Lecture 14: Inherited Disorders Flashcards Preview

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Flashcards in Lecture 14: Inherited Disorders Deck (78):
1

Neutrophil deficiency is associated with inefficient:

Pathogen clearance

2

What cells (other than NK) will be affected by a genetic deficiency in proper perforin formation?

CTL

3

NFkB

Transcription factor involved in toll like receptor signaling

4

Defective NFkB

Defective innate recognition of infection

5

Deficiency results in RBC destruction by MAC (2)

RBC are not correctly protected from complement proteins due to DAF or CD59 (prevents C9 binding) deficiency

6

What is the consequence of IgM having no Fc receptors?

Degradation of antigen relies on complement cascade (not macrophages)

7

What is the cause of immune-complex disease?

Failure to clear Ag-Ab immune complexes

8

What results from improper immune-complex disposition? In what major locations does this occur (2)?

Inflammation, especially vasculitis and glomerular nephritis

9

What role does MBL (mannose binding lectin) play in protection against sepsis?

Protects circulation against infection (because recognizes pathogen specific components)

10

Why is MBL a better complement pathway than alternative?

Alternative relies on constantly produced C3, but MBL recognizes structures on pathogens

11

Glycophosphatidylinosital deficiency

Paroxysmal Nocturnal Hemoglobulinuria

12

Glycophosphatidylinosital is...

molecule that anchors proteins into the cell membrane

13

How does Paroxysmal Nocturnal Hemoglobulinuria affect RBC?

RBC are destroyed--usually protected from complement-related degradation by DAF/CD59 (which are deficient in PNH)

14

X-Linked Agammaglobulinemia results in

Patient lacks mature B cells, thus no immunoglobulin in the serum (B cell maturation halts at pre-B cell stage due to defective tyrosine kinase signaling; Small B cell repertoire)

15

T/F: AID deficiency results in no activated B cells

F: activation occurs, but no class switching + somatic hypermutation (because AID enzyme required for these)

16

In X linked hyper IgM syndrome, a defect of _____ causes susceptibility to extracellular and intracellular bacteria

CD40L; B cells (and macrophages) do not receive the 2nd signal of activation on their CD40, thus do not undergo germinal center reactions (isotype switching)

17

Associated with no germinal center reactions

X linked hyper IgM syndrome (B cells do not receive the second signal of activation due to CD40L deficiency on T cells)

18

What immune cell will be affected by IgG1 deficiency?

NK

19

TAP deficiency results in

few CD8 T cells produced (because MHC I do not provide signal for positive selection in thymus)

20

No MHC Class II results in..

No CD4 T cells (because MHC II do not provide signal for positive selection in thymus)

21

How does gamma chain deficiency relate to failure in T cell proliferation?

gamma chain is a signaling component for cytokine receptors--such as IL2 and IL4

22

How does CD3 deficiency affect T cells?

It is the signal transduction unit, so no T cell function (SCID)

23

What is the result of RAG enzyme defect?

No VDJ recombination, which results in no B cells and low numbers of oligoclonal autoreactive T cells

24

Asplenic patients are especially susceptible to this pathogen

encapsulated bacteria

25

What is the immuno role of the spleen?

As it filters blood, splenic macrophages take up bacteria in the blood--this guards against sepsis

26

What is the disease?
Defective CD18 (adhesion molecules) results in defective migration of phagocytes into infected tissue.

Leukocyte adhesion deficiency

27

What is the disease?
Defective NADPH oxidase results in the inability of phagocytes to produce ROS, impairing their ability to kill bacteria.

Chronic granulomatous disease

28

What is the disease?
Deficiency of G-6P dehydrogenase results in a defective respiratory burst

Glucose-6-P dehydrogenase deficiency (duh)

29

Deficiency of this enzyme found in neutrophil granules and macrophage lysosomes results in impaired production of ROS

Myeloperoxidase (catalyzes production of hypochlorous acid)

30

What is the disease?
Defective vesicle fusion (endosomes and lysosomes) results in impaired phagocytosis

Chediak-Higashi Syndrome

31

Neutropenias are characterized by low numbers of:

granulocytes (neutrophils <500 cells/ul)

32

T/F: Neutrophil specific autoimmune antibodies can cause neutropenia.

T

33

What is the difference between Absolute, Classical, and Functional NK Cell Deficiency?

ANKD: complete lack of cells or functional cells
CNKD: ANKD, but NKT cells are present
FNKD: Normal # NK cells, but their function is absent or severely decreased

34

What infections are common in patients with NK deficiency?

varicella zoster virus, Mycobacterium avium, Trichophyton

35

3 Possible causes of NK Cell Deficiency Disorders.

Defective granule formation
Defective perforin
Improper development of NK cells in bone marrow

36

What's the disease?
Defect in protein necessary for NFkB activity, resulting in recurrent bacterial infections

NEMO Deficiency (innate recognition disorder in which PRR's recognize PAMPs, but there is an error in getting the proper genes transcribed)

37

Most likely result of Inherited Complement Deficiencies

Susceptibility to extracellular bacteria (especially encapsulated, because PRRs cannot not recognize them)

38

Why does Factor I deficiency cause C3 depletion?

C3 is produced at a constant rate; when C3b is cleaved by Factor I the cascade stops; in the absence of Factor I C3 is utilized in the pathway

39

HANE is caused by:

C1INH deficiency (classical pathway)--and overproduction of anaphylatoxins

40

C5-C9 deficiency causes:

Neisseria susceptibility

41

Deficiency of this causes susceptibility to encapsulated bacteria and Neisseria, but no immune-complex disease

Factor D

42

Why are encapsulated bacteria tough to eliminate?

They are not susceptible to phagocytosis

43

What is the result of Ab deficiencies?

increased susceptibility to extracellular pathogens

44

Result of X-Linked Agammaglobulinemia?

Very few B cells develop, patient has no humoral immunity

45

Defect causing X-Linked Agammaglobulinemia

Defect in protein tyrosine kinase involved in B cell development

46

Result of Lambda-5 Deficiency?

B cell deficiency due to lack of pre-B cell receptor

47

What is Lambda-5?

Portion of surrogate light chain that pairs with heavy chain during somatic recombination of B cells

48

What two defects cause X-linked hyper IgM Syndrome?

T cell function due to defective CD40L and AID deficiency

49

What are the lymph nodes of patients with X-linked hyper IgM Syndrome different than a normal patient's?

no germinal center reactions

50

Selective IgG deficiency--with deficiency of IgG2 subtype--results in susceptibility to what?

encapsulated bacteria

51

TAP Transporter Deficiency (aka Bare Lymphocyte Syndrome) results in....which ultimately leads to...

Low levels of MHC I; low CD8 due to low positive selection during thymic development

52

Defect in CD8 alpha chain results in:

lack of CD8

53

Low/No CTL activity, normal CD8, inability of CTL to induce apoptosis. What is defective?

Perforin

54

Defects in what causes SCID?

CD4/(8 T Cell) ** mostly CD4 bc w/o these, no B cells active

55

Defective cytoskeleton reorganization, resulting in a lack of cytokine delivery to B cells and macrophages

Wiskott-Aldrich Syndrome (cross-talk deficiency)

Defective T cells --> no active B cells = SCID

56

Toxic nucleotide metabolites accumulate and kill developing B/T cells

Adenosine Deaminase or Purine Nucleotide Phosphorylase Deficiency

57

Result of Jak3 Deficiency:

impaired cytokine signaling, resulting in failed T cell proliferation--no effector T cells

58

Caused by partially active RAG enzymes:

Omenn Syndrome (disorder characterized by no B cells and low numbers of oligoclonal auto-reactive T cells)

59

DiGeorge Syndrome

absent or underdeveloped thymus, resulting in few/no T cells

60

ZAP-70 Deficiency

No signaling at TCR (because ZAP is a component of a tyrosine kinase involved in TCR complex); results in no CD8 and normal # of non-functional CD4

**implies that intracellular signaling is required for CD8 development but not required for CD4 development

61

Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy

deficiency in AIRE, a transcription factor that regulates the proteins responsible for negative selection of T cells in thymus

**results in many auto-reactive T cells -> develop myriad of autoimmune disorders

62

What's the disease?
Deficiency in FoxP3 expression in Treg cells

IPEX (results in nonfunctional Treg cells)

63

ALPS

Result of failure of immune cells to undergo apoptosis following an immune response (due to Fas, FasL or caspase 10 mutation)

64

ALPS has what effect on secondary lymphoid tissue

causes overpopulation due to lack of apoptosis

65

Indicative of Good's Syndrome (3):

hypogammaglobulinemia, low levels of B cells, benign thymic tumor

(Decreases CD4:CD8 ratio (from tumor)-> dec CD4 is why you see no B cells) * this is just so that it makes sense in my mind, don't actually know if that is all true)

66

Myelokathexis

neutrophil retention in the bone marrow

67

Short stature/arms/legs, sparse hair, anemia, and immune problems

Cartilage Hair Hypoplasia

68

What's the disease?
Genetic defect in a cluster of proteins responsible for DNA repair, results in bone marrow failure

Fanconi's Anemia

69

Disorder characterized by albinism and immunodeficiency, with mutations involving vesicular transport (thus affecting granule/cytokine delivery by NK and T cells)

Griscelli Syndrome

70

What are the 2 clinical interventions for asplenia?

1. Vaccination for encapsulated organisms
2. Prophylactic abx prior to dental procedures and at the 1st signs of respiratory infection or fever

71

What are the 3 most common types of neutropenia?

1. severe congential
2. cyclic
3. benign chronic

72

What do NKT cells recognize?

CD 1 (NOT MHC-Ag complex)`

73

What disorder causes a lack of immune response to the binding of PAMPs to Toll-like receptor on the surface of phagocytes?

NEMO deficiency

74

What is the treatment for NEMO?

-biweekly injections of gamma globulin from healthy donor
-Bone marrow transplant

75

SCID (severe combined immune deficiency) is associated with defective:

T cells (CD4 and CD8) and B cells

76

Asplenic patients are especially susceptible to this condition:

Sepsis (no macrophage mediated blood filtering)

77

What is NFkB?

Transcription factor involved in the expression of cytokines/chemokines, which occurs after a Toll-like receptor recognizes a pathogen

78

What would be the immuno result of Toll-like receptor deficiency?

The patient would have a reduced ability to recognize bacterial and viral pathogens