03/15c Inborn and Acquired Immunodeficiencies Flashcards Preview

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Flashcards in 03/15c Inborn and Acquired Immunodeficiencies Deck (28)
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1
Q

What is immunodeficiency?

A

Increased susceptibility to infection, certain types of cancer, and sometimes increased incidence of autoimmunity

2
Q

What are the two broad categories of immunodeficiency disorders?

A

Congenital

Acquired

3
Q

What types of immune defects result from congenital immunodeficiencies?

A

Defects in innate immunity
Defects in B cell and T cell development, activation, and function
Severe combined immunodeficiencies

4
Q

What two functions are typically affected by defects in innate immunity?

A

Complement pathway

Phagocyte function

5
Q

What are the typical clinical presentations of defects in the complement pathway?

A

Failure to clear circulating immune complexes and higher incidence of SLE
Susceptibility to infection with pyogenic encapsulated bacteria
Propensity for disseminated infections by Neisseria species

6
Q

What are the typical clinical presentations of defects in phagocytes? List a few specific diseases as well

A
Infections of the skin and respiratory tract with bacteria or fungi (particularly Aspergillus and Candida)
Chronic granulomatous disease
Leukocyte adhesion deficiency
Chédiak-Higashi syndrome
TLR signaling defects (rare)
7
Q

What is chronic granulomatous disease? Describe its mechanisms, symptoms, and treatment

A

Defective production of ROS and failure to kill microbes by phagocytes, due to a defect in phagocyte oxidase
Results in recurrent infections with catalase-positive intracellular bacteria and fungi
Infections stimulate chronic cell-mediated immune responses and formation of granulomas
Treatment - aggressive antibiotic therapy, IFN-gamma

8
Q

What are leukocyte adhesion deficiencies? Describe their mechanisms and symptoms

A

Autosomal recessive disorders caused by defects in leukocyte and endothelial adhesion molecules
Results in a failure of neutrophil recruitment to site of infections and inability to make pus
Symptoms - early severe periodontitis and recurrent infections

9
Q

What is Chédiak-Higashi syndrome?

A

Defect in phagosome-lysosome fusion in phagocytic cells as a result of mutations in a lysosomal trafficking regulator protein
Results in giant lysosomes in phagocytic cells and general lysosomal defects in melanocytes, platelets, and the CNS
Symptoms - recurrent infections by pyogenic bacteria

10
Q

By what features are B cell defects diagnosed?

A

Reduced levels of serum Ig
Defective antibody responses to vaccination
Reduced numbers of B cells
Absent plasma cells in tissues

11
Q

What are agammaglobulinemias?

A

Defects in B cell development that result in reduced number of B cells and all serum Igs
Most common form is X-linked autosomal recessive, and is due to a defect in Bruton’s tyrosine kinase

12
Q

What are hypogammaglobulinemias?

A

Defects in B cell differentiation that lead to deficiencies in one or a few Ig isotypes
Number of B cells is usually normal

13
Q

What is the most common primary immunodeficiency? Describe its mechanisms and symptoms

A

IgA deficiency due to a block in differentiation of B cells
Results in low levels of serum IgA
Symptoms - recurrent intestinal and respiratory infections (often asymptomatic), possible anaphylaxis with transfusions

14
Q

What is common variable immunodeficiency?

A

Block in differentiation of B cells into plasma cells that results in reduced levels of serum Ig, impaired antibody responses, and normal B cell numbers
Symptoms - high frequency of autoimmune disorders and tumors
Presentation and pathogenesis are highly variable

15
Q

What are hyper-IgM syndromes?

A

Defects in somatic mutations and class-switching, often due to a lack of T cell help, that result in elevated IgM and decreased IgG and IgA
Normal B cell numbers
Caused by mutations in CD40L (X-linked), AID, and CD40

16
Q

What are the symptoms of X-linked hyper-IgM syndrome?

A

Increased infection due to lack of IgG, IgA, and IgE
Defects in cell-mediated immunity
Most common hyper-IgM syndrome

17
Q

By what features are T cell defects diagnosed?

A

Reduced numbers of peripheral blood T cells
Poor responses to T cell activators
Deficient cutaneous DTH reactions to ubiquitous microbial antigens, like Candida

18
Q

Why are isolated T cell deficiencies typically limited to CD8 defects?

A

Because a defect in CD4 cells (helper T cells) automatically leads to a defect in B cells

19
Q

What is Bare Lymphocyte Syndrome Type I?

A

Deficiency in MHC I due to mutations in TAP
Results in decreased CD8 cell numbers and function, activated NK cells, perforin deficiencies, and granule fusion defects

20
Q

What causes severe combined immunodeficiencies? List the general and a few specific causes

A

Deficiencies in B and T cells, OR in just T cells which results in defects in humoral immunity
MANY causes, including defects in ADA, the common gamma chain, and V(D)J recombination

21
Q

What is the result of adenosine deaminase deficiency?

A

SCID (most common cause)
Causes accumulation of deoxyadenosine and its precursors (toxic to rapidly proliferating cells)
Results in defects in lymphocyte development and thus reduced B and T cells

22
Q

What is the common gamma chain?

A

A common motif of MANY cytokine receptors, including IL-2, 4, 21, 7, 9, and 15
Gene is found on the X chromosome

23
Q

What is the result of common gamma chain deficiency?

A

X-linked SCID (most common cause)
Result in a lack of growth of immature T cells, deficient NK cells, and no T cell help
B cell numbers are usually normal

24
Q

What are the common characteristics and clinical presentations of SCID?

A

Deficiencies in both humoral and cell-mediated immunity, resulting in a high susceptibility to all sorts of infections
Presentations - failure to thrive, chronic diarrhea, recurrent infections
Usually fatal in the first few years of life

25
Q

What is Wiskott-Aldrich syndrome?

A

Mutation in WASP (WA syndrome protein) - expressed in leukocytes and megakaryocytes
Symptoms - eczema, thrombocytopenia with small platelets, bleeding, infections, low IgM levels

26
Q

What is ataxia telangiectasia?

A
Autosomal recessive deficiency in a DNA repair protein that results in accumulated DNA damage, defects in VDJ recombination and class switching, and decreased B and T cells
Symptoms - progressive ataxia, telangiectasias, variable immunodeficiency 
Often present with recurrent sinopulmonary infections
27
Q

What are the two main causes of acquired immunodeficiencies?

A

1) Biologic complication of another disease process

2) Complication of therapy for other diseases - the most frequent cause

28
Q

What are the mechanisms by which HIV causes immunodeficiency?

A

Direct cytopathic effects of infection of CD4 cells - decreased T cell functions
Also infects and injures macrophages and dendritic cells