Inherited Acquired Immune Deficiencies Flashcards Preview

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Flashcards in Inherited Acquired Immune Deficiencies Deck (46)
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What is X-Linked agammaglobulinemia?

X-linked mutation in Bruton's tyrosine kinase

BTK is required for B cell production in the bone marrow (signal transduction).

Patient has very few B cells and hence no humoral immune system.

Susceptible to extracellular bacterial and many viral pathogens because cannot neutralize virions
e.g. influenza

Classical phenotype: underdeveloped tonsils


A patient who has recurrent infections and underdeveloped tonsils probably has what deficiency?

X-linked agammaglobulinemia


A deficiency in Bruton's tyrosine kinase results in what disease?

X-linked agammaglobulinemia


What is Pre B-cell receptor deficiency?

Mutation in lambda 5 gene.

The surrogate light chain is absent during B cell development (surrogate holds BCR intact during light chain recombination).

Developing B cell receptors become unstable and undergo apoptotic death.

PROFOUND B cell deficiency.

Susceptible to extracellular bacteria and many viral pathogens.


A deficiency in lambda 5 gene results in what?

Pre B-cell receptor deficiency


What are 2 types of X-Linked Hyper IgM syndromes?

1) Deficiency in CD40 Ligand so T cells cannot activate B cells.
- Results in low Ab production (compared to immunocompetent person)
- Results in only IgM antibodies in system.
- No germinal centers.

2) Deficiency of AID (activation-induced cytidine deaminase)
- Cannot class switch after activation of B cell
- Can activate B cells
- Results in higher IgM levels compared to CD40L def.


Deficiency in AID results in what?

Inability to class switch, so high IgM levels when B cells are activated


Deficiency in CD40 ligand results in what?

Cannot activate B cells, so
VERY low Ab production
Ab production is only IgM Ab's

No germinal centers.


What is Selective IgA Deficiency?

Genetic mutation where patients do not produce IgA
- Typically, undiagnosed
- Noticed when receiving blood transfusion because patient develops antibodies to the IgA in the blood product.
--- This results in an anaphylactic reaction.



A patient that goes into anaphylactic response following a blood transfusion most likely has what kind of immune genetic deficiency?

(NOTE: Blood transfusion reactions have MANY reasons other than this condition)

Selective IgA Deficiency


What is Selective IgG Deficiency?

Unknown genetic mutation that causes deficiency in IgG isotypes
- Most important:
Deficiency of IgG1 -- Results in increased susceptibility to bacteria and viruses
(probably most important because 60-70% of IgG in body is IgG1)

IgG2 Def -- Seen in children; Susceptible to encapsulated bacteria

IgG3 Def -- Seen in adults

IgG4 Def -- Ignore


What is the most important form of selective IgG deficiency? Why?

IgG1 deficiency

Majority of IgG in body is IgG1 (60-70%)


What is Common Variable Immunodeficiency (CVI)?

Collection of 150 related primary immunodeficiencies that have common features that typically include reduced antibodies = hypogammaglobulinemia.
- Unknown etiologies
- Susceptible to recurring bacterial and some viral pathogens


What diagnosis is characteristic of unknown genetic hypogammaglobulinemia with recurring bacterial and viral infections?

Common variable immunodeficiency


What is ataxia telangiectasia?

- Inherited defect in the ATM gene (encodes a DNA repair enzyme)

- Typically have clinical triad:
(1) Ataxia (cerebellar defects)
(2) Spider angiomas
(3) Either IgA (most commonly) or IgE deficiency

•• elevated alpha-fetoprotein levels are also common

[Can have T cell depletion and/or T cell & B cell depletion in some cases]


A patient that presents with ataxia, spider angiomas and IgA deficiency should be tested for what?

ataxia telangiectasia

(Can have IgE deficiency)


What is an IL-12 Signaling Deficiency?

Either 1) Defective IL-12 heterodimer or 2) Defective IL-12 receptor
--That leads to small production of IFN-gamma
----Decreased activation of Th1 CD4 T cells
----Lack of activation of macrophages

Particularly susceptible to disseminated mycobacterial infections.


A patient with persistent disseminated mycobacterial infection and small amount of IFN-gamma should be tested for what deficiency?

IL-12 signaling deficiency


What is Job's Syndrome?

Genetic deficiency of STAT-3 in T-cells
- Cannot make INF-gamma
- Immune responses are polarized towards Th2 responses
- HIGH IgE levels in blood.
- Neutrophils do not respond well to chemokines (unknown reason)

Clinical manifestations:
- Eczema
- Recurrent abscesses with Staph aureus (primarily).
- Characteristic facial features that include a
---broad nose
---frontal bossing
---deep set eyes
---retention of primary teeth

F = coarse facies
A = cold staph Abscesses
T = retained primary Teeth
E = increased igE
D = Dermatologic problems (eczema)


A patient with recurrent Staph abscesses, frontal bossing, eczema and retention of primary teeth needs to be tested for what disease?

What is the mechanism of disease?

Job's Syndrome

Genetic deficiency of STAT-3 in T-cells
- Cannot make INF-gamma
- Immune responses are polarized towards Th2 responses
- HIGH IgE levels in blood.


What is Chronic Mucocutaneous Candidiasis?

Group of disorders that results in recurrent or persistent Candida infections (typically albicans) of the nails, skin and mucous membranes

Undefined T cell dysfunction


A patient with recurring and sometimes persistent Candida infections of the skin, nails and mouth probably has what condition? What causes this?

Chronic Mucocutaneous Candidiasis

Some type of T cell dysfunction. Not understood.


What is TAP-1 or TAP-2 Deficiency?

- Genetic deficiency of either TAP result in very low levels of MHC Class I because cannot load peptides
- Results in very low levels of CD8 T cells because these cells cannot pass positive selection in the thymus
- Highly susceptible to viral infections and some intracellular infections -- Cannot produce a CTL response.

Also called: bare lymphocyte syndrome (MHC class I)


What is CD8 alpha chain defect?

Lack of CD8 T cell

- Highly susceptible to viral infections and some intracellular infections -- Cannot produce a CTL response.


What is perforin deficiency?

- non-sense mutation of perforin.
- Normal CD8 T cell levels
- ineffective CTLs and NK cells

- highly susceptible to viral and some intracellular bacterial infections.


Why do genetic defects that prevent CD4+ T cell effector functions result in SCID?

because B cell responses require effector T cell function
cell-mediated responses require effector T cell function too (Macs)


What is Bare lymphocyte syndrome (classic MHC class II version)?

- lack expression of MHC class II molecules
- unable to mount acquired CD4+ T cells responses or acquired B cell responses



What is Wiskott-Aldrich syndrome (WAS)?

- defect in cytoskeletal reorganization
- T cells reorganize their cytoskeleton so that they can deliver their effector molecules directly onto their target cell. This goes for both CD4+ and CD8+ T cells
- The defect in WAS causes a crosstalk deficiency that prevents proper cytokine signaling from effector T cells to B cells and macrophages.



What is Adenosine deaminase (ADA) or Purine nucleotide phosphorylase deficiencies?

- result in accumulation of toxic nucleotide catabolites that kills all lymphocytes during their development

- these two deficiencies result in patients that have no B cells or T cells



What is Common gamma chain deficiency?

- Deficiency of a component of several important cytokine receptors
- prevents signaling through each of those receptors
- receptor chain interacts with Jak3

- Because several of the cytokine receptors are critical for B and T cell development
(IL-2 [T cell growth factor], IL-7 [B cell growth factor], etc)
This deficiency results in SCID.

These patients have elevated B cells but are nonfunctional and few T cells or NK cells