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