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The Immune System
What does it mean to be “immune” to something?
The Immune System
How does the immune system get rid of a pathogen?
• Humoral immunity: B lymphocytes produce antibody (Ab)
• Cell-mediated immunity (CMI): cytotoxic T lymphocytes (TC) kill infected cells
Y
YY
Y
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neutralizationof a virus
Y
Y
Y
opsonizationof a bacterial cell
The Immune System
The immune response must:
• Respond to a specific pathogen (specific Ag)
• Distinguish “self” from “foreign” Ag
• Choose appropriate response (Ab, CMI or both)
• Have memory: respond more quickly 2nd time
opsonizationof a bacterial cell
Cell-Cell Interactions
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specific activatedB cell makes Ab
specific activatedTC cell kills infected cells
specific activated TH cellactivates effector cells
TA
RG
ET
macrophage or dendtritic cell= antigen-presenting cell (APC)
activates specific TH cell
pathogen(foreign Ag)
Two Immune System Questions
How does an immune-system cell specifically interact with and activate another cell?
How does the APC recognize the foreign Ag?
The “Immunological Synapse”
e.g., APC interacts with TH
• APC digests Ag, presents peptides bound to MHC II
• TH with specific T-cell receptor recognizes Ag + MHC
• CD4 on TH binds MHC II
The “Immunological Synapse”
Multiple receptor-MHC complexes cluster Signalling molecules recruited Adhesion molecules strengthen interaction, e.g. ICAM-LFA1 Additional interactions, e.g. CD28 – B7
The “Immunological Synapse”
Inner ring of signalling molecules (c-SMAC) Outer ring of adhesion molecules (p-SMAC) Specific, directional release of activating cytokines
The “Immunological Synapse”
Initial data is primarily descriptive What is the function of the synapse? Assumed to be necessary for specific
cell-cell communication to occur
Pathogen recognition
Innate immunity:
• Phagocytosis of pathogens by macrophages and neutrophils
• Inflammation
• Activation of defensive molecules (e.g., complement)
• Protection against many different pathogens
• Involved in activation of specific defenses
• Originally thought to be “non-specific”
…BUT, how would a pathogen be recognized?
must be some kind of specific receptors!
Pathogen recognition
PAMPs: pathogen-associated molecular patterns
• LPS in outer membrane of Gram-negative cell
• Peptidoglycan in bacterial cell wall
• Lipoteichoic acid in Gram-postive cell wall
• Flagellin protein of motile bacteria
• Zymosan from fungal cell wall
• dsRNA
• unmethylated CpG nucleotides
Pathogen recognition
PAMPs recognized by Toll-like receptors (TLRs)
Pathogen recognition
PAMPs recognized by Toll-like receptors (TLRs)
• APCs: macrophages and dendritic cells
• Signal transduction expression of adhesion and costimulator molecules
• Interaction with TH cell triggers immune-system activation
Pathogen recognition
Specific roles of TLRs in response to specific microbes have yet to be thoroughly studied
Understanding TLRs could lead to better vaccines…