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

Nursing College, Second Stage Immunology Assist.Professor Dr. Mays Hadi

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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.

Nursing College, Second Stage Immunology Assist.Professor Dr. Mays Hadi

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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

Nursing College, Second Stage Immunology Assist.Professor Dr. Mays Hadi

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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

Nursing College, Second Stage Immunology Assist.Professor Dr. Mays Hadi

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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

Nursing College, Second Stage Immunology Assist.Professor Dr. Mays Hadi

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Figure 5-A: Antibody Forms

Nursing College, Second Stage Immunology Assist.Professor Dr. Mays Hadi

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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).

Nursing College, Second Stage Immunology Assist.Professor Dr. Mays Hadi

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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.