The Immune Response:

Humoral and Cell Mediated

Lecture # 9th A
By: Dr.Humera Kausar
 Overview of Immune response
Definition:
Immune response is the reaction of the body to the presence of a substance which
is recognized as a foreign to the body.

In order to initiate an immune response antigen must be

recognized.
Antigen recognition depends on detection of antigen by
special receptors.
Antigen recognition depends on cellular cooperation.
Cellular cooperation is controlled by recognition of
MHC-encoded receptors.
Depending on the kind of foreign invasion, two
different immune responses occur:

1) The humoral response (or antibodymediated

response).

2) The cellmediated response involves mostly T

cells and responds to any cell that displays Ag

with MHC
The Humoral Immune Response
Humoral immune Response, also called the antibody-mediated
Immune response, is the aspect of immunity that is mediated by
macromolecules, found in extracellular fluids such as secreted
antibodies and complemant proteins.
Primary & Secondary Humoral Responses

Figure 21.10
The Humoral Immune Response
Primary immmune response:
First exposure to antigen x
begin to make low levels of antibody in about a week
Secondary Immune response:
Second exposure to antigen x:
produces a much faster response, and
several orders of magnitude higher levels of antibody.
Ability of antibody to bind antigen also increases dramatically in the secondary response.
Injecting a new antigen y with x"
Elicits
only a primary response
Shows that a memory or prior exposure is required for the accelerated response .
The Humoral Immune Response
Clonal Selection Theory
Pre-existence of of many different potential
antibody producing cells
Each cell displays surface receptors for specific
antigens
Antigen encounter selects cells
The Humoral Immune Response
 The Humoral Immune Response
Postulates of the Clonal Selection Hypothesis
Each lymphocyte bears a single type of receptor of a unique
specificity
Interaction between a foreign molecule and a lymphocyte
receptor with high affinity leads to lymphocyte activation
The differentiated effector cells derived from an activated
lymphocyte will bear receptors of identical specificity to those
of the parental cell from which that lymphocyte was derived
Lymphocytes bearing receptors specific for self molecules
are deleted at an early stage in lymphocyte development and
are therefore absent from the repertoire
The Humoral Immune Response
Clonal Expansion Following Antigen
Exposure
Virgin lymphocyte pool

PRIMARY RESPONSE

effector cells memory cell pool

SECONDARY
RESPONSE
effector cellsmemory cell pool
The cell mediated or Cellular
Immune Response
The cell mediated Immune Response
The principal role of cell-mediated immunity is to detect
and eliminate cells that harbor intracellular pathogens.
Important defense mechanism against:
viral infections,
some fungal infections,
parasitic disease and
against some bacteria, particularly those inside
cells.
 T cells develop in the thymus
undergo positive and negative selection
Positive selection: T cells which can react to self MHC carrying
peptides are allowed to live. Those that cannot, undergo apoptosis.

Negative selection: T cells that react strongly to self-antigens on

MHC are eliminated.

Only those T cells that can react to MHC, but do not bind strongly to
self-antigens emerge as mature T cells from the thymus.

Only about 2% of immature T cells make it through positive and

negative selection.
T cells continuously circulate via the blood and
lymph through different lymph nodes until they
either find presented antigen or eventually die
When a T cell encounters an APC displaying
antigen to which it can bind, it stops migrating and
binds strongly to the APC.

Within about 2 days (48 hours), most antigen-

specific T cells have been trapped by antigen and
within about 4 to 5
days armed effector T
cells are migrating
out of the lymph node.
 The cell mediated Immune response
PHASE I
T cell Activation,
T-cell Proliferation
Differentiation of CTLs

PHASE II
Conjugation Formation
Membrane Attack
CTL Dissociation
Target Cell Destruction
PHASE I
Cell Mediated Immune Response
T-cell activation: involves recognition surface
antigens only
Antigen is combined with MHC & displayed on PM
T-cell receptors: bind to the MHC & are stimulated by
the associated antigen
The addition of a co-stimulator (cytokines,
interleukins, etc) prompts the T-cell to form a clone
In the absence of a co-stimulator the T-cell becomes
tolerant to antigen (anergy)
 TARGET CTL-P ACTIVATED
CELL CTL-P CTL

IL-2R - + +
expression
IL-2 - Low
expression
Proliferation - - +

Effecter - - +
Cytotoxic
Function
 PHASE II
CTL Mediated Destruction of Target Cell
Conjugation Formation
Membrane Attack
CTL Dissociation
Target Cell Destruction
 Conjugation Formation
Cell adhesion
Recognition of MHC I:Ag on target cell
Cell Adhesion Molecules
Selectins
Mucins
Integrins
Immunoglobulin superfamily
 Membrane Attack
Granules in CTLs
Perforin
Granzymes

Exocytosis of granule contents

Perforin
action similar to C9
Granzymes act as nucleases

Fas ligand to Fas triggers target cell death

 Membrane Attack
TC binds to cell & releases perforin &
granzymes
In the presence of Ca2+ perforin forms
pores in target cell PM
Granzymes enter through pores &
degrade cellular contents
TC then detaches & moves on
Macrophages clean up
Granzymes cannot directly
mediate cell death .
 Dissociation and Target Cell Death

CTL interacts for about five minutes

Dissociates and can conjugate with other
target cells
Target dies after several hours
 Antibody-Dependent Cell-Mediated
Cytotoxicity

NK cells, macrophages, neutrophils

Bind to Fc region of Ab
Multiple cytotoxic mechanisms
 PERFORIN ASSISTED CYTOTOXICITY
Mannose 6-phosphate receptors on target cell binds
with granzymes.
Granzyme/mannose complex internalize and appear
as a vesicle inside.
Perforin helps to release granzyme from into target
cell cytoplasm.
Granzyme initiate a cascade of reactions that result
in the fragmentation of target cell DNA in to oligomers
of 200 bp.
Granzymes cannot directly mediate DNA
fragmentation, they activate an apoptotic pathway
with in the target cell.
 PERFORIN ASSISTED CYTOTOXICITY

Within 5 min. of CTL contact, target cells

begins to exhibit DNA fragmentation.

Viral DNA within target infected cell also be

fragmented during this process.

The rapid onset of DNA fragmentation after

CTL contact may prevent continued viral
replication and assembly in the period before
the target cell is destroyed.
ANTIGEN NON - SPECIFIC

CELL MEDIATED

CYTOTOXICITY
 NATURAL KILLER CELLS MEDIATED
CYTOTOXICITY

NK cells make up 5-10% of the

recirculating lymphocyte population.
Express some membrane markers that are
found on monocytes and granulocytes, as
well as some that are typical of T cells.
NK cells involved in immune defenses
against viruses and tumors.
 NATURAL KILLER CELLS MEDIATED
CYTOTOXICITY

NK cells are the first line of defense

against viral infection, controlling virus
replication during the time required for
activation, proliferation and differentiation
of CTL-P cells into functional CTLs at about
day 7.
NATURAL KILLER CELLS MEDIATED
CYTOTOXICITY
 NK Cells
~5% of lymphocytes
Nonspecific cytotoxicity
No TCR/CD3
Not MHC restricted
No memory
 KILLING OF TARGET CELL BY NK CELL IS
SIMILAR TO CTL-MEDIATED KILLING
NK cells bear FasL on their surface and readily induce
death in Fas-bearing target cells.
The cytoplasm of NK cells contains numerous
granules containing perforin and granzymes.
Unlike CTL,s, NK cells are continuously cytotoxic,
always having large granules in cytoplasm.
NK CELLS DIFFER FROM CTL,S
NK cells do not express Ag. Specific TCR or CD3.
Recognition of target cells is not MHC restricted.
NK cell responses generate no immunologic memory.


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Surah: An-Naziat