Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Immunology Exam 3 > Lecture 23: Primary Immunodeficiencies > Flashcards

Lecture 23: Primary Immunodeficiencies Flashcards

1
Q

When do primary immunodeficiencies (PIDs) manifest?

A

w/in first year of life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

HX and PE thinking suspected PID?

  • Recurrent sinopulm. bacterial infections screen for –>
  • Recurrent viral/fungal infections screen for –>
  • Recurrent skin absesses/fungal infections screen for–>
  • Bacteriemia or meningitis w/ encapsulated bacteria screen for –>
A
  • humoral immunity (B cells and Abs)
  • cellular immunity (T cells)
  • Phagocyte defect
  • Complement deficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q
  1. What is SCID?
  2. Typically associated w/ severe T-cell ________.
  3. What is SCID characterized by?
  4. A fetus w/ SCID is at risk of abortion due to inability to do what?
A

Severe Combined Immue Deficiency

  • rare, potentially fatal syndrome of diverse genetic causes in which there is a profound deficiency of T-cells w/o or w/o dec. in B cells or NK cells
    2. Lymphopenia
    3. Severe opportunistic infections (due to pathogens that don’t normally cause infections in ppl w/ normal IS), chronic diarrhea, and FTT
    4. reject maternal T cells that cross the placenta –> cause immunological rejection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q
  1. What deficiency leads to accumulation of deoxyadenosine which is a toxic for T/B cells?
  • ImmunoPT = T-B-NK-
    • which causes what Ig’s to be low/absent?
  1. What type of vaccines should be avoided?
  2. What is the inheritance pattern?
A
  1. Adenosine deaminase (ADA) deficiency
  • ADA normally converts deoxyadnosine –> deoxyinosine (not harmful)
    • deficient ADA esp. harmful to T cells
  • IgG, IgA, and IgM
  1. All live vaccines
    - tx = HSCT (hemolytic stem cell transplantation)
  2. Autosomal recessive
    - second most common cause of SCID
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

1. RAG1/RAG2 deficiency is a rare autosomal recessive disorder that causes impaired V(D)J recomination leading to defective expression of what? (which causes SCID)

  • what is the immunophenotype?
  • Pt presentation starts in infancy w/ diarrhea, candidiasis and opportunistic infections with what bacteria?
  1. Leaky RAG1/RAG2 defects allows for partial fxn of RAG1/RAG2 causing an atypical form of SCID known as?
    * hint, sx = severe erythroderma, splenomegaly, eosinophilia, and high IgE
  2. What type of vaccines should be avoided?
A
  1. pre-TCR and pre-BCR
  • T-B-NK+ –> low/absent IgG, IgA, and IgM
  • Pneumocystic jiroveci
  1. Omenn syndrome
  2. All live vaccines
    - tx = HSCT (hemolytic stem cell transplantation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q
  1. What is the deficiency causing a rare form of autosomal recessive radiosensitive SCID?
    * T and B cell # are _____ and NK cell # are ____
  2. Pts have an increased risk of developing what?
  3. What is the cause of radiosensitivity?
  4. What type of vaccine should be avoided?
  5. When and what does the pt present w/?
A
  1. Artemis deficiency
    * absent; normal –> T-B-NK+ –> low/absent IgG, IgA, and IgM
  2. Lymphomas
  3. Artemis is an enz in VDJ recombo and serves to protect dsDNA breaks, which radiation causes
  4. All live vaccines
    - tx = HSCT (hemolytic stem cell transplantation)
  5. Infancy; diarrhea, cadidiasis, opportunistic infections w/ pneumocystis jiroveci
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

1. Common γ Chain Deficiency (γc or IL-2Rγ) is the an _____ recessive trait, that is the most _____ form of SCID.

  1. What is it’s immunoPT and what are the associated Ig levels?
  2. What cell type is present, however NON-functional?
A
  1. X-linked; common
  2. T-B+NK<strong>-</strong> –> IgM+, but l_ow/absent IgG, IgE, and IgA_
  • genes encoding GAMMA-CHAIN are shared by T cell growth factor receptor (IL-2Rγ)
  • IL-2Rγ also shared with IL-4, IL-7, IL-9, IL-15, and IL-21
  1. B cells are present but non functional bc T cells are unable to help
  • pt’s present in infancy w/ FTT, severe thrush, opportunitic infections, chronic diarrhea
  • Avoid ALL live vaccines
  • HSCT used for tx
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q
  1. IL-7R Alpha Chain Deficiency is an _____ recessive form of SCID.
  2. What does IL-7 play a key role in?
  3. What is the immunoPT and the corresponding Ab levels?
  4. What is used to confirm the dx?
A
  1. autosomal
  2. early T cell development
  3. T-B+NK<strong>+</strong> (B cell present but not functional)–> IgM+, low/absent IgG, IgE, IgA (still low/absent despite B cell presence due to absence of T cell co-stim. signaling)
  4. IL-7R Gene sequencing
  • pt’s present in infancy w/ classic SCID sx = cadidiasis, chronic diarrhea, pneumocystic jiroveci PNA, severe viral infections
  • Avoid ALL live vaccines
  • HSCT used for tx
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q
  1. Deficiency of Jak3 causes a defect in _______ signaling, resulting in SCID.
  2. What is the immunophenotype?
  3. What are the Ig levels?
  4. What is the inheritance pattern?
A
  1. IL-2R (IL-2R_α_)
  2. T-, B+, NK-
    * NK cells activated through IL-15R_α_
  3. IgM+, low/absent IgG, IgE, and IgA (bc B cells are non functional and not getting T cell help)
  4. Autosomal recessive
  • Avoid ALL live vaccines
  • HSCT used for tx
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q
  1. CD3 complex deficiencies (subunits inlucing ___, ___, ___, ___) can cause SCID.
  2. What is the immunophenotype?
  3. How does it present?
  4. What are the Ig levels?
  5. What is the inheritance pattern?
A
  1. delta, gamma, epsilon, zeta
  2. T-, B+, NK+
  3. During infancy with acute T cell lymphopenia, FTT, opportunistic infection and chronic diarrhea
  4. IgM+, low/absent IgG, IgE, IgA —> Ab responses typically dec.
  • Avoid ALL live vaccines
  • HSCT used for tx
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What type of immunodeficiency comprise approximately half of all 1° immunodeficiencies?

A

B cell immunodeficiencies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q
  1. B cell immunodeficiencies are a group of heterogenous disorders resulting from what?
  2. Dysfunction of B cells results in imparied ab production and inc. susceptibility to recurrent infections particulalry by what bacteria type?
A
  1. Disruption of B cell maturation and fxn
  2. Encapsulated bacteria

B cell immunodeficiencies comprise half of all PIDs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Primary agammaglobulinemia is most commonly inherited as what?

Early B-cell development is arrested at what stage?

  • what does this result in?
  • what halts B cell development at this stage? (name the prtn)
A

X-linked trait

Pre-B cell stage

  • circulating B cells are absent or have very low #s
  • BTK
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q
  1. X-linked Btk deficiency is a result of a mutation in what?
  2. What is the immunophenotype?
  3. Titers of all serum abs (IgG, IgA, and IgM) are ______.
  4. What type of vaccine should be avoided?
  5. Who does this condition effect?
A
  1. Tyrosine kinase
    * due to a defect in the rearrangement of the Ig heavy chain genes
  2. T+, B-, NK+
  3. Absent or very low
  4. All live vaccines
    * tx with HSCT
  5. Males
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q
  1. What is the immunoPT and corresponding Ig levels of ppl w/ IgA deficiency?
  2. Diagnosis includes pt’s presenting w/ recurrent infections typically with what kind of bacteria?
  3. Most patients are _____ bc IgM is still able to cross mucosal epithelium and other Abs can make up for the loss of IgA.
  4. Pts may have serum anti-IgA IgG which is linked to development of non-IgE mediated ________ in response to IV Ig transfusion.
  5. What are the restrictions for vaccinations?
A
  1. T+, B+, NK+ –> NO IgA, but nl IgM, IgE, IgG
  2. Encapsulated
  3. asymptomatic
  4. Anaphalyxis
    * bc donor blodo will contain IgA abs –> serum sickness

higher prevanlence in males

  1. There are none
    * symptomatic tx
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q
  1. Isolated IgG Subclass deficiencies have what type of immunoPT and what are the corresponding Ig levels?
  2. Are these pt’s usually asymptomatic or symptomatic?
  3. It can be assoc. w/ recurrent viral/bacterial infections frequently involving what area of body?
  4. What are the restrictions for vaccinations?
A
  1. T+, B+, NK+ –> Decreased [] of 1 or more IgG subclasses, but nl IgM, IgA, IgG
  2. Asymptomatic
  3. Respiratory tract
  4. There aren’t any
    * tx symptomatically
17
Q
  1. In patients with hyper IgM syndrome (HIGM), they have normal # of _____ B cells, but low #s of _______ B cells.
  2. What are the two impairments w/in the periphery causing this syndrome?
  3. What is the immunoPT and what are the corresponding Ab levels?
A
  1. peripheral B cells; memory
  2. Ig class switching and somatic hypermutation
  3. B+, T+, NK+ –> HIGH IgM, but low IgG, IgE, IgA
18
Q
  1. Mutations in what cause HIGM?
  2. X-linked _____ deficiency (male only) is responsible for 2/3 of all cases.
  3. Autosomal _____ deficiency (male only) is responsible for 1/3 of all cases.
  4. What vaccination is not recommended for these patients?
  5. What is not required for IgM, explaining why they are high and other Ig’s are low?
A
  1. CD40 and CD40L (costimulatory signaling from Th cells)
  2. CD40L
  3. CD40
  4. Polio
  5. Does not require T cell help, ie does not require any signaling for proliferation, affinity maturation, or isotype switching
19
Q
  1. In transient hypogammaglobulinemia of infancy, intrinic __ production is delayed for up to 36 months.
    * this results in low __, ___, ___, but normal ____.
  2. These infants have inc. susceptibility to what kind of infections?
  3. When do the majority of these patients [Ig] normalize?
  4. What vaccine is not recommended?
A
  1. Ig production is delayed
  • IgA, IgG, IgE, but normal IgM
  • immunoPT = B+/-, T+, NK+
  1. Sinopulmonary infections
  2. b/w 2-4 years
  3. Polio
    * symptomatic tx

Normally Maternal IgG in infant disappears after 6 mo and intrinsic IgG production usually beings immediately after birth

20
Q
  1. T cell immunodeficincies are defined as T cell deficiency w/ <300-500 circulating CD3+ cells –> these pt’s are susceptible to ____ infections and malignancies.
  2. Clinical manifestations may be indistinguishable from what?
  3. T-cell repertoire and T cell subpopln’s (including _____ and ____ T cells) are abnormal.
A
  1. viral infections
  2. SCID (bc have functional deficiency of B cells***)
    * predominant clinical manifestation is autoimmunity or lymphoid malignacy
  3. Treg and memory

Ig’s and specific Abs maybe variable (primarily IgM, but dec IgA, IgG, and IgE)

21
Q
  1. Bare Lymphocyte Syndrome Type 2 (BLS II) is a rare autosomal recessive genetic disorder causing HLA class ___ negative SCID.
  2. What type of T cells would be deficient?
  3. Which parts of body would be affected by recurrent infections causing death in early childhood?
  4. What is the immunoPT? and corresponding Ig
  5. What vaccines should be avoided?
A
  1. Class II
    * Mutations are in genes which encode for TFs taht nlly reg. expression of MHC II genes
  2. CD4+ T cells
  3. respiratory, GI, and urinary tract infections
  4. T+, B+, NK- ; –> normal IgM, IgG, IgE, IgA
    * variable hypogammaglobulinanemia (mainly IgA and IgG2)
  5. All viral live
    * HSCT is curative
22
Q
  1. MHC Class I deficiency is caused by a mutation in what mlcls that transport peptides to the ER?
  2. What T cell would be deficient?
    * this deficiency would result in what type of reccuring infections?
  3. What vaccines should be avoided?
  4. What is the immunophenotype and corresponding Ig levels?
A
  1. TAP1 and TAP2
  • Ag processing to peptides in proteosome
  • TAP1 transports them to the ER where they can bind MHC Class 1
  1. CD8+ –> viral infections
  2. All viral live
  3. T+, B+, NK-
  • normal Ab production (nl IgM, IgG, IgE, IgA)
  • normal DTH (delayed type hypersensitivity)
23
Q
  1. What syndrome is a classic example of T-cell deficiency that results from a microdeletion of 22q11.2 region containing more than 35 genes?
  2. What is the classic triad that this syndrome causes?
  3. What type of immunity would be intact for most pt’s?
  4. What type of vaccine should be avoided?
  5. What is the immunoPT and corresponding Ig levels?
A

1. DiGeorge Syndrome (DGS)

  1. Cardiac anomalies, hypocalcemia, and hypoplastic thymus (which leads to T cell immune dysfunction)
    * Patients often suffere from frequent URI’s.
  2. Humoral (bc portion of CD4 remaining cells will still have B cells)
  3. All viral live
  4. T-, B+, NK+ –> nl IgM, IgE, IgG, IgA

treat symptomatically or thymus transplantation

Immunology Exam 3 (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions