Lecture 1 - Immunodeficiencies (Dr. Powell)

Question 1

What are Primary/Congenital Immunodeficiencies?

Answer 1

genetic defects that result in an increased susceptibility to infection

1/500 ppl in US affected

Question 2

How do secondary/acquired immunodeficiencies develop?

Answer 2

1. malnutrition
2. disseminated cancer
3. immunosuppressive drugs
4. infection of cells of the immune system

Question 3

__________ are conserved across widely diverse species and are part of the ______ immune system.

Answer 3

Toll-Like Receptors, innate

Question 4

What can predict the type of immunodeficiency a patient has?

Answer 4

The types of recurring infections that they suffer from

Question 5

Deficient ________ immunity usually results in infections by PYOGENIC bacteria.

Answer 5

humoral

Question 6

If HUMORAL immunity is compromised, which type of infection will a patient get?

Answer 6

infection by PYOGENIC bacteria

Question 7

What is another names for X-linked Agammaglobulinemia (XLA)?

Answer 7

Bruton’s Agammaglobulinemia

Question 8

X-linked Agammaglobulinemia (XLA) is characterized by…

Answer 8

1. all antibody isotypes are very low
2. circulating B cells are absent
3. a FEW Pre-B cells are in bone marrow
4. T cells are normal.

Question 9

How is lymphocyte maturation affected by X-linked Agammaglobulinemia?

Answer 9

BRUTON TYROSINE KINASE nonfunctional

-important for Pre-B cell expansion and maturation into Ig-expressing B cells

Question 10

Why are boys with X-linked Agammaglobulinemia healthy up until they are 6-9 months of age?

Answer 10

Passive immunity (IgG antibodies) from their mothers

Question 11

Characterize X-linked immunodeficiency with hyper IgM

Answer 11

B cells present
low IgG, IgA, and IgE
high IgM
lymphoid hyperplasia (unlike boys w/ XLA)

Question 12

Why do boys with X-linked immunodeficiency with hyper IgM have lymphoid hyperplasia?

Answer 12

They have B cells, but they only make IgM.
CLASS SWITCHING DEFECT
Just keep making antibodies b/c we need all 5 classes, but it builds up as the default IgM b/c class switching doesn’t occur.

Question 13

Which specific receptor is absent in X-linked immunodeficiency with hyper IgM?

Answer 13

CD40 of T-cells
   -normally tells the B cells to class switch

Question 14

What are two examples of deficient humoral immunity?

Answer 14

1. X-linked Agammaglobulinemia (XLA)
   
   • no B cell maturation
2. X-linked immunodeficiency with hyper IgM
   
   • B cells, but no CD40 on T cell to initiate class switching

Question 15

What is the routine treatment for deficient humoral immunities?

Answer 15

1. prophylactic antibiotics and/or
2. gamma-globulin therapy

both give passive immunity

Question 16

Deficient _______________ usually results in increased susceptibility to viruses and other intracellular pathogens

Answer 16

Cell-mediated immunity

Question 17

If your cell-mediated immunity is deficient, what will you be susceptible to?

Answer 17

viruses and other intracellular pathogens

Question 18

Tx for _______ deficiencies are routine, but Tx of _________ deficiencies are few.

Answer 18

humoral = routine Tx
Cell-mediated = few Tx (low survival rate beyond infancy/childhood)

Question 19

What is a patient w/ DiGeorge’s syndrome missing?

Answer 19

Thymus

Question 20

Characteristics of DiGeorge’s syndrome

Answer 20

• no thymus
• decreased T-cells
• increased B -cells, but they need T cells to fxn well
• most infants die; survivors are mentally retarded

Question 21

What syndrome is clinically similar to DiGeorge’s syndrom?

Answer 21

Fetal alcohol syndrome

Question 22

What conditions are due to deficiencies in the cell-mediated immune system?

Answer 22

1. DiGeorge’s syndrom

2. X-linked recessive Severe Combined Immunodeficiency Diseasse (SCID)

Question 23

What does SCID stand for?

Answer 23

X-linked recessive Severe Combined Immunodeficiency Disease (SCID)

Question 24

SCID involves B and T cells

Answer 24

True

diarrhea, infections, pneumonia, otitis (middle ear infections), sepsis, in first few months of life.

Question 25

Bubble Boy had _____

Answer 25

SCID
could go outside the bubble after a bone marrow transplant from sister
viral infection in bone marrow later caused him to die

Question 26

XSCID
_____ T cells
______ NK cells
______ B cells

Answer 26

Few or no T cells
Few or no NK cells
Many B cells
-but don’t produce Ig normally, even after T-cell reconstitution via bone marrow transplant

Question 27

What are the two goals of treatments for immunodeficiencies?

Answer 27

1. minimize and control infections

2. replace defected or absent component of the immune system by adoptive transfer and/or transplantation

Question 28

Tx for agammaglobulinemic patients

Answer 28

passive immunization w/ pooled IgG (gamma globulin)

life-saving

Question 29

Tx for SCID & other similar diseases

Answer 29

bone marrow transplant

Question 30

HIV is an ______ immunodeficiency disease

Answer 30

secondary/acquired

Question 31

Cellular reservoirs of HIV (3)

Answer 31

1. Activated CD4+ cells
2. Resting/Memory CD4+ cells
3. Macrophages

Question 32

HIV leads to ____-

Answer 32

AIDS
destruction of lympoid tissue
depletion of CD4+ cells

Question 33

Which cells are depleted w/ AIDS?

Answer 33

CD4+