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COLLABORATION OF
INNATE AND ADAPTIVE IMMUNITY
ANTIBODY STRUCTURE AND FUNCTION
8th week
Physiotherapy BSc
2015
IMMUNE SYSTEM
Innate / Natural Acquired / Adaptive
- limited specificity
- immediate reaction
- does not improve
- no memory
Cellular
Granulocytes
Monocytes/Macrophages
Natural Killer cells
Dendritic cells
Mast cells
Humoral
Complement proteins
Cytokines
Acute phase proteins
Antimicrobial proteins
- highly specific
- develops in several days
- improves after exposure
- has memory
CD4+ (helper) T cells
CD8+ (cytotoxic) T cells
B cells
Plasma cells
Antibodies
THE EFFECTS OF
ANTIGEN-PRESENTING CELLS
ON THE ADAPTIVE ARM OF THE
IMMUNE SYSTEM
THE LOCATION OF INNATE AND ADAPTIVE CELL
INTERACTIONS
THE EFFECTS OF T CELLS ON
THE INNATE ARM OF THE
IMMUNE SYSTEM
RECEPTORS AND CELL-SURFACE MOLECULES OF
MACROPHAGES
TLR4 + CD14
Scavenger receptor
Mannose receptor
MHCI
TLR – pattern
recognition Rs
FcRI (CD64)
Ag + IgG
complex
FcRII (CD32)
FcRIII (CD16)
LFA1 (CD11a/CD18)
MHCII
Mϕ
CR1 (CD35)
CR3 (CD11b/CD18)
KILLING THROUGH LYSOSOMAL ENZYMES, OXYGEN
AND NITROGEN SPECIES
Activation of macrophages
THE EFFECTS OF B CELLS ON
THE INNATE ARM OF THE
IMMUNE SYSTEM
EFFECTOR FUNCTIONS
OF ANTIBODIES
Antibody-mediated immune responses
• NEUTRALIZATION
• OPSONIZATION
• opsonized phagocytosis
(IgG)
• ADCC (NK cell-mediated
killing) (IgG)
• mast cell degranulation
(IgE)
• COMPLEMENT ACTIVATION
THE CONSTANT REGION OF AN ANTIBODY CAN BIND TO Fc RECEPTORS
(FcR)
Antigen binding
Complement binding site
Binding to Fc receptors
Placental transfer
FcR activation occurs when the antibody forms a complex with an antigen
Opsonization facilitate and accelerate the recognition of
the pathogens by phagocytes
Major opsonins:
Phagocytes must express
receptors for the opsonins:
• ANTIBODIES
• Complement molecules
• Acute-phase proteins (CRP, SAP)
IgG  FcγRI
C3b  CR1
RECEPTORS AND CELL-SURFACE MOLECULES OF
MACROPHAGES
TLR4 + CD14
Scavenger receptor
Mannose receptor
MHCI
TLR – pattern
recognition Rs
FcRI (CD64)
Ag + IgG
complex
FcRII (CD32)
FcRIII (CD16)
LFA1 (CD11a/CD18)
MHCII
Mϕ
CR1 (CD35)
CR3 (CD11b/CD18)
ANTIBODY EFFECTOR FUNCTIONS
ANTIBODY-DEPENDENT CELL CYTOTOXICITY
Antibodies target virus infected cells, flagging them for the
recognition by natural killer (NK) cells
IgE
• most important
isotype against
helminths
• triggers ADCC by
eosinophils
• mast cells carry
high affinity Fcε
receptors
• same mechanism
in allergic
reactions
HUMAN IMMUNOGLOBULIN CLASSES
Encoded by different heavy chain constant gene segments
Ig isotype
Heavy chain types:
• IgG - gamma (γ)
heavy chains
• IgM - mu (μ)
heavy chains
• IgA - alpha (α)
heavy chains
• IgD - delta (δ)
heavy chains
• IgE - epsilon (ε)
heavy chains
Serum
concentration
Characteristics, functions
Trace
amounts
 Major isotype of secondary
(memory) immune response
 Complexed with antigen activates
effector functions (Fc-receptor
binding, complement activation
 The first isotype in B-lymphocyte
membrane
 Function in serum is not known
Trace
amounts
 Major isotype in protection against
parasites
 Mediator of allergic reactions (binds
to basophils and mast cells)
3-3,5 mg/ml
 Major isotype of secretions (saliva,
tear, milk)
 Protection of mucosal surfaces
12-14 mg/ml
1-2 mg/ml
 Major isotype of primary immune
responses
 Complexed with antigen activates
complement
 Agglutinates microbes
 The monomeric form is expressed in
B-lymphocyte membrane as antigen
binding receptor
GC reaction:
• proliferation (clonal
expansion) of
activated B cells
• affinity maturation
(stronger binding to
epitopes)
• isotype switch
(different effector
functions)
• memory B cell
formation (from
improved clones)
Only by the help of
Th cells!
ISOTYPE SWITCH
• heavy chain constant
gene segments are
divided
• always the closest to the
variable domain is
expressed (first always
IgM)
• the switch is driven by the
cytokines produced by
helper (CD4+) T cells
ISOTYPE SWITCHING IS T-DEPENDENT
Helper T cell
IL-2
IL-4
IL-5
IL-2
IL-4
IL-5
IL-2
IL-4
IL-6
IFNγ
IL-5
TGFβ
IgM
IgG
IgA
B cell
IL-4
B cell proliferation, differentiation and isotype switching
IgE
IgA transport to mucosal surfaces and body secretions
Poly Ig receptors for IgA transport
across the epithelium to the
mucosal surface
• additional help for
the natural barriers
of our body –
defense of the
epithelial surfaces
• mainly
neutralization
NATURAL PASSIVE IMMUNIZATION
Pathological consequences of placental
transport of IgG
(hemolytic disease of the newborn)
anti-Rh
IgM
Passive anti-D IgG
EFFECTOR FUNCTIONS
OF ANTIBODIES
Antibody-mediated immune responses
• NEUTRALIZATION
• OPSONIZATION
• opsonized phagocytosis
(IgG)
• ADCC (NK cell-mediated
killing) (IgG)
• mast cell degranulation
(IgE)
• COMPLEMENT ACTIVATION
ANTIBODY EFFECTOR FUNCTIONS
COMPLEMENT FIXATION
Binding of complement protein 1 to IgG or IgM
immunoglobulins on a bacterial surface
ANTIBODY EFFECTOR FUNCTIONS
COMPLEMENT FIXATION
Complement 1 protein and the immunoglobulin bound to the
bacteria cause the binding of more complement proteins
ANTIBODY EFFECTOR FUNCTIONS
COMPLEMENT FIXATION
More complement proteins are recruited leading to the death of
the extracellular pathogen (bacteria) by forming pores in it