Antibody Deficiency

981 Pages·2017·58.63 MB·English

ACAAI/AAAAI
Joint Board
Certification
Review Course
Syllabus
Nashville 2018
PROVIDED by the American College of Allergy, Asthma and Immunology in cooperation with the American Academy of Allergy,
Asthma & Immunology.
© 2018 American College of Allergy, Asthma & Immunology. Distribution is prohibited.
Table of Contents
Friday, May 18, 2018
T cell Biology 1
Troy Torgerson, MD, PhD
B cell Biology and Immunoglobulin 19
Structure James “Tom” Thomas, II, MD
Innate Immunity (NK cells, Pattern Recognition Receptors) 42
Jordan Orange, MD, PhD
Innate Immune Disorders (NK defects, GATA2, XLP, HLH, TLR defects) 67
Jordan Orange, MD, PhD
Cell Signaling 102
John Routes, MD
Autoinflammatory Syndromes 130
Karyl Barron, MD
Laboratory Testing 151
Thomas Fleisher, MD
Cytokines 174
Robert Schleimer, PhD
Genetics and Molecular Biology 192
Sergio Rosenzweig, MD, PhD
T cell Immunodeficiency 210
Thomas Fleisher, MD
B cell Immunodeficiency 230
John Routes, MD
Saturday, May 19, 2018
Disorders of Phagocytes and Macrophages 254
Steven Holland, MD
Mast Cell and Basophil Biology and Disorders 309
Matthew Giannetti, MD
Eosinophil Biology and Disorders 335
Paneez Khoury, MD, MHSc
IV/SC Ig and Biologic Modifiers 359
Mark Ballow, MD
HLA and Transplantation 382
Troy Torgerson, MD, PhD
Atopic Dermatitis 395
Kelly Stone, MD, PhD
Urticaria and Angioedema 419
David Khan, MD
Anaphylaxis 457
David Lang, MD
Systemic Autoimmunity 488
Carol Langford, MD, MHS
Allergen Immunotherapy 514
Mike Tankersley, MD, MBA
Vasculitis 541
Carol Langford, MD, MHS
Drug Allergy 571
David Khan, MD
Sunday, May 20, 2018
Pharmacology 630
Joseph Spahn, MD
Asthma (and VCD): Pathophysiology, Diagnosis, Treatment 677
David Lang, MD
Food Allergy 713
Carla Davis, MD
Bullous Dermatoses, Immunologic Skin Disease, Contact Dermatitis 761
Anthony Gaspari, MD
Occupational Asthma and Immunologic Lung Disease 798
(Hypersensitivity, Alpha 1-antitrypsin Deficiency, Cystic Fibrosis)
Mark Sands, MD
Rhinitis, Polyposis, Sinusitis and Otitis Media 860
Anju Peters, MD
Review Questions
Friday Section Review Questions 934
Friday Section Answers 947
Saturday Section Review Questions 952
Saturday Section Answers 962
Sunday Section Review Questions 970
Sunday Section Answers 974
T cell Biology
Troy R. Torgerson, MD PhD
Pediatrics, Immunology/Rheumatology
University of Washington and Seattle Children’s Hospital
Disclosures
1. Consulting:
• Shire
• CSL Behring
• ADMA Biosciences
• UCB Biopharmaceuticals
2. Research Funding:
• National Institutes of Health
• Shire
• CSL Behring
• Casebia Therapeutics
2018 ACAAI/AAAAI Joint Board Certification Review Course 1
Learning Objectives
1. Describe the general structure & composition of the T cell
Receptor Complex
2. Describe how T cells get activated through the TCR
3. Describe the general mechanisms involved in thymic
development of T cells
4. Describe the functions of different T cell subsets
5. Describe the clinical consequences of T cell deficiency.
The T cell Receptor Complex
TCR
Recognition
Ag Binding
CD3 CD3
Site
V V
a b
C C
a b
ITAMs
Signaling
2018 ACAAI/AAAAI Joint Board Certification Review Course 2
Process of Recombination
• Similar to B cell VDJ recombination
• Recombination of V, D, and J gene segments is
coordinated by recombinase-activating genes RAG-1
and RAG-2 (like in B cells) and repair done by double-
strand break repair proteins.
• Unlike Ig genes, TCR genes do not undergo class
switching or somatic mutation. There is no change in
TCR structure or affinity during activation, differentiation,
and expansion of T cells. Once a TCR is set, it is set.
Learning Objectives
1. Describe the general structure & composition of the T cell
Receptor Complex
2. Describe how T cells get activated through the TCR
3. Describe the general mechanisms involved in thymic
development of T cells
4. Describe the functions of different T cell subsets
5. Describe the clinical consequences of T cell deficiency.
2018 ACAAI/AAAAI Joint Board Certification Review Course 3
T cell Activation via TCR – MHC Interaction
• T cell activation depends on both the strength
and duration of TCR signaling
• Full T cell activation requires prolonged T cell-
APC interactions
• T cell-APC interactions need to be stabilized to
be effective.
• Adhesion molecules provide this stabilization
T cell Activation Requires Multiple Signals
2018 ACAAI/AAAAI Joint Board Certification Review Course 4
• Initial binding of T cell
APC
with APC is through T
cell adhesion molecules
MHC II
like LFA-1 ICAM
• If no TCR activation, T
CD4
cells let go and move on.
• If TCR is activated, this V V
CD3 a b
activates the integrins to LFA-1
C C
a high affinity state and a b
recruits additional
integrins to the point of
cell-cell contact. T cell TCR
The Immunologic Synapse
BasuR and HuseM (2017) Trends in Cell Biology 27:241-54
• Requires the actin cytoskeleton to organize the synapse.
• Problems with organizing/assembling actin (WAS deficiency)
lead to poor synapse formation.
2018 ACAAI/AAAAI Joint Board Certification Review Course 5