Immunodeficiency diseases

Question 1

Difference between primary and secondary immunodeficiency diseases

Answer 1

Primary: inherited defects in different components of the immune system
Secondary: due to environmental factors such as immunosuppressive drugs

Question 2

SCID

Answer 2

• RAG1 RAG2
• immune defect: no gene rearrangement in B and T cell
• suscepibility: all types of infection

Question 3

Omenn syndrome

Answer 3

• RAG 1, RAG 2, artemis
• immune defect: impaired RAG function
• susceptibility: all types of infection

Question 4

Bare lymphocyte syndrome

Answer 4

• TAP1, TAP2
• immune defect: low MHC class 1 expression
• susceptibility: respiratory viral functions

Question 5

Complete DiGeroge’s syndrome

Answer 5

• no affected genes known
• immune defect: absence of the thymus and T cell
• susceptibility: all types

Question 6

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy

Answer 6

• AIRE
• reduced T cell tolerance to self antigens
• autoimmune diseases

Question 7

IPEX

Answer 7

• FOXP3
• lack of regulatory T cells and peripheral tolerance
• autoimmune disease

Question 8

Rare primary immunodeficiency diseases

Answer 8

• caused by exceedingly rare mutant alleles of immune genes without selective benefit for the individuals who carry them
• found in small or culturally isolated populations
• help recognize novel forms of immunodeficiency syndrome
• other less dramatic effects in other immune genes are more frequent

Question 9

Primary immunodeficiency diseases

Answer 9

• dominant
• recessive
• x linked

Question 10

____ and ___ mutations in the INF-gamma receptor cause disease of different severity

Answer 10

Recessive; dominant
- INF- gamma: major cytokine that activates macrophages, make by NK, Th1 CD4 and CD8 T cells (important defense against intravesicular bacteria)

Question 11

X linked agammaglobulinemia

Answer 11

B cells do not develop beyond pre-B cell stage
- Bruton’s tyrosine kinase protein that contributes to intracellular signaling form the BCR involved in growth and differentiation of pre-B cells

Question 12

Antibody deficiency (B cells)

Answer 12

Leads to an inability to clear extracellular bacteria

Question 13

Antibody deficiency (T cell help)

Answer 13

X linked hyper IGM syndrome - absence of CD40L, poor development of GC and isotype switching

• no specific antibody is made against T cell dependent antigens
• IgG, IgA, IgE are virtually absent, but IgM is extremely high
• treat with regular injections of gamma globulin

Question 14

Defects in _____ result in enhanced susceptibility to bacterial infection

Answer 14

Phagocytes

Question 15

SCID T cell function

Answer 15

Do not make T cell dependent antibody responses nor cell mediated immune responses

• T cell development and function depend on the action of many proteins, so SCID phenotype can arise from defects in any gene
• ADA OR PNP deficiences

Question 16

X linked deficiency

Answer 16

Common gamma chain syndrome, cytokine signaling is affected

- severe: affected infants survive if kept isolated

Question 17

Wiskott-Aldrich syndrome

Answer 17

Impairment of platelets and T cells
- WASP protein involved in cytoskeletal reorganization of T cells, T cell cannot deliver cytokines and signals to B cells, macrophages, etc

Question 18

Bare lymphocyte syndrome

Answer 18

Lack of MHC class 1-2
- class 1 absence is less severe

Question 19

HIV infects

Answer 19

CD4 T cells, macrophages, and DC

Question 20

HIV life cycle in humans

Answer 20

Virion binds to CD4 and coreceptor on T cell –> viral envelope fuses with cell membrane and viral genome enters cell –> reverse transcriptase copies viral RNA genome into double stranded cDNA –> viral cDNA enters nucleus and integrates into host DNA –> T cell activation induces some transcription of provirus –> RNA transcripts are spliced to allow synthesis of early proteins Tat and Rev –> Tat amplifies transcription of viral RNA and Rev increases transport of RNA to cytoplasm

Question 21

Depletion of CD4 T cells

Answer 21

Flu-like disease (infection) –> asymptomatic phase (seroconversion) –> symptomatic phase –> AIDS

Question 22

Immune response to HIV

Answer 22

• HLA polymorphism: influences progression of AIDS
• KIR polymorphism: influences progression of AIDS suggesting that the type of NK cell response at the start of HIV infection affects the relative success of the subsequent adaptive response
• genetic deficiency of the CCR5 co receptor for HIV confers resistance to infection

Question 23

High mutation rate

Answer 23

Seen in HIV and other retroviruses

- complicates vaccines and limits effectiveness of antiviral drugs

Question 24

Potential targets for anti-HIV drugs

Answer 24

• viral reverse transcriptase that is responsible for the provirus synthesis
• viral protease that cleaves viral proteins

Question 25

Highly active anti-retroviral therapy

Answer 25

Destroys the entire population of viruses before any one of the them has accumulated enough mutations to resist all the drugs

Question 26

For protease inhibitors, resistance develops in ____

Answer 26

A few days

Question 27

Mechanism of antiviral drugs (HAART)

Answer 27

Productive infection of CD4 T cells accounts for more than 99% of virus in plasma –> infected cells are short-lived, so HIV must continuously infect new cells –> if virus production is blocked by a drug, the virus is rapidly cleared –> CD4 T cell numbers rapidly increase, replacing those lost by infection

Question 28

HIV infection leads to _____ and death from ______

Answer 28

Immunodeficiency; opportunistic infections

Question 29

Inherited immunodeficiencies are caused by a defect in one of the genes necessary for

Answer 29

Development or function of the immune system

Question 30

Immunodeficiencies can also be acquired as the result of ___

Answer 30

Infection