Acquired Immunity

Acquired (Adaptive)
Immunity
Defensive mechanisms include :

1) Innate immunity (Natural or Non specific)

2) Acquired immunity (Adaptive or Specific)

Cell-mediated immunity Humoral immunity

 Aquired (specific) immunity
* The acquired immune response is more specialized
than innate immune response

* The acquired immune response involves a combination

of two mechanisms :

1) Humoral immune response

2) cell mediated immune response

* They interact with one another to destroy foreign body

(microorganisms, infected cells, tumor cells)
 Aquired (specific) immunity
Two mechanisms
1) Humoral immune response:
- Antibodies are produced by B-lymphocytes
- These have the ability to recognize and bind
specifically to antigen that induced their formation

2) The cell mediated immune response (CMI)

- It is mediated by certain types of T-lymphocytes
- T-lymphocytes recognize foreign material by
means of surface receptors
- T-lymphocytes attack and destroy foreign material
directly or through release of soluble mediators
i.e. cytokines
FUNCTIONING OF THE IMMUNE SYSTEM
HUMORAL (ANTIBODY MEDIATED) IMMUNE RESPONSE CELL MEDIATED IMMUNE RESPONSE
ANTIGEN (1ST EXPOSURE)
ENGULFED BY

MACROPHAGE ANTIGENS
FREE
DISPLAYED
ANTIGENS BECOMES BY
DIRECTLY
INFECTED
ACTIVATE APC CELLS
ACTIVATE
STIMULATES
HELPER CYTOTOXIC
B CELLS T CELLS
STIMULATES STIMULATES T CELL

MEMORY
GIVES RISE TO HELPER T GIVES RISE TO
CELLS
STIMULATES STIMULATES
STIMULATES
ANTIGEN (2nd EXPOSURE)
PLASMA MEMORY STIMULATES ACTIVE
MEMORY
CELLS B CELLS CYTOTOXIC T
T CELLS
CELL

SECRETE ANTIBODIES

Defend against extracellular pathogens by binding to Defend against intracellular pathogens and cancer by
antigens and making them easier targets for phagocytes binding and lysing the infected cells or cancer cells
and complement
 Mechanism Of Acquired Immune Response
Acquired immune response is initiated by:

* Recognition of the antigen by specific lymphocytes

* Activation of these specific lymphocytes

* Proliferation and differentiation into effector cells;

-The effector cells eliminate the antigen

-Return of homeostasis and development of memory cells

* Memory cells evoke a more rapid and long response on re-exposure to

same antigen
 Characters Of Acquired Immune Response

1) Highly specific for the invading organism

2) Discrimination between “self and “non self” molecules

The response only occurs to “non self” molecules

3) Diversity:
- It can respond to millions of different antigens
- Lymphoctes population consists of many different clones (one cell
and its progeny)
- Each clone express an antigen receptor and responds only to one
antigenic (epitope)
4) Immunologic memory
 The Adaptive Immune System Requires Cooperation Between
Lymphocytes and Antigen-Presenting Cells
An effective immune response involves two major groups of
cells: T lymphocytes and antigen-presenting cells.
 Lymphocytes are one of many types of white blood cells
produced in the bone marrow by the process of
hematopoiesis.
Hematopoiesis:-All blood cells arise from a type of cell called
the hematopoietic stem cell (HSC)
 Lymphocytes leave the bone marrow, circulate in the blood
and lymphatic systems, and reside in various lymphoid
organs. Because they produce and display antigen binding
cell-surface receptors, lymphocytes mediate the defining
immunologic attributes of specificity, diversity, memory, and
self/nonself recognition.

Maturation of immune system cells
 Cells of Immune System
Stem cells of bon marrow
differentiate into
cytokines (IL-&, IL-3)
colony stimulating factor

Lymphoid series Myeloid series

B-lymphocytes T-lymphocytes NK

monocytes –macrophages dendritic cells eosinophils mast cells

Primary Lymphoid Organs The primary
lymphoid organs,
are bone marrow
and the thymus,
where
lymphocytes
originate and/or
mature
(depending on
type).
Secondary Lymphoid Organs The secondary lymphoid
organs, such as Lymph
Nodes, are the sites of
interaction among
immune system cells
including with antigens
presented by Antigen
Presenting Cells.
-APC is a cell that
displays foreign antigen
complex with MHC on
its surface. T-cells may
recognize this complex
using their T-cel
l receptor (TCR).
 The Life Of The B Cell
• The B lymphocyte derived its letter designation from its site
of maturation, in the bursa of Fabricius in birds or bone
marrow is its major site of maturation in a number of
mammalian species, including humans and mice.

• Mature B cells are definitively distinguished from other

lymphocytes by their synthesis and display of membrane-
bound immunoglobulin (antibody) molecules,
They have the following functions:
To interact with antigenic epitopes, using their
immunoglobulin receptors
• To subsequently develop into plasma cells, secreting large
amounts of specific antibody, or
• To circulate as memory cells
• To present antigenic peptides to T cells.
 * B cells become plasma cells, which produce
antibodies when a foreign antigen triggers the immune
response
 B-lymphocytes
* Immature B-cells that express high affinity receptors for self
antigens, die or fail to mature i.e negative selection or clonal
deletion
• This process induces central self tolerance and reduces autoimmune
diseases
• Immature B cells are tested for auto-reactivity by the immune
system before leaving the bone marrow. In the bone marrow (the
central lymphoid organ), central tolerance is produced. The
immature B cells whose B cell Receptors (BCRs) bind too strongly
to self antigens will not be allowed to mature. If B cells are found
to be highly reactive to self, three mechanisms can occur.
1- Clonal deletion: the removal, usually by apoptosis, of B cells of a
particular self antigen specificity.
• 2- Receptor editing: the BCRs of self reactive B cells are
given an opportunity to rearrange their conformation. This
process occurs via the continued expression of the
Recombination activating gene (RAG).
• Through the help of RAG, receptor editing involves light
chain gene rearrangement of the B cell receptor. If receptor
editing fails to produce a BCR that is less autoreactive,
apoptosis will occur.
• Note that defects in the RAG-1 and RAG-2 genes are
implicated in Severe Combined Immunodeficiency (SCID).
• The inability to recombine and generate new receptors lead
to failure of maturity for both B cells and T cells.
• 3- Anergy: B cells enter a state of permanent
unresponsiveness when they bind with weakly cross-
linking self antigens that are small and soluble
 B-lympocytes types
* Immature B cells express IgM receptors on the surface

* Mature B cells express IgM, IgD molecules on surfaces

* IgM and IgD molecules serve as receptors for antigens

* Memory B-cells express IgG or IgA or IgE on the surface

* B-cells bear receptors for Fc portion of IgG and a receptor for C3

component of the complement

* They express an array of molecules on their surfaces that are important

in B-cells interactions with other cells such as MHC II, B7 and CD40
 Mechanism of Humoral immunity
* Antibodies induce resistance through:

1) Antitoxin neutralize bacterial toxins (diphtheria,tetanus)

Antitoxin are developed actively as a result of:

a- Previous infection

b- Artificial immunization

c- Transferred passively as antiserum

* Neutralization of toxin with antitoxin prevents a combination with tissue

cells
Figure. Neutralization. Neutralization occurs when antibodies block the structures on
infectious agents or toxin molecules that are used to attach to and enter host cells.
 Mechanism of Humoral immunity
2) Antibodies attach to the surface of bacteria and

a- act as opsonins and enhance phagocytosisd

b- prevent the adherence of microorganisms to

their target cells, e.g. IgA in the gut

c- Activate the complement and lead to bacterial lysis

d- Clump bacteria (agglutination) leading to phagocytosis

Agglutination. Antibodies can crosslink Figure 11.5 Uptake and opsonization via
infectious agents (A), host cells (B) or Fc receptors
antigen bound the surface of particles
(C).
Activation of B cells to make antibody
 Antibodies or Immunoglobulins

* Definition:
Glycoprotein in serum and tissue fluid

* Produced by:
B-lymphocytes in response to exposure to antigen

* React specifically with antigen

* Five classes of Antibodies:

IgG
IgM
IgA
IgD
IgE
 Antibody Structure
Immunoglobulins are glycoproteins made up of
- Four polypeptid chains (IgG):
a- Two light (L) polypeptide chains
b- Two heavy (H) polypeptide chains

- The four chains are linked by disulfide bonds

- Terminal portion of L-chain contains part of antigen
binding site and the order of amino acids in the variable
region determines the shape of the binding site
- H-chains are distinct for each of the five
immunoglobulins
- Terminal portion of H-chain participate in antigen
binding site
- The other (Carboxyl) terminal portion forms Fc fragment
 ANTIBODY STRUCTURE
An antibody molecule is composed of two
identical Ig heavy chains (H) and two identical
light chains (L), each with a variable region (V)
& constant region (C).
 light chains
The amino-terminal half of the chain,
consisting of 100–110 amino
acids, was found to vary among
different Bence-Jones proteins .
This region was called the variable (V) region.
 The carboxyl-terminal half of the molecule,
called the constant (C) region
had two basic amino acid sequences.
 This led to the recognition that there were two light chain types, kappa
κ and lambda λ.
In humans, 60% of the light chains are kappa and 40% are lambda,
**Bence Jones is a monoclonal globulin protein found in the blood or urine, which
particularly diagnostic of multiple myeloma in the context of end-organ manifestations
heavy chains (H )
 The amino-terminal part of the chain, consisting of 100–
110 amino acids, showed great sequence variation among
myeloma heavy chains and was therefore called the variable
(V) region.
The remaining part of the protein revealed five basic
sequence patterns, corresponding to five different heavy-
chain constant (C) regions (μ, δ, γ , ε ,and α). Each of these
five different heavy chains is called an isotype.
 The length of the constant regions is approximately 330
amino acids for δ, γ , and α and 440 amino acids for μ and ε.
The heavy chains of a given antibody molecule
determine the class of that antibody: IgM(μ), IgG(γ),
IgA(α), IgD(δ), or IgE(ε). Each class can have either κ or λ
light chains.
 Variable(V) and Constant (C) Regions
- Each H-chain and each L-chain has V-region and C-region
-V-region lies in terminal portion of molecule
-V-region shows wide variation in amino a. sequences
-Hypervariable region form region complementary to Ag
determinant
- It is responsible for antigen binding

- C-region lies in carboxyl or

terminal portion of molecule
- C-region shows an unvarying amino
acid sequence
- It is responsible for biologic functions
 Antibody Fragments
• Fab fragment: antigen binding site

• Fc (crystallizable fragment):
a- Complement fixation (IgM and IgG)

b- Opsonization (IgG)

C- Placental attachment (IgG)

d- Mucosal attachment (IgA)

e- Binding to mast cells (IgE)

 Antibody Classes
• The various immunoglobulin isotypes and classes have
been distinguished by unique amino acid sequences in the
heavy-chain constant region that confer class-specific
structural and functional properties.
• Immunoglobulin G (IgG)
• IgG, the most abundant class in serum, constitutes about
80% of the total serum immunoglobulin.
• The IgG molecule consists of two γ heavy chains and two κ
or two λ light chains
Properties:-
-Major serum Ig - Major Ig in extravascular spaces
-The only Placental transfer Ig -Fixes complement
-Phagocytes – opsonization
There are four human IgG subclasses, distinguished by
differences in γ-chain sequence and numbered according to
their decreasing average serum concentrations: IgG1, IgG2,
IgG3, and IgG4

amino acid differences between subclasses of IgG affect the

biological activity of the molecule:
1-IgG1, IgG3, and IgG4 readily cross the placenta and play
an important role in protecting the developing fetus.
2- IgG3 is the most effective complement activator, followed
by IgG1; IgG2 is less efficient, and IgG4 is not able to
activate complement at all.
3- IgG1 and IgG3 bind with high affinity to Fc receptors on
phagocytic cells and thus mediate opsonization. IgG4
has an intermediate affinity for Fc receptors, and IgG2
has an extremely low affinity.
 Immunoglobulin M (IgM)
• IgM accounts for 5%–10% of the total serum immunoglobulin.
• IgM is secreted by plasma cells as a pentamer in which five
monomer units are held together by disulfide bonds that link
their carboxyl- terminal heavy chain domains (C4/C4) and
their (C3/C3 domains)
• Each pentamer contains an additional Fc-linked polypeptide
called the J (joining) chain, which is disulfide-bonded to the
carboxyl-terminal cysteine residue of two of the ten chains.
Properties
– First Ig made by fetus and B cells
– Present in colostrum and mother milk protect newly born.
– Fixes complement
 Immunoglobulin A (IgA)
• IgA constitutes only 10%–15% of the total immunoglobulin
in serum, it is the predominant immunoglobulin class in
external secretions such as breast milk, saliva, tears, and
mucus of the pulmonary, genitourinary, and digestive
tracts.
– Major secretory Ig on Mucous surfaces (secretory IgA)
give Local Immunity by coating m.o, bacteria or viruses
preventing their adherence to mucosal cells
– Does not fix complement (unless aggregated)
– Present in colostrum and mother milk protect newly
born.
• In serum, IgA exists primarily as a monomer, but
polymeric forms (dimers, trimers, and some tetramers) are
sometimes seen, all containing a J-chain polypeptide.
 Immunoglobulin E (IgE)
• The potent biological activity of IgE allowed it
to be identified in serum despite its extremely
low average serum concentration (0.3 g/ml)
(Least common serum Ig)
• IgE antibodies mediate the immediate hypersensitivity
reactions that are responsible for Allergic and
hypersensitivity reactions
• Binds to basophils and mast cells (Does not
require Ag binding)
– Parasitic infections (Helminths)
• Binds to Fc receptor on eosinophils
– Does not fix complement
 Immunoglobulin D (IgD)
• The new class, called IgD, has a serum concentration of 30
g/ml and constitutes about 0.2% of the total
immunoglobulin in Serum (present in very small amount
in serum)
• IgD, together with IgM, is the major membrane bound
immunoglobulin expressed by mature B cells, and its role
in the physiology of B cells is under investigation (B cell
surface Ig)
• No biological effector function has been identified for IgD.
– Does not bind complement
 Properties of Immunoglobulins
Property IgG IgA IgM IgE IgD

Heavy chain γ α µ ε δ

symbol
Molecular 150 170-400 900 190 180
weight KDa KDa KDa KDa
KDa

Percentage 75 % 15 % 10 % 0.004 % % 0.2

in serum
Complement Yes No Yes No No
fixation
Transplacental Yes No No No No

passage
Acquired Immunity: Antigen-Specific
Responses
 Monoclonal Antibody
• most antigens offer multiple epitopes and therefore
induce proliferation and differentiation of a variety of B-
cell clones, each derived from a B cell that recognizes a
particular epitope.
• The resulting serum antibodies are heterogeneous,
comprising a mixture of antibodies, each specific for one
epitope
• Such a polyclonal antibody response facilitates the
localization, phagocytosis, and complement-mediated
lysis of antigen; it thus has clear advantages for the
organism in vivo.
• Unfortunately, the antibody heterogeneity that increases
immune protection in vivo
 Monoclonal Antibodies
• Derived from a single B cell clone

• For most research, diagnostic, and

therapeutic purposes,
• monoclonal antibodies, derived from a
single clone and thus specific for a single
epitope, are preferable.
 Primary and Secondary antibody response

Primary antibody respone Secondary antibody response

* first exposure to antigen * Subsequent exposure

* lag period: days or weeks * Lag period: hours

(slow onset) (rapid onset)

* Small amount immunogl. * large amount immunogl.

low Ab level with gradual increase high Ab with rapid increas

* Ab Persist for short duration * Persist for long periods Weeks then decline
rapidly (monthes or years)

* Antibody is IgM * Antibody is IgG

 Primary and Secondary antibody response

Secondary response
to Ag

Amount of
Primary response
antibodies to Ag
in serum

1 2 3 4 Time (months)
5 6
2 Ag
nd
injection of Ag
1 injection of
st
Thanks