Primary and Acquired Immunodeficiency Disorders

Vocabulary flashcards covering key immunodeficiency and autoimmune disease terms from the lecture notes.

Primary immunodeficiency

usually present in infancy; commonly a lack of B- or T-cells

Primary immunodeficiency diagnosis

noticed in infants because of increased infection susceptibility

serum is low or no levels of specific immunoglobulins

Primary vs Secondary immunodeficiency

primary is congenital/genetic (usually X linked or autosomal recessive)

secondary is acquired

Secondary immunodeficiency

often involves inability to distinguish self from non-self; affects women 5x more often

Primary immunodeficiency disorders

DiGeorge Syndrome

Chronic Mucocutaneous Candidiasis

Congenital X-Linked Agammaglobulinemia

Selective IgA Deficiency

Common Variable Immunodeficiency

Wiskott-Aldrich Syndrome

Severe Combined Immunodeficiency

X-linked agammaglobulinemia (Bruton) characteristics

X-linked recessive (limited to males)

near absence of all serum immunoglobulins

absence of mature B cells and loss of B cell follicles

X-linked agammaglobulinemia (Bruton) and vaccines

live polio virus can lead to poliomyelitis infection

X-linked agammaglobulinemia (Bruton) symptom presentation

recurrent pyogenic (pus) infection, recurrent conjunctivitis, pharyngitis, otitis media, bronchitis, and pneumonia

X-linked agammaglobulinemia (Bruton) genetics

located on long arm of X chromosome; inactivation of B cell tyrosine kinase

X-linked agammaglobulinemia (Bruton) comorbidities

increased frequency of autoimmune disorders; SLE; dermatomyositis; RA like condition

X-linked agammaglobulinemia (Bruton) treatment

replacement of all immunoglobulins

B Cell tyrosine kinase

essential for B-cell maturation from pre-B to B cells

defect seen in X-linked agammaglobulinemia (Bruton)

Selective IgA deficiency characteristics

Most common primary immunodeficiency

low IgA with normal IgG/IgM

Selective IgA deficiency symptoms

often asymptomatic; can present with GI or respiratory infections; mucosal infections and allergies

Chronic mucocutaneous candidiasis cause

Yeast infections due to congenital lack of T-cell function; response only impaired for candida antigens

Chronic mucocutaneous candidiasis susceptibility

increased susceptibility to candidal infections

Chronic mucocutaneous candidiasis endocrinopathies

diabetes mellitus, Addison’s disease, hypoparathyroidism

Selective IgA deficiency pathophysiology

Block in terminal differentiation of B cells to IgA-producing plasma cells.

only boys

Common Variable Immunodeficiency (CVID)

Group of disorders with pronounced hypogammaglobulinemia due to defective B-cell maturation or T-cell action

Common Variable Immunodeficiency (CVID) presentation

recurrent pyogenic infections and giardia diarrhea

Common Variable Immunodeficiency (CVID) histology

Hyperplastic B-cell follicles with poor antibody production.

Common Variable Immunodeficiency (CVID) and neoplasma

50 fold increased incidence of CVID and stomach cancers; higher incidence of lymphomas in women than men

Wiskott-Aldrich syndrome characteristics

severe thrombocytopenia

small platelets

Wiskott-Aldrich syndrome presentation

recurrent infections, hemorrhages secondary to thrombocytopenia, petichiae

Wiskott-Aldrich syndrome genetics

X linked recessive mutation causing production of WASP

only impacts males

WASP

expressed in high levels in lymphocytes and megakaryocytes causing immunity defects; Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome immunoglobulins

IgM deficiency (so cannot combat bacteria and viruses)

Wiskott-Aldrich syndrome and neoplasms

increased incidence of lymphoproliferative malignancies

Tetany

involuntary muscle contractions due to low calcium; seen in DiGeorge syndrome

DiGeorge syndrome

thymic hypoplasia; lack of thymus and parathyroid causes susceptibility to viral, parasitic, and fungal infections

DiGeorge syndrome cause

deletion of gene TBX1 on chromosome 22 (90%) or inherited deletion (10%)

DiGeorge syndrome symptoms

T-cell deficiency with hypocalcemia and congenital heart defects

DiGeorge syndrome physical features

microcephaly, mental retardation, low set ears, hearing defects, cleft lips and palates

Interruption in aortic arch (VSD/Aorta defects)

Congenital heart abnormality of DiGeorge

Severe Combined Immunodeficiency (SCID)

swiss type agammaglobulinemia; defect affecting both T- and B-cell lineages

Severe Combined Immunodeficiency (SCID) presentation

recurrent viral, bacterial, fungal, and protozoan infections; hypoplastic thymus; no germinal centers in appendix or lymph nodes

Severe Combined Immunodeficiency (SCID) inheritance

X linked (60%) or autosomal recessive

Antinuclear antibodies (ANA)

Serologic markers directed against nuclear components; useful for autoimmune screening but not diagnostic alone.

Indirect immunofluorescence for ANA

Serum incubated on tissue substrate; fluorescent pattern reveals autoantibody binding to nuclear antigens.

ANA titer

Highest serum dilution still showing positivity; higher titers reflect stronger antibody presence.

ANA pattern: Homogeneous

Diffuse nuclear staining; non-specific.

ANA pattern: Rim

Peripheral staining often indicates anti-dsDNA, associated with SLE.

ANA pattern: Speckled

Speckled pattern suggests ENA antibodies (e.g., SSA/SSB, RNP) seen in MCTD/Sjögren.

ANA pattern: Nucleolar

attachment to nucleolar RNA staining seen in scleroderma (PSS).

ANA pattern: Centromere

Centromere staining associated with CREST syndrome.

Systemic lupus erythematosus (SLE)

Chronic multisystem autoimmune disease; commonly involves kidneys, joints, skin; female predominance; ANA positive.

Butterfly (malar) rash

Erythematous rash over cheeks/nose in SLE.

Libman–Sacks endocarditis

Nonbacterial vegetations on heart valves seen in SLE.

Anti-dsDNA antibodies

Autoantibodies to double-stranded DNA; highly specific for SLE and correlate with disease activity.

Anti-Smith (Sm) antibodies

Autoantibodies to Sm antigen; highly specific for SLE.

SS-A (Ro) antibodies

Autoantibodies associated with Sjögren syndrome and some CTDs.

SS-B (La) antibodies

Autoantibodies associated with Sjögren syndrome.

Anti-centromere antibodies

Antibodies associated with CREST variant of scleroderma.

Scleroderma (systemic sclerosis)

Autoimmune disease with excessive collagen deposition causing fibrosis and vascular changes.

Scl-70 (topoisomerase I) antibodies

Antibodies highly associated with diffuse scleroderma.

CREST syndrome

Milder form of scleroderma: Calcinosis, Raynaud, Esophageal dysfunction, Sclerodactyly, Telangiectasia; often anticentromere positive.

Sjogren syndrome

Autoimmune destruction of lacrimal and salivary glands; dry eyes and mouth; often with extraglandular manifestations.

SS-A (Ro) and SS-B (La) antibodies in Sjogren

Autoantibodies commonly present in Sjögren syndrome; linked to glandular and extraglandular disease.

Rheumatoid factor in Sjogren

Frequently detected in saliva, tears, and circulation of Sjögren patients.

Myositis autoantibodies

Muscle-specific antibodies, including anti-Jo-1; seen in polymyositis and dermatomyositis.

Polymyositis

Chronic inflammatory myopathy with T-cell–mediated muscle damage; may be paraneoplastic and coexists with other CTDs.

Dermatomyositis

Inflammatory myopathy with characteristic skin involvement (heliotrope rash, Gottron papules); often immune complex–mediated and cancer-associated.

Heliotrope rash

Purple eyelid rash classic for dermatomyositis.

Gottron papules

Violaceous, scaly papules over extensor joints seen in dermatomyositis.

Jo-1 antibody

Anti-histidyl-tRNA synthetase; myositis-specific antibody found in inflammatory myopathies.

Mixed Connective Tissue Disease (MCTD)

Overlap syndrome with features of SLE, scleroderma, and RA; high anti-U1 RNP titer; predominantly female.

Anti-U1 RNP antibodies

Autoantibodies associated with MCTD; used in diagnosis.

Raynaud phenomenon

Vasospastic color change of digits; common in CTDs including SLE and scleroderma.

Hematologic involvement in SLE

Anemia, leukopenia, and thrombocytopenia due to immune mechanisms.

Drug-induced lupus

Lupus-like syndrome triggered by certain drugs; serology often shows anti-histone antibodies; resolves after stopping the drug.

Impact of ANA titer

Serum dilution strength; higher titers correlate with greater likelihood/severity of autoimmune disease; negative ANA does not exclude disease.

SLE diagnosis by serology

Presence of dsDNA and/or Sm antibodies with compatible clinical features.

SLE joint disease

Nonerosive arthritis with swelling and pain, common in SLE.

Extractable Nuclear Antigens (ENA)

Group of nuclear antigens including Sm, Ro/La, RNP; patterns help differentiate CTDs.

EBV association with Sjogren

Proposed link between Epstein-Barr virus and Sjögren syndrome.

Scleroderma pathology

Excessive collagen deposition with vascular injury and organ fibrosis.

Esophageal dysfunction in scleroderma

Esophageal hypomotility due to fibrous replacement of smooth muscle.

CREST antibodies

Anticentromere antibodies associated with the limited cutaneous form of scleroderma.

Paraneoplastic syndrome (polymyositis/dermatomyositis)

Inflammatory myopathies associated with underlying cancers, more common in older men.

Anti-dsDNA vs anti-Sm specificity

Anti-dsDNA is highly associated with SLE activity; anti-Sm is highly specific for SLE.

Adenosine deaminase (ADA) deficiency

Autosomal recessive cause of SCID due to toxic metabolites affecting lymphocytes.

Immunoglobulin replacement therapy

Treatment for antibody deficiencies (e.g., XLA, CVID) with pooled IgG to prevent infections.

Bone marrow transplantation (BMT)

Curative option for several severe primary immunodeficiencies; can restore immune function.