Immune Deficiency Flashcards
What is a primary immunodeficiency?
Congenital
Inherited genetic defect affecting immune function
Inherited deficiency in enzyme affecting immune response
What is a secondary immunodeficiency?
Acquired
Loss of previously functioning immunity
an be due to an infection, toxin, splenectomy, irradiation
What autoimmune disease are caused by neutrophil deficiencies?
Congenital neutropenia
Chediak-Higashi syndrome
Leukocyte adhesion deficiency
Chronic granulomatous disease
What are the autoimmune diseases caused by B-cell deficiencies?
Congenital X-linked agammagloulinemia Common variable immunodeficiency Selective IgA deficiency Hyper IgM syndrome Hyper IgE syndrome (job;s syndrome)
What are the autoimmune diseases caused by T-cell deficiencies?
DiGeorge sydrome
Severe combined immunodeficiency
Wiskott-Aldrich syndrom
Ataxia-Telangiectasia
Which is the most common primary immunodeficiency syndrome?
Selective IgA
How many cases of chronic granulomatous disease (CGD) are X linked?
2/3
1/3 or autosomal
What is the main deficiency in chronic granulomatous disease?
Cytochrome-B deficiency = no NADPH oxidase No oxidative burst Can't recycle NADP - no ROS Impaired killing by neutrophils Inflamm response - granulomas
What does chronic granulomatous disease cause clinically?
Life-threatening bacterial and fungal infections
“walling off” of microbes within granulomas
Children often die of septicemia by age 7 yrs
What is the treatment for chronic granulomatous disease?
Antibiotics and IFNy
How does the nitroblue test work?
The nitro blue chemical reacts with macrophages making NADPH and if they are it makes the cell walls a dark blue color
If there is not function you see a clear color indicitive of an NADPH or myeloperoxidase deficiency
What are the clinical features of chronic granulomatous disease?
Inflammation of the nares
Granuloma in the neck
Severe gingivitis
As esophageal stricture caused by granuloma
What is the main cause of Chediak-Higashi syndrome?
Defect in polymerization of microtubules in neutrophils
Defective neutrophil migration
Failure of phagocytosis
Failure of lysosomal function in neutrophils
What is the defective gene in Chediak-Higashi syndrome?
CHS1 on chromosome 1
What are the clinical manifestations of Chediak-Higashi syndrome?
Recurrent pyogenic infections
Partial albinis,
Peripheral neuropathy
Abnormal platelet formation = thrombocytopenia
What is the main cause of Leukocyte adhesion defect (LAD)?
Deficient chemotaxis defect in CD18 integrin gene expression = deficiency in LFA-1 leading to; No adhesion to ICAM Neutrophils unable to bind endothelium Inability of neutrophils to extravaste
What are the clinical manifestations of Leukocyte adhesion defect?
Recurrent soft tissue, peridontitis, skin, respiratory infections
Impaired wound healing (no pus, little infla)
Inc WBC
What signs would you see in a pt with Leukocyte adhesion defect?
Normal neutrophil aggrigation
Neutrophils form but fails to aggregate
What is the main cause of hyper IgE disease (Job’s disease)
Failure to produce IFNy by T helper cells Humoral immune response not inhibited Inc in Th2 cells (no neg feedback) High IgE High histamine, eosinophilia Recurrent staph infections Eczema
What are some characteristics of compliment defeciencies?
Rare, mostly autosomal recessive
What happens if there is a deficiency in early components C1, 2, and 3?
Pyogenic infections (oposonin deficiency)
What happens if there is a deficiency in late component C5?
Causes issues with the membrane attack complex
What happens if there is a deficiency late components C6, 7, 8 and 9?
Little adverse effects, slow lysis
Intracellular infection risk
What is the main cause of hereditary angioedema?
A deficiency in C1-inhibitor (C1-INH)
Unabated activation of C2 and C4
Generation of Kinins = inc vascular perm = edema
What are the clinical manifestations of hereditary angioedema?
Facial edema
Abdominal pain
Asphyxiation
What are defective in paroxysmal noctournal hemogloinuria?
CD59 and DAF (decay accelerating factor)
rare
What are the clinical manifestations of paroxysmal noctournal hemogloinuria?
Complement mediated RBC destruction (intravascular)
Hemolytic anemia
What are the characteristics of B-cell deficiencies?
Overall dec in antibody production (Bruton's aggamaglobulinemia) Selective deficiency involving a class or subclass
What is the main defect in X-linked Aggamaglobulinemia (XLA)?
Mutation of the gene encoding for Tyrosine Kinase
What are the main issues with X-linked aggamaglobulinemia?
Interfere with VDJ gene rearrangement machinery
Failure of pre-B cells to differentiate to B-cells
Cell mediated function is normal
When would XLA begin?
6 mo of life, after maternal immunity wears off
What are the clinical manifestations of XLA?
Recurrent otitis media, diarrhea, pneumonia
Individual infections may be no more severe then in general population but they are chronic
How would XLA be diagnosed?
No IgM or IgA
Dec in IgG
T-cells in normal numbers and function
What is the treatment for XLA?
Periodic gamm-globulin injection - passive protection
Antibiotics for individual infections
No live viral vax
What is transient hypogammaglobulinemia?
Delay in production of immmunoglobulins
Recurrent extracellular bacterial infections
How is transient hypogammaglobulinemia diagnosed?
Dec IgG
Dec but measurable IgM and IgA
What is the treatment for transient hypogammaglobulinemia?
Antibiotics for individual infections
No need to IVIG
What characterizes common variable immunodeficiency?
Defective antibody production
M:F equal
B-cells present but do not change into plasma cells
Recurrent pyogenic infections
When does common variable immunodeficiency appear?
Age 15 to 30
What is the diagnosis for common variable immunodeficiency?
Dec IgG, IgA and IgM
B cells normal
What is the treatment for common variable immunodeficiency?
IVIG
What is selective IgA deficiency?
May be an issue with differentiation of B-cells into IgA-secreting plasma cells (class switching) Most common primary immunodeficiency
How is selective IgA deficiency diagnosed?
Very love IgA
Normal IgG
IgM usually normal to elevated
What are the clinical manifestations to IgA deficiency?
Asymptomatic
Recurrent GI infection, respiratory infections
Inc incidence of autoimmune disease
What are the characteristics of hyper IgM syndrome?
Rare, X-linked
Defective express of CD40L (CD154) on T cells
How is hyper IgM diagnosed?
CD40L mutation analysis
Inc IgM
Dec other Igs
What are the clinical manifestations of hyper IgM?
Recurrent bacterial infections
Sinopulmonary infections
Sclerosing cholangitis
Inc incidence of autoimmune disease
With a T-cell deficiency what is a person more susceptible to?
Inc intracell pathogens; viral, fungal, parasitic
Inc frequency of opportunistic and low virulence pathogens; cryptosporidium, candida, pneumocystis, MAI
What are the congenital malformations in DiGeorge syndrome?
I, II, III, IV, VI
Most deletion at 22q11
What are the clinical manifestations of DiGeorge?
Cardiac defects Abnormal facies Thymic aplasia Cleft palate Hypocalcemia (CATCH 22)
What is done in the lab analysis for DiGeorge?
of peripheral blood lymphocyte dec
CD3+ dec
Serum calcium dec
No thymic shadow
What are the clinical manifestations of DiGeorge?
Recurrent infections
Tetany
Tetrology of fallot
Cleft palate
What are the typical presentations for severe combined immunodeficiency (SCID)?
Chronic diarrhea
Pneumonia
Persistent fungal infection
What is implicated in at least 50% of all SCID cases?
X-linked IL-2Ry deficiency
What are the micro signs for X-linked IL-2Ry deficiency ?
B cells present but not functional Hypogammaglobulinemia IL-2R needed for T cell prolif IL-15R needed for NK development IL-17R prolif of lymph stem cells
What is the main deficit of Adenosine deaminase (ADA) deficiency?
Accumulation of deoxyadenosine derivatives
Inc intracell adenosine
Inhibits ribonucleotide reducatse = dec DNA precursors
How id ADA dianosed?
Low or absent ADA levels and inc d-Ado in urine
How is ADA treated?
ADA replacement, BMT, gene therapy
What characterizes Wiskott-Aldrich syndrome?
Rare, X-linked defect in the WAS protein gene
What are the understood (sort of) mechanisms to Wiskott-Aldrich?
Defective actin polymerization - poor leukocyte trafficking
Dec expression of CD43 (major receptor on T-cell)
What are the findings in Wiskott-Aldrich?
Lymphocytes: dec T-cells, low IgM, normal IgG, elevated IgA and IgE
Clinically: Recurrent pyogenic infections, thrombocytopenia (severe), eczema
What is the treatment of Wiskott-Aldrich?
BMT
Life expectancy 11 yrs
What is the cause of ataxia-telangiectasia?
ATM gene mutation on chromosome 11
Pleimorphic changes in cellular response to radiation, cell cyclecontrol, intracell transport of proteins
What are the three types of bare lymphocyte syndrome?
Type I: defective MHC-I
Type 2: defective MCH-II
Type 3: both are defective
