Recognition of extracellular - University of Nottingham · SAP SP-A SP-B Fibrinogen . Examples of...

Recognition of extracellular pathogens

Neutrophils Eosinophils Basophils

Mast cells

Monocytes/ Macrophages

Dendritic cells

NK cells

CD8+ Tc lymphocytes CD4+ Th lymphocytes

B lymphocytes

Myeloid

Lymphoid

PMN/ Granulocytes

Mononuclear cells

Innate

Adaptive

PRR

PAMP

eg. macrophages

Production of acute phase proteins by the liver in response to interleukin-6 (IL-6)

Liver

IL-6

C-reactive protein

Mannan- binding lectin

Other acute phase proteins, eg: SAP SP-A SP-B

Fibrinogen

Examples of Pattern Recognition Receptors (PRRs) expressed by macrophages

LPS receptor Mannose receptor

Glucan receptor

Scavenger receptor

Toll-like receptors (TLRs)

TLR6

TLR2

TLR2 TLR1 TLR4

TLR5

TLR3

TLR7

TLR8

TLR9

Peptidoglycans (Gram +) Lipoproteins Lipopolysaccharides GPI (T. cruzi) Zymosan (Yeast)

Lipopolysaccharides (Gram -) Lipoteichoic acids (Gram +) RS virus F protein

Flagellin

dsRNA

ssRNA

G-rich oligonucs

Unmeth CpG DNA

CD14

Plasma membrane

Endosome

Antigen receptor

Antigen

eg. B lymphocytes

Principles of vaccination illustrated by immunization with tetanus toxoid

Antibody response to tetanus toxin

Time

Immunization with tetanus

toxoid

Infection with tetanus

bacterium

Memory lymphocytes

present

Naïve lymphocytes

present

Antigen combining site

Classes/isotypes: IgM; IgG (1, 2, 3, 4); IgA (1, 2); IgE; (IgD) Heavy chains: µ, γ, α, ε, δ Light chains: κ, λ

Fab

Fc

Heavy chain Light chain

VH

Cµ1

Cµ2

Cµ1

Cµ2

Cµ3 Cµ3

Cµ4 Cµ4

Cε1 Cε1

Cε2 Cε2

Cε3 Cε3

Cε4 Cε4

Class

Switch IgM IgE

Antibody isotypes: distribution

IgM (pentamers) blood

IgG (monomers) blood, tissues, placental transfer

IgA blood/tissues (monomers) mucosal secretions and milk (dimers)

IgE (monomers) tissues (bound to mast cells)