Nursing College, Second Stage Immunology Assist.Professor ...
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Nursing College, Second Stage Immunology Assist.Professor Dr. Mays Hadi
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2-The adaptive (specific) immune system makes antibodies and uses them to
specifically fight certain germs that the body has previously come into contact with.
This is also known as an “acquired” (learned) or specific immune response.
Because the adaptive immune system is constantly learning and adapting, the body
can also fight bacteria or viruses that change over time.
Adaptive immune system, which is composed of lymphocytes (also called
lymphoid cells) and their secreted factors
A critical property of adaptive immunity is that the immune response is specifically
tailored against different microbes. This is achieved by first generating an enormous
number of diverse lymphocytes, each with a unique antigen specificity.
The immune system has the capability of self and non-self-recognition.
Human leukocyte antigens (HLA) are a group of identification molecules located
on the surface of all cells in a combination that is almost unique for each person,
thereby enabling the body to distinguish self from nonself. This group of
identification molecules is also called the major histocompatibility complex.
The human leukocyte antigen (HLA) system (the major histocompatibility
complex [MHC] in humans) is an important part of the immune system and is
controlled by genes located on chromosome 6. It encodes cell surface molecules
specialized to present antigenic peptides to the T-cell receptor (TCR) on T cells.
These cell-surface proteins are responsible for the regulation of the immune system.
Major histocompatibility complex (MHC), group of genes that code for proteins
found on the surfaces of cells that help the immune system recognize foreign
substances. MHC proteins are found in all higher vertebrates. In human beings the
complex is also called the human leukocyte antigen (HLA) system.
Nursing College, Second Stage Immunology Assist.Professor Dr. Mays Hadi
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An antigen is a substance that ignites the immune response. The cells involved in
recognizing the antigen are Lymphocytes. Once they recognize, they secrete
antibodies. Antibodies are proteins that neutralize the disease-causing
microorganisms. Antibodies don’t directly kill pathogens, but instead identify
antigens as targets for destruction by other immune cells such as phagocytes or NK
cells.
The humoral (antibody) response is defined as the interaction between
antibodies and antigens.
Antibodies are specific proteins released from a certain
class of immune cells known as B lymphocytes, while antigens are defined as
anything that elicits the generation of antibodies.
ORIGIN OF LYMPHOID CELLS
All white and red blood cells originate from stem cells in the fetal liver and yolk sac
during embryonic life and in the bone marrow after birth. The common lymphoid
progenitor is a type of stem cell that gives rise to lymphocytes of the adaptive
immune system, including B cells and T cells. The common lymphoid progenitor is
also the source of innate lymphocytes, such as natural killer (NK) cells. The process
by which common lymphoid progenitors develop into lymphocytes depends on
cytokines.
The ratio of T cells to B cells is approximately 3:1. Often T cells are named by
markers we can detect on their cell surface, called “cluster of differentiation”
(CD) markers: helper T cells are CD4-positive (CD4+), whereas cytotoxic T cells are
CD8-positive (CD8+).
Nursing College, Second Stage Immunology Assist.Professor Dr. Mays Hadi
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FIGURE 3- Origin of Immunity Cells
Adaptive Immunity: T-Cell–Mediated Immunity
Cell-mediated immunity is an immune response that does not involve antibodies.
Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific
cytotoxic T-lymphocytes, and the release of various cytokines in response to
antigen. CD4 cells or helper T cells provide protection against different
pathogens. Naive T cells, which are immature T cells that have yet to encounter
an antigen, are converted into activated effector T cells after encountering antigen-
presenting cells (APCs). These APCs, such as macrophages, dendritic cells, which
phagocytize microbes and present antigens to T cells.
Nursing College, Second Stage Immunology Assist.Professor Dr. Mays Hadi
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effector/helper CD4-positive T cells, which use antigen receptors to recognize
antigen and make cytokines that enhance or suppress immune functions; cytotoxic
CD8-positive T cells, which use antigen receptors to detect and kill infected cells.
that it is critically dependent on cytokines produced by these cells. Although the
interactions between various cells are complex, the result is relatively
simple: opportunistic microbes only cause disease when T-cell–mediated immunity
is compromised.
ACTIVATION OF T CELLS
lymphocyte precursors develop into mature B cells and T cells in the bone marrow
and thymus, respectively, and these are therefore called primary lymphoid organs .
The result is an enormous diversity of adaptive immune cell “clones,” and each clone
has a unique and specific antigen receptor, which is either a B-cell receptor (BCR) or
a T-cell receptor (TCR). At this stage, a lymphocyte is considered mature, because it
has a functional antigen receptor, but naïve, because it has not yet encountered a
foreign antigen that can strongly bind to its TCR or BCR. Note that only a few
lymphocyte clones might be specific for any given antigen.
Nursing College, Second Stage Immunology Assist.Professor Dr. Mays Hadi
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FIGURE 4- Development of naïve lymphocytes. Common lymphoid progenitors
give rise to B-cell precursors, which develop into mature B lymphocytes in the bone
marrow, and T cell precursors, which leave the bone marrow and complete their
development into mature CD4-positive and CD8-positive T cells in the thymus.
Mature naïve lymphocytes migrate throughout the secondary lymphoid
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Secondary lymphoid organs concentrate and filter antigenic material so that
immune cells can sample it and remove it if necessary. After lymphocytes complete
their maturation ,they exit to circulate through the secondary lymphoid organs
via blood and lymphatic vessels.
Adaptive Immunity: (Antibody mediated immunity or Humoral immunity).
INTRODUCTION
B cells perform two important functions: (1) they differentiate into plasma cells that
produce antibodies and (2) they differentiate into long-lasting memory cells that
respond robustly and rapidly to reinfection. Antibodies are the principal defense used
by the immune system to prevent infection, because by binding to the microbes’
surfaces they can inhibit them from attaching to target cells and/or recruit innate
immune killing mechanisms. Antibodies can also inhibit toxins such as those made
by tetanus and diphtheria. Nearly all vaccines are designed to generate these
protective, or neutralizing, antibodies.
Advances in cell biology have allowed the generation of large quantities of
engineered antibodies. The ability of these antibodies to strongly bind a specific
antigen with very limited “cross-reactive” binding of other antigens is the basis for
many common diagnostic tests and an increasing array of therapies for cancer and
inflammatory and infectious diseases.
B-CELL MATURATION
B cells come from stem cells called common lymphoid progenitors, which give rise
to all lymphocytes. Unlike T cells, B cell precursors differentiate into fully functional
B cells in the bone marrow. They do not pass through the thymus. Like T cells, every
mature B cell has a B cell receptor (BCR). A mature B cell that enters the circulation
to bind with the antigen.
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Antiodies, Immunoglobulin classes (IgG, IgM, IgD, IgE and IgA):-
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-
shaped protein produced mainly by plasma cells that is used by the immune system to
neutralize pathogens such as pathogenic bacteria and viruses. The antibody
recognizes a unique molecule of the pathogen, called an antigen, via the fragment
antigen-binding (Fab) variable region. Each tip of the "Y" of an antibody contains
a paratope (analogous to a lock) that is specific for one particular epitope (analogous
to a key) on an antigen, allowing these two structures to bind together with precision.
Using this binding mechanism, an antibody can tag a microbe or an infected cell for
attack by other parts of the immune system, or can neutralize its target directly (for
example, by inhibiting a part of a microbe that is essential for its invasion and
survival). Depending on the antigen, the binding may impede the biological process
causing the disease or may activate macrophages to destroy the foreign substance.
The ability of an antibody to communicate with the other components of the immune
system is mediated via its Fc region (located at the base of the "Y"), The production
of antibodies is the main function of the humoral immune system.
Maternal factors also play a role in the body’s immune response. At birth, most of
the immunoglobulin present is maternal IgG. Because IgM, IgD, IgE and IgA don’t
cross the placenta, they are almost undetectable at birth. Some IgA is provided
by breast milk. These passively-acquired antibodies can protect the newborn for up to
18 months, but their response is usually short-lived and of low affinity .
Antibodies can come in different varieties known as isotypes or classes. In mammals
there are five antibody isotypes known as IgA, IgD, IgE, IgG, and IgM. They are
each named with an "Ig" prefix that stands for immunoglobulin (a name sometimes
used interchangeably with antibody) and differ in their biological properties,
functional locations and ability to deal with different antigens, as depicted in the
table. The different suffixes of the antibody isotypes denote the different types of
heavy chains the antibody contains, with each heavy chain class named
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alphabetically: α (alpha), γ (gamma), δ (delta), ε (epsilon), and μ (mu). This gives rise
to IgA, IgG, IgD, IgE, and IgM, respectively.
The types of antibodies:-
IgG
This isoform accounts for 70–75% of all human immunoglobulins found in the blood.
Depending on the molecular weight of the antibody, IgG can be further divided into 4
subclasses: IgG1, IgG2, IgG3, and IgG4.
In addition, IgG triggers phagocytosis to initiate opsonization reaction – a process
used to destroy foreign particles (e.g. bacteria) . Apart from these functions, IgG is
the only antibody that can cross the placenta and provides passive immunity to the
fetus and infants in the first few months of life.
IgM
IgM is the largest antibody and the first one to be synthesized in response to an
antigen or microbe, accounting for 5% of all immunoglobulins present in the blood.
IgM typically exists as polymers of identical subunits, with a pentameric form as the
prevalent one.
In its pentameric form, five basic antibody units are attached by disulfide bonds.
Other forms include secretory IgM, which is synthesized by glandular-associated B
cells, and monomeric form, which is present in the B cell membrane and functions as
a B cell antigen receptor.
pentameric IgM has 10 antigen binding sites, it has higher avidity (overall binding
strength) for antigens than IgG and acts as an excellent activator of the complement
system.
IgA
It accounts for 10–15% of all immunoglobulins and is prevalent in serum, nasal
mucus, saliva, breast milk, and intestinal fluid. It has two subtypes namely IgA1 and
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IgA2, which mainly differ in terms of their hinge region characteristics. At mucosal
surfaces, IgA provides the primary defense against inhaled and ingested pathogens.
IgE
IgE is the least prevalent one, with a serum concentration 10,000 times lower than
IgG. However, the concentration of IgE increases significantly in allergic conditions,
such as bronchopulmonary aspergillosis, and parasitic diseases, such as
schistosomiasis.
In response to pathogens, IgE binds to mast cells via specific receptors, followed by
pathogen-mediated cross-linking of these receptors (degranulation). This causes
recruitment of eosinophil at the site of infection and destruction of pathogens via
ADCC-type mechanisms.
IgD
IgD functions as a B cell antigen receptor and may participate in B cell maturation,
maintenance, activation, and silencing. Although the exact function is still unclear
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Figure 5-A: Antibody Forms
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Figure 4-B:- An illustration that shows how antigens induce the immune
system response by interacting with an antibody that matches the
antigen's molecular structure.
The main categories of antibody action include the following:
• Antibodies are secreted into the blood and mucosa, where they bind to
and inactivate foreign substances such as pathogens and toxins
(neutralization).
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• Antibodies activate the complement system to destroy bacterial cells
by lysis (holes in the cell wall).
• Antibodies facilitate phagocytosis of foreign substances by phagocytic
cells (opsonization).
Activated B cells differentiate into either antibody-producing cells called plasma
cells that secrete soluble antibody or memory cells that survive in the body for years
afterward in order to allow the immune system to remember an antigen and respond
faster upon future exposure.
Figure 6:- (1) Antibodies (A) and pathogens (B) free roam in the blood. 2) The
antibodies bind to pathogens,. 3) A phagocyte (C) approaches the pathogen, and the
Fc region (D) of the antibody binds to one of the Fc receptors (E) of the phagocyte. 4)
Phagocytosis occurs as the pathogen is ingested.
B-CELL ACTIVATION
B cells constitute about 30% of the recirculating pool of small lymphocytes, and their
life span is short (i.e., days or weeks). Within lymph nodes, they are located
in follicles; within the spleen, they are found in the white pulp.
Reactions of antigens and antibodies are highly specific. An antibody will react
only with the antigen that induced it or with a closely related antigen. Because of the
great specificity, reactions between antigens and antibodies are suitable for
identifying one by using the other. This is the basis of serologic reactions.