Diseases Of Immunity (Lecture 2) Flashcards
Defect in the Beta chain of CD11/18
Leukocyte Adhesion Deficiency 1
CD11/CD18: Integrin Beta 2 (LFA-1/MAC-1) on neutrophils
- The fucose-containing ligand (binds to E- and P-selectins)
- Deficiency in this ligand will lead to what disease?
- Sialyl-Lewis X
- Leukocyte Adhesion Deficiency Type 2
What is the deficiency in Chediak-Higashi Syndrome
Dysfunctional gene for LYST cytosolic protein (regulated lysosomal trafficking)
Characterized by defective fusion of phagosomes and lysosomes
What are the gene defects in the following Chronic Granulomatous Disease:
1. X-linked
2. Autosomal recessive
- gp91phox : membrane bound phagocyte oxidase
- p47phox and p67phox : cytoplasmic phagocyte oxidase
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
Chronic Granulomatous DIsease
Defect that causes recurrent herpes simplex encephalitis
Defects in TLR signaling
Defect in TLR 3 - receptor for viral RNA
Causes destructive bacterial pneumonia
Defects in TLR Signaling
Defect in MyD88
MyD88 is a downstream adaptor protein for multiple TLRs
What are the diseases linked to Defects in complement regulatory proteins
- Hereditary angioedema
- Paroxysmal nocturnal hemoglobinuria
- Hemolytic uremic syndrome
- Age-related macular degeneration
What defects in the complement system is associated with pyogenic infections
Defects in the Alternative pathway (properdin and factor D)
Most common complementary deficiency
Deficiency in C2
Associated with increased susceptibility to recurrent Neisseria infections
Defects in the late-acting complement components (C5, 6, 7, 8, and 9: Membrane attack complex)
Most common autosomal recessive deficiency in SCID (Sever Combined Immunodeficiency)
Deficiency in ADA enzyme (Adenosine Deaminase)
Defect Causes of Autosomal Recessive SCID
- Adenosine deaminase (ADA)
- Recombinase-activating genes (RAG)
- JAK3 - intracellular kinase
- T-cell receptor kinases
- Components of calcium channels
What autosomal recessive SCID has similar pathogenesis as X-linked SCID
Defect in JAK3 signaling
Adaptive immunodeficiency that has:
- severely defective T-cell
- defective NK cell
- normal level of B-cell
- decreased synthesis of B-cell
X-linked SCID
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)
X-linked Agammaglobulinemia (Bruton Agammaglobulinemia)
What are the T-cell and B-cell characteristics of classic X-linked agammaglobulinemia
- Absent plasma cells
- Decreased/absent B cells
- Decreased Immunoglobulin
- Normal pre-B cell levels in bone marrow (CD19)
- Underdeveloped germinal centers lymphoid tissues
- Normal T-cell
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
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
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?
Chediak-Higashi disease
What are the features seen in Hyper IgM syndrome
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
Wiskott-Aldrich Syndrome Triad
VET
- Vulnerability to recurrent infections
- Eczema
- Thrombocytopenia
Features in DiGeorge Syndrome
- 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)
Structures that do not develop normally in DiGeorge Syndrome (Thymic Hypoplasia)
- Thymus (3rd and 4th pharyngeal pouches)
- parathyroids
- C-cells of the thyroid
- ultimobranchial body
X-linked SCID affects the signal transducing component of receptors for which ligands
IL-2, IL-4, IL-7, IL-9, IL-11, IL-15, IL-21
