Innate Immunodeficiencies Flashcards
- Affected Gene: Not Known
- Immune Defect: Absence of Spleen
- Susceptibility: Encapsulated EC Bacteria (S. Pneumonia, H. Influenza); septic infections
Asplenia
- Affected Gene: C3
- Immune Defect: Lack of C3
- Susceptibility: Recurrent infections w/ G- bacteria
C3 Deficiency
- Affected Gene: Somatic and Germline genes involved with Phosphatidylinositol Glycan biosynthesis
- Immune Defect: Lack of DAF, HRF, and CD59
- Susceptibility: Lysis of erythrocytes by complement
- Characterized by complement-induced intravascular hemolytic anemia, red urine, and thrombosis
- Phosphatidylinositol is needed for surface expression of CD59 and DAF
- Treatment: Allogenic Bone Marrow Transplantation
Paroxysmal Nocturnal Hemoglobinuria
- Affected Gene: NEMO
- Immune Defect: Impaired activation of NF-kB
- Susceptibility: Chronic bacterial and viral infections
- Symptoms: develpomental defects (deep set eyes, sparse hair, conical teeth, and skin conditions)
- Treatment: Biweekly injections of gamma globulin; bone marrow transplant
X-Linked hypohidrotic ectodermal dysplasia and immunodeficiency (NEMO Deficiency)
- Affected Gene: NADPH Oxidase (gp91 protein)
- Immune Defect: Impaired Neutrophil Function
- Susceptibility: Chronic Bacterial and Fungal infections
- Cellular Abnormality: Defective NADPH Oxidase
- Immune Defect: Impaired killing of phagocytksed bacteria
- Associated Infections/ Diseases: chronic bacterial and fungal infections. Granulomas form more readily.
- Phagocytes cannot produce toxic oxygen intermediates
- Sensitive to Serratia Marcescens (seen commonly in infants)
Chronic Granulomatous Disease
- Affected Gene: Mannose-Binding Lectin
- Immune Defect: Lack of MBL
- Susceptibility: Meningitis due to Neisseria Meningitidis
- The acute phase response is impaired in these patients
MBL Deficiency
- Affected Gene: May encode perforin, be involved in cytoplasmic granule formation, or a role in NK cell development in bone marrow
- Immune Defect: Absence of NK Cells
- Susceptibility: Viral Infections (Herpesvirus, Varicella Zoster, Cytomagaloviruses, and Epstein-Barr), opportunistic species of mycobacterium, and Tricophyton (fungus)
- Diagnosis: Flow cytometry for NK cells and NKT cells
NK Cell Deficiency
- Cellular Abnormality: Defective CD18
- Immune Defect: Defective migration of phagocytes into infected tissues
- Associated Infections/ Diseases: Systemic infections w/ capsulated bacteria
- Delayed sloughing of umbilical cord
Susceptibility: EC pathogens, especially to encapsulated bacterial pathogens
Leukocyte Adhesion Deficiency
- Cellular Abnormality: Deficiency of G6. Defective Respiratory Burst.
- Immune Defect: Impaired killing of phagocytosed bacteria
- Associated Infections/ Diseases: Chronic bacterial and fungal infections. Anemia is induced by certain agents
- Susceptibility: EC pathogens due to an inability to produce and release superoxide radicals and hydrogen peroxide
- Also involved in erythrocyte metabolism
Glucose-6-Phosphate Dehydrogenase Deficiency
- Cellular Abnormality: Defieicnecy of myeloperoxidase in neutrophil granules and macrophage lysosomes and impaired production of toxic oxygen species
- Immune Defect: Impaired killing of phagocytksed bacteria
- Associated Infections/ Diseases: Chronic bacterial and fungal infections
Myeloperoxidase Deficiency
- Cellular Abnormality: Defect in vesicle fusion
- Immune Defect: Impaired phagocytosis due to inability of endosomes to fuse with lysosomes
- Associated Infections/ Diseases: Recurrent and persistent bacterial infections. Granulomas
- Patients also suffer from partial albinism because of improper trafficking of melanosomes
- Gene Defect: Defect in LYST gene
- Main Symptoms: partial albinism, recurrent pyogenic Infections, and neurological disorders
- Neutrophils have unique appearance with large and irregularly shaped granules
- Treatment: Bone marrow transplant
Chediak-Higashi Syndrome
- Tests for CGD
- Normal phagocytes with NADPH oxidize NTB to produce a blue color
- Patients with CGD are unable to make color change
Nitroblue Tetrazolium Dye
- Tests for CGD
- Flow cytometric assay
- Determines if neutrophils produce oxidative burst by reducing dihydrorhodamine to rhodamine
- Patients with CGD cannot catalyze this conversion
Dihydrorhodamine Test
- A condition characterized by low neutrophil counts below 500 cells/ul
- Susceptibility: bacterial and fungal infections, including normal flora
- ## Cellular Deficiency: 1. Non-functional Granulocyte Colony Stimulating Factor (G-CSF) or its receptor 2. defect of gene for elastase, a serene protease (ela-2)
Neutropenia
What are the 4 diseases that cause patients to produce autoantibodies that are specific for neutrophil determinants resulting in decreased neutrophil numbers?
- X-Linked Hyper IgM Syndrome
- X-Linked Aggamglobulinemia
- WHIM Syndrome
- Griselli Syndrome
Effects of Complement Deficiency: Immune Complex Disease
C1, C2, C4
Effects of Complement Deficiency: Susceptibility to capsulated bacteria
C3
Effects of Complement Deficiency: Susceptibility to Neisseria
C5-C9
Effects of Complement Deficiency: Susceptibility to capsulated bacteria and Neisseria but no immune-complex disease
Factor D, Factor P
Effects of Complement Deficiency: Susceptibility to capsulated bacteria
Factor I
Effects of Complement Deficiency: Autoimmune-like conditions including paroxysmal nocturnal hemoglobinuria
DAF, CD59
- Effects of Complement Deficiency: HANE
- Treatment: monthly injections of C1INH replacement therapy
C1INH
Effects of Complement Deficiency: No MAC formation, susceptible to neisseria
C5-C9
C5 is more severe than C6-C9
