Immunodeficiency Part 1 Lecture 3 Flashcards Preview

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Flashcards in Immunodeficiency Part 1 Lecture 3 Deck (29):

Primary Immunodeficiency Diseases

Primary immunodeficiency diseases are conditions characterized by intrinsic deficits within the immune system and are caused by inherited or de novo genetic defects


Various PID classification system

Predominately antibody deficiencies: 65% T cell immunodeficiencies or combined immunodeficiency 5% Syndromic immunodeficiencies complement defects 5% phagocytic defects 10% defects of innate immunity disease immune dysregulation autoinflammatory disorders phenocopies of PIDS Antibody deficiencies are the most predominant disease of the groups.


Symptoms of immunodeficiency

1. Infections: frequent severe, unusual organisms, difficult to treat. Failure to thrive. 2. Autoimmune disease: Immune system no longer able to properly distinguish self from non-self 3. Immune dysregulation: impaired tumor surveillance. Hematopoietic malignancy


10 warning signs of primary immunodeficiency (normally children) (One for adults too but did not put. Less stringent)`

1. Four or more new ear infections within 1 year 2. two or more serious sinus infections within 1 year 3. two or more months on antibiotics with little effect 4. two or more pneumonias within 1 year 5. failure of an infant to gain weight or grow normally 6. recurrent, deep skin or organ abscesses 7. Persistent thrush in mouth or fungal infection on skin 8. Need for intravenous antibiotics to clear infections 9. two or more deep seated infections including septicimia 10. A family history of PI


Diagnosis of primary immunodeficiency

Medical history: family history and characteristic infectious susceptibilities and patterns of infection Physical examination laboratory testing referral to an immunologist: specific diagnosis and treatment. Co management with primary care.


Immune effector mechanisms ****

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B cell/ humoral/ antibody deficiencies

Issue with B cells getting to the appropriate safety maturation to create antibody. Lacking help from T cells.

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Antibdy deficiency: pattern of infections

Bacteria: Pneumococcus, H. Flu, MOraxella, Staph aureus, meningococcus, pseudomonas campylobacter, mycoplasma, ureaplasma Viruses: Common respirtory and esp. enteroviruses, rotavirus protozoa: giardia, cryptosporidium


Combined immunodeficiency ****


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Combined immunodeficiency: pattern of infections

Same as for antibody and cellular deficiencies plus: Bacteria: listeria, enteric flora viruses: herpesviruses, rSV, influenza, parainfluezna, measles fungi: pneumocystis, candida, cryptococcus, histoplasma protozoa: toxoplasma, cryptosporidium


Cellular immunodeficiency: defects in IL12/IFN gamma axis ****


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Cellular immunodeficiency: pattern of infections

Mycobacteria salmonella candida herpes viruses pneumocystis


Phagocyte defects


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Phagocyte defects: pattern of infections

Bacteria: catalase positive. Most commonly: staphylococcus aureus, burkholderia cepacia, serratia marcescens, nocardia. Also klebsieela, enteric flora. Mycobacteria including BCG vaccine Fungi: candida, spergillus, paeciomyces


complement deficiency ****

photo decreased opsonization

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complement deficiency: pattern of infection

encapsulated organisms: neisseria (terminal mac components) pyogeneic infection autoimmune disease frequent: (early combonents


X linked agammaglobulinemia/XLA or Bruton's agammaglobulinemia

Infection susceptibility: pyogenic infection, viral meningoencephalitis, vaccine strain poliomyelitis, mycoplasma arthritis. clinical features: infancy/childhood with recurrent sinopulmonary pyogenic infections, 25% with neutropenia Inheritance: X linked diagnosis: absent B cells, approximately 50% positive family history, IgG usually <100 mg/dl, B cells <2% of lymphocytes, normal T cell number and function


Common variable immunodeficiency

infection susceptibility: bacteria, common respiratory and enteroviruses (including vaccine strains), rotavirus, giardia, crptospordium clinical features: recurrent sinopulmonary infections, bronchiectasis, diarrhea, arthritis, giardiasis, autoimmunity (20%), asthma (10%), lymphoproliferative disease, gastic CA and lymphoma inheritance: sporadic, autosomal recessive diagnosis: hypogammaglobulinemia (IgG, IgA, IgM), B cells present. Impaired antibody response


Antibody deficiency in CVID vs Xlinked agammaglobulinemia

CVID: low IgG, LowIgA, and variable IgM X-AG: universally low IgG, IgA, and IgM


Antibody deficiencies: Specific diagnosis

???? TX: generally immunoglobulins and/or antibiotic prophylaxis


Severe combined Immunodeficiency or SCID

Infection susceptibility: All infectious organisms including live vaccine strains and opportunistic infections clinical features: failure to thrive, chronic diarrhea, erythroderma or other skin eruption. Specific gene defects may have associated features inheritance: X linked most common or autosoma recessive diagnosis: lymphopenia in most, diminished or absent T cells in most (maternal T cell engraftment or aberrant oligoclonal T cells in Omenn, may confuse the picture), poor/absent in vitro mitogen0induced T cell proliferation in all



TX: eventual definitive treatment for most SCID patients is hematopoietic stem cell transplantation (HSCT). Prior to transplant patients are placed in infectious isolation and given prophylactic antimicrobials and replacement immunoglobulin. Curative: stem cell transplantation, gene therapy (ADA, XL-SCID) experimental Adjuvant: Enzyme replacement (PEG-ADA), Prophylactic antibiotics, IVIG, Avoidance live viral vaccines, irradiation of blood products, CMV negative blood products only


Lymphocyte phenotype of selected SCID types

Gene mutation: common gamma chain deficiency (xlinked) or JAK3 only have B cells ADA deficiency: No B, T, and NK cells


Chronic granulomatous disease

INfection susceptibility: catalase positive organisms, and indolent fungal infections clinical features: recurrent infections. Granulomas of skin, liver, lungs, lymph nodes, viscera, bones, joints. Gi/GU obstruction secondary to granulomas diagnosis: neutrophil oxidative bursh assay by flow cytometry using dihydrorhodamine 123 TX: prophylactic antibiotics, gamma interferon, bone marrow transplantation


Complement component deficiency

Infection susceptibility and clinical features: Recurrent pyogenic infection and also connective tissue disease (especially C2 and C4) Late component deficiency (C5-9) recurrent Neisseria species infection. Deficiency of regulatory protein C1 esterase inhibitor is associated with angioedema Diagnosis: CH50 for classical pathway, AH50 for alternative pathway, and/or individual complement component levels TX: prophylactic antibiotics, immunization with bacterial polysaccharide vaccines


Diagnostic tools for antibody deficiency


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diagnostic tools for T cell deficiency


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diagnostic tool for Neutrophil defects


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Diagnostic tools for complement deficiency


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