Specific Host Defenses:
Adaptive Immunity
ACQUIRED or SPECIFIC
IMMUNITY
Two major kinds of defense
Innate immunity
Acquired
immunity
The Immune System is the Third Line of
Defense Against Infection
Immune Response: Third line of defense.
Involves production of antibodies and
generation of specialized lymphocytes against
specific antigens.

Innate or Natural or Non specific Immunity:

Immunity an organism is born with.
 Genetically determined. Effective from birth.
 Present before exposure to pathogens
 Nonspecific responses to pathogens
Acquired or Specific Immunity:

Immunity that an organism develops during lifetime.

Not genetically determined.
Develops after exposure to antigens (microbes,
toxins, or other foreign substances)
 Very specific response to pathogens
 May be acquired naturally or artificially.

Types of Acquired Immunity
Acquired
Immunity
Types of acquired immunity

(1). Natural Acquired Active immunity (2). Natural
Acquired Passively, (3) Artificially Acquired Active
Immunity, & (4) Artificially Acquired Passive Immunity

Serum: Fluid that remains after blood has clotted and
cells have been removed.

Antiserum: Serum containing antibodies to a specific
antigen(s). Obtained from injecting an animal (horse,
rabbit, goat) with antigen (snake venom, botulism or
diphtheria toxin).

Serology: The study of reactions between antibodies
and antigens.

Gamma Globulins: Fraction of serum that contains
most of the antibodies.

Serum Sickness: Disease caused by multiple
injections of antiserum. Immune response to foreign
proteins. May cause fever, kidney problems, and joint
pain. Rare today.
Types of Acquired Immunity
1.
Naturally Acquired Immunity:
- Obtained in the course of daily life.
1A. Naturally Acquired Active Immunity:

Antigens or pathogens enter body naturally.

Person contracts disease; generates specific immune response
to the antigen.
Immunity may be lifelong (chickenpox or mumps) or
temporary (influenza or intestinal infections).

1B. Naturally Acquired Passive Immunity:




Antibodies pass from mother to fetus via placenta or breast
feeding (colostrum). No immune response to antigens.
Develops immediately immunity & is usually short-lived
(weeks to months).
Affects all antigens to which the mother has immunity.
Protection until child’s immune system develops.
2. Artificially Acquired Immunity:

Obtained by receiving a vaccine or immune serum.
2A. Artificially Acquired Active Immunity:




Involves production of Antibody following exposure of
specially prepared Antigen
Antigens are introduced as vaccines (immunization).
Body generates an immune response slowly and is specific
to the antigen for which the immunization was given.
Immunity can be lifelong (oral polio vaccine) or temporary
(tetanus toxoid & Diphtheria toxoid).
2B. Artificially Acquired Passive Immunity:




Transfer of immunity from the immunised person to a nonimmunized person by trnsfering Abs or sensitised cells.
 Eg. Snake antivenom injection from horses or rabbits
 Used in the ttt. Of Tetanus, Diphtheria &Mumps
Immunity is immediate, but short lived (half life 3 weeks).
Affects all antigens to which the donor has the immunity.
Host immune system does not respond to antigens.
Lymphocytes


Lymphocytes mount a
dual defense
Two kinds of ( B & T)
lymphocytes carry out
the immune responses
1. Humoral immunity
(Antibody mediated)
involves the production
of antibody by the B
cells which attack Ag.
2.Cell mediated immunity
- is governed by Tlymphocytes. T cells
attack cells infected
with pathogens
BONE MARROW
Thymus
Stem cell
THYMUS
Via
blood
Immature
lymphocytes
Antigen
receptors
B cell
T cell
B cell
HUMORAL
IMMUNITY
OTHER PARTS
OF THE
LYMPHATIC
SYSTEM
Via
blood
Lymph nodes,
spleen, and other
lymphatic organs
CELLMEDIATED
IMMUNITY
Final
maturation of
B and T cells
in lymphatic
organ
Duality of Immune System
I. Humoral (Antibody-Mediated) Immunity
Involves production of antibodies by B cells
against foreign antigens (bacteria, bacterial toxins,
and viruses).
 B cells develop from stem cells in the bone marrow
of adults (liver of fetuses).
 After maturation, B cells migrate to lymphoid
organs (lymph node or Spleen).
 B cells are the main warriors of humoral immunity

Humoral Response to T Independent Antigens
Selection of B cells
Cell growth
division, and
differentiation
Triggering of the B cell
in a lymph node
Clone of many
effector cells
secreting
antibodies
ER
ER
ER
ER
Humoral Response to T Dependent Antigens
Activation of B-Cells

1.
2.
3.
4.
5.
6.
7.
8.
Activation of B cells involves various steps.
Selection of B cells – 1 from many B-cell (Each
lymphocyte bears a specific receptor to the antigen)
Recognition of Antigens – by B cells or Macrophage
Processing of Ag by Macrophages - immunogenic
Antigen presentation by Macrophages to B cells. T dept Ag
– needs the co operation of Th cells --(BSF) activate B
cells
Triggering of the B cell by the Ab or Th cells R-TCn-TLn
Clonal proliferation–Cell division & prolfn- by BSF, BCGF
Production of Plasma cells & Memory cells
Secretion of Immunoglobulin into the serum.
Humoral Immunity (Continued)
Apoptosis
Programmed cell death (“Falling away”).
 Human body makes 100 million lymphocytes every
day. If an equivalent number doesn’t die, will
develop leukemia.
 B cells that do not encounter stimulating antigen
will self-destruct and send signals to phagocytes to
dispose of their remains.
 Many virus infected cells will undergo apoptosis, to
prevent spread of the infection.

Clonal Selection

Clonal deletion - Some self-reactive B cells are killed in
the bone marrow (Not immunocompetent).
 Clonal selection- When antigen binds to antigen
receptor, the “Selected” B cell undergoes proliferates into
clones that will recognize one specific antigen.
 Clonal selection must be a defensive forces against a
specific antigen.
 Stimulated B cell growth forms clones bearing the same
antigen-specific receptors
■ A naive, immunocompetent B cell is activated when
antigens bind to its surface receptors.
■ These, along with T cell interactions, trigger clonal
selection
Fate of the Clones
■ Most clone cells become antibody-secreting
plasma cells (effector cell - short-lived cells)
■ Plasma cells secrete specific antibody at a higher
rate than B cells
■ Secreted antibodies:
Bind to free antigens
Mark the antigens for destruction by specific or
nonspecific mechanisms
■ Clones that do not become plasma cells become
memory cells (long-lived) that can mount an
immediate response to subsequent exposures of
the same antigen
Antigen
PRIMARY RESPONSE
(initial encounter
with antigen)
Antigen receptor on a B cell
Antigen binding
to a B cell
Cell growth,
division, and
differentiation
Clone of cells
Plasma cell
Memory B cell
Antibody
molecules
SECONDARY RESPONSE
(can be years later)
Cell growth,division, &
further differentiation
Later
exposure
to same
antigen
Larger clone of cells
Plasma cell
Antibody
molecules
Memory B cell
Immunological Memory
Antibody Titer: The amount of antibody in the serum.
Pattern of Antibody Levels During Infection
Primary Response:
 After initial exposure to antigen, no antibodies are
found in serum for several days.
 A gradual increase in titer, first of IgM and then of
IgG is observed after 3 to 6 days.
 Most B cells become plasma cells, but some B cells
become long living memory cells.
 Peak levels of plasma antibody are achieved in 10
days
 Gradual decline of antibodies follows.
Immunological Memory - Secondary Response:




Subsequent exposure to the same antigen displays a faster and
more intense antibody response with in an hour.
It is due to the existence of memory cells, which rapidly produce
plasma cells upon antigen stimulation.
Antibody levels peak in 2 to 3 days
Antibody levels in the blood can remain high for weeks to months
Unstimulated lymphocyte
First exposure to antigen
FIRST CLONE
Memory cells
Second exposure to antigen Effector cells
SECOND CLONE
More memory cells
New effector cells
Antibody Response After Exposure to Antigen
Monoclonal antibodies
Monoclonal antibodies are pure
antibody preparations
Specific for a single antigenic
determinant
Produced from descendents
of a single cell
Hybridomas – cell hybrids
made from a fusion of a
tumor cell (easy-to-grow) and
a B cell (specific for a single
antigenic determinant)
Antigen injected
into mouse
B cells
(from spleen)
Tumor cells grown
in culture
Tumor cells
Cells fused to
generate hybrid
cells
Single hybrid cell
grown in culture
Antibody
Hybrid cell culture,
producing monoclonal antibodies
Uses - Monoclonal Antibodies
■ Monoclonal Abs are powerful tools in the lab
Commercially prepared antibodies are used:
In research & clinical testing
To provide passive immunity
These cells are useful in medical diagnosis
They are also useful in the treatment of certain
cancers.
■ Have desirable properties of both parent cells –
indefinite proliferation as well as the ability to
produce a single type of antibody
Acquired Immunity: Ag-Specific Responses
T Lymphocytes: Cell Mediated Immunity
Figure 24-16: T lymphocytes and NK cells
T Cells and Cell Mediated Immunity
Cellular Components of Immunity:
T cells develop from stem cells in bone marrow and
mature in the thymus gland.
 After maturation they migrate to lymphoid organs
T cells are key cellular component of immunity.
 T cells have an antigen receptor that recognizes and
reacts to a specific intracellular antigen (T cell
receptor).
 T cell receptor only recognize antigens combined
with major histocompatability (MHC) proteins on
the surface of cells.
 MHC Class I: Found on all nucleated cells &
 MHC Class II: Found on phagocytes.


T Cells Only Recognize Antigen Associated
with MHC Molecules on Cell Surfaces
II. Cell Mediated Immunity

Clonal selection increases number of effector T cells
and destroy the invader.

T cells regulate proliferation and activity of other
cells of the immune system: B cells, macrophages,
neutrophils, etc.

Defense against:
 Bacteria
 Cancer

,Viruses, Fungi, protozoa, and helminths
cells & Transplanted tissue
Unlike humoral immunity, cell mediated immunity is
not transferred to the fetus (no passive immunity).
Types of T cells
1.
2.
3.
4.
Helper T (CD4+ TH) Cells - have central role in
immune response, these activate macrophages and
help form cytotoxic T cells
Cytotoxic T (CD8+ CTLs) destroy target cells on
contact by producing perforin that lysis an infected
cells
Delayed hypersensitivity T (TD) Cells: Mostly T
helper and a few cytotoxic T cells that are involved
in some allergic reactions (poison ivy) and rejection
of transplanted tissue.
Suppressor T (Ts) Cells -inhibit the production of
CTL cells to shut down immune response once
they are unneeded, least they cause more damage
than necessary. (Now called regulatory T cells).
APC = e.g., Macrophage
MHC
Class II
Peptide
Antigen
TCR
CD4 T Cell
CD4
T Cells and Cell Mediated Immunity
1. T Helper (TH) Cells: Central role in immune response.
Most are CD4+ (clusters of differentiation)
 The helper T cell’s receptors recognize antigen on the
surface of antigen presenting cells (e.g.: macrophage).
 The interaction activates the macrophages & TH cells
 The helper T cell releases IL2 & other cytokines
to activate itself, Cytotoxic T cells & the B cell

Activated CTL directly attack the infected cells by Cell
mediated immune response
 B cells produce plasma cells which secrete antibodies –
Humoral immune response.

T
cells mount the cell-mediated defense and aid
humoral immunity
Central Role of Helper T Cells
Cytokines
Mediators involved in cellular immunity, including hormone
like glycoproteins released by activated T cells and
macrophages
■ Interleukin 1 (IL-1) released by macrophages co-stimulates
bound T cells to release IL 2.
 IL-2 is a key growth factor, which activates T cells to divide
■ Other cytokines amplify and regulate immune and
nonspecific responses. Examples includes:
Perforin and lymphotoxin – Cell toxins
Gamma interferon – enhances the killing power of
macrophages
Inflammatory factors

Cytotoxic T cells



T cells that express CD8 molecule on their surface
Class I MHC molecules (nucleated body cells) expose foreign proteins
 Recognize antigens on the surface of all cells:
 Kill host cells that are infected with viruses or bacteria.
 Recognize & kill - Foreign cells from blood transfusions or transplants.
 Recognize and destroy cancer cells & transplanted tissue.
TC cell release protein called perforin and granzymes which forms a pore in
target cell membrane, causing lysis of infected cells and/or Apoptosis
Cytotoxic T cell binds
to infected cell
Perforin makes holes
in infected cell’s membrane
Infected cell is destroyed
Interrelationship between cell mediated
and humoral immunity
Antibody production depends on macrophages and T cells
(T dependent antigen)
1. Antigen is ingested and presented by the APC
2. The helper T cells reacts with this MHC-antigen complex
3. This activates the T cell and it begins to proliferate and
produce cytokines.
4. The cytokines activate macrophages, CD8 cells, and natural
killer cells
5. IL-2 influences a B cell to differentiate into a plasma cell that
produces antibody
 Sometimes antigen can stimulate B cells directly without the
help of T cells. This is called T independent antigen.
 In this case the antigen reacts directly with the B cell
receptors. This is usually weaker

The big picture…Integration of innate and adaptive immunity
Courtesy: Abbas and Litchman; Basic Immunology
Summary

Evolutionary need for adaptive immunity:


T and B cells are mediators of adaptive immunity





T cells: specific recognition of peptide/MHC complex (signal 1) and
costimulatory signals by APC (Signal 2)
B cells: recognize native proteins (signal 1). May/may not require signal 2
from CD4+ Th cells (TD and TI antigens)
Immunological memory: an important hallmark


T cells: cell-mediated immunity
B cells: humoral immunity
Cells of innate immunity also participate (DCs, Macrophages)
Activation of T and B cells are different:


Self/non-self discrimination, specificity, amplification, regulation, duration
and memory
Faster and rapid response on a second antigen encounter
Innate immune response shapes the adaptive immunity