Diseases Of Immunity (Lecture 2)

Question 1

Defect in the Beta chain of CD11/18

Answer 1

Leukocyte Adhesion Deficiency 1
CD11/CD18: Integrin Beta 2 (LFA-1/MAC-1) on neutrophils

Question 2

• The fucose-containing ligand (binds to E- and P-selectins)
• Deficiency in this ligand will lead to what disease?

Answer 2

• Sialyl-Lewis X
• Leukocyte Adhesion Deficiency Type 2

Question 3

What is the deficiency in Chediak-Higashi Syndrome

Answer 3

Dysfunctional gene for LYST cytosolic protein (regulated lysosomal trafficking)

Characterized by defective fusion of phagosomes and lysosomes

Question 4

What are the gene defects in the following Chronic Granulomatous Disease:
1. X-linked
2. Autosomal recessive

Answer 4

1. gp91phox : membrane bound phagocyte oxidase
2. p47phox and p67phox : cytoplasmic phagocyte oxidase

Question 5

The name of this disease comes from the macrophage-rich chronic inflammatory reaction that tries to control the infection when the initial neutrophil defense is inadequate

• leads to collections of activated macrophages that wall off the microbes, forming granulomas

Answer 5

Chronic Granulomatous DIsease

Question 6

Defect that causes recurrent herpes simplex encephalitis

Answer 6

Defects in TLR signaling

Defect in TLR 3 - receptor for viral RNA

Question 7

Causes destructive bacterial pneumonia

Answer 7

Defects in TLR Signaling

Defect in MyD88

MyD88 is a downstream adaptor protein for multiple TLRs

Question 8

What are the diseases linked to Defects in complement regulatory proteins

Answer 8

1. Hereditary angioedema
2. Paroxysmal nocturnal hemoglobinuria
3. Hemolytic uremic syndrome
4. Age-related macular degeneration

Question 9

What defects in the complement system is associated with pyogenic infections

Answer 9

Defects in the Alternative pathway (properdin and factor D)

Question 10

Most common complementary deficiency

Answer 10

Deficiency in C2

Question 11

Associated with increased susceptibility to recurrent Neisseria infections

Answer 11

Defects in the late-acting complement components (C5, 6, 7, 8, and 9: Membrane attack complex)

Question 12

Most common autosomal recessive deficiency in SCID (Sever Combined Immunodeficiency)

Answer 12

Deficiency in ADA enzyme (Adenosine Deaminase)

Question 13

Defect Causes of Autosomal Recessive SCID

Answer 13

1. Adenosine deaminase (ADA)
2. Recombinase-activating genes (RAG)
3. JAK3 - intracellular kinase
4. T-cell receptor kinases
5. Components of calcium channels

Question 14

What autosomal recessive SCID has similar pathogenesis as X-linked SCID

Answer 14

Defect in JAK3 signaling

Question 15

Adaptive immunodeficiency that has:
- severely defective T-cell
- defective NK cell
- normal level of B-cell
- decreased synthesis of B-cell

Answer 15

X-linked SCID

Question 16

Immunodeficiency characterized by the failure of B-cell precursors (pro-B cell and pre-B cells to develop into mature B-cells)

Due to mutations in Bruton tyrosine kinase (BTK)

Answer 16

X-linked Agammaglobulinemia (Bruton Agammaglobulinemia)

Question 17

What are the T-cell and B-cell characteristics of classic X-linked agammaglobulinemia

Answer 17

1. Absent plasma cells
2. Decreased/absent B cells
3. Decreased Immunoglobulin
4. Normal pre-B cell levels in bone marrow (CD19)
5. Underdeveloped germinal centers lymphoid tissues
6. Normal T-cell

Question 18

One of the following is not associated with defects in leukocyte function:

• Leukocyte Adhesion Deficiency 2
• Chronic Granulomatous Disease
• Deficiency of Complement Regulatory Proteins
• Chediak-Higashi Syndrome

Answer 18

Deficiency of complement Regulatory Proteins

Defects in leukocyte Function Include:
1. Leukocyte Adhesion deficiency type 1 & 2
2. Chediak-Higashi Syndrome
3. Chronic granulomatous disease
4. Myeloperoxidase deficiency
5. Defects in TLR signaling

Question 19

In innate immunity with defects in leukocyte function, what disease would manifest decreased leukocyte function because of mutations affecting proteins involved in lysosome membrane traffic?

Answer 19

Chediak-Higashi disease

Question 20

What are the features seen in Hyper IgM syndrome

Answer 20

X-linked: mutations in CD40L on Xq26
Autosomal recessive: loss of function mutation on CD40 or activation-induced cytidine deaminase (AID)

• Normal IgM
• No IgA or IgE
• extremely low IgG
• Normal numbers of B-cells and T-cells
• present with recurrent pyogenic infections

Question 21

Wiskott-Aldrich Syndrome Triad

Answer 21

VET
- Vulnerability to recurrent infections
- Eczema
- Thrombocytopenia

Question 22

Features in DiGeorge Syndrome

Answer 22

• Hypoplasia or lack of the thymus
• tetany
• congenital defect of the heart and great vessels
• abnormal mouth, ear, and facies (slanted eyes, folded low set ears, small upper lip, cleft lip/cleft palate, small jaw)

Question 23

Structures that do not develop normally in DiGeorge Syndrome (Thymic Hypoplasia)

Answer 23

• Thymus (3rd and 4th pharyngeal pouches)
• parathyroids
• C-cells of the thyroid
• ultimobranchial body

Question 24

X-linked SCID affects the signal transducing component of receptors for which ligands

Answer 24

IL-2, IL-4, IL-7, IL-9, IL-11, IL-15, IL-21