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Acquired immune response

Defense Mechanisms of the Host


• Defenses
• Innate, natural defenses: present at birth, provide nonspe
cific Host resistance to infection
• Adaptive immunities: specific, must be acquired

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Adaptive (Specific) immunity
 depends on coordinated activity of T & B lymphocytes
 T cells- involved in “cell-mediated (cellular) immunity”;
defense against abnormal cells & intracellular pathogens
 B cells- involved in “antibody-mediated (humoral) immunity”;
defense against pathogens (Ag’s) in body fluids (blood/lymph
Adaptive immune system
• When infection begins the innate immune system skin in immediately
and uses non non specific mechanism(inflammation) to destroy the
invading pathogen and keep them from spreading . During this time
the adaptive immune system is mobilized and begin to gear up to
fight the infection several days may be needed to activate the specific
defense mechanism of the adaptive immune system can be devided
in to Ab – mediated cell(humoral) immunity and cell mediated
immunity
Antibody-Antigen Interactions
Principle antibody activity is to unite with the Ag, to call attention
to, or neutralize the Ag for which it was formed
• Opsonization – process of coating microorganisms or other
particles with specific antibodies so they are more readily
recognized by phagocytes
• Neutralization – Abs fill the surface receptors on a virus or the
active site on a microbial enzyme to prevent it from attaching
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Bacterial cell Opsonization Neutralization


“tagged” with Abs
Antibodies
block binding

Viruses

Opsonized bacteria
engulfed more readily

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Antibody-Antigen Interactions
• Agglutination – Ab aggregation; cross-linking cells or particles
into large clumps
• Complement fixation – Activation of the classical complement
pathway can result in the specific rupturing of cells and some
viruses
• Precipitation - Aggregation of particulate antigen
Agglutination Cross-linked Complement fixation Precipitation
bacterial cells
Abs

Antibodies aggregate antigen molecules

Lysing
bacterial
cells

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Antibody mediated immunity
• Humoral immunity involves B lymphocyte .Bcell are produced and
mature in bone marrow and found in lymph nodes
• During the innate response macrophage engulf pathogen.B cell
contain B cell receptor on their membrane can bind to these
macrophage –boun Ag
• B cell bind to specific Ag calls up on TH cell help differentiate,
undego mitosis , plasma cell and memory cell
• Plasma cell produce Ab that are specific Ag
• Bcell bind to memory cell keep acopy Ab in reinfection
Specific Immunity:
The Adaptive Line of Defense
Third line of defense – acquired
• Dual System of B and T lymphocytes
• Immunocompetence
• Antigen – Molecules that stimulate a response by T and B cells
• Two features that characterize specific immunity:
• Specificity – antibodies produced, function only against
the antigen that they were produced in response to
• Memory – lymphocytes are programmed to “recall” their
first encounter with an antigen and respond rapidly to
subsequent encounters

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Antibody mediated immunity
• Abs call immuno globulin and to specifi Ag boubd they call up on
leukocyte or canaggregate form long insoluble complex via process
agglutination
Cell mediated immunity
• T lymphocyte found in bone marrow, nature in thymus
• TH cell release interleukin and interferon help B cell mature into
plasma cell and memory cells
• Tcell contain membrane Tcell receptor , bind to Ag with help Thcells .
Differentiate into cytotoxic T cells(killer cells) travel toto the infected
area and bind to specifi Ag , releas powerful protein (perforins can
drill holes and kill pathogen
• In addition , T-lymphocyte can also form its own memory cells as well
as suppressor cell , regulate immune response
Specific B-Cell Receptor: Immunoglobulin
Receptor genes of B cells govern immunoglobulin (Ig)
synthesis
• Immunoglobulins are large glycoproteins that serve as specific
receptors of B cells(which mediate humoral or antibody mediated
immunity
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Light chains
Antigen binding sites

V V
V V
C C
C C

-S-S-

Disulfide
bonds
C C

Heavy chains 11
(a)
Specific B-Cell Receptor: Immunoglobulin

• Composed of 4 polypeptide chains:


Copyright © McGraw-Hill Education. Permission required for reproduction or display.

• 2 identical heavy chains (H)


Light chains
• 2 identical light chains (L) Antigen binding sites

• Y shaped arrangement – ends of V


V V
V
the forks formed by light and heavy C C
chains contain a wide range of C C

variable antigen binding sites


-S-S-

• Variable regions and Constant Disulfide


bonds
regions C C

(a) Heavy chains


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Antibodies
• Also known as immunoglobulins
• Globular glycoproteins
• The heavy and light chains are polypeptides
• The chains are held together by disulphide bridges
• Each ab has 2 identical ag binding sites – variable regions.
• The order of amino acids in the variable region determines the shape
of the binding site
How Abs work
• Some act as labels to identify
antigens for phagocytes
• Some work as antitoxins i.e. they block toxins for e.g. those causing
diphtheria and tetanus
• Some attach to bacterial flagella making them less active and easier
for phagocytes to engulf
• Some cause agglutination (clumping together) of bacteria making
them less likely to spread
Forms of Antibodies
• Membrane bound Ig→expressed Bcell surface (IgM&IgD) as BCR for
Ag
• If bound with Ag initiate B cell receptor
• Secreted Ig →in plasma & mucosa&interstitial fluids of tissues
Production &distribution of antibodies
• In lymph node→Ag stimulation of B cells with helper of T helper
cytokines→B cell proliferate →differentiatiate into plasma cell which
secret antibodies →enter circulation→site of infection
• Also mature B cell in Bone marrow express membrane bound
antibodies(BCR)
• So antibodies are produced in lymphoid tissue
The structure of antibodies

• Y shaped molecule of 4 peptide chain


• 2 identical heavy chain(1 variable domain(VH)& 3 or 4 constant
domains(CH)
• 2identical light chain(1variable domain(VL) &1 constant domains (CL)
Antibody Structure and Functions
• Immunoglobulins
Copyright © McGraw-Hill Education. Permission required for reproduction or display.

• Large Y-shaped protein Antigen binding sites

• Consist of 4 polypeptide V
V V

V
chains Fab
C Disulfide C
Fab

• Contain 2 identical
bonds
C C

fragments (Fab) with ends -S-S-

that bind to a specific Hinge


regions

antigen Complemet C C
binding

• Fc binds to various cells and site Fc

molecules of the immune


system
(a) Binding site for cells

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Antibody
Regions of antibody according to proteolytic
fragment of Ig
• Fab=fragment Ag binding→ contain whole light chain+VH+CHI
• 2 in number part for Ag recognition and binding
• Fc=fragment crystalline →tend to crystallize in solution
• One in number contain
• Remainin of both heavy chain C domain
• Give effector & biological function
• Hinge region= flexible region lies between Fab&Fc to give mobility to
both Fab to accommodate different Ag
Ig classes
• Ig divided five different classes according to the difference in
structure in constant domains of heavy chain
• Gamma hea→y chain-IgG→opsomize, Comp,ADCC
• Alpha heavy chain-IgA →mucosal
• immunity
• Mu heavy chain-IgM →primary immune response,complement
activation
• Epslon heavy chain-IgE →parasite, allergy
• Delta heavy chain-IgD→Bcell, receptor
Heavy chain class(isotype)switching
• In the swith from one Ig isotype to another . After activation of B
lymphocyte, the Ag specific clone proliferate and differentiate into
progeny secrete IgM .And other progeny of the same B cells produce
antibodies of different isotypes to mediate different function and
combat different types of microbes
Antigen-Antibody Binding

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Functions of the Fc Fragment
• Fc fragment binds to cells – macrophages, neutrophils,
eosinophils, mast cells, basophils, and lymphocytes
• Certain antibodies have regions on the Fc portion for fixing
complement
• Binding of Fc may cause release of cytokines

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Classes of Immunoglobulins
5 classes of immunoglobulins (Ig):
1. IgG – monomer, produced by plasma cells (primary
response) and memory cells (secondary), most
prevalent
2. IgA – monomer circulates in blood, dimer in mucous
and serous secretions
3. IgM – five monomers, first class synthesized
following Ag encounter
4. IgD – monomer, serves as a receptor for antigen on B
cells
5. IgE – Involved in allergic responses and parasitic
worm infections

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Immunoglobulin Classes

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Using Monoclonal
Antibodies for Treatment

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Antibody Mediated (Humoral) Immunity
 The body has millions of different B cell populations, each B cell
has its own particular antibody (Ab) molecule (transmembrane
protein) within its cell membrane
 When the corresponding Ag invades the interstitial fluid
surrounding the B cell, the Ag binds to the Ab molecule, & is
taken into the cell, eventually being displayed on the B cell’s
MHC protein. The B cell is now “sensitized
Humoral immunity
• The humoral immune response begins with the recognition of Ag by B
cell .These cell then undergo a process of clonal expansion and
differentiation through this process the B cell matures into Ab
secreting plasma cells which secret Ab
• If the body re-exposure to the Ag these memory cells will recognize
the Ag and respond much more quickly and effectively
Antibody Mediated (Humoral) Immunity
 The body has millions of different B cell populations, each B cell
has its own particular antibody (Ab) molecule (transmembrane
protein) within its cell membrane
 When the corresponding Ag invades the interstitial fluid
surrounding the B cell, the Ag binds to the Ab molecule, & is
taken into the cell, eventually being displayed on the B cell’s
MHC protein. The B cell is now “sensitized