Brainscape's Knowledge GenomeTM

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


See full index

H&D > Wk 3 TBL Primary Immunodeficiencies > Flashcards

Wk 3 TBL Primary Immunodeficiencies Flashcards

1
Q

What are 3 categories of adaptive IS immunodeficiencies?

A
  1. SCID
  2. B cell/antibody deficiencies
  3. T cell deficiencies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are 2 types of SCID?

A
  1. X-linked
  2. autosomal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are 3 B cell/Ab deficiencies?

A
  1. X-linked agammaglobulinemia
  2. Hyper-IgM syndrome
  3. Combined variable immunodeficiency (CVID)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is an example of a T cell deficiency?

A

DiGeorge Syndrome

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

What is SCID?

A

simultaneous loss of B and T cell fxn
- can be absence of B cells, or B cells that can’t make Abs, absence of T cells, T cells that can’t make cytokines
- results in defects in early lymphocyte development

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are signs/ characteristics of SCID?

A
  1. susceptibility starts at birth
  2. unexpected severity, frequency
  3. opportunistic infections
  4. failure to thrive
  5. fatal if untreated
  6. stem cell transplant
  7. corrective gene therapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is special about IL-2, related to immunodef?

A

Activatd T cells express high affinity IL-2R w/ beta, alpha and gamma components on intracellular domain

-when bound to IL-2 -> clonal expansion

-not expressed on thymocytes except IL-2R-gamma, which is called the common gamma chain and is a shared component of multiple cytokine receptors (IL-2R, IL-4R, IL-7R, IL-15R, IL-21R)
-when binds IL-7 -> lyphoid commitment -> survival, proliferation, and differentiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What happens in X-linked SCID?

A

Loss of IL-2R gamma -> impaired IL-7 signaling
-absence of T and NK cells
-B cell may be present or increased but can’t make Ig

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the fxn of IL-2?

A

=common gamma chain
=shared component of multiple cytokine receptors
-critical for lymphoid survival, proliferation and differentiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is X-linked SCID?

A

=absence of IL-2gamma receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is autosomal recessive SCID?

A

-can be induced by loss of or defects in adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) (scavenger molecules that clean up toxic metabolites and prevent them from killing lymphoid progenitors)
-> loss of B cells, T cells, NK cells

-progressive

OR
loss of Rag recombinase gene (AKA Omenn’s syndrome) - induces recombination of VDJ regions during lymphocyte development
-w/o it, no antigen receptor rearrangement
-> apoptosis during B or T cell development
-NK cell remain present

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are PNP and ADA?

A

=purine nucleoside phosphorylase
=adenosine deaminase
Both clear toxic metabolites from cells
-w/o them -> autosomal recessive SCID

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

What is Omenn’s syndrome?

A

mutations in RAG (recombination-activating gene) -> autosomal recessive SCID

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are 4 key features of antibody deficiencies?

A
  1. onset of disease susceptibility starts ~4-6 months after birth
  2. recurrent bacterial infections w/ unexpected frequency, severity, and complications
  3. common features: sinusitis, otitis, bronchitis, pneumonia
  4. can be susceptible to diseases even with vaccination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

X-linked agammaglobulinemia

A

AKA Bruton’s Tyrosine deficiency
Btk gene on X-chromosome

-normal pre-B cell populations in BM, but unable to mature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

X-linked agammaglobulinemia

A

AKA Bruton’s Tyrosine Kinase deficiency
- w/o Btk, there is no survival signal -> apoptosis of all developing B cells -> no Ig
- recurrent infections: sinusitis, otitis media, pneumonia
- chronic enteroviral meningoencephalitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the fxn of Bruton’s tyrosine kinase?

A

Intracellular molecule that is induced in B cells after heavy chain of Ab is expressed on the surface (a successful heavy chain rearrangement, positive selection of developing B cell)
-mediates signal that promotes cell survival

18
Q

What happens if the B cell heavy chain fails rearrangement?

A

apoptosis of developing B cell

-occurs in absence of successful heavy chain rearrangement b/c no Btk-mediated survival signal

19
Q

What is Hyper-IgM syndrome?

A

X-linked antibody deficiency
-results from lack of CD40L on Th cells so cannot provide costimulatory signal to B cells ->
-> poor AID acticity -> defective affinity maturation and isotype switching
-> poor GC formation
-> high titers of IgM, low of others
-poor vaccine response
-neutropenia
-increased susceptibility to severe bacterial infection and opportunistic infections
-autosomal recessive versions too: deficiencies in CD40, AID
-give immunoglobulin therapy

20
Q

What is a key illness associated w/ X-linked hyper IgM?

A

Pneumocystis jirovecii pneumonia

21
Q

What is CVID?

A

=combined variable immunodeficiency
-can have later onset (2nd-3rd decade)
-10% result from defects in TACI
-variable defects in Ab production (can be decrease in one to absence of all isotypes)
-recurrent and chronic infections

22
Q

What is TACI?

A

a receptor for B cell activation factor (BAFF)
-defective in 10% of CVID cases

23
Q

What is IgA deficiency?

A

most common immunodeficiency
-80-90% asymptomatic
-recurrent infections, giardiasis
-may progress to CVID
-linked to increased risk of autoimmune disease

24
Q

DiGeorge Syndrome

A

-22q11.2 chromosomal deletion
-partial or complete failure (aplasia) of thymic development
-partial -> some T cell defects, complete -> absence of T cells (~1% cases)
-hypoparathyroidism and hypocalcemia
congenital heart defects
-heterogeneous facial deformities, cleft palate, rounded jaw
-severe viral, fungal, mycobacterial infections

25
Q

4 congenital deficiencies that impact the adaptive immune response

A
  1. Wiskott-Aldrich syndrome
  2. Ataxia-telangiectasia
  3. Chronic cadidiasis
  4. Hyper-IgE (Job syndrome)
  5. MHC Class I (TAP, beta-2- microglobulin) and Class II deficiency
26
Q

What is Wiskott-Aldrich syndrome?

A

defective cytoskeletal structure -> defects in T cell activations and migration
-X-linked
1. Thrombocytopenia
2. recurrent bacterial, viral and fungal infections
3. Eczema of the skin

27
Q

Ataxia-telangiectasia

A

Defect in ATM kinase (repairs of dsDNA breaks)
-> defects in lymphocyte development

-neurological disorder that affects motor movement (intended movement of muscles) and speech.
-affects the spine and immune system.
-begins before age 5.

28
Q

Chronic candiddiasis

A

Defects in IL-17 or Th-17 development
->chronic fungal infections of the mouth, scalp, skin, and nails

29
Q

Hyper-IgE (Job syndrome)

A

Defects in transcription of factor STAT3
-> loss of Th1 and Th17
-> hyperactive Th2 responses
->clinical triad of atopic dermatitis, recurrent skin staphylococcal infections, and recurrent pulmonary infections. The disease is characterized by elevated IgE levels with early onset in primary childhood.

30
Q

What are 3 immunodeficiencies that affect the innate response?

A
  1. LAD - leukocyte adhesion deficiency (trafficking)
  2. CGD = chronic granulomatous disease (phagolysosome fxn)
  3. TLRs: MyD88, IRAK4, TLR3
31
Q

What are 3 primary bacterial susceptibilities w/ complement deficiencies?

A
  1. Neisseria meningitidis
  2. Streptococcus pneumoniae
  3. Haemophilus influenzae
32
Q

What are 5 complement path deficiencies that can -> susceptibility to encapsulated bacteria?

A
  1. Classical pathway (C1, C2, C4)
  2. Alternative pathway (Factor D, Factor B, C3)
  3. lectin pathway (MASP proteases, MBL- mannose-binding lectin)
  4. MAC (C5-9)
  5. Complement inhibitors (Factor H/I, C3 overconsumption)
33
Q

PNH

A

=paroxysmal nocturnal hemoglobinuria
-complement-induced intravascular hemolytic anemia, dark urine (esp in am), thrombosis
-mutation in PIGA gene, which forms GPI anchors for CD59 and DAF (membrane proteins that inhibit complement)
-> lack surface CD59 and DAF -> overactivation of MAC
-> increased susceptibility to Neisseria meningitidis b/c constant over-activation -> overconsumption of C3 and impairment of normal complement fxn

-acquired mutation on X-chromosome, not inherited

34
Q

Hereditary angioedema

A

HAE
-loss, depression or misfunctioning C1 inhibitor (C1 INH) -> over production of bradykinin
-> rapid swelling hands, face, limbs, larynx, intestinal tract
-can become more severe in late childhood

35
Q

Hereditary angioedema

A

HAE
-loss, depression or misfunctioning C1 inhibitor (C1 INH) -> over production of bradykinin
-> rapid swelling hands, face, limbs, larynx, intestinal tract
-can become more severe in late childhood

36
Q

Chronic granulomatous Disease

A

Defects in NADPH oxidase complex
-X-linked version is defect in gp91 subunit
-> reduced oxidative burst, reduced ROS, impaired phagolysosome fxn
-failure to control infections -> granulomas
-bacterial and fungal infections

37
Q

Leukocyte adhesion deficiency

A

Loss of LFA-1 (high affinity integrin) -> failure of leukocytes to adhere to endothelial lining and traffic into tissues
-> neutrophilia in blood, unresolved cytokine response
-severe bacterial infections
-no pus

38
Q

What is a primary immunodeficiency?

A

Immune system defect
* SCID
* CVID
* Hyper IgE
* CGD

39
Q

What is a secondary immunodeficiency?

A

Have a compromised immune system and develop a disease response:
* DM
* RA
* SLE
* Malnutrition
* * Etc.

40
Q

Humoral vs cell-mediated

A
41
Q

3 clinical findings for X-linked agammaglobulinemia

A

absent tonsils
absent antibody
absent B cells
absent GCs

H&D (23 decks)

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