Brainscape's Knowledge GenomeTM

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


See full index

Micro and Immuno > Immunodeficiency > Flashcards

Immunodeficiency Flashcards

1
Q

congenital or primary immunodeficiency

A

immunodeficiencies due to genetic defects in one or more components of the immune response that result in increased susceptibility to infections

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

acquired or secondary immunodeficiency

A

non-genetic, develops in response to exogenous trauma or factors, e.g., malnutrition, treatment with immunosuppressive drugs (chemotherapy, prevention of transplant rejection, autoimmunity), bone marrow-derived cancers, infection (e.g., HIV)

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

what are some of the Immune System Abnormalities in Immunodeficiencies?

A
  • Components of innate immune response
  • Various stages of lymphocyte development/
    maturation
  • Specific responses of mature lymphocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Three main categories of Congenital Immunodeficiency Diseases

A
  • B cell deficiency
  • T cell deficiency
  • innate immune response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

mechanism behind chronic granulomatous disease

A
  • defect in production of reactive oxygen intermediates by phagocytes
  • can be due to mutations in genes encoding components of the phagocyte oxidase enzyme
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

mechanism behind leukocyte adhesion deficiency-1

A
  • absent or deficiency in expression of B2 integrins causing defective leukocyte adhesion-dependent functions
  • can’t bind to endothelium or T cells to APC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

mechanism behind leukocyte adhesion deficiency-2

A
  • absent or deficient expression of leukocyte ligands for endothelial E- and P-selectins, causing failure of leukocyte migration into tissues
  • binds to endothelium weakly
  • lack of good migration into site of infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

mechanism behind Chediak-Higashi syndrome

A
  • defective lysosomal function in neutrophils, macrophages, and dendritic cells, and defective granule function in natural killer cells
  • not able to kill microorganism
  • mutation in gene encoding a lysosomal trafficking regulatory protein
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe some of the Mutations in critical components of early lymphocyte development/ maturation pathways that result in defects in B and T cell maturation

A

…

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

molecules required for the development of common lymphoid precursor cells into Pro-B and Pro-T cells

A

γc= common γ chain
JAK3 = (signaling molecule)
ADA
PNP

*defect in any of these creates problems for development of B and T cells

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

molecules required for the development of Pro-B and T cells into Pre-B and T cells

A

Molecules associated with VDJ recombination (for antibody production or TCR function)

RAG1
RAG2
ARTEMIS

*defect in any of these creates problems for development of B and T cells

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

molecules required for the development of Pre-T cell into immature CD4 CD8 T cells

A

Pre-TCR checkpoint: CD3

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

molecules required for the development of mature CD8 and CD4 T cells

A

CD8+ = ZAP70, TAP1, 2
CD4+ = MHC Class II

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

molecules required for the development of mature B cells

A

Pre-BCR checkpoint for BTK

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

defects in innate immunity that can cause immunodeficiencies

A
  • cannot express B2 integrins: can’t bind to endothelium or T cells to APC
  • defect in E or P selectins: needed for trafficking of cells to infection
  • deficiency in complement cascade
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Severe Combined Immunodeficiencies (SCID)

A

Affects both humoral and cell-mediated immunity:
- Defects in cytokine signaling
- Defects in nucleotide salvage pathways
- Defects in V(D) J recombination
- Defective thymic development

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

mechanisms behind some of the forms of SCID

A
  1. Decreased T cells with normal or increased B cells but with reduced Ig ability: defect in common gamma chain; defective T cell maturation due to lack of IL-7
  2. Progressive decrease in T and B cells (mostly T): cells are poisoned because of ADA or PNP deficiency leading to accumulation of toxic metabolites in lymphocytes
  3. decreased T and B cells; reduced serum Ig: defective maturation of T and B cells; may be mutations in RAG genes and other genes involved in VDJ recombination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

oral symptoms of SCID

A

Candidiasis, viral infections, ulcerative stomatitis

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

Antibody Deficiencies

A
  • Agammaglobulinemias *Hypogammaglobulinemias/isotype defects *Hyper-IgM syndromes

*defects in B cell maturation

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

Decrease in all serum Ig isotypes and reduced B cell numbers is a defect in…

A

Pre-B receptor checkpoint defect; Btk mutation (Bruton tyrosine kinase); mutations in IgM (can’t isotype switch)

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

Selective IgA deficiency

A

Decreased IgA and association with increased susceptibility to bacterial infections and protozoa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

common variable immunodeficiency

A
  • decreased IgG (hypogammaglobulinemias)
  • normal or decreased B cell numbers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What would a mutation in CD40L (x-chromosome) or CD40 result in?

A

Defects in T helper cell-mediated B cell, macrophage, and dendritic cell activation; defects in somatic mutation, class switching, and germinal center formation; defective cell-mediated immunity

24
Q

Defects in T cells

A
  • Defects in MHC expression
  • Defective T cell signaling/activation
  • Defective thymic development
25
Q

Bare lymphocyte syndrome

A

defective MHC class II expression and deficiency in CD4+ cells; defective cell-mediated immunity and T-cell dependent humoral immune responses

26
Q

MHC Class I

A
  • mutations in TAP1 or TAP2 (responsible for shuttling antigens into APC mechanism)
  • results in decreased MHC Class I levels; reduced CD8+ T cells
27
Q

Wiskott-Aldrich syndrome

A
  • Defective T cell activation and leukocyte mobility
  • mechanism based on TCR-dependent actin-cytoskeletal rearrangements are defective because of mutations in WAS, an X-linked gene mutation in WIP
28
Q

DiGeorge Syndrome

A
  • decreased T cells; normal B cells; normal or reduced Ig
  • mutations in gene required for thymus development
29
Q

Distribution of primary immunodeficiencies

A
  • B cell defect make up 65%: this is because patient most likely to still survive
  • SCID makes up 15%: surprising
  • IgA deficiency by far most common
30
Q

statistics on HIV

A
  • ~37.9 million people living with HIV worldwide
  • ~1.7 million people become infected per year; ~75 million people have been infected with HIV total
  • 770,000 die per year, down from a high of 1.7 million per year in 2004; ~32 million have died total
  • 70% in Africa and 20% in Asia
31
Q

HIV transmitted through…

A

exchange of body fluids (e.g.,
blood, semen, etc):
- Sexual contact
- Mother-to-child transmission
- Infected blood or blood products

32
Q

HIV virus family

A

Lentivirus family of retrovirus: RNA genetic material - 2 strands reverse transcribed into double-
stranded DNA incorporates into host genome (provirus)

33
Q

HIV glycoproteins required for infection

A

gp120 and gp 41

34
Q

HIV enzymes required for viral replication

A

Reverse transcriptase, integrase, and viral protease

35
Q

Receptors required for HIV infection

A

CD4 and chemokine receptors, CXCR4 (T cells) and CCR5 (macrophages) required for infection; some HIV strains are macrophage-tropic, some are T cell-tropic (more virulent)

36
Q

HIV primarily infects what cells?

A

CD4 T cells, macrophages and dendritic cells

37
Q

HIV ___ Provirus can remain inactive for months-years, and activation (e.g., antigen, cytokines) of infected cells induces viral production

A

provirus

38
Q

HIV infection of cells occurs…

A

Infection of cells occurs directly by free viral particles or through fusion of infected and non-infected cells.

39
Q

HIV life cycle

A
  1. viral particles floating in serum binds to CD4 surface and chemokine receptor
  2. integrates into membrane and fuses with membrane
  3. viral material enters the cell
  4. in the cell, RNA in reverse transcribed from RNA into DNA
  5. upon activation, transcription of HIV genome occurs
  6. viral RNAs make proteases and other enzymes create the HIV core structure which gets incorporated into membrane

*provirus can reman latent for many years

40
Q

progression of HIV infection

A
  1. infection of mucosal tissue
    2 death of mucosal memory CD4 cells
  2. DC or draining of lymphatics takes It to lymph nodes where infection is then established
  3. spread of infection throughout whole body: viremia
  4. immune response: some antibodies formed and CTL induced: partial control of virus infection
  5. over time, establishment of chronic infection: clinical latency. More infections occur.
  6. AIDS: destruction of lymphoid tissue: depletion of CD4+ T cells
41
Q

clinical course of HIV

A
  • acute response within first few weeks
  • clinical latency over years
  • 200 or below CD4+ cells is AIDS: opportunistic infections develop from here
42
Q

Mechanisms of Immunodeficiency caused by HIV

A
  • Direct toxic effects of infection on CD4 T cells
  • Chronic activation of CD4 cells results in apoptosis
  • Infected CD4 cells can be killed by CTL or ADCC
  • Possible viral-mediated interference with CD4 function
  • Macrophages are not killed by HIV and may act as viral reservoir (virus enters through CCR5); may have impaired APC function and cytokine secretion
  • Dendritic cells are not killed by HIV and likely infect CD4 cells directly.
  • Follicular dendritic cells may act as viral reservoir and/or may be impaired and/or destroyed by virus
43
Q

What are the Direct toxic effects of HIV infection on CD4 T cells?

A
  • Viral production compromises plasma membrane, leading to lethal influx of Ca++ or osmotic lysis
  • Viral production compromises cellular protein synthesis
  • Non-cytopathic HIV infection activates inflammasome pathway, and induces cell death; can lead to recruitment of cells that then become infected.
  • HIV-induced fusion between cells results in cell death
44
Q

What is the Immune Response to HIV?

A
  • CD8 cells expand but provide only limited protection (primarily during acute phase); may be initially effective but result in virus that has lost specific CTL epitopes
  • CD4 cells help CD8 cells, and may also be directly cytotoxic.
  • Initial antibody response not neutralizing, later antibody response neutralizing (against gp120, critical for binding CD4) but cannot keep up with production of virus; only a small percentage of individuals develop high affinity neutralizing antibody to the critical CD4 binding site of gp140.
  • Elimination of CD4 cells severely limits immune response capacity over time
  • HIV has effective immune evasion strategies
45
Q

Mechanisms of Immune Evasion by HIV

A
  • HIV has extremely high mutation rate (error-prone reverse transcription) and can, therefore, evade immune response (most effective)
  • Viral epitopes may be shielded by N-linked sugars
  • HIV may downregulate Class I expression (less likely to be CD8 target)
  • Induce immune deviation: HIV may induce Th2 cytokine- producing cells that inhibit cell-mediated (Th1-mediated) activity
  • Impairs dendritic cell activity
  • May also induce/activate regulatory T cells
  • The latter two could also contribute to the compromised response to other microbes
46
Q

clinical features of acute HIV disease

A

fever, headaches, sore throat with pharyngitis, generalized lymphadenopathy, rashes

47
Q

clinical features of Clinical latency period of HIV

A

Declining blood CD4+ T cell count

48
Q

clinical features of AIDS

A

opportunistic infections: protozoa, bacteria, fungi, viruses, tumors

49
Q

Untreated oral manifestations in AIDS patients

A
  • Oral hairy leukoplakia (Epstein-Barr Virus, EBV)
  • Kaposi’s sarcoma(Human Herpesvirus 8, HHV-8)
  • Necrotizing periodontitis
  • Candidiasis (fungus)
50
Q

Treated AIDS patients oral manifestations

A
  • Human papillomavirus (HPV)
  • Caries
51
Q

what treatment mechanisms are helpful in HIV/AIDS?

A
  • reverse transcriptase inhibitors
  • protease inhibitors
  • Fusion or Entry inhibitors
  • integrase inhibitors
52
Q

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

A

nucleoside analogues that inhibit reverse transcriptase activity - several different types now available and used in combination (e.g., AZT)

53
Q

Non-Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NNRTIs)

A

bind directly to reverse transcriptase and inhibit its activity - several different types now available and used in combination

54
Q

Protease inhibitors

A

inhibit proteases that are required for protein processing into viral capsid and core proteins, and therefore, HIV replication

55
Q

Fusion or Entry inhibitors

A

prevent virus from binding or entering cells (target CD4 or CCR5 on cells or gp41 or gp120 on virus)

56
Q

Integrase inhibitors

A

interferes with integrase which is needed for HIV to insert its genetic material into cells

57
Q

what makes vaccines for HIV/AIDS very difficult?

A

ability of HIV to mutate; must elicit both cell-mediated and humoral response; other new approaches include gene therapy where antibody against HIV or a CD4/CCR5 fusion protein that blocks viral entry is expressed via viral vectors in individuals

Micro and Immuno (17 decks)

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