.

An acute-phase reactant synthesised by the liver whose sustained elevation during chronic inflammation provides the precursor protein for AA amyloid fibrils.

A systemic Type III hypersensitivity reaction occurring 7–10 days after administration of a foreign protein (e.g., equine antiserum); characterised by fever, arthralgia, urticarial rash, and glomerulonephritis due to widespread immune complex deposition.

The stable plasma HIV RNA level reached after the acute phase immune response; reflects the balance between viral replication and host immunity; the primary predictor of rate of CD4 decline and time to AIDS.

Historical term for the cysteinyl leukotrienes LTC4, LTD4, and LTE4; potent bronchoconstrictors synthesised de novo from arachidonic acid in the late phase of Type I hypersensitivity.

A CD4⁺ T helper subset that secretes IFN-γ and TNF, activates macrophages, and drives defence against intracellular pathogens; central to granuloma formation and Type IV hypersensitivity.

A CD4⁺ T helper subset that secretes IL-4, IL-5, and IL-13, driving IgE class-switching, eosinophil activation, and mast cell responses; the dominant subset in Type I hypersensitivity and atopy.

Intimal smooth-muscle proliferation and fibrosis in graft arteries, the histological hallmark of chronic rejection, leading to progressive ischaemia and graft loss.

A tetrameric plasma protein that normally transports thyroxine and retinol; mutations or age-related instability cause it to dissociate and misfold into amyloid fibrils.

A CD4⁺ T cell subset (characterised by FoxP3) that secretes IL-10 and TGF-β, suppressing excessive immune responses and maintaining self-tolerance; deficiency contributes to autoimmunity.

A serine protease stored exclusively in mast cell granules and released during degranulation; serum tryptase elevated > 11.4 ng/mL within 1–3 hours of a suspected event is the most specific marker for systemic mast cell activation (anaphylaxis).

Quantitative measurement of HIV RNA copies per mL of plasma; reflects active viral replication; goal of ART is undetectable viral load (< 20–50 copies/mL); high viral load predicts faster progression.

Confirmatory HIV test that electrophoretically separates viral proteins and detects specific antibody bands (p24, gp41, gp120/160) in patient serum; positive if ≥ 2 bands present; high specificity used after reactive ELISA screen.

The interval between HIV infection and the appearance of detectable antibodies or antigens; 4th-generation ELISA (p24 Ag + Ab) reduces the window to ~2 weeks; RNA PCR can detect infection within days; patients are infectious during this period.

Histological appearance of glomerular capillary walls thickened by large subendothelial immune complex deposits on light microscopy in Class IV diffuse proliferative lupus nephritis.

A secondary protein structure in which polypeptide chains are arranged in parallel or antiparallel sheets stabilised by hydrogen bonds; the cross-β configuration adopted by all amyloid fibrils regardless of precursor protein.