Transcript Immune3-Innate and adaptive immunity,Igs , Cytokines

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
Adaptive
immunity
Humoral
Cell mediated
B
lymphocytes
T lymphocytes
Antibodies
Cytokines
Extra cellular
infections
Intra cellular
infections
Soluble mediators of the immune
system:
Immunoglobulins
Cytokines
 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)

N
epitopes
Immunoglobulins are divided into
five classes:
• 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.
N
• Heavy chains consist of two different
domains (constant, and variable).
• Light chains also have 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 hinge region.
• Heavy chains are designated by
using of Greek letters (μ, γ, α, δ,
and Є), and the immunoglobulins
produced are IgM, IgG, IgA, IgD,
and IgE, respectively.
• The light chain consists of two
kappa(κ) or two lambda(λ) chains.
Immunoglobulins Isotypes:
 IgG
• IgG accounts for approximately 75-85%
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:
• Found either as a B cell bound
monomer or as a secreted pentamer.
• Present on B lymphocyte surfaces.
• Normally secreted as a J-chain
containing pentamer with molecular
mass of 900 KD.
• Form ~ 5-8 % of normal serum
immunoglobulin.
• 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.
 Most abundant in saliva, tears,
intestinal mucus, bronchial secretions,
milk, prostatic fluid (body fluids &
secretions). Called secretory IgA
 The predominant Ig produced in
Peyer’s patches (illume submucosa),
tonsils and other submucosal
lymphoid tissue.
It has two subclass: in
 IgA1: Monomer in the serum.
 IgA2: Dimer when secreted
(secretory IgA).
 IgA1: IgA2 ratio in blood is 5:1
IgD
• Has a Molecular weight of 180 KD.
• Present 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.
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: are 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
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IL-2
•
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IL-4, IL-5
IL-10, IL13
TNF-α
TNF-β
Cellular
Targets
Source
Macrophage, T cell, B cell,
B cell
End.
CD4 cell
(TH1)
CD4 cell
(TH2)
TH2, CD8
cells
T cell, B cell,
NK cell, Mac.
B cell, T cell,
Eos
B cell, TH2,
Mac.
Function
Leukocyte
activation, End.
Adhesion
T cell proliferation.
Differentiation of
TH2 and B cell
Inhibits IL-2, and
INFγ.
Down reg. IL-12
Mac, PMN, Mac, PMN, T, Inflammatory
Mediator.
T, B cells.
End.
Lymphocytes Wide Variety Inflammatory
Mediator.
Cytokines and Immune cells interaction:
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Interferons (IFNs): are low molecular
weight soluble proteins.
• Activated by presence of intracellular
pathogens such as viruses ,bacteria, and
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
N
Cellular Source
Targets
Function
INF-α
Lymphocytes,
Epithelium,
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, M, NK,
End.
Anti-Viral.
Anti-Parasitic.
Enhances MHC
Class I and II
expression.
Complement system:
Complement system: series of soluble
enzymes and proteins (C1,C2…….C9)
that function in both innate and adaptive
immune response against pathogens.
Complement activation can be initiated
via:
▫ Alternative pathway.
▫ Classical pathway
▫ Mannan-binding lectin pathway.
Alternative pathway:
• Activation of the alternate pathway
started from C3 in the presence of
the microbe, and continue tell
activation of membrane attack
complex (MAC)
Classical pathway of Complement:
• Starts by antigen - antibody
interaction which enables C1 binding
and continue tell MAC activation.
Mannan-binding lectin pathway
• Lectins are proteins that bind to
carbohydrates.
• Mannan is polymer of the sugar
mannose.
• This pathway is activated by
binding of mannan-binding lectin
(MBL) to certain microbes, and
continue tell MAC formation.
•
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The Complement Anaphylatoxins:
• The small fragments (C3a, C4a, C5a)
generated in the alternative and the
MBL pathway act as anaphylotoxins.
• They attract and activate some cells
(neutrophils, phagocytes and mast cells)
to the site of infection to produce an
inflammatory reaction.
Mechanism of Inflammation:
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