Immunodeficiency Flashcards
What immune cell deficiency presents with recurrent fungal, viral, or protozoal infections?
T-cell deficiency
X-linked hypogammaglobulinemia (Bruton agammaglobulinemia) has low levels of all immunoglobulins due to what underlying deficiency?
Deficiency of B-cell tyrosine kinase receptors, leading to failure of differentiation of pre-B cells to mature B cells
How does Bruton agammaglobulinemia manifest clinically?
Recurrent bacterial infections
Who typically gets Bruton agammaglobulinemia and why?
Young boys due to the X-linked recessive inheritance
How is Bruton agammaglobulinemia treated?
Treat with pooled immunoglobulin (Ig)
Mnemonic: Bruton He X-iBITS: He=boys, X-linked, Bacterial infections, Immunoglobulins are low, Tyrosine kinase gene, six months=start symptoms
At what age do most congential B cell immunodeficiencies manifest?
About 6 months as levels of maternal IgG acquired transplacentally during the fetal period begin to fall
What immune cell deficiency presents with recurrent infections with encapsulated bacteria such as Staphylococcus and Haemophilus influenzae?
B cell deficiency
What is the most common selective immunoglobulin deficiency and how do patients present?
Selective IgA deficiency causes recurrent sinus and lung infections (recall IgA is typically present in mucous)
What can occur when patients with selective IgA deficiency receive a blood transfusion?
Anaphylactiv reaction if the patients have anti-IgA antibodies that react against IgA in the donor serum
What embryologic process is defective in DiGeorge syndrome?
Development of third and fourth pharyngeal arches, and subseqent aplasia of thymus (third arch) and parathyroids (third arch: inferior parathyroids, fourth arch: superior parathyroid)
What immune deficiency is part of DiGeorge syndrome and how is it treated?
Deficit of T cells due to thymic aplasia results in fungal, viral, and protozoal infections (eg, Pneumocystis pneumonia [PCP] and Candida albicans ) Treat with fetal thymic transplant
What elyctrolyte disturbance is seen in DiGeorge syndrome?
Hypocalcemia (and tetany) due to failure of parathyroid development
Mnemonic: DiGeorge syndrome affects TWO arches (3 and 4), TWO organs (thymus and parathyroid), and has TWO defects (defective T cells and hypocalcemia)
What are the clinical and laboratory manifestations of hyper IgM syndrome?
Clinical: recurrent pyogenic bacterial infections early in life
Lab: see high IgM but low IgG, IgA, IgE
What is the underlying genetic defect in hyper IgM syndrome?
A mutation in CD40 ligand gene leads to a defective CD40 L on T cell surfaces. Without the proper CD40L-CD40 signaling, B cells cannot switch isotypes from IgM to other classes
Mnemonic: Hyper IgM Alphabet: A….HIJK_MMMMMMM…Z (No L=CD40Ligand and a lot of IgM)
To what infections are patients with IL12 receptor deficiency predisposed?
Disseminated myobacterial infections because IL-12 is involved in development of cell mediated Th1 response against myobacteria
What types of immune cells are defective in SCID and how is it inherited?
B and T cells. Most cases (75%) are X-linked
How does SCID clinically manifest and how is it treated?
Patients are predisposed to recurrent bacterial, viral, fungal, and protozoal infections. Treat with bone marrow transplant
What defects can lead to SCID?
Most common, 50%, is the lack of the common gamma chain of the IL-2, IL-4, IL-7, and IL-15 receptors (needed for T cell development); the next most common, about 16% is an adenosine deaminase (ADA) deficiency required for the purine salvage pathway
How is Wiskott-Aldrich syndrome inherited and how does it present?
X-linked recessive; presents with pyogenic infections, eczema and bleeding due to thrombocytopenia
What is the major defect in Wiskott Aldrich syndrome and how is it treated?
Lack of an IgM response to bacterial capsules; treat with bone marrow transplant
Mnemonic:
Turn the W in Wiskott upside down: W–> IgM
X-PECT infections with Wiskott Aldrich: Xlinked, Pyogenic infections, Capsular response impaired, thrombocytopenia
What cancer are patients with Wiskott-Aldrich syndrome prone to develop?
Non-Hodgkin lymphoma
How does ataxia-telangiectasia present?
Patients have recurrent infections at a young age in addition to uncoordinated gait (ataxia) and skin lesions consisting of small, dilated terminal vessels (telangiectasias)
How is ataxia telangiectasia inherited and what is the genetic defect?
Autosomal recessive mutation in DNA repair enzymes
What immunoglobulin deficiency is often seen with ataxia telangiectasia?
IgA deficiency
What is the genetic defect in chronic granulomatous disease (CGD) and how is it inherited?
Lack of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; usually X-linked recessive
What is the function of NADPH oxidase and in what cell is it found?
NADPH oxidase helps generate H2O2 used in respiratory bursts of neutrophils
What are the principal sources of infection in chronic CGD and the most common cause of death?
Fungal and bacterial infections; pneumonia due to Aspergillus fumigatus is the most common cause of death from chronic CGD
What bacteria typically infect patients with CGD?
Catalase positive bacteria (staphylococcus aureus and Escherichia coli) that use catalase to degrade their endogenous H2O2, which is then utilized by neutrophils. The bacteria provide the bullet!
Chediak-Higashi syndrome is due to a microtubule dysfunction, and presents with recurrent pyogenic infections. What are the two abnormalities seen in the immune cells of these patients?
Failure of lysosome/phagosome fusion–>large granular inclusions of abnormal lysosomes
Abnormal neutrophil chemotaxis
What are the features of Job syndrome (hyper IgE syndrome)?
High IgE, recurrent cold staphylococcal abcesses, eczema, and skeletal abnormalities
What is the underlying deficiency in Job syndrome?
Lack of interferon gamma production by Th1 cells (inflammatory cells)
What is a cold abscess?
Low interferon gamma favors the development of Th2 cells that are anti-inflammatory (and the source of Il-4 that induces B cell production of IgE). Therefore, staphylococcus abscesses cannot trigger the hot or inflammatory response
Mnemonic: GEt an EASy Job (Gamma IFN, IgE, Eczema, Abcesses, Skeletal abnormalities)
What is leukocyte adhesion deficiency syndrome? How does it present?
Autosomal recessive defect of lymphocyte function associated 1 (LFA1), an adhesion protein on leukocytes, leads to severe pyogenic infections
Common variable immunodeficiency presents with recurrent pyogenic infections. What is the underlying cause of this disorder?
Hypogammaglobulinemia due to a block in B cell differentiation to plasma cells
What immune cells are most affected in HIV/AIDS and what types of immunity are compromised?
HIV targets CD4+ helper T cells which results in dysfunction of both humoral and cell mediated immunities
What are some examples of bacterial infections that are common in AIDS patients?
Mycobacterium tuberculosis, Mycobacterium avium complex, stereptococcus pneumoniae (most common case of pneumonia in AIDS patients, not PCP), Salmonella, etc
What are some examples of fungal infections that are common in AIDS patients?
Cryptococcus, Candida, Histoplasma, Mucor, Pneumocytis jiroveci (formerly pneumocytis carnii), Coccidioides, Blastomyces, etc
What are some examples of protozoal infections that are common in AIDS patients?
Cryposporidium, Toxoplasma, etc
AIDS patients are at increased risk for what malignancies?
Kaposi sarcoma, Anal carcinoma, Non-Hodgkins lymphoma, and Cervical cancer (KANCer)
