Chapter 6- Transplants, Immunodeficiency Flashcards
The gene assoaciated with Chediak higashi codes for what
LYST, which helps regulate lysosomes transportation
What is the cause of bare lymphocyte syndrome
Mutations in the transcription factors needed for MHC 2 molecules
Which protein is mutated in Wiskott-Aldrich syndrome
Wiskott-Aldrich syndrome protein (WASP)
What is the intestinal protazoan that is common in patients with X linked agammaglobulinemia
Giardia lamblie (usually protected by IgA)
What are the clinical presentation of common variable immunodeficiency
Antibody deficient, resembling X link gammaglobulinemia
What is the function of the ataxia telangiectasia mutated (ATM) protein
A sensor of DNA damage (double stranded breaks) and works to activate p53
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
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
Defects in the SAP protein lead to what
Attenuation of NK and T cells, leading to viral infections, inability to form germinal centers
How does a C1q inhibitor lead to hereditary angioedema
Unregulated proteases leads to increase of kallikrein and bradykinin, which increases permeability
What type of pathogens are Digeorge patients prone to
Fungal and viral infections
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
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
What deletions ion the gene are the cause of DiGeorge symptoms
-TBX1 (brachial arch development)
What is the location of defect in X linked agammaglobulinemia
Xq21.22
Patients with Chediak-Higashi syndrome have defects in what
Defective fusion of phagosomes and lysosomes, which inhibit phagocytes function
What condition does X linked lymphoproliferative syndrome commonly lead to
Fulminant infectious mononucleosis and B cell tumors
What are the main abnormalities seen in Chediak higashi syndrome
1) Nuetropenia
2) Defective degranulation
3) delayed microbial killing
What infections are patients with common variable immunodeficiency prone to
Recurrent sinopulmonary pyogenic infections and recurrent herpesvirus infections
What is the genetic component to Wiskott-Aldrich syndrome
X linked
Which infections are ataxia telangiectasia prone to
Upper and lower respiratory bacterial infections, cancers
What are the cytokines that are affected by X linked SCID
IL-2,4,7,9,11,15,21
What happens when isolated IgA deficient patients are transfused with IgA therapy
Go into anaphylaxis reaction as IgA is treated as a foreign antigen
Patients with chronic granulomatous disease have defects in what
Defects in phagocyte oxidase, which is used to create superoxide
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
C2
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
No
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
RA
