Adaptive &
Innate Immunity
The Immune Response and
Immunity
• Immune response
▫ Innate (non-specific)
▫ Adaptive (specific):
Primary: when encountering the
microorganism for the first time.
Secondary: in recurrent
infections (memory)
Acquisition of Immunity
▫ Natural:
- active
- passive
▫ Artificial:
- active
- passive
Naturally Acquired Immunity
• Active:
▫ Acquired through contact with
microorganisms (infection).
▫ Provides long term protection.
• Passive:
▫ Antibodies pass from mother to fetus
across placenta or in breast milk (IgG)
▫ Provides immediate short term protection
(few months)
Artificially Acquired Immunity
• Active:
▫ Antigens introduced through
vaccination.
▫ Provides long term protection.
• Passive:
▫ Induced by the transfer of antibodies.
▫ Referred to as: Immune serum.
globulins(ISG), immune globulins (IG) or
gamma globulins
▫ Provides immediate short term protection
active
natural
passive
adaptive
active
immunity
artificial
innate
passive
Soluble mediators of the
adaptive immune system:
 Immunoglobulins.
 Cytokines and interferons.
 Complement.
Immunoglobulins
Immunoglobulins (Ig):
• Are gamma globulins (proteins) of
defined specificity for different epitopes
that make up antigens.
• They are produced by plasma cells
(differentiated B cells).
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epitopes
Immunoglobulins are divided into five
classes (isotypes):
• Three major classes ( IgG, IgM,
IgA).
• Two minor classes (IgD and IgE).
Basic Structure of Immunoglobulin:
• The immunoglobulin molecule consists
of four polypeptides chains: two heavy
(H) and two light (L) chains fastened
together by disulfide bonds.
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• Heavy and light chains consist of two
different domains (constant, and
variable).
• A light chain variable domain and a
heavy chain variable domain together
form a pocket that constitutes the
antigen-binding region (Fab).
• The flexibility of Ig is associated with
the presence of the hinge region.
• Heavy chains are designated by
using of Greek letters (α, γ, δ, Є,
and μ), and the immunoglobulins
produced are IgA, IgG, IgD, IgE,
and IgM, respectively.
• Each immunoglobulin isotype carry
one type of light chain kappa(κ) or
lambda(λ) chains.
Immunoglobulins Isotypes:
IgG
• IgG accounts for approximately 7585% of the total serum Ig
• It is the most abundant antibody
produced during secondary humoral
immune response.
• Have monovalent affinity.
• It is the only class that can cross the
placenta.
IgG structure:
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IgM:
• Form ~ 5-8 % of serum immunoglobulins.
• Present on B lymphocyte surfaces.
• Normally secreted as a J-chain containing
pentamer. (either as a B cell bound
monomer or as a secreted pentamer).
• Dominates in early primary immune
response.
• Anti-A and Anti-B blood groups.
• Complement fixation.
• Multivalent avidity (10 antigens).
IgM Structure:
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IgA:
 It accounts for 10-16% of serum Igs.
 Abundant in saliva, tears, intestinal mucus,
bronchial secretions, milk, prostatic fluid
(body fluids & secretions, secretory IgA).
 The predominant Immunoglobulin produced in
Peyer’s patches (illume submucosa), tonsils
and other submucosal lymphoid tissue.
 It has two subclass: in
- Monomer in the serum.
- Dimer when secreted (secretory IgA).
 IgA1: IgA2 ratio in blood is 5:1
IgD
• Has a molecular weight of 180 KD.
• Present as monomer on B-cell surface.
IgE:
 Form less than 1% of total serum Igs.
 A unique high affinity Fc receptor on
mast cell and basophils. (bounded)
 Great role in allergy, through cross
linking and release of histamine from
mast cells and basophils.
 Play a role in helminths infection.
Summary
• There are 5 isotypes of
immunoglobulins.
• IgG is the most abundant in serum,
the most important in secondary
infections and the only one that can
cross the placenta.
• IgM is the most important in the
primary exposure and in complement
fixation.
• The secretory IgA is most important
in immunity in body secretions,
submucosa and lumens.
• IgD is bounded to the surface of B
cells.
• IgE is bounded to the mast cells and
basophils and is the most important
in allergic reactions and helminths
infestation.
Second Lecture
Primary & Secondary Antibody Response
• Primary Response
▫ Following the first exposure to an
antigen, there is a slow rise in IgM
followed by a slow rise in IgG
• Secondary Response
▫ Following exposure to previously
encountered antigen, there is a rapid rise
in IgG and slow or no rise in IgM
Molecules of Cellular Interaction:
 Cytokines: low-molecular weight soluble
protein messengers that are involved in:
▫ Cellular interaction; inflammatory
response in innate and adaptive immunity.
▫ Cellular growth, differentiation, and
repair mechanism.
 Cytokines are produced by a wide variety
of immune and non-immune somatic cells.
 Cytokines produced by lymphocytes are
known as lymphokines.
Cytokine
IL-1
Targets
Function
Macrophage, B T cell, B cell,
Leukocyte
cell
Endothelial cells. activation,
endothelial adhesion
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IL-2
Cellular
Source
CD4 cell
(TH1)
T cell, B cell, NK T cell proliferation.
IL-4, IL-5
CD4 cell
(TH2)
B cell, T cell, Eos Differentiation of
TH2 and B cell
IL-10, IL-13
TH2, CD8 cells B cell, TH2,
Macrophage.
Inhibits IL-2, and
INFγ.
Down reg. IL-12
TNF-α
Mac, PMN, T,
B cells.
Mac, PMN, T,
End.
Inflammatory
Mediator.
TNF-β
Lymphocytes
Wide Variety of
cells
Inflammatory
Mediator.
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cell, macrophages
Cytokines and Immune cells interaction:
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IL-4, IL-10, IL-13
- B cell
- Immunoglobulin
- Extracellular pathogens (humoral mediated immunity;
phagocytosis independent)
- Macrophages (phagocytosis)
- CD8 T cytotoxic
- Intracellular pathogens (cell mediated
immunity)
Interferons (IFNs):
are low molecular weight soluble proteins.
• Activated by presence of intracellular
pathogens such as viruses ,bacteria,
parasites or tumor cells.
• Released by lymphocytes and other somatic
non-immune cells.
• Major action:
- anti-viral infection.
- Fight tumors.
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Interferons
Cellular Source
Targets
Function
INF-α
Lymphocytes,
Epithelium, DC
fibroblasts.
Wide variety of
cells.
-Up-regulates
MHC Class I.
-Inhibit viral
proliferation
INF-β
Epithelium,
fibroblasts.
Wide variety of
cells.
Up-regulates
MHC Class I.
Inhibit viral
proliferation
INF-γ
CD8*& CD4*T
cells, and NK
cells.
T , B,
macrophages,
NK, endothelial
cells.
Anti-viral.
Anti-parasitic.
Enhances MHC
Class I and II
expression.
Complement system:
 Complement system: series of soluble
enzymes and proteins (C1,C2…….C9) +
other actors that function in both innate
and adaptive immune response against
pathogens.
 Complement activation can be initiated
via:
▫ Classical pathway.
▫ Alternative pathway.
▫ Mannan lectin pathway.
Classical pathway of complement:
 Starts by antigen - antibody interaction.
 C1 (q, r, s) binding to the Ag- Ab complex.
 C1qrs will split C2 and C4.
 C4b2b will split C3. (C4b2b = C3
convertase).
 C4b2b3b = C5 convertase.
 C5b will adhere to the microbe.
 continue tell MAC formation (C5, C6, C7,
C8 and multiple C9).
Alternative pathway:
• Activation of the alternate pathway
started from C3 in the presence of the
microbe.
• C3 splits into C3a and C3b.
• C3b bind to the microbe surface with
factor B.( C3bBb= C3 convertase)
• C3Bb3b = C5 convertase, this will split
C5 and the process will continue tell
formation of the membrane attack
complex (MAC).
Mannan lectin pathway
• Mannan is polymer of the sugar
mannose (part of the bacterial cell
wall).
• Lectins are serum proteins that bind
to mannan.
• This pathway is activated by binding
of lectin to mannan on certain
microbes, and continue tell MAC
formation.
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The Complement Anaphylatoxins:
• The small fragments (C3a, C4a, C5a)
act as anaphylotoxins.
• They attract and activate neutrophils,
phagocytes and mast cells to the site of
infection.
• Produce an inflammatory reaction.
Mechanism of Inflammation:
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