Type 1 Immunodeficiency

Front 1

What are the two types of primary immunodeficiency?

Back 1

Hereditary and congenital

Front 2

What is the most common primary immunodeficiency?

Back 2

Selective IgA deficiency

Front 3

Amongst which population is Selective IgA deficiency?

Back 3

Caucasians

Front 4

Which gender is more likely to be afflicted by primary immunodeficiency?

Back 4

Males

Front 5

Malfunction in these organs will lead to primary immunodeficiency.

Back 5

Soluble molecules (antibodies, cytokines)
Bone marrow precursor stem cells
Blood cells

Front 6

What other malfunction can lead to immunodeficiency?

Back 6

Malfunctions in signlling molecules, and signal transduction, and cell development.

Front 7

What age group is generally afflicted by primary immunodeficiency?

Back 7

Children.

Front 8

Diagnosis of a primary immune defiency based on what clinical symptoms.

Back 8

Increased frequency, severity and duration of an infection.
Susceptibility to opportunistic pathogens.

Front 9

The first immune defense to be breached:

Where would you find this?

Back 9

The skin.
Respiratory tract, GI tract, epidermis.

Front 10

Immune deficiency can be related to which cell type defects:

Back 10

Humoral immunity defects
Cellular immunity defects
Phagocytic defects
Complement defects.

Front 11

Primary immune deficiency is not only recognized by increased susceptibility but has other manifestations. (2)

Back 11

Increased incidence of cancer, and autoimmunity.

Front 12

Pathogenesis of Primary immunodeficiency: what clinical features are identifiable as primary immunodeficiency?

Back 12

Differentiation defects
Immunoregulatory abnormalities
Defective synthesis of specific protein
Enzyme deficiency

Front 13

What is the most common humoral immune defect?

Back 13

Transient lack of Ig production in the first 6-12 months of a newborn due to waning of maternal IgG.

Front 14

Selective IgA deficiency complication:

Back 14

When receiving blood transfusions, antibodies will be created against IgA. This can lead to severe anaphylactic reactions.

Front 15

How does IgA deficiency arise?

Back 15

B cell maturation arrest.
IgA bearing B cells do not differentiate to plasma cells

Front 16

Which subgroups in IgG deficiency are affected?

Back 16

IgG2, 4

Front 17

IgG deficiency is associated with what other type of deficiency?

Back 17

IgA deficiency

Front 18

IgG subgroup deficiency has a clinical manifestation of:

Back 18

Recurrent pyogenic infection.

Front 19

Common Variable Immunodeficiency occurs at what stage of life?

Back 19

2nd or 3rd decade of life

Front 20

CVI is a deficiency in what type of antibody:

Back 20

hypogammaglobulinemia- decreased IgG and at least IgM or IgA

Front 21

What is the most important Adult primary immunodeficiency?

Back 21

CVI- common variable immunodeficiency.

Front 22

Is there a gender bias?

Back 22

No, males and females are equally affected.

Front 23

What antibodies are present and at what concentration?

Back 23

IgG or IgM is present in low concentrations or absent
Low memory B cells
Abesent IgA or B cells
Low T cells (CD4+)

Front 24

Based on immunohistology, what cells express CD27?

Back 24

Memory B cells

Front 25

What cells express IgD but not CD27?

Back 25

Naive mature B cells

Front 26

What CD marks B cells?

Back 26

CD19

Front 27

CVI have an enlarged organ. Which one?

Back 27

Large Spleen.

Front 28

Since CVI is a primary immunodeficiency, which subgroup is it?

Back 28

Inheritable. Sporadic
Predisposition is caused by autosomal dominant inheritance.

Front 29

What are the gene defects in CVI?

Back 29

TACI, ICOS, CD19, BAFF-R

Front 30

What percent of patients die after the diagnosis of CVID?

Back 30

1/3

Front 31

What is used to estimate the time of death? (CVID)

Back 31

The percent of B cells

Front 32

The mean time of death with people of CVID.

Most likely cause of death in CVID.

Back 32

40-45 years old
Major single cause of death was lymphoma. Then chronic pulmonary infections.

Front 33

Bruton's X-linked Agammaglobulinemia differs from CVID in what manner?

Back 33

While CVID has some IgG present in the blood, XLA patients have NO gamma globulin. NO IgG/A/M

Front 34

When is XLA detected? (Age)

Back 34

After 6 months of birth.

Front 35

At what stage do B cells arrest in XLA?

Back 35

At the pre-B cell stage.

Front 36

What treatment is given to XLA patients?

Back 36

Antibiotics and IgG.

Front 37

What is the gene defect in XLA?

Back 37

Defect in Tec family called Btk. Failure to activate PLCgamma.
Maturation arrest at pre-Bcell stage.

Front 38

Depending on what event, females present with XLA?

Back 38

When the normal X chromosome is suppressed by X inactivation.

Front 39

XLA symptoms include:

Back 39

Enteroviral infections resulting in neurological symptoms

Weakness, hearing loss, lethargy, seizures, coma.

Front 40

Hyper-IgM syndrome

Back 40

Marked by elevated IgM levels with low IgG, and IgA, and IgE

Front 41

X-linked hyper-IgM syndrome is caused by defect in what cell? Through what molecule is this cell affected?

Back 41

T cell defect, due to defect in CD40L.
CD4+ cells cannot induce isotype switch and formation of germinal centers.

Front 42

How would you diagnose hyper-IgM syndrome?

Back 42

Lymph node biopsy and see if the germinal center exists.

Front 43

Loss of T-cells decreases what chemokine?

Back 43

INF gamma is decreased and IL-12. The lack of INF gamma leads to decrease in macrophage activation.

Front 44

Another cause of Hyper-IgM syndrome:
List both the original cause and the other cause.

Back 44

Loss of NEMO which induces NFkB secreation

Original: mutation in CD40L leads to lack of B cell activation.

Front 45

NEMO is in what pathway of NFkB production?

Back 45

In canonical pathway. NEMO holds the cytoplasmic TFs in the cytoplasm. P-NEMO leads to rele

Front 46

The third cause of Hyper-IgM syndrome:

Back 46

AID (activation induced cytidine deaminase) deficiency. AID is required for isotype switch.

Front 47

DiGeorge Syndrome:

Back 47

Organ development defect.
Absent thymus, and para-thyroids.
Congenital heart disease

Front 48

What is the cause of DiGeorge Syndrome?

Back 48

Deletion of a single copy of TBX1 gene.

Front 49

SCID- 5 types.

Back 49

X-linked SCID
Adenosine deaminase deficiency
Omenn syndrome
Bare Lymphocyte syndrome
CD8 lymphopenia

Front 50

X-linked SCID caused by:

Back 50

Defect in gamma-c chain of IL-2 receptor. Improper response to ILs.

Front 51

Ommen Syndrome (SCID)

Back 51

No rearrangment of B cell receptors.
Mutations in RAG-1 and RAG-2.

Front 52

Ommen Syndrome, unlike the other SCID related diseases:

Back 52

Have normal or increased T cell counts. These T cells are of only one restricted repertoire.
No B cells.
Graft-versus host phenotype.

Front 53

Bare lymphocyte syndrome: 2 types.

Back 53

1)- BLS II: lack of MHC class II molecules
2)- BLS I: lack of MHC class I molecules.

Front 54

BLS II:

Back 54

Lack of proper CD-4 T cells due to no selection in the thymic epithelial levels.

Front 55

BLS I:

Back 55

CD-8 cells will not have Alpha:Beta T cell receptor.
Defects in TAP1, TAP2.

Front 56

CD8 Lymphopenia.

Back 56

Lack of CD8+ cells.

Front 57

Wiskott-Aldrich Syndrome:
Response to antigen.

Back 57

Defect in WASP. Lack of structural integrity of cells.
Cannot respond to polysaccharide antigens.

Front 58

Ataxia Telangiectasia:

Back 58

Lack of Hassall's corpuscles in hypoplastic thymus. Defect in cellular responses to DNA damage.

Front 59

Chronic Granulomatous Disease:

Back 59

Genetic mutation in the NADPH oxidase genes. Failure to activate the oxidative bursts in macrophages.

Front 60

Treatment of Chronic Granulomatous Disease:

Back 60

INvolves Immunization, antibiotics, IFN gamma, and Surgical drainage.

Front 61

Leukocyte adhesion deficiency.

Back 61

Neutrophils cannot migrate towards inflammatory stimuli. Absent glycoproteins on neutrophil.

Front 62

Complement Component Deficiency: (which complement components can be affected?)

Back 62

C2
C2 and C4
C5/C6/C7/C8
C1 esterase inhibitor.

Front 63

Lack of C2 and C4 is associated with what infections?

Back 63

Pyogenic infection and connective tissue disease.

Front 64

Lack of C5/C6/C7/C8 is associated with what infections?

Back 64

Neisseria infection.

Front 65

At what age are complement defects usually detected?

Back 65

18 months- adulthood.

Front 66

Physical examination of primary immunodeficient patients reveal:

Back 66

Organomegaly
skin leasions.

Front 67

Therapy of primary immunodeficient:

Back 67

IVIG: intravenous Ig therapy.
SCIG: subcutaneous Ig therapy.

Front 68

Treatment of cellular defects causing primary immunodeficiency:

Back 68

Bone marrow transplants (grafts)
IL-2: for T cell function
Gene therapy: ADA deficiency

Front 69

Treatment of phagocytic cell defects: (4)

Back 69

Administer prophylactic antibiotics
Avoid giving viral vaccines
Administer IFN gamma for CGD patients
Bone marrow transplants.

Front 70

Epidermodysplasia verruciformis:

What type of cancer? How is it caused?

Back 70

Squamous carcinoma.

Immunodeficient response to viruses such as HPV.

Front 71

Epidermodysplasia verruciformis have a lower production of what IL?

Back 71

IL-10

Front 72

Instead of thinking that diseases stand alone.

Back 72

Diseases are a manifestation of a lack of an immune response.