ADAPTIVE IMMUNE SYSTEM

Selectively attack by limiting or neutralizing particular target

Two classes of adaptive immune response:
o Antibody-mediated (humoral ) immunity production of antibodies by plasma
cells
o Cell-mediated immunity production of activated T lymphocytes
B cells recognize free-existing foreign invaders ie. bacteria and their toxins and a
few viruses where they secrete antibodies specific for invaders
T cells recognize and destroy body cells gone awry, including virus-infected cells
and cancer cells
THYMOSIN: hormone that maintains lineage of T cell
o Enhances proliferation of new T cells within peripheral
lymphoid tissue
o Increases immune capabilities of existing T cells

Antibody-Mediated Immunity; B cells

1. Binding of BCR to antigens :
B cells have receptors ( B cell receptors [ BCRs] ) for antigens
They bind to two main antigens:
o T-independent antigens(polysaccharide antigens) = stimulate production of
antibody without T cell involvement
o T-dependent antigens(typically protein antigens) = requires help of helper T
cells for production of antibody
2. Conversion of B cells to plasma cells + production of antibodies
Upon binding to antigens, B cells differentiate into active plasma cells while others
become dormant memory cells
o During B cell differentiation, B cell swells as the rough ER expands
o Plasma cells formed become prolific protein factories producing up to 2000
antibodies/s
o Plasma cells die after 5-7 days
Antibodies are then secreted into blood or lymph, but eventually gain access to
blood where they are known as gamma globulins/ immunoglobulins
Subclasses of antibodies :
o
o
o
o

IgM serves as BCR for antigen attachment; produced in early stages of plasma
cell response
IgG most abundant; produces in large quantity when body exposed to same
antigen
IgE protect against parasitic worms; antibody mediator for common allergic
responses ie. Hay fever , asthma, hives
IgA found in secretions of digestive, respiratory, urogenital system, milk and

tears
IgD present on surface of B cells

B cells differentiate into two cell types plasma cells and memory cells
o Plasma cells then switch to produce IgG antibodies which are secreted rather
remaining membrane bound
o Memory Cells
Small portion of B lymphocytes becine memory cells, which do not
participate in current immune attack against antigen but remains
dormant and expand specific clones
Memory cells are primed and ready for immediate action when person
is reexposed to same antigen

3. Role of antibodies
Antibodies cannot directly destroy foreign organisms but exert protective influence
by physically hindering antigens ( amplifying innate immune response)
Antibodies physically hinder antigens through neutralization and

agglutination.
1. Neutralization
o Antibodies combine with bacterial toxin, preventing harmful chemicals from
interacting with susceptible cells
o Antibody neutralize some viruses by binding with their surface antigens,
preventing these viruses from entering cells
2. Agglutination
o Multiple antibodies cross-link numerous antigen molecules into chains/ lattice of
antigen-antibody complexes
o Foreign cells( bacteria, mismatched transfused rbc) will then bind together in a
clump
o Sometimes, antigen-antibody complex which involve soluble antigens(tetanus
toxin) forms lattice that is so large that it precipitates out of solution
Antibodies amplify innate immune responses
o Mark foreign materials as targets for actual destruction by complement
system, phagocytes or natural killer cells while enhancing the activity of
these other defense systems
Activation of complement system
Antigen bind with antibody, receptors on tail portion of antibody
bind with and activate C1.

Activation of C1 activated other proteins and forms membrane

attack complex ( MAC) which is directed at membrane of
invading cell
Enhancing phagocytosis
Antibodies especially IgG acts as opsonins.
The tail portion of antigen-bound IgG antibody binds with
receptor on surface of phagocyte and thus promotes
phagocytosis of antigen-containing victim
Stimulating NK cells
NK cells have receptor for tail portion of antibodies
When target cell is coated with antibodies, tail portion of
antibodies link target cells to NK cells which then destroy the
cells by lysing the plasma membrane
This process is called antibody-dependent cellular
cytotoxicity (ADCC)

4. ACTIVE AND PASSIVE IMMUNITY

Primary response: Upon contact with microbial antigen, antibody response is

delayed for several days until plasma cells are formed and then reaches its peak
for a couple of weeks.
o After reaching peak, antibody levels gradually decline over period of time
although some are still circulating in the blood

Secondary response: longer-lasting, rapid and more potent response by longlived memory cells in contact with same antigen
o Important in preventing and minimizing overt infection on subsequent
exposure to same microbes, forming long term immunity against specific
disease

Formation of memory cells occur through the person either actually having the
disease/ being vaccinized already

Active Immunity

A production of antibodies as a results of exposure to an antigen

Vaccination:
o Exposes person to pathogen that has been stripped of its disease-inducing
capability but still can induce antibody formation against itself
Passive Immunity

Second way in acquiring active immunity

o Direct transfer of antibodies actively formed by another person/ animal.
o Usually occurs from transfer of antibodies of IgG class from mother to fetus
across placenta during intrauterine development
o Mothers colostrums(first milk) contains IgA antibodies that provide further
protection for breast-fed babies
Passively transferred antibodies are usually broken down in less than a month
Provides immediate protection/ bolster resistance against extremely virulent infectious
agent / potentially lethal toxin to which a person has been exposed( rabies, tetanus
toxin)
Antiserums:
o Antibodies that are harvested from another nonhuman source that has been
exposed to attenuated form of antigen ( usually horse/sheeps)
Sometimes recipient may be allergic to serum serum sickness

Cell-mediated immunity ;T lymphocytes

 T cells do not secrete antibodies but directly contact their targets.

Contains receptor proteins called T-cell receptors ( TCRs)

Are only activated by foreign antigen when it is on the surface of a cell that also
carries marker of individuals identity
o Example: both foreign antigens and self antigens ( MHC molecules) must be
on a cells surface before a T cell can bind with it
Mechanism:
o A delay of few days generally follows exposure to the appropriate antigen
before activated T cells are prepared to launch cell-mediated immune attack.
o When exposed to specific antigen combination, cells of complementary T cell
clone proliferate and differentiate , yielding large number
o T cells will also form memory pool and displays primary and secondary
responses
o Primary response ;
Initiated in lymphoid tissue
90% of T cells in primary response die by apoptosis after infection is
cleared
o Once pathogen is gone, majority of lymphocytes commit suicide because
antigens and stimulatory signals are withdrawn
This prevents congestion in lymphoid tissue
o Remaining surviving T cells become memory T cells that migrate to all area of
bodies, ready for a secondary response

1. Types of T cells:
Classified by function : Cytotoxic T cells , helper T cells, regulatory T cells
Classified by specific membrane protein type: CD8+ T cells, CD4+ T cells, CD4+CD25+
T cells
i.
Cytotoxic (killer) T cells
Destroy invaded hosts cells which bear foreign antigen ( eg: body cells invaded by
virus, cancer cells that have mutated proteins)
TCR associated with coreceptors designated CD8, which are inserted into plasma
membrane as these cells pass through the thymus.
ii.

Helper T cells
Do not directly participate in immune destruction of pathogens
Turn on and activate lymphocytes and macrophages
Makes up 60-80% of circulating T cells
Can be subdivided into two subsets T helper 1 (TH1) , T helper 2(TH2)
o TH1
Rally cell mediated ( killer T cell) response for viruses
activated by IL-12
o

TH2

Promotes antibody-mediated immunity by B cells

Activate eosinophils for defense against parasitic worm

iii.

Activated by IL-4
TH17(new subclass)
Produces IL-17.
IL-6 from macrophages guide their production
Promote inflammation; effector molecules in development of
inflammatory autoimmune disease

Regulatory T cells/ suppressor T cells

Have same CD4 coreceptors as helper T cells, in addition CD25 ( component of
receptor for IL-2 which promotes Treg activities)
Represent 5-10% of CD4 cells suppress immune responses
Inhibit both innate and adaptive immune responses in check-and-balance fashion to
minimize harmful immune pathology
Contains large amount of intracellular protein Foxp3 that turns developing T cells in
Tregs and thus quieting other immune cells.

2. T killer cells role in immune system

Mechanism:
Upon invasion of virus, viral antigen loaded
onto newly synthesized MHC self-antigen of
host cell.
Self antigen and viral antigen complex
inserted into host cells surface membrane,
serving as a red flag
Cytotoxic T cells of clone that is specific for
particular virus recognize and bind to viral
antigen and self antigen on surface of infected
cell.
T killer cells can kill in 2 ways: direct, indirect
1. Direct attack:
Releases chemicals that lyse
invaded cell before viral
replication can begin
T killer cells and Nk cells destroy
by releasing perforing molecules
which penetrate cells surface
membrane and join to form
porelike channels.
Same method of killing as
membrane attack complex (MAC)
of complement cascade
2. Indirect attack:
Releases granzyme ( enzymes similar to digestive enzymes)

Granzymes enter target cell

through perforin channels.
Once inside, these chemicals
trigger virus-infected cell to self
destruct through apoptosis
Upon released of virus in ECF, it is destroyed
by phagocytic cells, neutralizing antibodies
and complement system
Surrounding healthy cells replace lost cells by
cell division
To stop virus infection, some of the host cells
must be destroyed ( sometimes T killer cells
sacrifice loads of host cells when virus
replicated )

3. T helper cells in immune response

Secrete cytokines that aid in nearly all aspect of immune system
Chemicals secreted by T helper cells:
a. IL-4,IL-5,IL-6 that serve as B cell growth factor contributing in B cell
function in concert with IL-1 secreted by macrophages
IL-4 promotes development of IgE antibodies for defense against
parasitic worms
IL-5 activates eosinophils

b. IL-2 T-cell growth factor which increases activity of T killer cells and other
helper T cells
IL-1 secreted by macrophage not only enhances activity of B and T cells
but alsmo stimulate secretion of IL-2 by activated helper T cells
c. Chemicals act as chemotaxin luring more neutrophils and macrophage-to-be
d. Macrophage-migration inhibition factor released once macrophages attracted
to area.
Keeps large phagocytic cells by inhibiting outward migration
Resulting more attraction of macrophages in injured area
This factor also makes macrophages phagocytic power [ angry
macrophage important in defending against bacteria that causes TB

because the microbes can survive simple phagocytosis by nonactivated

macrophages]
In order to perform tasks, T cells must be introduced to antigens first.
Antigen presenting cells(APCs) process and process antigen, complexed with MHC
molecule on their surface to T cells.
APCs include : macrophages and dendritic cells

Dendritic cells abundant in the skin and mucosal lining of lungs and
digestive tracts
After exposure to appropriate antigens, dendritic cells migrate
through lymphatic system to lymph nodes and activate T cells

Mechanism:
1. Dendritic cells
phagocytize
invading bacteria :
2. Endocytic vesicle
containing engulfed
bacteria fuses with
lysosome, which
break down
bacteriums protein
into antigenic
peptides

3. Each antigenic
peptide then binds
to newly
synthesized MHC
molecule within the endoplasmic reticulum/Golgi complex
4. Peptides load onto MHC through organelle within APC ( compartment for
peptide loading )
5. MHC then transport bound antigen to cell surface, where it is presented to
pass T lymphocytes
6. When helper T cells bind to APC, APC secrete cytokines IL-1 and TNF which
activates T cells
7. Activated T cells then secrete cytokines in autocrine manner to stimulate
clonal expansion of the particular helped T cell which acts in a paracrine
manner on adjacent B cells, cytotoxic T cells and NK cells enhancing their
ability

MHC

Each person has two main classes of MHC encoded

o MHC Class I recognized by cytotoxic T cells
o MHC class II recognized by T helper cells
Class I and II markers serve to guide both T cells to precise cellular location
Coreceptors on T cells bind with MHC molecule on target molecules, linking both cells
together

Class I MHC glycoproteins:

o Cytotoxic T cells can only respond to foreign antigens associated with class I
MHC glycoprotein which are only found on body cells with nucleus
o Cytotoxic T cells can only bind to invaded cells, and cancer cells ( because class I
MHC molecule also display mutate cellular proteins characteristics of these
abnormal cells)
Class II MHC glycoproteins
o Recognized by helper T cells
o Restricted to surface of few special types of immune cells ( macrophages,
dendritic cells) , B cells