Immunopathology: HIV/AIDS, Autoimmunity, Systemic Sclerosis, and Inflammatory Myopathies

Comprehensive vocabulary flashcards covering the etiology, epidemiology, pathogenesis, and clinical pathology of HIV/AIDS, mechanisms of autoimmunity, systemic sclerosis (scleroderma), and inflammatory myopathies.

CDC Staging System for HIV Infection and AIDS

A clinical classification system that categorizes HIV infection into stages 0, 1, 2, 3, and unknown, based on two specific criteria: characteristic clinical manifestations and laboratory assessment of decreased CD4+ T cell counts.

UNAIDS 2017 Global Report Epidemiology

Global surveillance statistics documenting an estimated $37\text{ million}$ individuals living with AIDS (comprising $50\%$ women and $2\text{ million}$ children under $15\text{ years}$ of age), with approximately $1.8\text{ million}$ new cases diagnosed each year ($\approx 5{,}000\text{ cases/day}$).

Major Capsid Protein p24

The most abundant structural protein composing the cone-shaped icosahedral core of the HIV virion, serving as a primary serological target for the laboratory detection of active HIV infection.

Envelope Glycoproteins gp120 and gp41

Host-derived lipid bilayer surface proteins of HIV; gp120 mediates selective tropism and high-affinity binding to the host CD4 receptor and chemokine coreceptors (CCR5 or CXCR4), while gp41 mediates fusion and penetration into the host target cell.

Transforming vs. Cytopathic Retroviruses

The two primary classifications of human retroviruses; transforming retroviruses include HTLV-I and HTLV-II (etiological agents of leukemias and lymphomas), whereas cytopathic retroviruses include HIV-I and HIV-II (etiological agents of AIDS).

Perinatal Transmission of HIV

Vertical transmission from an infected mother to a newborn occurring transplacentally during gestation, peripartum via contact with contaminated maternal blood or amniotic fluid, or post-partum through breast milk.

Gut-Associated Lymphoid Tissue (GALT) Depletion

An early pathogenic phase following mucosal HIV entry via dendritic/Langerhans cell transport, wherein the virus disseminates to GALT and causes massive, irreversible depletion of memory CD4+ T cells.

Host Restriction Factors (TRIM5-α and APOBEC3)

Intracellular host cellular defense proteins located in the cytoplasm that normally restrict retroviral replication, but fail to eliminate HIV because they are neutralized and degraded by viral regulatory proteins.

HIV Provirus

The double-stranded DNA copy of the viral genomic RNA synthesized by reverse transcriptase, which traverses to the host nucleus and integrates stably into host chromosomes via viral integrase to serve as a permanent template for viral replication.

HIV Neuropathogenesis

Neurological involvement documented in $75\text{--}90\%$ of AIDS autopsies, resulting from indirect viral entry and infection of microglial cells by infected circulating macrophages without direct viral infection of neurons.

Wasting Syndrome (AIDS)

A constitutional manifestation of chronic advanced HIV disease characterized by profound involuntary weight loss accompanied by persistent diarrhoea, anorexia, nausea, vomiting, and prolonged fever.

Autoimmunity

A pathological state characterized by the breakdown of self-tolerance mechanisms, prompting an aberrant humoral (autoantibody) or cellular (autoreactive T cell) immune response directed against host self-tissues.

Autoimmune Regulator (AIRE) Gene

A critical nuclear regulatory factor whose absence or functional defect impedes the presentation of peripheral self-antigens in the thymus, leading to defective negative selection and the escape of autoreactive T cells.

Molecular Mimicry

An exogenous mechanism of autoimmunity wherein microbial pathogens express peptide sequences sharing structural or conformational homology with host self-antigens, thereby cross-activating autoreactive lymphocytes.

Organ-Specific Autoimmune Diseases

Disorders in which autoantibody production and tissue injury are restricted to a single anatomical organ or cell type; examples include autoimmune haemolytic anaemia, Myasthenia gravis, Graves' disease, Multiple sclerosis, Type 1 diabetes mellitus, and inflammatory bowel disease.

Organ Non-Specific (Systemic) Autoimmune Diseases

Disorders characterized by widespread immune complex deposition and broad autoantibody reactivities producing lesions across multiple diverse tissue beds, including Systemic lupus erythematosus, inflammatory myopathies, and rheumatoid arthritis.

CREST Syndrome

A localized variant of systemic sclerosis characterized by the constellation of Calcinosis (C), Raynaud's phenomenon (R), Esophageal hypomotility (E), Sclerodactyly (S), and Telangiectasia (T).

Diffuse Scleroderma

A subtype of systemic sclerosis characterized by widespread cutaneous involvement beginning distally in the fingers and extending proximally to the limbs, shoulders, neck, and face, often progressing rapidly to visceral organ fibrosis.

Fibroblast Activation by CD4+ T Cells

The principal immunologic driving mechanism of systemic sclerosis, wherein activated CD4+ helper T cells secrete profibrotic cytokines, notably TGF-β and IL-13, stimulating excessive extracellular matrix and collagen synthesis.

Renal Interlobular Artery Lesions (Systemic Sclerosis)

Vascular alterations in the kidneys resembling malignant hypertension, characterized by concentric intimal proliferation of intimal cells (onion-skinning) and fibrinoid necrosis of the arterial vessel wall.

Endarteritis of Small Arteries

Intimal cellular proliferation occluding the lumen of small peripheral vessels in systemic sclerosis, serving as the structural anatomical basis for Raynaud's phenomenon.

Inflammatory Myopathies

A clinicopathologic group of autoimmune muscular disorders presenting with progressive, symmetric skeletal muscle weakness, comprising polymyositis, dermatomyositis, and inclusion body myositis.

Dermatomyositis Pathogenesis

A humoral-driven autoimmune myopathy characterized histologically by perivascular B cell infiltration and clinically by proximal muscle weakness, periorbital oedema, and a characteristic heliotrope erythema rash.

Polymyositis and Inclusion Body Myositis Pathogenesis

Cell-mediated autoimmune myopathies characterized by antigen-directed cytotoxic CD8+ T cells and macrophages infiltrating the endomysium, causing progressive myofibre vacuolisation, fragmentation, and necrosis.