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Immunology Test #2 > Immunodeficiency > Flashcards

Immunodeficiency Flashcards

1
Q

Three broad scenarios in which people fail to mount an effective immune response.

A
  1. Congenital Immunodeficiency
  2. Pathogens incapacitate or evade immune system
  3. Host Conditions
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2
Q

Examples of ways pathogens may incapacitate of evade the immune system?

A

HIV, Multiple serotypes, mutations, gene conversion, hiding in dormant state, blocking immune response, auperantigens

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3
Q

Examples of host conditions that trigger immunodeficiency

A 
Pregnancy
Stress
Malnutrition
Cancer
Aging
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4
Q

Three general signs of Immunodeficiency diseases

A
  1. Chronic Infections of Opportunistic Pathogens
  2. Inflammatory diseases due to persistent infection
  3. High incidence of cancer
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5
Q

You are immunodeficient if you have defects in….

A 
TCR activation signalling molecules
Immune cell TFs
Mol/Organs of lymphocyte development
Antigen presentation
phagocyte function
cytokines/co-stimulators
Migration and Adhesion
Complement
DNA recombination/metabolism
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6
Q

Laboratory tests to assess T cell function?

A 
Enumeration (Flow Cytometry)
Functional Assays (Mitogen Resp., MLR, DTH Skin Tests)
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7
Q

Laboratory Tests to assess B cell function?

A

Enumeration

Circulating Ab levels

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8
Q

Lab tests to assess Macrophage function

A 
Enumeration
Functional Assays (Nitroblue tetrazolium)
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9
Q

Lab tests to assess complement

A

Direct measurement of complement components

Complement hemolysis assay

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10
Q

Three Primary B cell immunodeficiencies

A

X Linked Agammaglobulinemia (BTK Deficiency)
Common Variable Immunodeficiency (Acquired hypogammaglobulinemia)
Selective IgA dficiency (most common immunodefic.)

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11
Q

Three minor B cell immunodeficiencies

A

Transient hypogammaglobulinemia of Infancy
Selective deficiency of IgG subclasses
Immunodef. with hyper IgM

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12
Q

Primary T cell immunodeficiencies?

A

COngenital thymic aplasia (Digeorge’s or 3rd and 4th Phar Arch syndrome)

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13
Q

Two primary Combined B and T cell deficiencies (SCID)

A

X linked combined immunodef (defect of all cyto. receptors)

Adenosine Deaminase Deficiency

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14
Q

Less common causes of SCID?

A

Purine nucleoside phosphorylase def.
TCR immunodeficiency
MHC Class I or II Def.
Defective IL-2

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15
Q

Asplenia

Gene. Defect. Susceptibility.

A

Unknown
Absence of Spleen
Encapsulated extracellular Bacteria

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16
Q

C3 def.

Gene. Defect. Susceptibility.

A

C3
Lack of C3
Recurrent Infection with G- Bacteria

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17
Q

Factor I def.

Gene. Defect. Susceptibility.

A

CFI
Absence of Factor I, Depletion of C3
Encapsulated Bac

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18
Q

Look through the table in the powerpoint

A

I don’t care enough to type all of this out right now.

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19
Q

Immune defect in Paroxysmal nocturnal hemoglobulinuria

A

Lack of complement-regulatory proteins DAF, HRF, and CD59

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20
Q

Gene affected in chronic granulomatous disease?

A

NOX1 (NADPH Oxidase)

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21
Q

Genes potentially affected in Hyper-IgM deficiency

A

Activation induced cytidine deaminase
CD40
CD40L
IKBKG

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22
Q

Immune defect in Omenn Syndrome

A

Impaired VDJ Recombination

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23
Q

Immune defect in MHC Class I def.

A

Low MHC Class I Expression

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24
Q

Immune defect in X linked Agammaglobulinemia

A

B cells blocked at pro-B cell stage

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25
Q

Immune defect in Complete Digeorge Syndrome

A

Absence of Thymus/T cells

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26
Q

Immune defect in IPEX

A

Lack of Regulatory T cells and peripheral tolerance

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27
Q

MHC Class I and MHC Class II

Deficiency of which causes SCID?

A

Class II Def = SCID

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28
Q

Bubble Boy’s SCID was caused by…

A

Deficiency of Common gamma chain (CD132)

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29
Q

What is Common Gamma Chain?

A

Cytokine receptor subunit common to receptors for…

IL2, IL4, IL7, IL9, IL15, and IL-21 Receptor

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30
Q

What B cell immunodeficiency is most common?

What happens?

A

Selective IgA

Increased Respiratory Infections

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31
Q

X linked Agammaglobulinemia is caused by…

A

A defect in Bruton’s agammaglobulinemia tyrosine kinase (btk)
Causes Failure in B cell development

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32
Q

Three primary phagocyte deficiencies

A

Neutropenia
Chronic Granulomatous Disease
Leukocyte Adhesion Deficiency

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33
Q

Functional effect of Leukocyte Adhesion Deficiency

A

Defective Migration of Monocytes and Neutrophils to infected tissues.

Defective Uptake of opsonized pathogens

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34
Q

Functional effect of Chronic Granulomatous Disease

A

Defective respiratory burst

Phagocytes can’t kill pathogens

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35
Q

Primary complement deficiencies of Classic Pathway

A

C1, C4, C2, C3

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36
Q

Primary complement deficiencies of Alternative Pathway

A

Factor D, Properdin

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37
Q

Primary complement deficiencies of MAC

A

C5-9

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38
Q

Primary complement deficiencies of regulator proteins

A

Factors H, Factor I, C1 inhibitor hereditary angioedema

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39
Q

Problems seen in C1, C2, and C4 deficient?

A

Immune complex clearing

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40
Q

Problems seen in C3 deficiency

A

Major Immunodeficiency

Can’t opsonize

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41
Q

Problems seen in C5-C9 deficiency

A

Loss of Membrane Attack

42
Q

Problems seen in Factor D, Properdin deficiency?

A

Can’t make and stabilize C3 convertase of the alt. pathway

43
Q

How do we fix immunodeficiency?

A

Bone Marrow Transplant

44
Q

Why is a high degree of HLA matching required to do a bone marrow transplant

A
  1. To prevent alloreactions (GvH disease) and rejection

2. For effective presentation of antigen to donor cells

45
Q

Five categories of secondary immunodeficiencies

A
  1. Drug/Radiation Induced
  2. AIDS
  3. Nutritional Deficiency
  4. Autoimmune DIsease
  5. Other (Postviral, chronic infection, cancer)
46
Q

Common drug induced immunodeficiency?

A

Steroids

47
Q

Nutritional deficiencies associated with immunodef.?

A

Protein, Calorie, Biotin, B12, Iron, Vit A, Zinc

48
Q

HIV. Mechanism of Immunodeficiency.

A

Depletion of CD4 Helper T cells

49
Q

Protein-Calorie Malnutrition. Mechanism of Immunodeficiency.

A

Metabolic dearrangements inhibit lymphocyte maturation and function.

50
Q

Irradiation and Chemotherapy treatments

A

Decreased bone marrow precursors for leukocytes

51
Q

Cancer metastases to bone marrow

A

Reduced site of leukocyte development

52
Q

Removal of spleen

A

Decreased phagocytosis of microbes

53
Q

Describe the progression of AIDS (6 Steps)

A

Infection
Viremia
Immune Response to HIV
Temporary Reduction of Virus Infected CD4
Gradual decrease in CD4 Ts over 2-15 years
AIDS

54
Q

Lab determinant of AIDS?

A

CD4 T cell count drops below 200

55
Q

HIV enters through binding to what on the host?

A

CD4 and CCR5 or CXCR4

56
Q

What state must a T cell be in to become infected with HIV

A

Activated

Needs NF-kB for RNA transcription

57
Q

How do AIDS patients typically die?

A

Secondary Infection

58
Q

What is an M trophic virus?

A

Infects macrophages, DCs, and some Ts through CCR5 (early stage virus)

59
Q

What is a T trophic virus?

A

Infection T cells through CXCR4 (late stage virus)

60
Q

Does the switch from M trophic to T trophic occur in all cases of HIV?

A

It occurs in approx. 50%

61
Q

Two early proteins of HIV?

What do they do?

A

Tat and Rev

Increase transcription of viral RNA and RNA trans to cyto

62
Q

Some populations have mutant ______ that lends resistance to HIV

A

CCR5

63
Q

Progression of HIV infection is affected by what two genotypes

A

HLA-B

KIR3DL1/S1 (involved in NK activation)

64
Q

Common opportunistic parasites

A

Toxoplasma
Cryptosporidium
Leishmania
Microsporidium

65
Q

Common opportunistic bacteria

A

Mycobacterium

Salmonella

66
Q

Common opportunistic fungi

A

Pneumocystis carinii
Cryptococcus neuformans
Candida

67
Q

Common opportunistic viruses

A

Heres
CMV
VZV

68
Q

Common opportunistic cancers?

A

Kaposi’s
Non-Hodgkin’s
Primary lymphomas of the brain

69
Q

What makes HIV so bad?

A

High mutability and slow progression
Targets CD4
Single drugs are only transiently effective

70
Q

How does HIV manage to evade host response by rapid mutation

A

Error prone reverse transcriptases allow variance

Selection for variants without epitopes for Immune syst.

71
Q

Example of genetic variations within species preventing long term immunity

A

90 serotypes of strep pneumonia

72
Q

How does influenza escape from immune response?

A

Mutation and recombination

73
Q

Antigenic Shift –

Antigenic Drift –

A

Shift – Recombination/Swapping RNA, severe pandemics

Drift – Little genetic changes, mild/limited epidemics

74
Q

How do tyypanosomes and gonorhea escape from immune response?

A

Gene conversion to change surface antigens

75
Q

How does Herpes virus escape from immune response?

A

It hides in the dormant state in the nerves

76
Q

Whats so great about hiding from the immune system in a neuron?

A

Neurons have low levels of MHC I

77
Q

Two specific mechanisms for blocking antigen procesing and presentation?

A

Inhibition of MHC Class I upregulation of IFN-g

Inhibition of peptide transport by TAP

78
Q

How does Vaccina inhibit humoral immunity?

A

Virally encoded complement control protein

Inhibits complement activation of infected cell

79
Q

How does Vaccina inhibit inflammatory response?

A

Virally encoded soluble cytokine receptor

Blocks effects of cytokines by inhibiting their interaction with host receptors

80
Q

How does herpes simplex and CMV block antigen processing/presentation?

A

Inhibition of MHC Class I expression

Causes impaired recog. by CD8 T cells

81
Q

What does Herpes Simplex do to TAP to alter antigen processing and presentation?

A

Inhibition of Peptide Transport by TAP

Blocks Peptide Association with MHC I

82
Q

How does Epstein-Barr virus immunosuppress the host

A

Virlaly encoded IL10 homolog

Inhibits Th1 lymphocytes, inhibits IFN-g

83
Q

How does tuberculosis subvert the immune system

A

Prevents phagolysosome fusion

84
Q

How does listeria subvert the immune system?

A

Escapes phagolysosome

85
Q

How does Syphilis subvert the immune system?

A

Coats itself with human proteins

86
Q

How does Stephylococci subvert the immune system?

A

Production of Superantigens

87
Q

How does leprosy subvert the immune system?

A

Induces Th2 response to evade TH1 CMI response

88
Q

Effect of superantigens?

A

Induce poly-clonal T cell activation, inhibiting antigen-specific immunity
High Cytokine Levels lead to patient going into Shock

89
Q

How does SLP7 (stephylocccal superantigen like protein 7) work?

A

SSLP7 binds C5 and IgA, blocking the bacteria from opsinization

90
Q

Problems of elderly immunodeficiency

A

Frequent Infections

Ineffective Vaccinations

91
Q

Potential solutions for immunodeficiency in the elderly?

A

Almost none.
Administration of cytokines (IL2, 7, 10, leptin, GH, etc.)
New adjuvanted vaccine formulations for effective antigen presentation

92
Q

In pregnancy, immunity is actively suppressed by secretion of….

A

alpha-fetoprotein
IL-10
TGF-beta

93
Q

How do trophoblasts reduce their likelihood of immune rejection

A

Don’t express MHC I and II

94
Q

What tends to happen to auto-immune diseases in pregnancy? Exception to the rule?

A

They tend to be suppressed, with a rebound postpartum

Systemic Lupus Erythematosus is exacerbated in pregnancy

95
Q

What is hemolytic disease of the newborn?

How is it treated?

A

Anti-RhD (IgG) antibodies of the mother cross the placenta

Give mom anti-RhD antibodies during pregnancy/immediately post-delivery

96
Q

Why doesn’t a Type O mother reject a Type A fetus?

A

IgM antibodies can’t get across the placenta

97
Q

Two types of immunosuppressive drugs

A

Cycle-Nonspecific

Cycle-Specific

98
Q

Examples of Cycle Non-specific immunosuppressive drugs?

A

Radiation, Corticosteroids, NSAIDS, cyclosporins

99
Q

Examples of Cycle specific immunosuppresive drugs?

A

Cyclophosphamide
Chlorambucil
Azathioprine
Methotrexate

100
Q

Two types of pathologically induced immunosuppression?

A

Immunodeficient Diseases

Disease-Induced Anergy

Immunology Test #2 (8 decks)

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