Lecture 6: The Humoral Immune Response - Yeshiva...
Transcript of Lecture 6: The Humoral Immune Response - Yeshiva...
![Page 1: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/1.jpg)
Lecture 6: The Humoral Immune Response(based on lecture by Dr. Matthew Scharff, Einstein)
![Page 2: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/2.jpg)
centrocyteFDC
B Th
activation
centroblast Dark Zone
LightZone
selection
antigen
memory B cell plasma
B cell
apoptotic cell
anergic B cell
modified from Luo, Ronai, and Scharff. J Allergy Clin Immunol. 2004 and Harrison’s Principles of Internal Medicine 16th ed Ch. 97.
Pluripotent stem cell
Progenitor B cell
Pre-B cell
Immature B cell
mature B cell
SHMCSR
AID
AIDAID
![Page 3: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/3.jpg)
Questions to Consider
How can we make antibody to every possible pathogen-i.e. Diversity
How do we avoid making autoantibodies-i.e. Specificity
How do we rapidly increase amount of antibody-i.e. Mobilization
How do we switch from making IgM to IgG- i.e. Isotype Switching
How do we increase the the affinity of antibody-i.e. Affinity maturation
How do we generate memory
![Page 4: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/4.jpg)
Janeway and Travers, Immunobiology
Somatic HypermutationLow affinity high affinity
Class Switch Recombination
IgM IgG / IgE / IgA
Effector arm
Antigen-binding site
Humoral Immune Response
![Page 5: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/5.jpg)
Antibody Mediated Functions
![Page 6: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/6.jpg)
IgM is Polymeric Which Increases Its Avidity
![Page 7: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/7.jpg)
Neutralization of Viruses
![Page 8: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/8.jpg)
Antibodies Neutralize Toxins
![Page 9: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/9.jpg)
Binding of Antigen to Surface Ig Triggers The Proliferation And Differentiation of B Cells
![Page 10: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/10.jpg)
Generation of Antibodies To Polysaccharides by Conjugation to Proteins (Glycoconjugate Vaccines)
![Page 11: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/11.jpg)
Circulating Antibodies Reflect Somatic Mutation And Isotype Switching
![Page 12: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/12.jpg)
Isotypes Have Different C Region StructuresIg Isotype Are Encoded by Unique Constant Regions
![Page 13: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/13.jpg)
Isotypes Mediate Different Effector FunctionsIg Isotypes Have Different Functions Due to Their Unique Constant Regions
![Page 14: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/14.jpg)
IgM And IgA Are Polymeric Which Increases Their Avidity
![Page 15: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/15.jpg)
Binding of Antigen to Surface Ig Triggers The Proliferation And Differentiation of B Cells
![Page 16: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/16.jpg)
Different Cytokines Secreted By T Cells Induce Switching To Different Isotypes
![Page 17: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/17.jpg)
Different Cytokines Signal Transcription Of Different C-regions (Sterile Transcripts)
![Page 18: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/18.jpg)
Activation-inducedCytidine Deaminase (AID)
• AID is a cytidine deaminase whose in vitro substrate is ssDNA
• AID may associate with RPA, RNAP II &? others
• Transcription is required for somatic SHM and CSR
CUG
P182
CNESNLS
F15XR24W
H56Y
L59F
W68X
W80R
C87R
W84X
L106P
R112CR112H
M139VC147X
F151S
R174S R190X
L181
N alpha helix active site PS CSR
Deficiency causes Hyper IgM type II
Luo, Ronai, and Scharff. J Allergy Clin Immunol. 2004
![Page 19: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/19.jpg)
Activation-induced Cytidine Deaminase(AID) Mediates Class Switching
![Page 20: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/20.jpg)
Isotype Switching Requires Recombination Between Different Switch Regions
![Page 21: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/21.jpg)
The Poly-Ig Receptor Mediates the Transcytosis Of IgA Into Mucosal Secretions
![Page 22: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/22.jpg)
Cells Express Multiple Fc Receptors With Unique Functions
![Page 23: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/23.jpg)
Antibody Complexed To Antigen Binds to FcR’s and Activates Macrophages
![Page 24: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/24.jpg)
Antibody Complexed To Tumor Cells Targeting Their Killing by NK Cells Through FcRs
![Page 25: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/25.jpg)
IgE Complexed To Antigen Binds to FcR’s on Mast Cells and Mediates The Release Of Granules
![Page 26: Lecture 6: The Humoral Immune Response - Yeshiva …streaming.einstein.yu.edu/...6-Goldstein-the-humoral-immune-respons… · Lecture 6: The Humoral Immune Response (based on lecture](https://reader031.fdocuments.net/reader031/viewer/2022020215/5b46e2c37f8b9a3a058bd268/html5/thumbnails/26.jpg)
Questions to Consider
How can we make antibody to every possible pathogen-i.e. Diversity
How do we avoid making autoantibodies-i.e. Specificity
How do we rapidly increase amount of antibody-i.e. Mobilization
How do we switch from making IgM to IgG- i.e. Isotype Switching
How do we increase the the affinity of antibody-i.e. Affinity maturation
How do we generate memory