Immunodeficiency

Vocabulary flashcards covering key terms related to primary immunodeficiencies, combined immunodeficiencies, and autoimmune diseases described in the notes.

Primary immunodeficiency

A congenital defect in the immune system causing impaired immune function

Secondary immunodeficiency

Impaired immune function acquired after birth

Primary or Secondary: Sjogren’s Syndrome

secondary

Primary or Secondary: Drug Induced Lupus

secondary

Primary or Secondary: CREST

secondary

Primary or Secondary: MCTD

secondary

Primary or Secondary: Polymyositis/Dermatomyositis

secondary

Primary or Secondary: Progressive Systemic Sclerosis

secondary

Primary or Secondary: SLE

secondary

Primary or Secondary: DiGeorge Syndrome

primary

Primary or Secondary: Chronic Mucocutaneous Candidiasis

primary

Primary or Secondary: Congenital X-Linked Agammaglobulinemia

primary

Primary or Secondary: Selective IgA Deficiency

primary

Primary or Secondary: Common Variable Immunodeficiency

primary

Primary or Secondary: Wiskott-Aldrich Syndrome

primary

Primary or Secondary: Severe Combined Immunodeficiency

primary

No B cells results in?

BACTERIAL infections

DiGeorge syndrome characteristics

thymic hypoplasia; absent thymus and parathyroid glands

DiGeorge syndrome immunology

absence of T cell immunity; leads to viral, parasitic, and fungal infections

B cells are normal, but T cells are depleted

DiGeorge syndrome genetic cause

sporadic deletion of TBX1 gene on chromosome 22 (90%)

inheritance of autosomal dominant deletion (10%)

DiGeorge syndrome clinical presentation

congenital heart defects; severe hypocalcemia; tetany; characteristic facies; mental retardation

DiGeorge syndrome heart defects

interrupted aortic arch (definitive for DiGeorge)

VSDs

DiGeorge syndrome facial features

microcephaly, low set ears, abnormal mouth

DiGeorge syndrome tetany

involuntary muscle contractions due to low calcium levels; no calcium because no parathyroids

Chronic mucocutaneous candidiasis

T cell dysfunction specific to Candida; other T cell functions remain intact

possibly associated with endocrinopathies

Chronic mucocutaneous candidiasis clinical presentation

susceptibility to candidal infections (thrush)

T cell immunodeficiencies

DiGeorge Syndrome

Chronic Mucocutaneous Candidiasis

B cell immunodeficiencies

congenital x-linked agammablobulinemia (Bruton’s)

selective IgA deficiency

common variable immunodeficiency

Congenital X-linked agammaglobulinemia (XLA) characteristics

Bruton’s; X-linked recessive; only seen in males

Congenital X-linked agammaglobulinemia (XLA) pathophysiology

inactivation of ATK; no humoral immunity

Congenital X-linked agammaglobulinemia (XLA) B cells

mature b cells are absent

pre-b cells located in bone marrow

ATK gene

tyrosine kinase gene essential for B-cell maturation

Congenital X-linked agammaglobulinemia (XLA) infections

presents with recurrent pyogenic bacterial infections; can handle viral, fungal, and parasitic infections normally

Selective IgA deficiency prevalence

Most common primary immunodeficiency

Selective IgA deficiency immunology

low serum IgA; all other immunoglobulins normal

Common Variable Immunodeficiency (CVID)

Group of disorders with hypogammaglobulinemia due to defective B-cell maturation

Combined immunodeficiencies

wiskott-aldrich syndrome

severe combined immunodeficiency (swiss type)

Wiskott–Aldrich syndrome genetics

X-linked disorder that codes for WASP protein; only seen in males

Wiskott–Aldrich syndrome symptoms

thrombocytopenia; eczema; small platelets

Wiskott–Aldrich syndrome immunology

low IgM, all other immunoglobulins normal; deficiency of certain T cells

Severe Combined Immunodeficiency characteristics

Swiss type agammaglobulinemia; combined T- and B-cell immunodeficiency

Severe Combined Immunodeficiency inheritance

X linked recessive (60%)

autosomal recessive (40%)

ADA deficiency

Autosomal recessive cause of SCID; adenosine deaminase enzyme deficiency.

X-linked cytokine receptor defects

X-linked form of SCID; defects in receptors needed for lymphoid stem cell proliferation.

Shared feature of Swiss type agammaglobulinemia and Bruton’s

lack of b cells; no production of antibodies; no humoral immunity

Antinuclear antibodies (ANA)

Autoantibodies directed against nuclear “self” antigens; higher levels indicate higher severity

ANA staining patterns: Homogeneous

Diffuse nuclear staining pattern; nonspecific.

ANA staining patterns: Rim

Peripheral staining pattern often associated with anti-dsDNA

Rim Staining: Associated Disease

SLE

ANA staining patterns: Speckled

Speckled staining pattern associated with anti-ENAs

Spackled Staining: Associated Disease

MCTD

ANA staining patterns: Nucleolar

Nucleolar staining pattern associated with anti-nucleolar RNA

Nucleolar Staining: Associated Disease

Progressive Systemic Sclerosis

ANA staining patterns: Centromere

Centromere staining pattern associated with anti-centromeric protein

Centromere Staining: Associated Disease

CREST

Associated Disease: Anti-dsDNA

highly specific for SLE

Associated Disease: Anti-Smith (Sm)

highly specific for SLE.

Associated Disease: Anti-histone

drug-induced lupus.

Associated Disease: anti SS-A

Sjogren’s Syndrome

Associated Disease: anti SS-B

Sjogren’s Syndrome

Associated Disease: anti-DNA topoisomerase (Scl-70)

PSS

Associated Disease: anti-histidyl tRNA synthetase (Jo-1)

polymyositis

Associated Disease: anti-RNP (ribonucleoprotein)

MCTD

Associated Disease: anti-phospholipid (Cardiolipin) antibody

SLE

Systemic Lupus Erythematosus (SLE)

Chronic multisystem inflammatory autoimmune disease; mainly impacts kidneys, serosal membranes, joints, skin

SLE characteristic features

anti-Smith and anti-dsDNA

rim staining pattern

SLE: hormonal factors

female predisposition due to estrogens; disease exacerbation in menses and pregnancy

SLE: genetic factors

family members have increased risk; higher risk with monozygotic twins

SLE: Skin

butterfly malar rash; microscopic vasculitis and liquefactive degeneration of basal cells

Malar rash

Butterfly-shaped facial rash characteristic of SLE.

SLE: Joints

more than 90% experience arthralgias

SLE: Kidneys

glomerulonephritis, interstitial nephritis, renal vasculitis

SLE immunoglobulins

low blood levels of immunoglobulins/complement; present in interstitium

SLE: serous membranes

pleuritis with pleural effusion

SLE: lungs

pleural disease, pneumonia, progressive interstitial fibrosis

SLE: heart

pericarditis most common; myocarditis and endocarditis also seen

Libman–Sacks endocarditis

Nonbacterial endocarditis seen on valve leaflets in SLE.

SLE: brain

CNS vasculitis leading to hemorrhage and infarction

SLE: spleen

vasculitis; concentric fibrosis with onion-skin appearance

SLE presentation

joint inflammation with redness and pain; hematuria, proteinuria, crescent formation, renal failure; anemia; Raynaud’s

Causes of drug induced lupus

procainamide

hydralazine

isoniazid

Drug induced lupus ANA

anti-histone is typical

Sjögren syndrome characteristics

dry eyes and dry mouth from destruction of lacrimal and salivary glands; presence of rheumatoid factor

Autoimmune prototype

SLE

Viral autoimmune etiology prototype

Sjögren syndrome

Sjögren syndrome ANA

anti SS-A

anti SS-B

Sjögren syndrome possible neoplasm

40x increased risk of Non-Hodgkin’s B Cell Lymphoma

Progressive Systemic Sclerosis

scleroderma; excessive collagen deposition and fibrosis of skin and organs; usually begins with Raynaud’s

Progressive Systemic Sclerosis ANA

Scl70

anti-nucleolar

anti-centromere

Progressive Systemic Sclerosis: Skin

claw-like fingers; mask-like face

CREST syndrome

Milder form of scleroderma

CREST syndrome characteristics

Calcinosis

Raynaud’s

Esophageal dysfunction

Sclerodactyly

Telangiectasia

CREST syndrome ANA

anti-centromere

Myositis cancers

men- lungs, colon, stomach

women- breast, ovaries, uterus

Polymyositis/Dermatomyositis blood enzymes

elevated MM isoenzymes of CPK

Polymyositis/Dermatomyositis

inflammatory myopathies; rare

Polymyositis/Dermatomyositis ANA

anti-Jo1

anti-myosin

Dermatomyositis symptoms

microangiopathy; rash on eyelids

Mixed Connective Tissue Disease: SLE-like symptoms

rash, Raynaud’s, arthritis, arthralgias

Mixed Connective Tissue Disease: scleroderma-like symptoms

swollen hands, esophageal dysmotility, pulmonary disease