USMLE Step 1 Immunology & Rheumatology Master Guide Flashcards

Comprehensive vocabulary flashcards generated from the PIMG Academy USMLE Step 1 Immunology & Rheumatology Master Guide, detailing innate and adaptive immunity, immunodeficiencies, complement, hypersensitivity reactions, rheumatologic diseases, and core immunosuppressive pharmacology.

Pattern Recognition Receptors (PRRs)

Germline-encoded receptors, such as Toll-like receptors (TLRs), that recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).

Toll-like receptor 4 (TLR4)

Innate pattern recognition receptor that recognizes lipopolysaccharide (LPS) on gram-negative bacteria, triggering NF-κB activation and cytokine release.

Interferons (IFN-α/β)

Primary antiviral cytokines produced during the innate immune response that induce an antiviral state in neighboring cells.

Natural Killer (NK) cells

Innate lymphocytes activated by IL-12 and low MHC I expression ('missing self') that induce apoptosis in virus-infected and tumor cells via perforin and granzymes.

Acute phase reactants

Hepatic proteins (CRP, fibrinogen, ferritin, hepcidin) upregulated by IL-6 during inflammation; albumin and transferrin are negative acute phase reactants.

Pro-B cell

Early B-cell developmental stage in the bone marrow characterized by CD19+ and CD10+ surface marker expression.

Pre-B cell

B-cell developmental stage characterized by cytoplasmic µ heavy chain expression and VDJ recombination mediated by RAG1 and RAG2 genes.

IgG

Most abundant serum immunoglobulin; the only isotype that crosses the placenta, providing passive immunity; mediates opsonization, complement fixation, and neutralization.

IgM

First antibody produced in a primary response; exists as a pentamer in serum for potent complement activation and as a monomer on naive B-cell surfaces.

IgA

Dimeric, secretory immunoglobulin found in mucus, tears, saliva, and colostrum that provides mucosal immunity without fixing complement via the classical pathway.

IgE

Immunoglobulin that binds FcεRI on mast cells and basophils, mediating type I hypersensitivity and driving host defense against helminthic infections.

X-linked (Bruton) agammaglobulinemia

Primary immunodeficiency caused by a defect in the BTK gene (tyrosine kinase), halting B-cell maturation past the pre-B stage and resulting in absent B cells and severe deficiency of all immunoglobulin classes.

Hyper-IgM syndrome

Immunodeficiency caused by a CD40L defect on T cells, preventing immunoglobulin class switching and resulting in elevated IgM levels with severe decreases in IgG, IgA, and IgE.

Positive selection

Thymic selection process in the cortex where double-positive (CD4+/CD8+) thymocytes must weakly recognize self-MHC on cortical epithelial cells to avoid death by neglect.

Negative selection

Thymic selection process in the medulla where single-positive T cells with high affinity for self-antigen presented by medullary epithelial cells/AIRE undergo apoptosis to prevent autoimmunity.

CD4+ Th1 cells

T-helper subset driven by IL-12 that secretes IFN-γ to activate macrophages and orchestrate defenses against intracellular pathogens.

CD4+ Th2 cells

T-helper subset producing IL-4, IL-5, and IL-13 that assists B cells, promotes IgE class switching, and defends against helminth infections.

CD4+ Th17 cells

T-helper subset producing IL-17 that recruits neutrophils to fight extracellular bacterial and fungal infections; implicated in autoimmune conditions such as psoriasis and MS.

Regulatory T (Treg) cells

CD4+CD25+FoxP3+ T cells that secrete IL-10 and TGF-β to suppress immune responses and maintain peripheral tolerance; mutations in FOXP3 lead to IPEX syndrome.

Trisomy 21 (Down syndrome)

Most common autosomal trisomy; presents with flat facies, epicanthal folds, single palmar crease, duodenal atresia, AV septal defects, reduced IgG, increased risk of AML/ALL, and early-onset Alzheimer disease.

Trisomy 18 (Edwards syndrome)

Autosomal trisomy characterized by rocker-bottom feet, micrognathia, low-set ears, clenched fists with overlapping fingers, and congenital heart disease.

Trisomy 13 (Patau syndrome)

Autosomal trisomy characterized by cleft lip/palate, holoprosencephaly, microphthalmia, polydactyly, and cutis aplasia.

22q11.2 Deletion Syndrome

Microdeletion syndrome causing failure of development of the 3rd and 4th pharyngeal pouches, resulting in CATCH-22 features: Cardiac defects, Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia.

Williams syndrome

Microdeletion at 7q11.23 involving the elastin gene, leading to 'elfin' facies, friendly/overly social personality, supravalvular aortic stenosis, and hypercalcemia.

Cri-du-chat syndrome

Genetic disorder caused by a 5p chromosome deletion, characterized by a cat-like cry, microcephaly, intellectual disability, and epicanthal folds.

Wiskott-Aldrich syndrome

X-linked defect in the WAS gene defined by the WATER triad: Wiskott-Aldrich = Thrombocytopenia (small platelets), Eczema, Recurrent pyogenic infections, along with reduced IgM levels.

Ataxia-telangiectasia

Autosomal recessive DNA double-strand break repair defect due to an ATM gene mutation, leading to cerebellar ataxia, spider angiomas, IgA deficiency, and elevated AFP.

Classical complement pathway

Complement activation pathway initiated by IgG or IgM bound to antigen, which activates the C1 complement protein complex.

Lectin complement pathway

Antibody-independent complement pathway initiated by mannose-binding lectin (MBL) binding to mannose residues on microbial cell walls.

Alternative complement pathway

Primitive, antibody-independent complement pathway triggered by the spontaneous hydrolysis of C3 directly on microbial surfaces.

C3b

Complement protein fragment that acts as a primary opsonin to promote phagocytosis and facilitates the clearance of immune complexes.

C5a

Complement anaphylatoxin fragment that mediates mast cell degranulation and acts as a potent chemoattractant for neutrophils.

C1 esterase inhibitor deficiency

Complement regulation disorder causing hereditary angioedema with recurrent non-pruritic, non-pitting swelling and persistently low C4 levels; ACE inhibitors are contraindicated.

Paroxysmal nocturnal hemoglobinuria (PNH)

Complement-mediated hemolytic disorder resulting from a loss of GPI anchors for DAF (CD55) and CD59 on cell surfaces.

Paracortex

T-cell-rich anatomical region of the lymph node where dendritic cells present antigens to naive T cells; poorly developed in DiGeorge syndrome and hypertrophied in viral infections.

Splenic Red Pulp

Spleen region composed of sinusoids and macrophages that filter blood, removing aged red blood cells and encapsulated bacteria via culling and pitting.

Splenic White Pulp

Lymphoid structural region of the spleen containing the periarteriolar lymphatic sheath (PALS, T cells) and lymphoid follicles (B cells).

Howell-Jolly bodies

Nuclear remnants visible inside erythrocytes on peripheral blood smears, indicating functional or surgical asplenia.

Selective IgA deficiency

Most common primary immunodeficiency; often asymptomatic, but can manifest with recurrent sinopulmonary and GI infections, as well as severe anaphylaxis when exposed to IgA-containing blood products.

Common variable immunodeficiency (CVID)

Primary immunodeficiency marked by defective B-cell differentiation into plasma cells, presenting in young adulthood with low levels of all immunoglobulin classes.

IPEX syndrome

X-linked autoimmune condition caused by FOXP3 mutation leading to regulatory T-cell deficiency, presenting in infant boys with enteropathy, endocrinopathy, and dermatitis.

Severe combined immunodeficiency (SCID)

Combined T- and B-cell deficiency caused by IL-2R γ-chain, ADA, or RAG1/2 mutations; presents in infants with failure to thrive, chronic diarrhea, absent thymic shadow, and severe opportunistic infections.

Hyper-IgE (Job) syndrome

Autosomal dominant disorder caused by a STAT3 mutation featuring the FATED mnemonic: coarse Facies, cold Abscesses, retained primary Teeth, elevated IgE, and Dermatologic problems (eczema).

Chronic granulomatous disease (CGD)

Phagocyte defect caused by NADPH oxidase deficiency leading to abnormal oxidative burst and recurrent infections with catalase-positive organisms (e.g., S. aureus, Aspergillus).

Leukocyte adhesion deficiency type 1 (LAD-1)

Integrin (CD18/β-2) defect resulting in impaired neutrophil adhesion and migration, presenting with delayed umbilical cord separation, non-purulent skin infections, and marked peripheral neutrophilia.

Chediak-Higashi syndrome

Autosomal recessive lysosomal trafficking defect caused by a LYST gene mutation; presents with recurrent pyogenic infections, partial albinism, peripheral neuropathy, and giant cytoplasmic granules in leukocytes.

Hyperacute transplant rejection

Transplant rejection occurring within minutes on the operating table, mediated by pre-formed recipient antibodies (Type II hypersensitivity) causing graft thrombosis and vascular occlusion.

Acute transplant rejection

Transplant rejection occurring weeks to months after transplantation, driven by host CD8+ T cells targeting donor MHC (Type IV hypersensitivity) or new donor-specific antibodies.

Chronic transplant rejection

Transplant rejection occurring months to years post-transplant, characterized by cell- and antibody-mediated vascular injury, leading to graft fibrosis and irreversible tissue atrophy.

Graft-versus-host disease (GVHD)

Post-bone marrow transplant reaction where immunocompetent donor T cells attack host recipient tissues, classically presenting with maculopapular skin rash, jaundice/liver dysfunction, and bloody diarrhea.

Type I hypersensitivity

Immediate IgE-mediated allergic response triggered by antigen cross-linking pre-formed IgE on mast cells and basophils, releasing histamine, tryptase, and leukotrienes.

Type II hypersensitivity

Cytotoxic antibody-mediated reaction where IgG or IgM binds fixed tissue or cell-surface antigens, triggering complement activation, phagocytosis, or ADCC.

Type III hypersensitivity

Immune complex-mediated reaction where circulating antigen-antibody complexes deposit in vessel walls or tissues, inducing complement activation and neutrophilic inflammation.

Type IV hypersensitivity

Delayed-type, cell-mediated immune response taking 48–72 hours, driven by sensitized T cells without any antibody involvement.

Serum sickness

Type III hypersensitivity syndrome presenting with fever, urticaria, arthralgia, and lymphadenopathy 1–2 weeks after administration of foreign proteins (e.g., antivenom).

Systemic Lupus Erythematosus (SLE)

Systemic autoimmune disease driven by type III hypersensitivity against nuclear antigens, showing a strong female predominance (9:1) and presenting with SOAP BRAIN MD criteria.

Anti-dsDNA antibody

Highly specific SLE autoantibody that correlates with active disease severity and predicts lupus nephritis flares.

Anti-Smith antibody

Highly specific autoantibody for SLE directed against nuclear ribonucleoproteins; its titer remains stable and does not correlate with clinical disease activity.

Drug-induced lupus

Iatrogenic lupus variant caused by medications such as hydralazine, procainamide, and isoniazid; characterized by positive anti-histone antibodies and absence of renal or CNS involvement.

Rheumatoid Arthritis (RA)

Chronic systemic autoimmune disease characterized by symmetric inflammatory arthritis of small joints (MCP, PIP) with DIP joint sparing, morning stiffness >1 hour, and synovial pannus formation.

Rheumatoid factor (RF)

IgM antibody directed against the Fc portion of IgG; sensitive (~70%) but not specific for Rheumatoid Arthritis.

Anti-CCP (cyclic citrullinated peptide)

Highly specific diagnostic autoantibody for Rheumatoid Arthritis that can be present early in the course of disease.

Felty syndrome

Severe extra-articular manifestation of Rheumatoid Arthritis characterized by the triad of long-standing RA, splenomegaly, and neutropenia.

Sjögren syndrome

Autoimmune disease marked by lymphocytic infiltration and destruction of lacrimal and salivary glands, causing sicca symptoms (dry eyes, dry mouth), bilateral parotid enlargement, anti-Ro/La antibodies, and an increased risk of B-cell MALT lymphoma.

Limited cutaneous systemic sclerosis

Scleroderma subtype with skin thickening restricted to the face and distal extremities, strongly associated with anti-centromere antibodies and CREST syndrome.

Diffuse cutaneous systemic sclerosis

Aggressive scleroderma subtype featuring widespread skin involvement, early pulmonary fibrosis, scleroderma renal crisis, and positive anti-Scl-70 (anti-topoisomerase I) antibodies.

CREST syndrome

Limited scleroderma manifestation defined by Calcinosis cutis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasias.

Scleroderma renal crisis

Life-threatening complication of diffuse systemic sclerosis featuring abrupt onset of malignant hypertension and acute kidney injury; managed urgently with ACE inhibitors.

Giant cell (temporal) arteritis

Large-vessel granulomatous vasculitis in women >50 years presenting with unilateral headache, jaw claudication, and elevated ESR/CRP; requires immediate high-dose glucocorticoid therapy to prevent blindness.

Takayasu arteritis

Large-vessel vasculitis occurring predominantly in young Asian females (<40 years), characterized by granulomatous inflammation of the aortic arch and its branches ('pulseless disease').

Polyarteritis nodosa (PAN)

Medium-vessel necrotizing vasculitis strongly associated with Hepatitis B that spares the pulmonary vasculature, lacks ANCA association, and demonstrates 'string of pearls' microaneurysms on angiography.

Kawasaki disease

Medium-vessel vasculitis in young Asian children (<5 years) presenting with prolonged high fever, mucosal changes, and strawberry tongue; carries a risk of coronary artery aneurysms and is treated with IVIG and aspirin.

Granulomatosis with polyangiitis (GPA)

Small-vessel c-ANCA (anti-PR3) positive vasculitis characterized by necrotizing granulomas affecting the upper respiratory tract, lower respiratory tract, and kidneys.

Microscopic polyangiitis (MPA)

Small-vessel p-ANCA (anti-MPO) positive vasculitis involving the lungs and kidneys that lacks granulomas and upper respiratory tract involvement.

IgA vasculitis (Henoch-Schönlein purpura)

Most common pediatric small-vessel vasculitis; occurs after a URI and presents with IgA immune complex deposition causing palpable purpura on the buttocks/legs, arthralgias, abdominal pain, and renal disease.

Glucocorticoids

Anti-inflammatory steroid hormones that induce Annexin-1 (lipocortin-1) to inhibit phospholipase A2 and suppress NF-κB, blocking both prostaglandin and leukotriene synthesis.

NSAIDs

Analgesic anti-inflammatory agents that reversibly inhibit COX-1 and COX-2 enzymes, blocking conversion of arachidonic acid to prostaglandins and thromboxane A2.

Aspirin

Irreversible cyclooxygenase (COX-1/COX-2) inhibitor that acetylates COX enzymes; contraindicated in pediatric viral illnesses due to the risk of Reye syndrome.

Cyclosporine

Immunosuppressive calcineurin inhibitor that binds cyclophilin to inhibit IL-2 transcription; key adverse effects include nephrotoxicity, hypertension, hirsutism, and gingival hyperplasia.

Tacrolimus

Calcineurin inhibitor that binds FKBP to suppress IL-2 transcription; nephrotoxic and neurotoxic, but does not cause hirsutism or gingival hyperplasia.

Sirolimus (rapamycin)

Immunosuppressive agent that binds FKBP to inhibit mTOR, blocking IL-2 signal transduction; notable for being non-nephrotoxic but causing impaired wound healing and hyperlipidemia.

Azathioprine

Purine analog antimetabolite metabolized by xanthine oxidase; combination with allopurinol leads to severe, life-threatening bone marrow suppression.

Methotrexate

First-line DMARD for Rheumatoid Arthritis that inhibits dihydrofolate reductase to block DNA synthesis; requires supplementation with folate to limit hepatotoxicity, myelosuppression, and mucositis.

TNF-α inhibitors

Biologic agents (etanercept, infliximab, adalimumab) that block TNF-α activity; require mandatory pre-treatment screening for latent tuberculosis and hepatitis B due to reactivation risk.