Brainscape's Knowledge GenomeTM

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


See full index

Immunity Week 3 > ICL 7.2: Immunodeficiencies > Flashcards

ICL 7.2: Immunodeficiencies Flashcards

1
Q

what are the clinical features of x-linked hyper-IgM syndrome?

A

x-linked recessive

blockade of helper T cell-dependent activation of naïve B cells

no isotype switching

recurrent infection

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

what are the 5 immune defense mechanisms against infectious microbes?

A
  1. antibody-mediated immune defense
  2. T cell-mediated immune defense
  3. NK cell-mediated immune defense
  4. phagocyte-mediated immune defense
  5. complement-mediated immune defense
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

how are extracellular pathogens cleared by the immune system?

A

lots of bacteria replicate in extracellular spaces = extracellular pathogen

they can be cleared by antibodies, phagocytes, complement, and antimicrobial peptides

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

how are intracellular pathogens cleared by the immune system?

A

certain bacteria and all viruses must invade host cells to replicate = intracellular pathogens

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

which cells kill host cells infected with cytoplasmic pathogens?

A

CD8 cytotoxic T cells

NK cells

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

which cells promote the killing of intravesicular pathogens in phagocytes?

A

CD4 TH1 cells

NK cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

how can pathogens stick around in your body without being destroyed by the immune system?

A
  1. evade surveillance by altering their antigens
  2. persist in the hosts in a state known as latency
  3. become undetectable by the host immune system by down-regulating host receptors
  4. actively destroy the immune defense system by producing inhibitors of immunologically important host factors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are the two categories of immunodeficiency diseases?

A
  1. primary immunodeficiency diseases (inherited)

2. secondary immunodeficiency diseases (acquired)

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

what are primary immunodeficiency diseases?

A

mutations of genes involved in host immune system

they are genetically encoded

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

what are secondary immunodeficiency diseases?

A

they are acquired as a consequence of other disease, caused by environmental factors, or manifested as an adverse effect of medical intervention

they’re caused by an infectious agent, cancer, radiation, starvation, stress etc.

ex. AIDS

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

what does SCID stand for?

A

x-linked severe combined immunodeficiency

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

what causes SCID?

A

it’s caused by a mutation in the common gamma chain of interleukin receptors on T cells – all these IL receptors have the same gamma chain in their receptor

if there’s a mutation in the receptor it’ll cause issues with the IL signaling because they won’t be able to respond to any cytokines

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

which IL receptors are common gamma chain receptors?

A

IL-2R

IL4R

IL-7R

IL-9R

IL-15R

IL-21R

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

what are the consequences of SCID?

A

gamma chain of IL receptors is mutated

IL-2, IL-7, and IL-15 play crucial roles in the development, growth, and survival of T cells so people with common γ-chain gene mutations have almost complete depletion of T cells!

then, since T cells are required for activation of B cells recognizing T cell-dependent antigens, the X-SCID patients also fail to develop antibody-mediated immune responses to such antigens

NK cell development also require IL-2 and IL-15 too so there is decreased number of NK cells

  1. no T cells,
  2. reduced NK cells
  3. reduced B cell function
  4. severe immunodeficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

how are B cells effected in SCID?

A

B cell number remains normal

BUT their function is impaired because T cell development is impaired and without T cells, B cells don’t get activated

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

what clinical presentation would make you think someone has SCID?

A

if you have given someone a measles vaccine but then a month later they come in with the measles this could be due to SCID!

it’s showing you that they didn’t have a memory response against this antigen

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

what are ADA and PNP deficiency?

A

ADA and PNP are enzymes responsible for nucleotide catabolism (breakdown)

so if you don’t have these enzymes or mutations in them, you get buildup of adenosine & guanosine nucleotides which can be toxic in rapidly dividing cell types like T and B cells that are undergoing an immune response!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what are the effects of ADA and PNP deficiency?

A

there’s a mutation in the ADA or PNP gene that leads to a buildup of nucleotide metabolites that can be toxic in T and B cells

so then you have decreased T and B cells which can lead to SCID!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what clinical finding do you see in patients with ADA or PNP deficiency?

A

infants with ADA or PNP deficiency show under-developed thymus as detectable in chest X-ray

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what is a RAG gene mutation?

A

VDJ recombination of the immunoglobulin gene and the T cell receptor gene requires two enzymes encoded by the RAG1 and RAG2 genes

so you can have a RAG1 or RAG2 mutation that lead to abnormal RAG function or a totally non-functional RAG protein

RAG genes are important in B and T cell receptor generation so if you have a mutation in RAG1/RAG2, you can get either inactive receptors or poorly functional receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what are the effects of a RAG gene mutation that leads to an abnormally functioning T cell receptor?

A
  1. GVHD-like phenotype
  2. eosinophilia
  3. elevated IgE
  4. Omenn syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what are the effects of a RAG gene mutation that leads to a non-functional T cell receptor?

A

SCID!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what is Omenn syndrome?

A

can be result of abnormal RAG function

leads to:

  1. recurrent infections
  2. GVHD-like features: red rash, protracted diarrhea, and lymph node swelling
  3. eosinophilia with elevated IgE
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what do RAG1 and RAG2 do?

A

RAG 1 and RAG2 protein complexes bind to 12 and 23 bp spaced recombination signal sequences (RSSs) –> the RAG1 and RAG2 protein complexes bind to each other, bringing together the segments to be joined

they’re genes located at the ends of VDJ genes and shuffle and rejoin VDJ = VDJ recombination

they recognize RSS and cleave double stranded RNA between the Ag receptor and RSS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what is Bloom’s Syndrome?

A

it’s a mutation in DNA helicase which is responsible for unzipping DNA so that you can do DNA replication

without DNA helicase, you have reduced numbers of T cells, cancer, low antibody levels, etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what are the characteristics of Bloom Syndrome?

A

failure to repair DNA damage and abnormal cell cycle progression leads to:

  1. reduced T cell number
  2. reduced antiobdy levels
  3. premature aging
  4. cancer
  5. photosensticity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what is ataxia telangiectasia?

A

it’s due to a mutation in the ATM gene that is a signaling molecule in the cellular response to DNA damage

ATM protein activates p53 which is involved in DNA repair and regulating the cell cycle

failure to repair DNA damage leads to abnormal cell cycle progression and causes:

  1. reduced T cell number
  2. premature agining
  3. cancer
  4. neurodegeneration (which leads to ataxia)
  5. telangiectasia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what is Wiskott-Aldrich Syndrome inheritance?

A

x-linked

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what causes Wiskott-Aldrich Syndrome?

A

mutation in the WASP protein which is involved in reorganization of actin cytoskeleton of T cells

WASP plays important roles in T cell receptor-dependent activation of T cells

WASP is only expressed in leukocytes and megakaryocytes

this mutation leads to impaired T cell activation because the T cells are not able to form and maintain an immunological synapse and without a synapse, there’s impaired T cell activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what are the characteristics of Wiskott-Aldrich Syndrome?

A
  1. recurrent bacterial infections
  2. thrombocytopenia
  3. small platelets***
  4. cytoskeletal defects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

where is the WASP protein found?

A

WASP is expressed only in leukocytes and megakaryocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

what causes DiGeorge’s Syndrome?

A

it’s a translocation in chromosome 22 that effects T-box 1 protein

it’s caused by single-copy (hemizygous) deletion of a small piece of chromosome 22 (22q11) containing the T-box 1 (TBX 1) gene

TBX 1 is a transcription factor with unknown function. Single copy depletion of TBX 1 results in incomplete development of thymic epithelia

33
Q

what is DiGeorge’s Syndrom?

A

it’s a hemizygous deletion of 22q11 that leads to a single copy deletion of TBX1 gene

this causes failure of thymic epithelium development = poor T cell development since T cells develop in the thymus!

this leads to reduced T cell numbers and reduced humoral response

34
Q

what are the characteristics of DiGeroge Syndrome?

A
  1. SCID phenotype (mild)

2. Incomplete development of thymus (and parathyroids) = low T cell numbers

35
Q

what is MHCI deficiency?

A

it’s a mutation in the TAP transporter that takes proteins in the cytosol into the ER where they can bind to MHCI

if there’s a TAP mutation you have a problem because MHCI can’t generate a CD8 T cell response

this leads to chronic lung inflammation from recurrent viral infections in the lungs

36
Q

what are MHCI deficient patients more susceptible to?

A

sustained respiratory infections with certain viruses, leading to chronic respiratory inflammation

37
Q

what causes MHCII deficiency?

A

a mutation in CIITA trans-activator gene that turns on expression of MHCII

CIITA is a transcription factor that binds to the promoter region of the MHCII genes

38
Q

what is MHCII deficiency?

A

it’s a mutation in CIITA trans-activator gene that turns on expression of MHCII

if there a mutation in CIITA gene then there’s no expression of MHCII gene which means there’s no CD4 T cell response

MHCII is required for positive selection and activation of CD4T cells so without MHCII there’s no active CD4 T cells

without CD4 T cells, you’ll get recurrent infections because CD4 T cells are required for activation of naive B cells so there’s no antibody response

39
Q

what causes x-linked agammaglobulinemia?

A

mutation in Btk gene

Btk plays a key role in intracellular signaling from the B cell receptor, and is, thus, required for the differentiation of pre-B cells to B cells

so a mutatied Btk gene results in blockade of B cell development at the pre-B cell stage

40
Q

what is x-linked agammaglobulinemia?

A

mutation in Btk gene which leads to no B cells = recurrent infections

Btk plays a key role in intracellular signaling from the B cell receptor, and is, thus, required for the differentiation of pre-B cells to B cells

so people with XLA dont have antibodies!!!

41
Q

what are XLA patients more susceptible to?

A

extracellular bacterial pathogens

this is because XLA have no antibodies due to a block of B cell development – antibodies are needed to facilitate bacterial uptake by phagocytes via opsonization

42
Q

how do you treat XLA?

A

gamma globulin administration

systemic antibiotics

this is because their B cells never develop due to Btk mutation so they can’t make anitbodies

43
Q

what causes a CD40L deficiency?

A

a mutation in the CD40L gene

so then there’s no CD40L on T helper cells

upon initial exposure to an antigen, B cells produce IgM, which is much less efficient than IgG in neutralization and opsonization

antibody isotype switching from IgM to IgG, IgA, and IgE requires “help” from CD4 T cells

antigen-specific help is provided by molecular interaction between CD40 on B cells and CD40L on T cells

so CD40L gene mutation leads to defect in isotpe switching

44
Q

what is CD40L deficiency?

A

CD40L gene mutation

you need CD40L to be signal 2 in T cell-B cell interaction

without CD40L there is no isotype switching and you only have IgD and IgM

this leads to x-linked hyper-IgM syndrome and recurrent infections

sidenote: CD40 deficiency would clinically present the same exact way

45
Q

where is the CD40L gene located?

A

x chromomosome

46
Q

where is the CD40 gene located?

A

chromsome 20

47
Q

what is AID deficiency?

A

AID is involved in isotype switching and somatic hypermutation

so when there’s a mutation in the AID gene, there’s no somatic hypermutation or isotype switching which leads to recurrent infections

RAG-mediated VDJ recombination is responsible for the initial antibody repertoire of B cells in the BM

the secondary phase of diversification occurs in antigen-activated B cells via somatic hypermutation (leading to affinity maturation) and isotype switching – AID is required for both somatic hypermutation and isotype switching

patients with AID deficiency produce only IgM!!

48
Q

what is the difference between AID deficiency and CD40L deficiency?

A

AID deficiency has germinal center formation just without isotype switching

CD40L deficiency doesn’t even have germinal center formation because there isn’t good early T cell help and no T cell-B cell interaction to pair up and head to the germinal center

49
Q

what is X-linked hypohydrotic ectodermal dysplasia with ID?

A

mutation in NFκB essential modulator (NEMO) gene

ligation of of CD40 on B cells with CD40L on T cells triggers NFkB activation in B cells, leading to isotype switching

so if there’s a mutation in the NEMO gene there will be no isotype switching and you’ll have recurrent infections

50
Q

what is the clinical presentation of X-linked hypohydrotic ectodermal dysplasia with ID?

A

mutation in NEMO gene leads to no NFκB expression which is involved in isotype switching

there is abnormal sweat gland, hair, and tooth development

so they won’t be able to sweat, they’ll have crooked teeth and their hair won’t be well developed

51
Q

what causes X-linked lymphoproliferative syndrome?

A

XLP is a mutation in the SAP gene

SH2-domain containing gene 1A (SH2S1A) encodes a protein named SLAM-associated protein (SAP)

SAP interacts with cytoplasmic tails of SLAM on T cells and 2B4 (CD244) on NK cells, leading to the recruitment of Fyn, activation of the killing machinery, and inhibition of interferon γ production

so SAP mutation inhibits the ability of the SLAM receptor to induce killing of virus by NK and T cells

52
Q

what is X-linked lymphoproliferative syndrome?

A

it’s a mutation in the SAP gene – SAP is important in viral infections for regulation cytokine production, especially for NK and T cells

so a SAP mutation would mean you won’t be able to functionally signal to NK and T cells

there will also be a killing defect and high levels of INF-γ

high INF-γ levels will skew your TH1 responde and lead to uncontrolled EBV infections –> EBV will lead to B cell lymphoma

so SAP mutation inhibits the ability of the SLAM receptor to induce killing of virus by NK and T cells

in normal cells if killing is high, INFγ is low

53
Q

what is NK cell defect?

A

virally infected host cells are usually eliminated by NK cells and CD8 T cells

NK cells are looking for cells with low MHCI expression

herpes simplex virus (HSV) infection downregulates surface expression of MHC class I molecules, which are required for CD8 T cell activation

so HSV-infected host cells can be eliminated only by NK cells

so then, patients with NK cell defect exhibit increased susceptibility to HSV infection

54
Q

what causes leukocyte adhesion deficiency?

A

mutation of CD18 gene leads to impaired leukocyte migration and impaired phagocytosis

55
Q

what is LAD?

A

CD18 is β2 integrin

CD18 combines with CD11a, CD11b, and CD11c to form LFA-1, Mac-1/CR3, and CR4 receptors

these are responsible for complement and fibrinogen binding

LFA-1, Mac-1/CR3, and CR4 function as adhesion molecules mediating leukocyte adhesion to counter-receptors (ICAMs) and as complement receptors

without LFA1, Mac-1, and CR4 on your WBCs you’ll have issues with migration, and phagocytosis

this will cause tons of infections because WBC can’t get out of the blood to the tissues

56
Q

what causes chronic granulomatous disease?

A

it’s a mutation in the NADPH oxidase gene

57
Q

what is chronic granulomatous disease?

A

NADPH oxidase gene mutation

without NADPH oxidase there’s no oxygen radicals to kill pathogens that have been phagocytosed

eventually you get granulomas which are aggregates of phagocytic cells that can’t kill what’s inside them

so patients with chronic granulomatous disease have persistent infections with bacteria and fungi and develop granulomatous lesions

58
Q

why does X-linked SCID result in few, if any, T cells?

A

lack of IL2R and IL7R results in no T cell proliferation

59
Q

what immune defect does ADA deficiency cause?

A

no T or B cells

60
Q

what immune defect does PNP deficiency cause?

A

no T or B cells

61
Q

what immune deficiency does SCID cause?

A

no T cells

62
Q

what immune deficiency does DiGeorge syndrome cause?

A

thmic aplasia that causes variable numbers of t and B cells

63
Q

which abnormalities can cause SCID?

A
  1. ADA deficiency
  2. PNP deficiency
  3. γ chain deficiency
  4. autosomal DNA repair defect
64
Q

what immune deficiency does MHCI deficiency e cause?

A

TAP mutation that leads to no CD8 T cells

susceptible to chronic lung and skin inflammation

65
Q

what immune deficiency does MHCII deficiency cause?

A

lack of expression of MHCII leads to no CD4 T cells

66
Q

what is the specific abnormality and immune defect associated with Wiskott-Aldrich syndrome?

A

abnormality: x-linked defective WASP gene

immune defect: leads to defective anti-polysaccharide antibody and impaired T-cell activation responses

increased suceptibility to encapsulated extracellular bacteria

67
Q

what is the specific abnormality and immune defect associated with x-linked agammaglobulinemia?

A

abnormality: loss of Btk tyrosine kinase

immune defect: no B cells

susceptible to extracellular bacteria and viruses

68
Q

what is the specific abnormality and immune defect associated with X-linked hyper-IgM Syndrome?

A

abnormality: defective CD40L

immune defect: no isotype switching

suceptible to extracellular bacteria

69
Q

what is the specific abnormality and immune defect associated with common variable immunodeficiency?

A

abnormality: unknown

immune defect: defective IgA and IgG production

suceptible to extracellular bacteria

70
Q

what is the specific abnormality and immune defect associated with selective IgA?

A

abnormality: unknown, MHC linked

immune defect: no IgA synthesis

suceptible to respiratory infections

71
Q

what are NK cell defect patients suceptible to?

A

herpes virus

72
Q

what is the specific abnormality and immune defect associated with -linked lymphoproliferative syndrome?

A

abnormality: SH2D1A mutation

immune defect: inability to control B cell growth

suceptible to EBV and B cell tumors

73
Q

what is the specific abnormality and immune defect associated with ataxia telangiectasia?

A

abnormality: gene with PI 3-kinase homology

immune defect: T cells reduced

susceptible to respiratory infections

74
Q

what is the specific abnormality and immune defect associated with Bloom’s syndrome?

A

abnormality: defective DNA helicase

immune defect: T cells reduced

reduced antibody levels

susceptible to respiratory infections

75
Q

what is the specific abnormality and immune defect associated with LAD?

A

abnormality: defective CD18

immune defect: defective migration of phagocytes into infected tissues

76
Q

what is the specific abnormality and immune defect associated with chronic granulomatous disease?

A

abnormality: defective NADPH oxidase so phagocytes can’t produce superoxide

immune defect: impaired killing of phagocytesed bacteria

77
Q

what happens when there’s C1, C2, C4 deficiency?

A

immune-complex diseases

78
Q

what happens when there’s C3 deficiency?

A

susceptibility to capsulated bacteria

79
Q

what happens when there’s C5-C9 deficiency?

A

susceptibility to Neisseria

Immunity Week 3 (14 decks)

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