ADAPTIVE IMMUNITY (SPECIFIC/ACQUIRED IMMUNITY)

• Is the type of host defense that is stimulated by microbes or

foreign substances that invade tissues, that is it adapts to
the presence of microbial invaders.
• The adaptive immune system has three major functions:
1. To recognize anything that is foreign to the body
(nonself)
2. To respond to this foreign material
3. To remember the foreign invader
• Adaptive immunity is capable of recognizing and selectively
eliminating specific foreign microorganisms and molecules
(foreign antigens).
• Adaptive immune responses are not the same in all
members of a species but are reactions to specific antigenic
challenge.
Characteristic features/attributes displayed by adaptive
immunity
i. Antigenic specificity
ii. Diversity
iii. Immunologic memory
iv. Self/nonself recognition
 i. Antigenic specificity
• This permits the immune system to distinguish subtle/fine
differences among antigens.
• Antibodies can distinguish between two protein molecules
that differ in only a single amino acid.
ii. Diversity
• The system is able to generate an enormous diversity of
molecules such as antibodies that recognize billions of
different antigens.
 iii. Immunologic memory
• Once the immune system has recognized and responded to
an antigen, it exhibits an immunologic memory, that is, a
second encounter with the same antigen induces a
heightened state of immune reactivity.
• This makes the immune system to confer life-long immunity
to many infectious agents after an initial encounter (when
re-exposed to the same pathogen or substance, the body
reacts so quickly that there is no noticeable pathogenesis)
• The immune system mounts larger and more effective
responses to repeated exposures to the same antigen.
• The response to the first exposure to antigen, called the
primary immune response is mediated by lymphocytes,
called naïve lymphocytes—that are seeing/encountering
antigen for the first time.
• Naïve lymphocytes are the cells that are immunologically
inexperienced, not having previously recognized and
responded to antigens.
• Subsequent exposures with the same antigen lead to
secondary responses, which are usually more rapid, larger and
better able to eliminate the antigen than are the primary
responses.
• Secondary responses are the results of the activation of
memory lymphocytes which are long-lived cells that were
induced during the primary immune response.
• Immunologic memory optimizes the ability of the immune
system to combat persistent and recurrent infections, because
each encounter with a microbe generates more memory cells
and activates previously generated memory cells.
• Memory is one of the reasons why vaccines confer long-
lasting protection against infections.
 iv. Self/nonself recognition-discrimination between self
and nonself
• The ability of the immune system to distinguish self from
nonself and respond only to nonself molecules.
• Self-the host’s own antigenic substances. All immune
responses are self-limited and decline as the infection is
eliminated, allowing the system to return to a resting state,
prepared to respond to another infection.
• The failure to discriminate between self and nonself could
lead to the synthesis of antibodies directed against
components of the subject’s own body (autoantibodies)
• An effective adaptive immune system requires the
cooperation of/between 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.
• 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.
• There are three major populations of lymphocytes:
i. B lymphocytes
ii. T lymphocytes
iii. Natural killer cells
• Lymphocytes are the only cells with specific receptors for
antigens and are thus the key mediators of adaptive
immunity.
 B Lymphocytes
• B lymphocytes arise and mature within the bone marrow;
when they leave it, each expresses a unique antigen-binding
receptor on its membrane.
• This antigen-binding or B- cell receptor is a membrane-
bound antibody molecule. The B-cell receptors recognize
antigens and initiate the process of activation of the cells.
• When a naïve B cell (one that has not previously
encountered antigen) first encounters the antigen that
matches its membrane-bound antibody, the binding of the
antigen to the antibody causes the cell to divide rapidly; its
progeny differentiate into memory B cells and effector B
cells called plasma cells.
• B cells + antigen= effector B cells + memory B cells
(plasma cells)
• Memory B cells have a longer life span than naïve cells, and
they express the same membrane-bound antibody as their
parent B cells.
• Plasma cells produce the antibody in a form that can be
secreted and have little or no membrane-bound antibody.
• Although plasma cells live for only a few days, they secrete
enormous amounts of antibody during this time-2000/sec.
• Secreted antibodies are the major effector molecules of
humoral immunity.
 T-LYMPHOCYTES

• T-lymphocytes arise in the bone marrow, but they migrate to

the thymus gland to mature.
• During the maturation within the thymus, the T cells come
to express a unique antigen-binding molecule called the T-
cell receptor, on the membrane.
• T-cell receptors can recognize only antigen that is bound to
cell membrane proteins called Major Histocompatibility
Complex (MHC) molecules.
• MHC molecules that function in this recognition event
termed “antigen presentation” are polymorphic (genetically
diverse) glycoproteins found on cell membrane
• There are three major types of MHC molecules:
i. Class I MHC molecules- expressed by nearly all nucleated
cells of vertebrate species
ii. Class II MHC molecules—expressed only by antigen-
presenting cells.
iii. Class III MHC molecules
• When a naïve T cell encounters antigen combined with a
MHC molecule on a cell, the T cell proliferates and
differentiates into memory T cells and various effector T
cells.
T cells + antigen = effector T cells + memory T cells
(E.g., CTLs, THs)
 T cells have 3 subpopulations;
i. T helper (TH) cells
ii. T cytotoxic (TC) cells
iii. T suppressor (TS) is not distinct from TH and TC.
• T helper and T cytotoxic cells can be distinguished from one
another by the presence of either CD4 or CD8 membrane
glycoproteins on their surface.
• T cells displaying CD4 function as TH cells, whereas those
displaying CD8 function as TC cells.
• After a TH cell recognizes and interacts with an antigen-MHC class
II molecule complex, the cell is activated-it becomes an effector
cell that secretes various growth factors known collectively as
cytokines, which play an important role in activating B cells, TC
cells, macrophages and other immune response cells.
• A TC cell that recognizes an antigen-MHC class I molecule
complex under the influence of TH-derived cytokines, proliferates
and differentiates into an effector cell called cytotoxic T
lymphocytes (CTL).
• In contrast to the TC cell, the CTL generally does not secrete many
cytokines and instead exhibits cell-killing or cytotoxic activity.
• The CTL has a vital/important function in monitoring the cells of
the body and eliminating any that display antigen, such as virus-
infected cells, tumor cells and cells of foreign tissue graft.
• Cells that display foreign antigen complexed with a Class I MHC
molecule are called altered self –cells; these are targets of CTLs.
 ANTIGEN-PRESENTING CELLS

• Cytokines produced by TH cells are required for the

activation of both the humoral and cell-mediated
branches of the immune system.
• It is essential that the activation of TH cells themselves be
carefully regulated, because an inappropriate T- cell
response to the self components can cause fatal
autoimmune consequences.
• To avoid response to the self components, TH cells can
recognize only antigen that is displayed together with
Class II MHC molecule on the surface of antigen
presenting cells (APCs)
• APCs are specialized cells, and they include;
macrophages, B lymphocytes and dendritic cells.
• The APCs are distinguished by 2 properties:
i. They express Class II MHC molecules on their
membranes.
ii. They are able to deliver a co-stimulatory signal that is
necessary for TH cell activation.
• Antigen presenting cells first internalize antigen, either by
phagocytosis or by endocytosis, and then display a part of
that antigen on their membrane bound to a class II MHC
molecule.
• The TH cell recognizes and interacts with the antigen-class II
MHC molecule complex on the membrane of APC. An
additional co-stimulatory signal is then produced by the
antigen-presenting cell, leading to activation of the TH cell.