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

YY

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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YY

Y

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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…