Chapter 6- Transplants, Immunodeficiency Flashcards by Michael Dennis

The gene assoaciated with Chediak higashi codes for what

LYST, which helps regulate lysosomes transportation

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What is the cause of bare lymphocyte syndrome

Mutations in the transcription factors needed for MHC 2 molecules

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Which protein is mutated in Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome protein (WASP)

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What is the intestinal protazoan that is common in patients with X linked agammaglobulinemia

Giardia lamblie (usually protected by IgA)

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What are the clinical presentation of common variable immunodeficiency

Antibody deficient, resembling X link gammaglobulinemia

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What is the function of the ataxia telangiectasia mutated (ATM) protein

A sensor of DNA damage (double stranded breaks) and works to activate p53

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Patients with Leukocyte deficiency type 2 have defects in what

Defects in fucosyl transferase, which makes the sialyl-Lewis X, which is the ligand for the P and E selectin

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What is JOB syndrome

Defects in Th1 responses leading to mycobacterial infections, with Th17 defects leading to chronic mucocutaneous candidiasis and bacterial infections of skin

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Defects in the SAP protein lead to what

Attenuation of NK and T cells, leading to viral infections, inability to form germinal centers

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How does a C1q inhibitor lead to hereditary angioedema

Unregulated proteases leads to increase of kallikrein and bradykinin, which increases permeability

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What type of pathogens are Digeorge patients prone to

Fungal and viral infections

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What are the levels of T cells in Wiskott-Aldrich syndrome

-Normal early in life, but there is the progression of T cell loss in the peripheral LNs and blood

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What is the mechanism of disease in X linked agammaglobulinemia

Deficient BTK does not allow the signal transduction in B cells to allow the placement of a light chain in place of the surrogate light chain

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What deletions ion the gene are the cause of DiGeorge symptoms

-TBX1 (brachial arch development)

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What is the location of defect in X linked agammaglobulinemia

Xq21.22

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Patients with Chediak-Higashi syndrome have defects in what

Defective fusion of phagosomes and lysosomes, which inhibit phagocytes function

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What condition does X linked lymphoproliferative syndrome commonly lead to

Fulminant infectious mononucleosis and B cell tumors

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What are the main abnormalities seen in Chediak higashi syndrome

1) Nuetropenia
2) Defective degranulation
3) delayed microbial killing

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What infections are patients with common variable immunodeficiency prone to

Recurrent sinopulmonary pyogenic infections and recurrent herpesvirus infections

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What is the genetic component to Wiskott-Aldrich syndrome

X linked

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Which infections are ataxia telangiectasia prone to

Upper and lower respiratory bacterial infections, cancers

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What are the cytokines that are affected by X linked SCID

IL-2,4,7,9,11,15,21

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What happens when isolated IgA deficient patients are transfused with IgA therapy

Go into anaphylaxis reaction as IgA is treated as a foreign antigen

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Patients with chronic granulomatous disease have defects in what

Defects in phagocyte oxidase, which is used to create superoxide

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What are common non immuno related symptoms seen with Chediak higashi syndrome

- Albinism (abnormal melanocytes) - Nerve defects (abnormal nerves) - Bleeding disorders (abnormal platelets)

What are the clinical presentations of Ataxia Telangiectasia

Abnormal gait (ataxia), vascular malformations (telangiectases), neuro defects, increased tumors, and immunodeficiency

What protein is commonly mutated in X linked lymphoproliferative syndrome

SLAM associated protein (SAP)

Where is the location of WASP

Xp11.23

Leukocyte adhesion deficiency Type 1 and 2 lead to recurrent infections due to

Inadequate granulocyte function

At what age does X linked agammaglobulinemia become appearant and what are the signs

6 months after birth, and begins with recurrent bacterial infections

What about the donor APCs in direct rejection allow for T cell activation

Express high levels of MHC1,2 and costimulatory molecules

What is the most common complement deficiency

Deficiencies in the alternative pathway proteins properdin and factor D are assocaited with which infection

Recurrent pyogenic infections

X linked agammaglobulinemia is characterized by what

Failure of B cell precursors to develop into mature B cells

What is the defective gene product in ataxia telangiectasia

ataxia telangiectasia mutated (ATM)

What percentage of X linked lymphoproliferative syndrome is associated with a mutation in SAP

80%

Autosomal recessive SCID is caused by a defect in what

Adenosine deaminase (ADA)

How long after transplantation is the acute cellular rejection seen

Within months

paraxysomal nocturnal hemoglobinuria is marked by deficiencies of

Complement regulatory factors

What is the location of gene defect in ataxia telangiectasia

Chromosome 11

What is the genetic correlation with Chediak highashi syndrome

Autosomal recessive

How do genetics play a role in X-linked SCID

More common in makes than females

Gene therapy to fix X linked SCID is associated with which condition

T cel lymphoblastic leukemia (20% of pts)

What is the state of the APC in direct rejection

Donors APC present in the graft and activate host cells

What is the most common X linked variant of chronic granulomatous disease

The membrane bound component gp91phox

Patients with hyper IgM syndrome have defects in which products

Loss of function mutation in CD40 | Loss of function mutation in AID

How do genetics cause C1q inhibatory defects

Autosomal dominant

Are CTLs present in the indirect rejection

What is the most common autosomal recessive defect in chronic granulomatous disease

Cytoplasmic components p47phox and p67phox

What is the cause of DiGeorge’s

22q11 deletion syndrome

Acute antibody mediated rejection commonly sees what being deposited

C4d

What other conditions are seen with hyper IgM syndrome

Autoimmune hemolytic anemia, thrombocytopenia, and neutropenia

What is the mechanism of action for tacrolimus

Aka FK506, which is similar to cyclosporine and inhibits phosphatase calcineurin, which is required for NFAT activation

Hyper IgM syndrome are the result of a mutation in which chromosome area

Xq26

What are the clinical presentations of DiGeorge’s syndrome

Loss of T cell immunity, Tetany, defects of heart and great vessels

Which type of rejection is most similar to pathogen recognition

Indirect, since it is the host MHC presenting the donor antigens

Why can CTLs not kill donor tissue in the indirect pathway

CTLs recognize the graft antigens presented by the host’s APC, but can not recognize the graft tissue directly

What are the main defects in ataxia telangiectasia

Defective production of isotype switching antibodies IgG2 and IgA

What is the very common pathogen in HSC transplanted hosts

Cytomegalovirus, which induces pneumonitis

Defects in TLR3 leads to increased rates of which infection

Herpes simplex encephalitis

What are the clinical presentations of chronic granulomatous disease

Defects in killing bacteria and persistent recurring bacterial infections. Usually lead to granulomas

Defects in MyD88 is assocaited with increased infections of

Bacterial pneumonia

Digeorge syndrome is caused by the lack of development of what

3rd and fourth pharyngeal arch

What are the levels of CD19 and Ig receptors in patients with X linked agammaglobulinemia

CD19 levels are normal, but the Ig levels are low

What can not be given as a vaccine to kids with X linked agammaglobulinemia

Live poliovirus vaccine

Patients with isolated IgA deficiency also commonly are deficient in which antibody

IgG4 and IgG2

What is the effect of cyclosporine

Immunosuppressive drug that is nephrotoxic, so can cause damage

isolated IgA deficiency can be acquired via which infections

Toxoplasmosis, measles, or other viral infections

What are the three immunosupressor drugs being used

1) Steroids 2) Mycophenolate mofetil 3) Tacrolimus

What are the three common bacterial infections in X linked agammaglobulinemia

1) Haemophilus influenza’s 2) Streptococcus pneumoniae 3) Staphylococcus aureus

What are the clinical presentations of a patient undergoing acute GVHD

Damage to bile ducts, leading to jaundice, and mucosal ulceration leading to blood stool

What does hyperacute rejection show

Platelet and fibrin thrombin, neutrophil infiltrate, ischemic injury

Deficiency of C1 inhibator leads to which condition

Hereditary angioeema

Are allograft rejections more or less powerful than microbe reactions

More powerful due to higher frequency of T cells that recognize donor tissue as compared to microbe antigens

One of the most frequent infections from transplants is

Polyoma virus

X linked SCID is associated with a defect in what

Mutations in the common gamma chain subunit of cytokine receptors

What are the characteristics of Wiskott-Aldrich syndrome

Thrombocytopenia, eczema, recurrent infections

In antibody mediated rejection of an organ, what seems to be the initial target

Graft vasculature

What is the genetic component of Ataxia telangiectasia

X linked

What is the defective enzyme in X linked agammaglobulinemia

Briton tyrosine kinase (Btk)

What are the common viral infections associated with X linked agammaglobulinemia

-Enteroviruses (echovirus, poliovirus, coxsackievirus)

The condition of X linked lymphoproliferative syndrome is characterized by the inabilty to clear which infection

EBV,

Patients with Leukocyte deficiency type 1 have defects in what

Beta chain of integrins LFA-1 and Mac-1 (aka CD11/18)

Patients with hyper IgM syndrome are particularly prone to which pathogen

Pneumocystis jiroveci

Infants with SCID present with which conditions

Thrush, extensive diaper rash, failure to thrive.

Wha type of reaction is the indirect pathway rejection of organs

Delayed hypersensitivity reaction, but no CTLs

During the acute cellular rejection of a transplant organ, what is doing the damage

Increased permeability and accumulation of mononuclear cells, leading to activation and damage via macrophages

What are the Ig levels in Wiskott-Aldrich syndrome

- Low levels of IgM - High levels of IgA and IgE - Normal levels of IgG

What autoimmune condition is common even in immunodeficient patients