Acquired immunity

Acquired or adaptive immunity is the form of immunity that is mediated by

lymphocytes and is stimulated by exposure to infectious agents. The human
immune system recognizes foreign substances as not belonging to the body and it
develops an immune response against them. Organisms or substances that provoke
such a response are called antigens. This immune response involves the
production of proteins called antibodies and specialized lymphocytes, both of
them are specifically targeted for the antigens that cause their formation, and they
can destroy and inactivate those antigens if they encounter them again.

Acquired immunity is developed during an individual’s lifetime, and it can be

acquired either actively or passively. Immunity is acquired ACTIVELY when a
person is exposed to microorganisms or foreign substances and the immune system
responds. Immunity is acquired PASSIVELY when the antibodies are transferred
from one person to another. Passive immunity in the recipient lasts only as long as
antibodies are present, in most cases a few weeks or months. Both actively
acquired and passively acquired immunity can be obtained by natural or artificial
means.

NATURALLY ACQUIRED IMMUNITY:

 Naturally acquired active immunity: is obtained when a person

is exposed to antigens in the course of daily life. Once acquired,
immunity is lifelong for some diseased.
 Naturally acquired passive immunity: involves the natural
transfer of antibodies from mother to her fetus across the placenta
a mechanism known as placental transfer. If the mother is
immune to certain disease, the newborn will be temporarily
immune to these diseases as well.
 Certain antibodies are also passed from the mother to her nursing
infant in breast milk, especially in the first secretions called
colostrum. In the infant, immunity generally lasts only as long as
the transmitted antibodies are present, usually a few weeks or
months. These maternal antibodies are essential for providing
immunity to the infant until its own immune system matures.
ARTIFICIALLY ACQUIRED IMMUNITY:
 Artificially acquired active immunity: results from vaccination.
Vaccination also called immunization, introduces specially
prepared antigens- called vaccines into the body. Vaccines may be
inactivated bacterial toxins or killed microorganisms. These
substances can no longer cause disease, but they can still stimulate
an immune response.
 Artificially acquired passive immunity: involves the introduction
of antibodies (rather than antigens) into the body. These antibodies
come from an animal or person who is already immune to the
disease
When an antibody from an individual who is immune to a disease
is injected into the body, it confers immediate protection against
the disease. However, although artificially acquired passive
immunity is immediate it is short-lived because antibodies are
degraded by the recipient.
 Humoral (antibody mediated) immunity
Humoral immunity, or antibody-mediated immunity, involves the production of
antibodies that act against foreign organisms and substances. These antibodies are
found in extracellular fluids, such as blood plasma, lymph and mucus secretions.
Cells called B cells (or B lymphocytes) are responsible for the production of
antibodies. The humoral immune response defends primarily against bacteria,
bacterial toxins, and viruses that are circulating freely in the body fluids.

B lymphocyte Maturation
Maturation of lymphocytes from bone-marrow stem cells consist of 3 types
of processes, proliferation of immature cells, expression of antigen receptor
genes and selection of lymph that express useful antigen receptors. B cell
maturation depends on the rearrangement of the Ig DNA in the
hematopoietic stem cells, Generation of mature immunocompetent B cells
(maturation), Activation of mature B cells when they interact with antigen,
differentiation of activated B cells into plasma & memory B cells.
Lymphoid stem cells differentiate into progenitor B cell (pro-B cell).expressing a
tyrosine phosphatase called CD45 R. Pro-B cells proliferate within bone-marrow.
Pro-B differentiates into Pre-B cell in microenvironment provided by bone-marrow
stromal cells. Stromal cells interact directly with pro and pre B cells, secrete IL-7.

In pre-B cell, membrane  chain is associated with an unusual light chain complex
called “surrogate light chain”. Complex consists of 2 proteins: a V-like sequence
called V pre-B & a C-like sequence called 5, which associate non-covalently to
form a light-chain structure. Surrogate light chain appears on the pre-Bcell as a
complex consisting of the membrane bound  heavy chain and Surrogate light
chain associated with the Surrogate light chain heterodimer to form the pre-B cell
receptor.
Developmental progression is typified by a changing pattern of surface
markers:

 Pro-B stage: No heavy or light chains but CD45R plus Ig alpha\Ig beta.
  Pre-B Cells: begin to express CD25, chain of IL-2 receptor+ Pre-BCR.
 Immature B cells: loose pre-BCR & no longer express CD25 + IgM.
 Naïve mature B cells: IgD joins IgM.

While Bone-marrow produces 5 x 107 B cells\day, 90% die by apoptosis. Death

is due to negative selection & subsequent elimination (clonal deletion) of
immature B cells that express autoantibodies against self-antigens in the bone
marrow.

Mature B cells that are exported from bone marrow, their activation, proliferation
and differentiation occur in the periphery and require antigen.

Mechanism of humoral immunity:

Stimulation of B lymphocytes by antigen (T-dependent). Humoral immune
responses are initiated when antigen-specific B lymphocytes in the spleen, lymph
nodes, and mucosal lymphoid tissues recognize antigens. B lymphocytes specific
for an antigen use their membrane-bound immunoglobulin (IgM and IgD)
receptors to recognize the antigen in its native conformation (without need for
processing).

Antigen -induced signaling in B cells. Generally, antigen contact alone is not

sufficient to activate B-cell, because most protein antigens are T-dependent
antigens, which require the interaction with T-helper cells.

The antigen is processed and epitopes appear on the surface in conjunction with
class- II MHC proteins. B cells are used as the antigen presenting cells.

This complex is recognized by a helper T-cell with a TCR on its surface. The T-
helper cells now produce various cytokines, IL-2, IL-4, and IL-5 that stimulate the
growth and differentiation of the B cells to plasma cells.

Two co-stimulatory interactions are required for activation of B cells to produce a

full range of antibodies:

 CD28 on the T-helper cell must interact with B7 (B71, B72) on the B cell for
activation of T cells to produce IL-2.
  CD40 L on the T-cells must interact with CD40 on the B cell for class
switching from IgM to IgG and other immunoglobulin class to occur.

As mentioned previously, some of these activated B cells differentiate into plasma

cells, which secrete antibodies against the antigen. Each plasma cell lives only for
a few days but can produce about 2000 antibody molecules per second these
plasma cells produce antibodies with highest affinity to bind to the antigen.
Stimulation of a B cell by an antigen also results in the production of a population
of cells called memory cell, which function in long-term immunity, and are
capable of being activated rapidly.

Most memory cells have surface IgG that serves as the antigen receptor, but some
have IgM. The presence of these cells explains the rapid appearance of antibodies
in the secondary response.

Antibody responses to T-independent antigens:

Polysaccharides, lipids, and other non-protein antigens elicit antibody responses

without the participation of helper T cells. Recall that these nonprotein antigens
cannot bind to MHC molecules, so they cannot be seen by T cells. Many bacteria
contain polysaccharide-rich capsules, and defense against such bacteria is mediated
primarily by antibodies that bind to capsular polysaccharides.

Antibody responses to T-independent antigens differ in many respects from

responses to proteins, and most of these differences are attributed to the role of
helper T cells in antibody responses to proteins. It is though that because
polysaccharide and lipid antigens often contain multivalent arrays of the same
epitope, these antigens are able to cross-link many antigen receptors on specific B
cell. This extensive cross-linking may activate the B cells strongly enough to
stimulate their proliferation and differentiation without requirement for T cell help.

Effector mechanism of humoral immunity:

1-Effector functions of antibodies:
 Opsonization.
 Antibodies (IgM, IgG) can activate complement system.
 Antibody dependent cell-mediated cytotoxicity (ADCC)
  Neonatal immunity.
 Neutralization of toxins and viruses.

2- Effector functions of complement:

 Opsonization.
 Anaphylatoxins.
 Immune clearance
 Mediation of inflammatory reactions
 Lysis of target cell.

3- Biological function of cytokines:

Among the numerous physiologic responses that require cytokine
involvement are development of cellular and humoral immune responses,
induction of inflammatory response, regulation of hematopoiesis, control
of cellular proliferation and differentiation, and the healing of wounds.