Flashcards in Immunodeficiencies Deck (15):
B Cell deficiency: Bruton Agammaglobulinemia
X-linked (boys), all B-cells deficient 2/2 defective TKR gene yields recurrent bacterial infections after 6 months of age (after passive immunity declines)
B Cell deficiency: Selective Immunoglobulin Deficiencies
Most commonly, IgA is deficient.
Overall appears healthy but frequent sinus/lung infections (sinusitis, recurrent PNA, etc), prev= 1/600 among pts w/ European descent
Can have atopy, asthma, anaphylaxis 2/2 blood products.
T Cell deficiency: Thymic aplasia (DiGeorge)
3rd and 4th pouches fail to develop (no thymus so no mature T cells; no parathyroids so hypocalcemia and tetany) Chvostek (cheek), Trousseau (tight BP cuff yields carpopedal smasm). Recurrent viral, fungal, protozoal infections. 90% have chromosome 22q11 deletion (FISH).
CXR: no thymic shadow on newborn CXR.
T Cell deficiency: Chronic Mucocutaneous Candidiasis
T Cell dysfunction against C. Albicans
T Cell deficiency: Hyper- IgM syndrome: high IgM, low IgG
There are 3 types:
1. X- linked absence of CD40 ligand on T cells, so non-IgM immunoglobulins are decreased.
2. Autosomal recessive absence of CD40 on B cells
3. NEMO deficiency
T Cell deficiency: IL12 Receptor deficiency
Increased rate of mycobacterial infections
IL12 and IFN-gamma together promote Thelper cell differentiation in the direction of TH1. Tx by administering IL12
Combined B and T Cell Deficiencies: Severe Combined Immunodeficiency (SCID)
Autosomal recessive deficiency in early stem cell differentiation leading to Adenosine Deaminase deficiency, linked to one of at least 7 possible gene defects (including IL2R-gamma chain). Deficient T cell receptor excision circles (TREC)
Since there are no B Cells or T Cells this immune system relies on NK cells.
CXR: no thymic shadow (like DiGeorge)
1. Severe recurrent infections
1a. Chronic mucocutaneous candidiasis
1b. Fatal/recurrent RSV, VZV, HSV, measles, flu, parainfluenza episodes
1c. PCP pneumonia
2. Chronic diarrhea
3. Failure to thrive
Combined B and T Cell Deficiencies: Wiskott- Aldrich Syndrome
Immunodeficiency (aka X- linked Thrombocytopenia-Immunodefiency-Exzema Disorder)
Thrombocytopenia and purpura (small PLTs do not function properly; bruising, bloody diarrhea, nosebleeds)
Eczema on the trunk= atypical presentation for eczema
Recurrent pyogenic infections:
-No IgM against capsular polysaccharides of bacteria
-Low IgM, high IgA
Dx based on PBS and IgM levels
X- linked Combined B and T Cell Deficiencies
(C)hronic granulomatous disease (can be X-linked)
(H)yperIgM Syndrome (not always X-linked but can be)
Combined C and T Cell Deficiencies: Ataxia- Telangiectasia
Deficient IgA and T Cells, accompanied by defective DNA repair
Cerebellar ataxia and poor smooth pursuit of moving target and eyes
Telangiectasias of the face >5yo
Increased cancer risk (lymphoma and acute leukemia)
Radiation sensitivity (avoid x- rays)
Possible increased AFP in children >8mo
Average age of death: 25yo
Phagocyte disorders: Chronic Granulomatous Disease (CGD)
Lacking NADPH oxidase activity yields impotent phagocytes
Susceptible to catalase- positive organisms (PLACESS)
Dx: Negative nitroblue tetrazolium test (NBT test), where the normal yellow to blue-black oxidation is not seen
Prophylactic TMP-SMX, and perhaps IFN-gamma to help the macrophages along
Catalase enzyme catalyzes breakdown of hydrogen peroxide. If catalase-neg, normal metabolic functions cause accumulation of hydrogen peroxide which the host's immune system can use to fight off the infection. If catalase-pos, the bact enzyme breaks down any hydrogen peroxide produced in normal metabolism. Therefore hydrogen peroxide will not accumulate, leaving patient vulnerable to cat-pos bacteria.
Phagocyte disorders: Chediak-Higashi Syndrome
Autosomal recessive defect in intracellular lysosomal trafficking protein (LYST gene). Impaired bacteriolysis secondary to impaired lysosome degranulation with phagosomes, so phagocytosed bacteria are not destroyed by lysozomal enzymes.
Giant cytoplasmic granules (large lysosome vesicles) in PMNs are diagnostic. Recurrent infections, abnormal nuclear structures of leukocytes (secretion of lytic secretory granules by cytotoxic T cells is affected), anemia, hepatomegaly. Dohle bodies in neutrophil (ruptured RER).
Phagocyte disorders: Hyperimmunoglobulin E syndrome (Job syndrome)
Deficient IFN-gamma leads to impaired PMN chemotaxis. High levels of IgE and eosinophils are present.
2. Recurrent COLD s. aureus abscesses (PMNs can't get to it so warmth, inflammation impaired)
3. Coarse facial features; broad nose, prominent forehead ("frontal bossing"), deep set eyes, "doughy" skin
Retained primary teeth (2 rows of teeth)
Phagocyte disorders: Leukocyte Adhesion Deficiency Syndrome
Autosomal recessive, abnormal integrins. Phagocytes unable to to exit circulation (CD18s, Complement Receptor 3, LFA1).
Lymphocyte Function Associated-1 on neutrophils is needed for PMN's to adhere and extravasate from vessels. High PMN count expected.
Impaired immune cell interaction, immune recognition, and cell-killing lymphocyte functions. Lack of CR3 interferes with chemotaxis, phagocytosis, and respiratory burst.
Delayed separation of umbilical cord (impaired wound healing). Life-threatening, recurrent bacterial or fungal soft tissue infections often apparent at birth and may spread throughout the body. Periodontal disease, elevated neutrophils, and impaired wound healing, but NOT increased vulnerability to viral infections or cancer. Such patients have fever as the manifestation of infection, inflammatory responses are indolent.