congenital immunodeficiencies Flashcards

Question

what is BTK def? genetic trait? causes?

Answer 1

bruton tyrosine kinase- progresses pre-B cell to immature B-cell **T+ B- NK+** **no IgG, IgM, IgA** X linked defect in rearrangment of Ig heavy chains diagnosed in first 5-6 months of life

Answer 2

**T+ B- NK+** **some IgG subclasses low, normal IgM,IgA,IgE** caused by defects in several genes may be asymptomatic but also may present recurrent viral/bacterial infections in respiratory tract low levels of IgG2- poor responses to polysaccrhaides ags IgG4- many healthy people have none

Answer 3

**T+ B+ NK+** **no IgA, normal IgG, IgM** prevalance higher in males high incidence- most people are healthy pathogenic mechanism- IgA secreting B cells have disorders in the maturation/differentiation step syptoms are recurrent infections, allergies, autoimmune diease **pts with serum anti-IgA IgG respond with anaphlaxis to IVIG transfusion**

Answer 4

selective T lymphocyte immunodef in maturation of T cells- T cell def (complete dgs) or low levels **T- B+ NK+** **normal IgG, IgA, IgM** caused by microdeletion of 22q11.2 region classic triad: cardiac abnormalities, hypocalcemia, hypoplastic thymus humoral imm intact pts can have live virus vax

Answer 5

**T+ B+ NK+** **_high IgM_, low IgG and IgA** group of diseases characterized by impaired Ig class switching and somatic hypermutation normal levels of peripheral B cells but low numbers of cd27+ memory B cells

Answer 6

mutation in the **CD****40L**gene (normally CD40 on B cells binds to CD40L on T cells to cause**class switching and somatic hypermutation**)---**happens in periphery** increase suspectibility to bacterial infection 2/3 of causes of HIGM \*\*autosomal **CD40** def in males and females cause of 1/3 of HIGM

Answer 7

**T+ B+ NK+** **low IgG, IgA, normal or low IgM** fetus IgG production is delayed for up to 36 months increased suspebility to sinopulmonary infections

Answer 8

**Common Variable Immune Deficiency** **T+ B+/- NK+** **low IgG and IgA, sometimes low IgM** defect in ab production- associated with hypogammaglobulinemia B cells dont differentiate in to plasma cells due to mutations in B cell growth factors and co stimulators diagnosed based on history of recurrent pyogenic sinopulmonary infections after 20-30 years of age (onset begins around 4-5 years) pts have increased risk of infections, autoimmune diseases, malignancies autosomal disorder

Answer 9

group of disorders caused by problems with growth, maturation, and survival of T cells can also harm B cells, NK cells can span infancy to adulthood suspecible to opportunistis infections, autoimmunity, cancer

Answer 10

**T- B+ NK-** very low IgG, IgA, IgM most common form of SCID X linked recessive def in gene encoding gamma chain thats located in T cell growth factor receptor IL-2Ry (shared with other cytone receptors IL-4, IL-7, IL-19, IL-15, IL-21) no B cells- T cells cant help- cant produce abs symptoms: failure to thrive, severe thrush, opportunistic, chronic diarrhea

Answer 11

**T- B+ NK+** **very low IgG, IgA, IgM** autosomal recessive IL-7 important in early T cell development symptoms: candidiases, chronic diarrhea, pneumonia, severe viral infections diagnosis from sequencing **avoid all live vaccines**

Answer 12

**CD4T- CD8T+ B+ NK+** no MHC class II on APC's- causes def in CD4 T cells genes for MHC II are intact, but mutations in transcription factors that regulate expression associated with variable hypogammaglobulinameia (IgA and IgG2) recurrent respiratory, GI, urinary tract infections- frequently to death in early childhood

Answer 13

caused by mutation in TAP1 molecules CD8 def, CD4 normal normal ab production normal DTH (hypersensitivity)

Answer 14

**T- B+ NK+** **low IgG, IgA, IgM** autosomal recessive decreased T cells and lymphopenia ab decreased FTT, opportunistic infections, chronic diarrhea HSCT for severe types

Answer 15

problems in positive regulatory loop suspectibility to nontuberculosis myobacteria macrophages and dc's produce IL-12, which binds to IL-12R on T cells/nk cells, which produce IFN-y, which stimulates macrophages to produce H2O2, TNF-a, and IL-2, starting cycle over again IL 12- differentitates naive t cells into mature T cells (def leads to primary immunodeficiency- pts cant produce IFN-y which is necessary for fighting off intracellular bacterial infection) pts also cant produce Th17 which rely on IL-17 which relies on IL-2R

Answer 16

suspebility to chronic candidiasis impariment of Th17 development due to def in IL-17, IL-17r, STAT1, STAT3, AIRE associated with hyper IgE syndrome sympotoms are severe aptoic disease, recurrent staph

Answer 17

autoimmune lymphoproliferativ syndrome defect in Fas, FasL, caspase 8, caspase 10- leading to resistance of T cells to apoptosis

Answer 18

immunodysregulation, polyendocrinopathy, enteropathy X linked syndrome mutation in FoxP3, which inhibits Treg and cannot inhibit self reactive effector T cells

Answer 19

mutated protein called WASP **T- B+ NK-** **low IgM, normal Ig, elevated IgA and IgE** X linked disorder

Answer 20

over 40 known types to be considered NKD pts should have major immunologic abnormalities caused by mutations in multiple genes 1) classical NKD: absence of NK cells (ex: GATA2 def with NK cell lymphopenia) 2) functional NKD- presence of NK cells with defective activity without NK cell lymphopenia (ex: perforin def) symptoms include multiple severe or disseminated viral infections including herpesvirus, CMV, HSV

Answer 21

thats all :)

Answer 22

chronic granulomatous diease granulomas: masses of immune cells formed at infection sites phagocytic disorder characterized by tendency to form granulomas most frequent phagocytic ID (immunodeficiency) more common in males than females cause is enzymatic def in NADPH oxidase in phagocytes, which fails to generate superoxide and O2 radicals--- results in defective elimation of extracellular pathogens such as bacteria and fungi symptoms: suspectible to recurrent infection of **catalase-positive organisms** (staph)--- bacteria break H2O2 down into water and O2

Answer 23

X linked recessive associated with anemia- G6P is important in RBC metabolism creates a lack of substrate for NADPH most individuals are asymptomatic symptoms: form granulomas

Answer 24

leukocyte adhesion def **(CD18 def)** neutrophils and phagocutes cant migrate into infectitve tissues **widespread infectections with capsulated bacteria** neutrophil twice the normal count- they are unable to aggregate and cant bind to intracellular adhesion molecules on endothelial cells (cant transport to infection site)\* recurrent infections or oral and genital mucosa, skin, intestinal and respiratory tracts, **delayed detachment of umbilical cord**, **inability to form pus** infected foci with few neutrophils, slow healing, and have enlarged borders with scars prognosis is early death \*two types

Answer 25

LAD-1: caused by mutations in gene for B2 integrins (**CD11/CD18**) resulting in decreased or absent levels on leukocytes LAD-2: impaired adhesive functions of PSGL-1 caused by mutations in fucose transporter

Answer 26

abnormal **giant** granules in neutrophils that do not contain cethepsin g and elatase- disrupts chemotaxis and degranulation, delayed diapedesis diagnosed by giant granules, inclusions in blood, albinism, no NK activity autosomal recessive pts prone to recurrent pyogenic **granulomas** caused by strep and staph pts become wheelchair bound and die of infection in early 30s \*biphasic ID

Answer 27

first phase- suspectibility to infections second phase- accelerated lymphoproliferative syndrome with hepatosplenomegaly and lymphadenopathy

Answer 28

CP responsible for clearance of immune complexes, apoptotic cells, cell debris through complement receptors on RBC's that clear them from circulation without complement complexes become too large to clear and become deposited in tissues C1, C2, C4 def can manifest as systemic lupus erythematosus or RA c2- recurrent sinopulmonary infections (most common in caucasians, young children who get recurrent strep) defects in C3 clinically look like ab def, but a lot less frequent

Answer 29

defects in MAC (C5-C9) production increased suspibility to Neisseria spp (meningitis)

Answer 30

* def in properdin, factor B, factor D, factor H severe infections caused by N meningitis and other extracellular bacteria Factor H def associated with atypical hemolytic uremic syndrome or glomerulonephritis * C1 esterase inhibitor def causes hereditary angiodema * DAF def cause PNH

Answer 31

def in C1-Inh (C1 esterase inhibitor) C1-Inh responsible for blocking kallikrein from ( bound with kininogen) from releasing bradykinin, which causes vasodilation, capillary permeability, fluid extravasation and edema symptoms are recurrent swelling in extremities, face, lips, larynx, GI tract treatment includes C1-Inh replacement therapy \*three types of HAE and three types of swelling

Answer 32

autosomal recessive invasive Neisserial infections cause may be inherited def, acquired def, due to complement consumption diagnosis based on absent C8 levels but normal C3 and C4 levels absent C8 levels with low C3 and C4 levels suggest complement consumption

Answer 33

type 1- 85% of cases, C1-INH decreased or not present type 2- 15% cases, C1-INH not working properly type 3- rare, diagnosed by genetic testing

Answer 34

1. peripheral- swelling of hands, feet, face 2. abdominal- swelling of abdomen 3. episodes that can make breathing difficult due to swelling in airways

Answer 35

paroxysmal nocturnal hemoglobinuria failure to regulate formation of MAC caused by somatic mutation in glycosylphosphatidylinositol-- cells lack all GPI anchored proteins-- DAF and CD59 (complementary regulatory proteins that protect blood cells from complement) absent causes intravascular hemolysis

Answer 36

inhibits C3 and C5 convertase in both AP and CP by inducing rapid dissociation of C2a or Bb

Answer 37

inhibits formation of MAC by binding to sites on C8 and C9, thus blocking of polymerization of C9 onto MAC

Answer 38

impaired signaling for all TLR's **but TLR3** (TLR independent) frequent and severe infections caused by pyogenic bacteria, but normal resistance to other bacteria, viruses, fungi, parasites pts lack fever and elevated levels of ESR/CRP despite infection proinflammatory cytokines TNF-a, IL-1, IL-6 are low

Answer 39

increased susceptibility to HSV encephalitis autosomal dominant