Primary Immunodeficiencies

Primary Immunodeficiencies (PIDs)

Congenital or inherited genetic disorders impacting immunity

Secondary Immunodeficiencies

Acquired disorders impacting immunity, from environmental factors or immunosuppressive drugs

Recurrent, persistent, life expectancy

Primary Immunodeficiencies: 

• Are __ __ infections, resistant to standard treatment

• Reduce __ __

Vaccines, antimicrobial prophylaxis, Ig, IFN-gamma

Generalized Tx for Prim IDs - Preventing infectious diseases

• __

• __ __

• __ therapy

• ___ therapy

Antimicrobials, pain, decongestants

Generalized Tx for Prim IDs - Tx infections and sx

• __

• __ management

• __

Hematopoietic stem cell transplant, gene

Generalized Tx for Prim IDs - Curing immunodeficiency

• ______

• __ therapy

Cytokine signaling, phagocytosis, T/B

Inborn Errors of Immunity

• Errors in ____ (communication)

• Errors in ___ (process)

• Errors in ___ cells

IGN-GammaR1, surface, truncated, mycobacterium

Errors in cytokine signaling

• Interferon-Gamma R Deficiencies

  • __ mutation prevents any __ expression of IFNgammaR1

  • IFN-GammaR1 mutation produces __ IFNgammaR1 that cannot signal (Jak)

  • Enhanced susceptibility to __ (pathogen infection)

Macrophages, Th1

Interferon-Gamma R Deficiency

• Mycobacterium infection susceptibility

  • __ internalize microbacteria, will not be degraded and need help from __ cells that are absent

IL2RG, 2, 4, 7, 9, 15, 21, X-severe combined

Errors in cytokine signaling

• Deficiency in cytokine R ‘common gamma chain’ (__) on X chromosome

  • Used by many cytokines = IL… (6)…

  • Can lead to _-__ __ immunodeficiency

2, 4, 7, 9, 15, 21

(6) Cytokines using IL2RG “common gamma chain”

T, NK, T, B, B

X-severe combined immunodeficiency

• No _ cells or __ cells in circulation → Reduced _ and _ cell proliferation/survival

• Non-functional _ cell immunity

Myeloperoxidase

Expressed in neutrophils and macrophages to catalyze hypochlorite (bleach)

MPO Deficiency

Autosomal recessive mutation with impaired ROS production and phagocyte killing

Neutrophil granules, macrophage lysosomes, bacterial, fungal

MPO Deficiency

• MPO in __ __ and __ __ (2 locations)

• Mostly asymptomatic

• Susceptible to chronic __ and __ infections

Chediak-Higashi Syndrome

Autosomal recessive mutation with a defect in vesicle trafficking and fusion

Phagolysosome, degranulation, cytotoxicity, melanin, pyogenic, granulomas, albinism, neuro

Chediak-Higashi Syndrome

• Impaired __ and __ (immune processes)

• Impaired __ and impaired __ (skin) mobilization

• Sx - Recurrent __ infections, __ to lungs, partial __ (skin), __logic abnormalities

T, non-functional humoral

CD3 genes non-functional leads to:

• Lack of _ cellls

• ____ __ response

Wiskott-Aldrich Syndrome

X-linked mutation with NK and T cell abnormal cytoskeletal reorganization

Synapse, CTL, NK, Treg, autoimmune, B, TFH

Wiskott-Aldrich Syndrome

• Impaired cell division, mobility, and __ formation

• Impaired __ and __ cell cytotoxicity (virus, cancer susc)

• __ immune suppression is compromised (__ susc)

• Mature _ (B/T) cell depletion due to poor __ help (fungus, bacterial susc)

Selective IgA deficiency

Normal IgM, IgG, low Treg cells, low IgA

Common, autosomal, asymptomatic, autoimmune

Selective IgA deficiency

• The most __ immune defect in humans, __ inheritance

• Majority of cases are __ (symptomatic/asymptomatic)

• Recurrent infections and increased risk of __ disease

Bare Lymphocyte Syndromes

Deficiency in regulatory factors required for MHC transcription; autosomal

I, CD8(CTL), NK

Bare Lymphocyte Syndromes

• Type I BLS: MHC class _ deficiency

  • Reduced __ __ and __ killing

II, CD4, gammaglobulinemia

Bare Lymphocyte Syndromes

• Type II BLS: MHC class __ deficiency

  • Reduced __ → hypo___

Bare Lymphocyte Syndrome Type I

Patient is more susceptible to:

• Listeria - cytosolic bacteria

• Varicella-zoster virus

• Influenza virus

• Can fight off most bacteria and all fungi

Hyper IgM Syndrome

Patient is more susceptible to:

• Staph aureus

• Haemophilus influenzae

• Pneumocystis jiroveci (fungus)

• Mycobacterium tuberculosis

• Can fight off viruses

Wiskott-Aldrich Syndrome, Chediak-Higashi Syndrome

Patient is more susceptible to:

• All kinds of infection! Bacteria, fungus, viruses