Immune System
Leukocyte Dysfunctions
| Step | Endothelium | Leukocyte | Disease |
|---|---|---|---|
| Adhesion | CAM | Integrin | Leukocyte adhesion deficiency (LAD) |
| Fusion | - | Microtubule | Chediak-Higashi syndrome (CHS) |
| Degradation | - | NADPH oxidase | Chronic granulomatous disease (CGD) |
| - | Myeloperoxidase | Myeloperoxidase deficiency |
Presentation of Chediak-Higashi Syndrome (CHS)
- Lymphohistiocytosis
- Albinism :: partial
- Recurrent infections
- Neurodegeneration
- Peripheral neuropathy
Immunodeficiency {WASH-CHILD-CBS}
Combined Deficiency {WASH}
| Disease | Gene | Inheritance | IgM | IgG | IgE | IgA |
|---|---|---|---|---|---|---|
| Wiskott-Aldrich syndrome (WAS) | WAS | XR | ↓ | - | ↑ | ↑ |
| Ataxia telangiectasia | ATM | AR | - | ↓ | ↓ | ↓ |
| Severe combined immunodeficiency (SCID) | ADA | AR | ↓ | ↓ | ↓ | ↓ |
| IL-2R | XR | ↓ | ↓ | ↓ | ↓ | |
| Hyper-IgM syndrome | CD40L | XR | ↑ | ↓ | ↓ | ↓ |
T Cell Deficiency {CHILD}
| Disease | Gene | Inheritance | IgM | IgG | IgE | IgA |
|---|---|---|---|---|---|---|
| Chronic mucocutaneous candidiasis | - | - | - | - | - | - |
| Hyper-IgE [Job] syndrome | STAT3 | AD | - | - | ↑ | - |
| IL-12R deficiency | IL-12R | AR | - | - | - | - |
| DiGeorge syndrome | 22q11 | AD | - | - | - | - |
B Cell Deficiency {CBS}
| Disease | Gene | Inheritance | IgM | IgG | IgE | IgA |
|---|---|---|---|---|---|---|
| Common variable immunodeficiency (CVID) | - | - | ↓ | ↓ | ↓ | ↓ |
| Bruton agammaglobulinemia | BTK | XR | ↓ | ↓ | ↓ | ↓ |
| Selective IgA deficiency | - | - | - | - | - | ↓ |
Presentation of Wiskott-Aldrich syndrome (WAS) {WATER}
- Wiskott
- Aldrich
- Thrombocytopenia
- Eczema ← ↑ IgE & IgA
- Recurrent infections
Presentation of Hyper-IgE [Job] Syndrome {FATE}
- Facies :: coarse
- Abscess
- Teeth :: primary
- Eosinophilia
- Eczema ← ↑ IgE
Gell-Coombs Classification of Hypersensitivity {ACID}
Anaphylactic [Type 1]
| Disease | Antibodies |
|---|---|
| Atopy | IgE |
| Anaphylaxis | IgE |
| Transfusion reaction :: allergic | IgE |
| Urticaria | IgE |
Cytotoxic [Type 2]
| Disease | Antibodies |
|---|---|
| Autoimmune hemolytic anemia (AHA) | Anti-RBC |
| Bullous pemphigoid | Anti-hemidesmosome |
| Goodpasture syndrome | Anti-basement membrane |
| Graves disease | Anti-TSH receptor |
| Guillain-Barre syndrome | Anti-ganglioside |
| Heparin-induced thrombocytopenia (HIT) | Anti-platelet factor 4 (Anti-PF4) |
| Immune thrombocytopenic purpura (ITP) | Anti-Gp1b Anti-Gp2b/3a |
| Lambert-Eaton myasthenic syndrome | Anti-presynatic Ca channel |
| Membranous nephropathy | Anti-phospholipase A2 receptor (Anti-PLA2R) |
| Myasthenia gravis | Anti-ACh receptor |
| Pemphigus vulgaris | Anti-desmosome |
| Pernicious anemia | Anti-parietal cell Anti-intrinsic factor |
| Rheumatic fever | Anti-M protein |
| Transfusion reaction :: hemolytic | Anti-ABO Anti-Rh |
| Transplant reaction :: hyperacute | Anti-graft |
Immune Complex-Mediated [Type 3]
| Disease | Antibodies |
|---|---|
| ANCA-associated vasculitis (AAV) | Anti-PR3 [c-ANCA] Anti-MPO [p-ANCA] |
| Antiphospholipid syndrome (APS) | Anti-cardiolipin Anti-β2-glycoprotein I Lupus anticoagulant |
| Arthus reaction | - |
| Autoimmune hepatitis | Anti-smooth muscle Anti-liver cytosol |
| Crohn disease | ASCA |
| Dermatitis herpetiformis | Anti-tissue transglutaminase (Anti-tTG) IgA |
| Drug-induced lupus | Anti-histone |
| IgA nephropathy [Berger disease] | IgA |
| IgA vasculitis [Henoch-Schonlein purpura (HSP)] | IgA |
| Membranoproliferative glomerulonephritis (MPGN) | C3 nephritic factor |
| Mixed connective tissue disease (MCTD) | Anti-U1 RNP |
| Polyarteritis nodosa | - |
| Polymyositis Dermatomyositis | Anti-Jo-1 Anti-Mi-2 Anti-SRP |
| Primary biliary cirrhosis (PBC) | Anti-mitochondrium |
| Primary sclerosing cholangitis (PSC) | Anti-MPO [p-ANCA] |
| Rheumatoid arthritis | Rheumatoid factor [Anti-IgG] Anti-CCP |
| Scleroderma :: diffuse | Anti-Scl-70 [Anti-topoisomerase] |
| Scleroderma :: limited | Anti-centromere |
| Serum sickness | - |
| Sjogren syndrome | Anti-Ro [Anti-SSA] Anti-La [Anti-SSB] |
| Systemic lupus erythematosus (SLE) | Anti-dsDNA Anti-Smith [Anti-snRNP] |
| Ulcerative colitis | Anti-MPO [p-ANCA] |
Delayed [Type 4]
| Disease | Antibodies |
|---|---|
| Celiac disease | Anti-tissue transglutaminase (Anti-tTG) IgA Anti-endomysial IgA Anti-gliadin IgA |
| Contact dermatitis | - |
| DM type 1 | Anti-glutamate decarboxylase (Anti-GAD-65) |
| Graft-versus-host disease (GVHD) | - |
| Hashimoto thyroiditis | Anti-thyroglobulin Anti-TPO Anti-microsome |
| Multiple sclerosis | - |
| Tuberculin skin test (TST) | - |
| Stevens-Johnson syndrome (SJS) | - |
| Toxic epidermal necrolysis (TEN) | - |
| Transplant reaction :: acute | - |
| Transplant reaction :: chronic | - |
Presentation of Atopy
- Allergic conjunctivitis
- Allergic rhinitis
- Asthma
- Atopic dermatitis
Diagnostic Criteria for Anaphylaxis
- Hypotension
- Respiratory compromise
- Skin mucosal tissue symptoms
- Gastrointestinal symptoms
HLA Subtypes Associated With Diseases
| HLA | Diseases |
|---|---|
| A3 | Hemochromatosis |
| B27 | Psoriatic arthritis Ankylosing spondylitis Inammatory bowel disease Reactive arthritis |
| B51 | Behcet disease |
| B5801 | Stevens-Johnson syndrome (SJS) |
| DQ2 DQ8 | Celiac disease |
| DR2 | Multiple sclerosis Hay fever SLE Goodpasture syndrome |
| DR3 | DM type 1 SLE Graves disease Hashimoto thyroiditis |
| DR4 | Rheumatoid arthritis DM type 1 |
| DR5 | Pernicious anemia Hashimoto thyroiditis |
Etiology of Cold Sensitive Antibodies (CSA)
- Infection
- Mycoplasma
- HCV
- EBV
- Autoimmune disorders
- IgM monoclonal gammopathy
- Waldenstrom macroglobulinemia
- IgM monoclonal gammopathy of undetermined significance (MGUS)
Jones Criteria for Rheumatic Fever {JONES}
- Joint :: migratory polyarthritis
- Heart :: mitral regurgitation & stenosis
- Nodules :: subcutaneous
- Erythema marginatum
- Sydenham chorea [Chorea minor]
Presentation of Sarcoidosis {GAUSH}
- Granuloma :: non-caseating
- γ globulinemia
- ↑ Angiotensin converting enzyme (ACE)
- Asteroid body
- Arthritis
- Uveitis
- Schaumann body
- ↑ 1α-hydroxylase
- Hypercalcemia
Triad of Lofgren Syndrome
- Erythema nodosum
- Adenopathy :: hilar
- Arthritis :: migratory
Seronegative Spondyloarthropathy {PAIR}
- Psoriatic arthritis
- Ankylosing spondylitis
- Inflammatory bowel disease
- Reactive arthritis [Reiter syndrome]
Precipitating Factors of Reactive Arthritis
- Chlamydia
- Campylobacter
- Salmonella
- Shigella
- Ureaplasma
Triad of Reactive Arthritis {AUC}
- Arthritis
- Urethritis
- Conjunctivitis
SLICC Diagnostic Criteria for SLE {MD-SOAP-BRAIN}
- Malar rash
- Discoid rash
- Serositis
- Oral ulcer
- Arthritis
- Photosensitivity
- Blood disorders
- Renal disorders
- Autoimmune antibody
- Immunologic disorders
- Neurologic disorders
Presentation of Rheumatoid Arthritis
- Pannus
- Symmetric polyarthritis
- Swan neck deformity
- Boutonniere deformity
- Ulnar deviation
- Atlanto-axial subluxation
- Keratoconjunctivitis sicca
Diagnostic Criteria for Rheumatoid Arthritis
- Polyarthritis :: joints ≥ 3
- Chronicity :: duration > 6 weeks
- Positive RF / Anti-CCP
- Elevated ESR / CRP
- Exclusion of alternative diagnoses
Disorders Associated with Rheumatoid Arthritis
Felty syndrome
- Rheumatoid arthritis
- Splenomegaly
- Neutropenia
Caplan syndrome
- Rheumatoid arthritis
- Pneumoconiosis
- Lung nodules
Treatment of Rheumatoid Arthritis
| Mechanism | Medication |
|---|---|
| COX inhibitors | NSAIDs |
| Sulfasalazine Mesalazine | |
| ↓ Folate synthesis | Methotrexate |
| ↓ Purine synthesis | Azathioprine |
| ↓ Pyrimidine synthesis | Leflunomide |
| ↑ DNA crosslinking | Cyclophosphamide |
| NF-κB inhibitors | Corticosteroids |
| TNF-α inhibitors | Infliximab Adalimumab |
| CD20 inhibitors | Rituximab |
| - | Chloroquine |
Presentation of Limited Scleroderma {CREST}
- Calcinosis
- Raynaud syndrome
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasia
Triad of Henoch-Schonlein Purpura (HSP)
- Abdominal pain
- Arthritis
- Rashes
- ± IgA nephropathy [Berger disease]
Presentation of Dermatomyositis
- Heliotrope sign
- Shawl sign
- Gottron sign
- Gower sign
- Proximal muscle weakness
Diagnostic Criteria for Antiphospholipid Syndrome (APS)
- Clinical criteria ≥ 1
- Vascular thrombosis
- Pregnancy morbidity
- Unexplained fetal death > 10 weeks of gestation
- Premature births of due to eclampsia / placental insufficiency
- Three unexplained consecutive spontaneous abortions < 10 weeks of gestation
- Laboratory criteria ≥ 1
- Lupus anticoagulant at least twice > 12 weeks apart
- Anti-cardiolipin at least twice > 12 weeks apart
- Anti-β2 glycoprotein at least twice > 12 weeks apart
Presentation of Adult-onset Still's Disease
- Arthralgia
- Fever
- ↑ Ferritin
- Hepatomegaly
- Leukocytosis
- Lymphadenopathy
- Rashes :: salmon-colored
- Splenomegaly
Types of Transplants
- Autograft
- Isograft
- Allograft
- Xenograft
Types of Transplant Reactions
| Type | Causes | Onset |
|---|---|---|
| Hyperacute | Anti-graft | Minutes |
| Acute | T-cell | Days ~ Weeks |
| Chronic | T-cell | Months ~ Years |
Immunosuppressants
Immunosuppressants
| Mechanism | Medication | Indications |
|---|---|---|
| COX inhibitors | NSAIDs | Immunosuppression |
| ↓ Folate synthesis | Methotrexate | Immunosuppression |
| ↓ Purine synthesis | Mycophenolate Azathioprine | Immunosuppression |
| ↓ Pyrimidine synthesis | Leflunomide | Immunosuppression |
| ↑ DNA crosslinking | Cyclophosphamide | Immunosuppression |
| NF-κB inhibitors | Corticosteroids Mesalazine | Immunosuppression |
| Calcineurin inhibitors | Cyclosporine Tacrolimus | Immunosuppression |
| mTOR inhibitors | Sirolimus Everolimus | Immunosuppression |
| IL-2R inhibitors | Basiliximab Daclizumab | Immunosuppression |
| TNF-α inhibitors | Etanercept | Immunosuppression |
| Infliximab Adalimumab | Immunosuppression | |
| CD20 inhibitors | Rituximab | Immunosuppression |