Term
| List the (6) phagocytic defect immunodeficiency diseases? |
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Definition
1. Chronic granulomatous disease (CGD)****
2. Chediak-Higashi syndrome
3. Leukocyte adhesion deficiency (LAD)
4. G6PDH deficiency
5. Myeloperoxidase deficiency
6. Job's syndrome |
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Term
| What is CGD's molecular defect, what's effected, and what are the symptoms? What test do we use? |
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Definition
-Caused by an NAPDH oxidase deficiency; can't make superoxide ion or other O2 radicals
-Get recurrent infections with catalase-positive bacteria and fungi
-Remember; we can do a nitroblue tetrazolium (NBT) reduction test or a neutrophile oxidative index (NOI; a flow cytometry test) with a NEGATIVE result being abnormal (positive for O2* = negative for disease) |
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Term
| What is Chediak-Higashi syndrome's molecular defect, what's effected, and what are the symptoms? |
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Definition
-Microtubule polymerization defect; degranulation and chemotaxis are effected
-Can be seen as a granule structural defect; they can't fuse with each other, or get exocytosed
-Phagocytic cells get giant lysosomes
-Get recurrent bacterial infections with absent NK activity
-Also get partial albinism** |
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Term
| What is LAD's molecular defect, what's effected, and what are the symptoms? |
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Definition
-Absence of CD18; common β chain of leukocyte integrins (such as LFA-1), so can't adhere
-Failure to form pus, do not reject umbilical stump & omphalitis, and recurrent chronic infections (esp. mouth) |
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Term
| What is G6PDH deficiency? |
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Definition
-Part of the PPP for making NADPH; needed by NADPH ox
-Same symptoms as CGD, but with associated ANEMIA
-[More of a biochem question] |
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Term
| What is myeloperoxidase deficiency and symptoms? |
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Definition
-Can't make hyporchlorite
-Often no symptoms
-May get candida infections
-[not such a likely disease for questions]
-The NBT test won't work here, btw |
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Term
| What is Job's syndrome's molecular defect, what's effected, and what are the symptoms? |
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Definition
-TH1 cells cant make IFN-γ; neutrophils don't respond
-Resultantly, IgE production is not inhibited
-The symptoms are FATED;
coarse Facies
cold Abscesses
retained primary TEETH
increased IgE**
Dermatitis problems
-Note; it is also called hyper IgE syndrome |
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Term
| List the (5) humoral defect immunodeficiency diseases? |
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Definition
1. Bruton X-linked hypogammaglobulinemia*
2. X-linked hyper-IgM syndrome*
3. Selective IgA deficiency*
4. Common variable immunodeficiency
5. Transient hypogammaglobulinemia of infancy |
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Term
| What is Bruton X-linked hypogammaglobulinemia's molecular defect, what's effected, what are the symptoms, and what is the treatment? |
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Definition
-Def. in a tyrosine kinase (*Btk) for B-cell maturation; they get stuck at *pre-B stage in bone marrow
-Get absence of B-cells (no follicles) and Igs of **ALL classes, yet normal cel-mediated immunity
-Treat with monthly IgG replacement + antibiotics for infections
-Also called X-linked agammaglobulinemia |
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Term
| What is X-linked hyper-IgM syndrome's molecular defect, what's effected, what are the symptoms, and what is the treatment? |
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Definition
-T cells don't have *CD40L; so they can't activate and class switch the B cells
-Get lots of IgM, but no other isotypes, with normal B & T cell counts; leaving susceptible to extracellular pathogens
-No memory B cells
-Treat the same; IgG infusion + antibiotics |
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Term
| What is Selective IgA deficiency's molecular defect, what's effected, what are the symptoms, and what is the treatment? |
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Definition
-Deficient IgA; most common immunodeficiency*
-Get GI, sinus, and resp. infections (mucosal surfaces)
-Treat with antibiotics only |
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Term
| What is common variable immunodeficiency's molecular defect, what's effected, what are the symptoms, and what is the treatment? |
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Definition
-Cause is unknown, but basically it results in low antibody level (low plasma cells) with onset in TEENS**
-Get atopy; susceptibility to hypersensitivity
-Treat only with antibiotics |
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Term
| What is transient hypogammaglobulinemia of infancy's molecular defect, what's effected, what are the symptoms, and what is the treatment? |
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Definition
-Delayed IgG production; diff causes to this
-Get increased susceptibility to pyogenic bac. (pus forming)
-Detected in *5th-6th month of life and resolves by 16-30
-Treat with antibiotics (IgG if severe) |
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Term
| List the three defects in compliment? |
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Definition
1. Classic pathway
2. Both pathways
3. Deficiency in regulator proteins |
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Term
| Give the deficiencies that can cause classical pathway defects, and what are the signs/diagnosis? |
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Definition
-C1, 2, or 4 can go bad; mainly causes shortage of C3
-Get increase in immune complex diseases (classical works with Igs)
-Get infections with pyogenic bacteria |
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Term
| Give the deficiencies that can cause a both pathway defect, and what are the signs/diagnosis? |
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Definition
-C3 or MAC (C5-9)
-C3 will give recurrent bacterial infections along with immune complex diseases
-**MAC def.** will give meningococcal and gonococcal infections (both NEISSERIA types)
-[Alt path def. also gives rise in neisseria infections] |
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Term
| What specifically is deficient in complement regulatory protein deficiency, and what are the signs/diagnosis? |
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Definition
-C1-INH
-Presents as **hereditary angioedema; episodic attacks of swelling (extremities, airways, genitals, face)
-The overuse of compliment causes edema at mucosal surfaces (esp. mouth; gives that duck appearance)
-Presents with low levels of C1, C2, and **C4 (all early compliment components; others aren't effected) |
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Term
| What are the (6) T lymphocyte ID diseases, break up into only T cell, T cell and some B cell, and T cell and B cell? |
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Definition
Selective T-cell Deficiencies;
1. DiGeorge syndrome***
2. MHC class I deficiency
3. Bare lymphocyte syndrome/MHC class II def.
Combined Partial B & T cell Deficiencies;
4. Wiskott-Aldrich syndrome
5. Ataxia telangiectasia
Complete Functional B & T Cell Deficiency;
6. Sever Combined Immunodeficiency Syndrom (SCIDS) |
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Term
| What is DiGeorge syndrome's defect and clinical manifestations? |
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Definition
-3rd and 4th pharyngeal pouches don't form so we get thymic aplasia; caused by chromosomal deletion on 22
-Presents with facial abnormalities (fish lip), hypoparathyroidism (hypocalcemia and heart malformations), low T cells, absent T-cell response
-Will only be able to make IgM |
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Term
| What is MHC class I deficiency's defect and clinical manifestations? |
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Definition
-TAP I molecules (transporter for antigen processing) aren't doing their job of transporting into ER
-CD8+ cells are low, but CD4+ cells are fine
-Get recurrent viral infections
-Normal DTH (delayed type hypersensitivity; like for PPD) and antibody levels
-Antibody levels may actually be high, since CD8+ cells produce INF-γ, limiting TH2 type response (humoral) |
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Term
| What is bare lymphocyte syndrome's defect and clinical manifestations? |
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Definition
-MHC class II expression fails; transcription factor defects
-Deficient CD4+ cells (CTLs around, but less effective)
-Observed as SCIDS because TH cells direct everything
-Will only be able to make IgM (hypogammaglobulinemia)
-Do not get GVH if implanted with donor bone marrow (no MHC II to stimulate donor cells) |
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Term
| What is Wiskott-Aldrich syndrome's defect (gene and molecule) and clinical manifestations? |
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Definition
-Defect in cytoskeletal glycoprotein for signaling; *WAS-P gene error (X-linked)---> low CD43 (cytoskeletal protein)
-Gradual loss of humoral and cellular responses
-Thrombocytopenia** (low platelets), eczema, and bloody stool
-Low platelets results in the obvious bleeding problems; purpura, nose bleeds, gum bleeds, etc. |
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Term
| What is ataxia telangiectasia's defect and clinical manifestations? |
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Definition
-A cell cycle kinase is bad (ATM; detects DNA damage)
-Ataxia; muscle discoordination (most evident in gait*)
-Telangiectasia (dilation at end); capillaries expand (most obvious in the eye*)
-Get low IgA & IgE |
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Term
| What is SCIDS's defect and clinical manifestations? |
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Definition
Several possible defects;
-γ chain of IL receptor is bad; in IL-2R and other IL-receptors as well (X-linked) [50% of cases**]
-Adenosine deaminase def.; gives toxic metabolites in rapidly dividing cells (boy in bubble lol) [40% of cases]
-rag1 or rag2 nonsense mutations (remember, a partial mutation leads to Omenn Syndrome)
Lima;
-ZAP-70 defect (part of T cell receptor)
-JAK-3 defect (IL-2R signaling component)
-In all cases, we get chronic infections with pretty much everything (esp. opportunistic infections like fungi)
-In rag defects (recombinases) we get total absence of B and T cells as well
-Remember also that bare lymphocyte presents as SCIDS |
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Term
| What are 5 clinically useful mitogens to asses B and T cell proliferation in immunodeficient patients? |
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Definition
For T cells; (PHAConA T)
1. Phytohemagglutinin (PHA) [red kidney been]
2. Concanavalin (ConA) [jack bean]
For B cells;
3. Epstein Barr virus (EBV)
4. Lipopolysaccharide (LPS)
For both;
5. Pokeweed mitogen (PWM) |
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Term
| Lazy leukocyte syndrome (Lima)? |
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Definition
-Often from problem with actin polymerization or chemotaxin generation
-Would present similarly to LAD |
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