Exam 1: L 25

Question 1

Name the congenial B cell immunodeficiencies

Answer 1

• Bruton agammaglobulinemia
• selective IgA deficiency
• Common variable immunodeficiency ( CVID)

Question 2

Name the congenial T cell immunodeficiencies

Answer 2

• DiGeorge syndrome
  -autosomal hyper IgE syndrome(Job Syndrome)
• IL-2 receptor deficiency
• Chronis mucocutaneous candidiasis
  -IPEX syndrome

Question 3

Name congenital combined immunodeficiencies

Answer 3

• Severe combined immunodeficiency
• Wiskott Aldrich syndrome
• Hyper IgM syndrome
• Ataxia telangiectasia

Question 4

Name the congenital Neutrophil and phagocyte disorders

Answer 4

• chronic granulomatous disease
• leukocyte adhesion deficiency- type 1
• Chediak- Higashi syndrome
• myeloperoxidase deficiency
  severe congenital neutropenia

Question 5

Name the complement disorders

Question 6

Bruton Agammaglobulinemia

Answer 6

• x- linked disorder (males affected most)
• Problem: B cell formation @ Pre- B cell level; BTK enzyme deficient (involved in converting Pre-B cell to immature B cell)
• Pathogenesis: 1) Will be no immunoglobulins produced
• Normal mechanism: (in bone marrow) pluripotent stem cell–> lymphoid precursor–> pre-B cell–> immature B
• Lab: flow cytometry ( low B, normal T count)
• manifest by 3-6 months of age
• lymphoid tissue hypoplasia (due to having low B cells)
• repeated infections, especially encapsulated infections

Question 7

Selective IgA deficiency

Answer 7

• seen often in Caucasians
• reduced or complete lack of IgA
• normal IgM and IgG
• sinusitis, respiratory infections (mucosal issues)
• chronic diarrhea (increased risk for parasitic disease)
• ## gluten sensitivity enteropathy ( celiac disease)

Question 8

Common Variable Immunodeficiency (CVID)

Answer 8

• all immunoglobulin levels are low
• phenotypically normal B cells ( fails to differentiate to produce immunoglobulins)
• reduced number of plasma cells (secrete immunoglobulins)
• 20- 40 years of onset
• recurrent respiratory tract infections ( place of interface with outside world)
• increases risk of lymphomas, gastric cancer, and autoimmune disorders
• treatment: treat infections; prophylactic antibiotics; IV immunoglobulins

Question 9

DiGeorge Syndrome (CATCH 22)

Answer 9

• microdeletion at chromosome 22 on long arm of chromosome
• will cause a development issue with pharyngeal pouches 3 (give rise to thymus) and 4 (give rise to parathyroid)
• hypoplasia of thymus–> T cells require it to mature…. causes T cell maturation to be defective
• low levels of PTH… hypocalcemia
• clinical features: cleft palate, micrognathia, dysplastic ears, prominent nasal bridge, VSD, ASD, TGA
• Recurrent infection( viral, fungal, PCP)

Question 10

Autosomal Dominant Hyperimmunoglobulin E syndrome (Job Syndrome)

Answer 10

• autosomal dominant
• Stat 3 mutation leading to decreased Th17 cells
• defective neutrophil chemotaxis
• increased IgE levels, so a lot of eosinophils
• reduced interferon gamma
• clinical features: coarse facies, recurrent infections (Staphylococcal), abscesses; retained primary teeth; hyper- eosinophilia

Question 11

SCID

Answer 11

• X linked recessive
• chromosome 20 –> supposed to encode for adenosine deaminase
• adenosine deaminase is supposed to convert deoxyadenosine triphosphate to deoxy inosine monophosphate–> hypoxanthine to xanthine ( then excreted to the kidney as uric acid)
• SCID, you don’t have adenosine deaminase because of the mutation
• accumulation of deoxy adenosine triphosphate–> delays the cell proliferation.. affecting lymphoid cell line
• body cannot produce anything from the lymphoid line ( B, T NK cell)
• Labs:abscent T cels; X ray- absent thymic shadow; LN- absent germinal centers; PCR- reduced Tcell receptor excision circles (TREC)
• Treatment: don’t give vaccines; IV immunoglobulins, BM transplant

Question 12

Wiskott- Aldrich Syndrome

Answer 12

• problem with T cell function and Thrombocytopenia
• WASP gene–> in BM, WASP helps reorganize the cytoskeleton (all cells in BM)
• w/o WASP–> cells have difficulty in mobility, impairing it function (actin-chain)
• migration and cell mobility is affected
• affect platelets because it comes from megakaryocyte–> you need actin- chain function for platelets to form properly
• will instead for small platelets ( micro)
• Lab: normal or decrease IgG/M and increased IgE/A; small platelets; deficiency or absence of WASP gene

Clinical features:
- symptoms manifest at birth, easy bruising
- Triad: purpura, eczema, recurrent opportunistic infections; increase association of autoimmune diseases

Question 13

Hyper IgM Syndrome

Answer 13

• X linked recessive
• impaired interaction between Th cells and B cells that lead to class switching defect
• T (CD40L) and B lymphocyte (CD40) –> problem with CD40L due to genetic error
• B cells are not able to be instructed by T cells, not able to undergo class- switch (production of other immunoglobulins… IgM to others)
• decrease IgG, IgA, IgE
• normal or increased IgM
• LN : absent germinal centers (because class switching typically occurs here)
• Clinical features: recurrent infections that begin in childhood; opportunistic infections: sino-pulmonary infections caused by pneumocystis jirovecci, histoplasma

Question 14

Chronic Granulomatous Disease (CDG)

Answer 14

• X linked recessive
• deficiency of NADPH oxidase
• NADPH to NADP generates free radicals after rxn… important on killing the microorganisms
• w/o NADPH oxidase you have phagocytic vacuole and microorganism inside, but you cannot kills it
• will have infections let loose
• catalase positive organism–> breaks down hydrogen peroxide… staph aureus
• neutrophils are replaced by macrophages and lymphocytes–> leading to granulomas (creates lumpy, bumpy field)
• Test: Nitroblue tetrazolium (NBT); abnormal in these patients

Question 15

Leukocyte adhesion deficiency Type 1

Answer 15

• autosomal recessive disease
• deficiency of beta 2 integrins (firm adhesion) –> neutrophils cannot migrate to tissues
• neutrophil won’t leave the blood vessels
• Labs: wouldn’t have many neutrophils in biopsy; but neutrophilia in the blood
• clinical feature: non-separation of the umbilical cord 9if stump doesn’t fall off after 2/3 weeks- on its own)
• impaired wound healing, recurrent suppurative bacterial infection

Question 16

Leukocyte adhesion deficiency 2

Answer 16

• milder than LAD-1
• deficiency of selectin which binds neutrophils
• poor wound healing
• delayed separation of the umbilical cord

Question 17

Chediak-Higashi syndrome

Answer 17

• autosomal recessive
• mutation of LYST (lysosomal regulator trafficking) gene
• “failure to dock”–> inability of neutrophilic granules to fuse with phagosomes
• Labs: neutropenia, defective platelet plug formation… neutrophils with less granules
• clinical features: recurrent pyrogenic infections, abnormalities in melanocytes( partial oculocutaneous albinism and silvery hair), nerve defects, bleeding disorders
• many die in childhood
• reason for albinism: melanosome (granules in melanocytes) cannot migrate to keratinocytes in the epidermis
• morphology: granulosomes are large in neutrophils

Question 18

Myeloperoxidase (MPO) deficiency

Answer 18

• autosomal recessive
• granule you find in neutrophil
• MPO not there, so hydrogen peroxide cannot be converted to bleach
• H2O2 has antibacterial properties
• clinical: mild disease, candida infections

Question 19

C1 esterase inhibitor deficiency (C1 INH)

Answer 19

• autosomal dominant
• inappropriate activation of complement—> bradykinin forms
• in absence of C1 INH, there is unregulated activation of Kallikrein
• leads to increase levels if bradykinin
• angioedema
• mucosal lining can start swelling up
• laryngeal edema
• Lab: CH50 assay- serum hemolytic complement decreased, but returns to normal with recovery ; C4 levels are low, especially during an episode of angioedema
• Clinical features: laryngeal edema, recurrent episodes of angioedema that begin in childhood
• triggers: trauma, surgery, infections, drugs