Immunodeficiency Disorders

Question 1

What causes X-linked agammaglobulinemia

Answer 1

Defect in BTK, a tyrosine kinase gene that results in no B cell maturation (X-linked recessive; think more in boys)

Question 2

How might X-linked agammaglobulinemia present?

Answer 2

recurrent bacterial and enteroviral infections after 6 months (decreased maternal IgG)

Question 3

What are the findings of X-linked agammaglobulinemia?

Answer 3

Absen B cells in peripheral blood

decreased Ig of ALL classes

Absent lymph nodes and tonsil

Question 4

What causes Selective IgA deficiency?

Answer 4

Unknown but most common primary immunodeficiency

Question 5

How might Selective IgA deficiency present?

Answer 5

Majority are ASYMPTOMATIC but can see upper respiratory and GI illness, autoimmune disease, atopy, and anaphylaxis to IgA containing blood products

Question 6

Common variable inmmunodeficiency is a defect in B cell DIFFERENTIATION that can be caused by a no. of things. How might it present?

Answer 6

Can be acquired in 20s-30s and shows an increased risk of autoimmune disease, bronchiectasis, lymphoma, and sinopulmonary infections

Question 7

What are the main findings of Common variable inmmunodeficiency?

Answer 7

Decreased plasma cells and immunoglobulins

Question 8

What causes DiGeorge Syndrome?

Answer 8

22q11 deletion causing failure of the 3rd and 4th pharyngeal pouches to develop (absent thymus and parathyroids)

Question 9

How does DiGeorge Syndrome present?

Answer 9

tetany (hypocalcemia)

recurrent viral/fungal infections

conotruncl abnormalities (e.g. tetralogy of Fallot or truncus arteriosus)

Question 10

What are the main findings of Digeorge Syndrome?

Answer 10

decreased T cells, PTH, and calicum

Absent thymic shadow on CXR (present below)

Question 11

How might IL-12 receptor deficiency present?

Answer 11

AR disease of decreased Th1 response and increased risk of disseminated mycobacterial and fungal infections (may present after BCG vaccine administration)

Decreased levels of IFN-y

Question 12

What is Job syndrome?

Answer 12

Defeciency of TH17 cells due to STAT3 mutation causing impaired recrutiment of neutrophils to infection sites

Question 13

How might Job syndrome present?

Answer 13

FATED

Facies

Cold (nonnflammaed) staph abscesses

retained primary teeth

elevated IgE (and decreased IFN-y)

Derm problems such as eczema

Question 14

Describe chronic mucocutanoeus candidiasis

Answer 14

Disease of noninvascice candida albicans infections of skin and mucous membranes due to T-cell dysfunction

Question 15

What causes SCID?

Answer 15

Several types including defective Il-2R gamma chain (most common, X-linked) and adenosine deaminase deficiency (AR)

Question 16

How does SCID present?

Answer 16

Failure to thrive, chronic diarrhea, and trush

Reucrrent infections of all sources (e.g. bacterial, viral, fungal, and protozoal)

Question 17

How is SCID tx?

Answer 17

Bone marrow transplant (no rejection concerns!)

Question 18

What are some classic findings of SCID?

Answer 18

Decreased T cell receptor excision cricles (TRECS)

Absense of thymic shadow on CXR, germinal centera on lymph node biopsy, and T cells via flow cytometry

Question 19

What causes ataxia-telangiectasia?

Answer 19

Defect in ATM gene leading to failure to repair DNA breaks and subsequent cell cycle arrest

Question 20

How does ataxia-telangiectasia present (classic triad)?

Answer 20

Cerebellar defects, spider angiomas, and IgA deficiency

Question 21

What are the findings of Ataxia-telangiectasia?

Answer 21

Elevated AFP

Decreased IgA, IgG, and IgE

Lymphopenia and cerebellar atrophy

Question 22

What causes hyper-IgM syndrome?

Answer 22

Most commonly due to defective CD40L on Th cells causes a class switching defect (X-linked recessive)

Question 23

What are the classic symptoms of hyper-IgM syndrome?

Answer 23

Severe pyogenic infections early in life

opportunistic infections with Pneumocytsis, CMV, and Cryptosporidium

Question 24

What are the lab findings of hyper-IgM syndrome?

Answer 24

Elevated IgM and vastly decreased IgG, IgA, and IgE

Question 25

What causes Wiskott-Aldrich Syndrome?

Answer 25

Mutation in WAS gene (X-linked recessive; think in boys) causing T cells to be unable to reorganize actin cytoskeleton

Question 26

How might Wiskott-Aldrich Syndrome present?

Answer 26

Thrombocytopenic purpura Eczema Recurrent Infections Increased risk of cancers

Question 27

What are the lab findings of Wisckott-Aldrich syndrome?

Answer 27

Decreased to normal IgG, IgM Elevated IgE and IgA Fewer and smaller platelets

Question 28

What causes leukocyte adhesion deficiency (type I)?

Answer 28

Defect in LFA-1 integrin (CD18) protein on phagocytes causing impaired migration and chemotaxis (AR)

Question 29

How might leukocyte adhesion deficiency (type I) present?

Answer 29

Recurrrent bacterial skin and MUCOSAL infections with absent pus formation **delayed seperation of the umbilical cord (30+ days)** and impaired wound healing NOTE: A pseudo-neutrocytosis will be seen

Question 30

What causes Chediak-Higashi syndrome (AR)?

Answer 30

Defect in lyosomal trafficking regulator gene (LYST) causes microtubule dysfunction in phagosome-lysosome fusion (AR)

Question 31

How might Chediak-Higashi syndrome present?

Answer 31

Recurrent pyogenic infections by staph and strep spp. infiltrative lymphohistiocytosis partial albinism peripheral neuropathy progressive neurodegeneration

Question 32

What are the lab findings of Chediak syndrome?

Answer 32

pancytopenia and mild coag defects

Question 33

What causes CGD?

Answer 33

Defect in NAPDH oxidase causing impaired formation of ROS and respiratory burst in neutrophils (X-linked recessive)

Question 34

CGD places one at an increased risk of infection with which bugs?

Answer 34

Catalase + including: **N**eed **PLACESS** Nocardia, Pseudomonas, Listeria, Aspergillus, Candida, E. Coli, S aureus, and Serratia

Question 35

Other findings of CGD?

Answer 35

Abnormal dihydrorhodamine test **Negative** nitroblue tetrazolium blue reduction test

Question 36

Note about Bacterial infections and immunodeficiency

Answer 36

Decreased T cells typically leads to risk of SEPSIS Decreased B cells leads to risk of encapsulated bacteria (SHiNE SKiS)

Question 37

Decreased granulocytes leads to increased risk of infection with which bacteria?

Answer 37

Stapylococcus Burkholderia cepacia Pseudomonas aeruginosa Serratia Nocardia

Question 38

T cell immunodeficiency mainly increases the risk of infection with which viruses?

Answer 38

CMV, EBV, JCV, VZV

Question 39

B cell immunodeficiency mainly increases the risk of infection with which viruses?

Answer 39

Enteroviral encaphalitis and poliovirus

Question 40

T cell immunodeficiency mainly increases the risk of infection with which fungi?

Answer 40

Candida and PCP

Question 41

B cell immunodeficiency mainly increases the risk of infection with which fungi?

Answer 41

Giardiasis (no IgA)

Question 42

Granulomatous immunodeficiency mainly increases the risk of infection with which fungi?

Answer 42

Systemic candida and Aspergillus

Question 43

Basic definitions of grafts:

Answer 43

Autograft- from self Syngereic graft (isograft)-f rom identical twin/clone Allograft- from nonidentical individual of same species Xenograft- from diff. species

Question 44

Describe a hyperacute transplant rejection

Answer 44

Onset within MINUTES nd occurs due to pre-exisiting recipient Abs reacting to donor antigens (type II rxn) and activating complement causing widespread thrombosis of graft vessels (necrosis) The graft must be removed

Question 45

Describe an acute transplant rejection

Answer 45

Onset with weeks to months and can be caused by a CD8 T cell rxn against donor MHCs or via Abs that develop after the transplant and induce complement marked by vasculitis of graft vessels with **dense lymphocytic infiltrate** Prevent with immunosuppressants

Question 46

Describe a chronic transplant rejection

Answer 46

Onset within MONTHS to YEARS and caused by a CD4+ T cell response to recipient APCs presenting donor peptides (both cellular and humoral components) Marked by proliferation or vascular smooth muscle and parenchymal fibrosis (dominated by ateriosclerosis) due to T cell response

Question 47

What causes graft-vs.-host disease?

Answer 47

Grafted immunocompetent T cells proliefrate in the immunocompromised host and reject host cells with foreign proteins leading to SEVERE organ failure Timeline varies

Question 48

How might GVD present?

Answer 48

Maculopapular rash, jaundice, diarrhea, and HTN Usually in bone marrow and livert transplants (rich in lymphocytes) Potential beneficial for BM transplant in leukemia pt.