Immune SystemThe body’s defense against disease causing organisms, malfunctioning cells, and foreign particles.

Host – human body!!!!

Foreign macromolecule, antigen – e.g. virus protein, worm, parasite (Everything that should not be in human body)

• Innate immunity: • It is non specific immunity• It is the natural resistance with which a person is born. • It provides resistance through following barriers:

1. Anatomic barriers (Skin,mucous membranes)

2. Physological barriers (temperature, pH)

3. Phagocytic Barriers (cells that eat invaders) • Adaptive (or acquired) immunity :• It is specific immunity• It occurs after an exposure to an antigen.• Creates immunological memory after an initial response to a

specific pathogen, leading to an enhanced response to subsequent encounters with that same pathogen.

Active and Passive Immunity• Passive immunity: Transfer of Ab with a given

specificity; • Passive immunity is the transfer of active

immunity, in the form of readymade antibodies, from one individual to another

• Important forMother to new bornShort term

• Active immunity: Production of Ab in host when it comes in direct contact with Ag.

Long term

Cells of the immune systemLymphocytesLymphocytes constitute 20%–40% of the body’s white

blood cells and 99% of the cells in the lymph. There are approximately 1011 (range depending on

body size and age: ~1010–1012) lymphocytes in the human body.

These lymphocytes continually circulate in the blood and lymph and are capable of migrating into the tissue spaces and lymphoid organs.

The lymphocytes can be broadly subdivided into three populations—

B cells, T cells, and natural killer cells

• Lymphocytes proliferate and eventually differentiate into

• Memory cells• Effector cells 1. MEMORY CELLS:• Some of the progeny of B and T

lymphoblasts differentiate into memory cells.

• Memory cells look like small lymphocytes but can be distinguished from naive cells by the presence or absence of certain cell membrane molecules.

2. EFFECTOR CELLS

• Effector cells function in various ways to eliminate antigen. (have short life span)

• Effector cells of the B cell are called the Plasma cells—the antibody-secreting

• The effector cells of the T-cell include – T helper cell (TH cell)

– T cytotoxic cell (TC cell).

B Lymphocytes

• Mature in Bursa of Fabricus/bone marrow.

• Mature B cells are distinguished from other lymphocytes as they have membrane-bound antibody molecules which serve as receptors for antigen. They are known as B-cell antigen receptor (BCR).

• Interaction between antigen and the membrane-bound antibody on a mature B cell, as well as interactions with T cells and macrophages, causes activation of B cells.

• In this process, the B cell divides repeatedly and differentiates over a 4- to 5-day period, generating a population of plasma cells (effector cells of B lymphocytes) and memory cells.

• They also act as antigen-presenting cells.

Major Histocompatibility complex (MHC)

• The Major Histocompatibility Complex (MHC) is a set of molecules displayed on cell surfaces that are responsible for lymphocyte recognition and "antigen presentation".

• MHC class II normally occurs only on antigen-presenting cells (APCs)

• MHC class I occurs on all nucleated cells

T- LymphocytesMaturation in thymus.Like B lymphocytes, these cells have membrane receptors for

antigen named as T-cell receptor (TCR) . TCR recognizes only antigen that is bound to particular classes

of antigen-presenting cells or on virus-infected cells, cancer cells.

Most T cells recognize antigen only when it is bound to the major histocompatibility complex (MHC).

All T-cell receptors can be distinguished by the presence of one or the other of two membrane molecules, CD4 and CD8.

T cells that express the membrane glycoprotein molecule CD4 are restricted to recognizing antigen bound to class II MHC molecules, whereas

T cells expressing CD8, a dimeric membrane glycoprotein, are restricted to recognition of antigen bound to class I MHC molecules.

CD4 T cells generally function as T helper (TH) cells and are class-II restricted;

CD8 T cells generally function as T cytotoxic (TC) cells and are class-I restricted.

TH cells are activated by recognition of an antigen–class II MHC complex on an antigen-presenting cell.

After activation, the TH cell begins to divide and gives rise to effector cells.

These TH cells secrete various cytokines, which play a central role in the activation of B cells and T cells.

A cytotoxic T cell is a T lymphocyte that kills cancer cells, cells that are infected (particularly with viruses), or cells that are damaged in other ways.

Cell-mediated immunity

• Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of phagocytes, natural killer cells (NK), cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen by T lymphocytes.

Humoral Immunity

• The humoral immunity is the aspect of immunity that is mediated by secreted antibodies produced in the cells of the B lymphocyte.

• B Cells transform into plasma cells which secrete antibodies. Secreted antibodies bind to antigens on the surfaces of invading microbes (such as viruses or bacteria), which marks them for destruction.

Overview of Humoral Immunity• Ingestion (phagocytosis) of foreign matter by special blood cells called

macrophages. • The macrophages digest the infectious agent and then display some of

its components on their surfaces. • Cells called helper-T cells recognize this presentation.• Activated helper-T cells use chemical signals to contact B-cells, which

then begin to multiply rapidly as well. • B-cell descendants become either plasma cells or B memory cells. • The plasma cells begin to manufacture huge quantities of antibodies

that will bind to the foreign invader (the antigen) and prime it for destruction. B memory cells retain a "memory" of the specific antigen that can be used to mobilize the immune system faster if the body encounters the antigen later in life.

Overview of cell mediated immunity

• The cell-mediated immune response involves cytotoxic T-cells, or killer-T cells.

• Body cells that have been infected by foreign matter often present components of that material on their surfaces.

• Killer-T cells recognize these displays and respond by ingesting or otherwise destroying the infected cell. Killer-T cells are also important in the body's defenses against parasites, fungi, protozoans, and other larger cells that might have found their way into the body. The killer-T cells recognize these large invaders by their foreign proteins and then destroy them.

NKCs

Natural killer cells (NK cells) are large, granular lymphocytes that do not express the set of surface markers typical of B and T cells .

Display cytotoxic activity against a wide range of tumor cells.

Constitute 5%–10% of lymphocytes in human peripheral blood.

IgG is an antitumor and antiviral antibody that binds to the surface of tumor cells.

Because NK cells express CD16, a membrane receptor for Ig G antibody, they can attach to these antibodies and subsequently destroy the targeted tumor cells.

Mononuclear phagocytesThe mononuclear phagocytic system consists of

monocytes circulating in the blood and macrophages in the tissues.

Monocytes circulate in the bloodstream for about 8 h, during which they enlarge; they then migrate into the tissues and differentiate into specific tissue macrophages or, into dendritic cells.

They also act as antigen-presenting cells.

Phagocytosis• Macrophages are capable of ingesting and digesting

exogenous antigens, such as whole microorganisms and insoluble particles, and endogenous matter, such as injured or dead host cells and cellular debris

• In the first step in phagocytosis, macrophages are attracted by and move toward a variety of substances generated in an immune response; this process is called chemotaxis.

• The next step in phagocytosis is adherence of the antigen to the macrophage cell membrane. Adherence induces membrane protrusions, called pseudopodia, to extend around the attached material.

Phagocytosis• Fusion of the pseudopodia encloses the material within a

membrane-bounded structure called a phagosome, which then enters the endocytic processing pathway.

• In this pathway, a phagosome moves toward the cell interior, where it fuses with a lysosome to form a phagolysosome. Lysosomes contain lysozyme and a variety of other hydrolytic enzymes that digest the ingested material.

• The digested contents of the phagolysosome are then eliminated in a process called exocytosis

Granulocytic CellsThe granulocytes are classified on the basis of cellular

morphology and cytoplasmic staining characteristics Neutrophils: 50%–70% eosinophils: (1%–3%) basophils: (1%).

The neutrophil has a multilobed nucleus and a granulated cytoplasm that stains with both acid and basic dyes

The eosinophil has a bilobed nucleus and a granulated cytoplasm that stains with the acid dye eosin red (hence its name).

The basophil has a lobed nucleus and heavily granulated cytoplasm that stains with the basic dye methylene blue.

Both neutrophils and eosinophils are phagocytic, whereas basophils are not.

Dendritic Cells Originate in the bone marrow. They function as antigen-presenting cells

(APCs). They capture bacteria, process them

intracellularly, and resulting protein fragments are presented to T cells.

Mature dendritic cells express very high levels of MHC Class II molecules which mediate the presentation of antigen to T cells.

Organs of the Immune SystemPrimary Lymphoid Organs (central) Sites for development and maturation of lymphocytesBone MarrowThymus

Secondary Lymphoid Organs (peripheral) Sites for the initiation of an immune response. Trap

antigens and provide microenvironment for lymphocyte and Ag interaction.

Lymph NodesSpleen

Bone marrowBone marrow is the flexible tissue found in the interior

of bones.

In humans and mice, bone marrow is the site of B-cell origin and development.

Immature B cells proliferate and differentiate here. Stromal cells within the bone marrow secrete various

cytokines that are required for development.

The thymus is the site of T-cell development and maturation.

It is a flat, bilobed organ situated above the heart.

Each lobe is surrounded by a capsule and is divided into lobules, which are separated from each other by strands of connective tissue called trabeculae.

Each lobule is organized into two compartments: the outer compartment, or cortex: densely packed with

immature T cells, called thymocytesthe inner compartment, or medulla: sparsely populated

with thymocytes.

THYMUS

Thymus

Lymphatic SystemAs blood circulates under pressure, its fluid component (plasma)

seeps through the thin wall of the capillaries into the surrounding tissue.

Much of this fluid, called interstitial fluid, returns to the blood through the capillary membranes.

The remainder of the interstitial fluid, now called lymph, flows from the spaces in connective tissue into a network of tiny open lymphatic capillaries and then into a series of progressively larger collecting vessels called lymphatic vessels.

In this way, the lymphatic system captures fluid lost from the blood and returns it to the blood, thus ensuring steady-state levels of fluid within the circulatory system.

When a foreign antigen gains entrance to the tissues, it is picked up by the lymphatic system and is carried to various organized lymphoid tissues such as lymph nodes, which trap the foreign antigen.

Lymph nodes are the sites where immune responses are mounted to antigens in lymph.

They are encapsulated bean shaped structures packed with lymphocytes, macrophages, and dendritic cells.

As lymph percolates through a node, any particulate antigen that is brought in with the lymph will be trapped by the cellular network of phagocytic cells and dendritic cells

As antigen is carried into a regional node by the lymph, it is trapped, processed, and presented together with class II MHC molecules by dendritic cells, resulting in the activation of TH cells that activate B cells.

Spleen

• The spleen plays a major role in mounting immune responses to antigens in the blood stream.

• It is a large, ovoid secondary lymphoid organ situated high in the left abdominal cavity.

• While lymph nodes are specialized for trapping antigen from local tissues, the spleen specializes in filtering blood and trapping blood-borne antigens.

ANTIBODY

An antibody (Ab), also known as an immunoglobulin (Ig), is a large Y-shaped protein produced by B-cells that is used by the immune system to identify and neutralize foreign objects such as bacteria and viruses.

Antibodies are heavy (~150 kDa) globular plasma proteins.

Antibodies are secreted by a type of white blood cell called a plasma cell

The production of antibodies is the main function of the humoral immune system

STRUCTURE OF ANTIBODY:

• 1. HEAVY AND LIGHT CHAINS :• All immunoglobulins have a four chain structure as their basic

unit.• They are composed of two identical small light chains (23kD)

and two identical large heavy chains (50-70kD).

2.DISULFIDE BONDSThe heavy and light chains and the two heavy chains are held

together by inter-chain disulfide bonds

– Heavy Chain:– There are five types of mammalian Ig heavy chain denoted by the

Greek letters: α, δ, ε, γ, and μ.– The type of heavy chain present defines the class of antibody;

these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively

– Light Chain:– In mammals there are two types of immunoglobulin light chain,

which are called lambda (λ) and kappa (κ).

3.VARIABLE (V) AND CONSTANT (C) REGIONS The heavy and light chain could be divided into two

regions based on variability in the amino acid sequences.

These are the:1. Light Chain - VL (110 amino acids) and CL (110

amino acids)2. Heavy Chain - VH (110 amino acids) and CH (330-

440 amino acids)Most H chains consist of one variable (VH) and three

constant(CH) domains.(IgG and IgA have three CH domains,whereas IgM and IgE have four.)

• The variable regions are responsible for antigen binding ,whereas the constant regions are responsible for various biologic functions e.g. complement activation and binding to cell surface receptors.

• 4.Fab Region:• The arms of the Y contain the sites that can bind two

antigens (in general, identical) and, therefore, recognize specific foreign objects. This region of the antibody is called the Fab (fragment, antigen binding) region. It is composed of one constant and one variable domain from each heavy and light chain of the antibody

• 6. Fc Region:• The base of the Y plays a role in modulating immune

cell activity. This region is called the Fc (Fragment, crystallizable) region. and is composed of two heavy chains that contribute two or three constant domains depending on the class of the antibody.

• Thus, the Fc region ensures that each antibody generates an appropriate immune response for a given antigen, by binding to a specific class of Fc receptors, and other immune molecules, such as complement proteins.

CLASSES OF IMMUNOGLOBINS:

• The immunoglobulins can be divided into five different classes, based on differences in the amino acid sequences in the constant region of the heavy chains.

• 1. IgG - Gamma heavy chains• 2. IgM - Mu heavy chains• 3. IgA - Alpha heavy chains• 4. IgD - Delta heavy chains• 5. IgE - Epsilon heavy chains