welcomeVmc-606Principles of immunology

Overview of immune system

By B.Rajashekar M.v.sc 1st year

What is overview?A general review or summary of a subject This overview describes key mechanisms used by

the immune system to respond to invading microbes and identifies disturbed immune function.

What is immune response?The reaction of the cells and fluids of the body to

the presence of a substance which is not recognized as a constituent of the body itself.

Comon invaders include bacteria, viruses, fungi, and various parasites including worms, amoeba, and other single-celled protozoans.

Major components involved in Immune response

1.Physical barriers

2.The Innate immune system

3.The Adaptive immune

system

3 Major parts are involved

Type Mechanism

Anatomic barrierS

Skin Mechanical barrier retards entry of microbes. Acidic environment (pH 3–5) retards growth of microbes.

Mucous membranes Normal flora compete with microbes for attachment sites and nutrients. Mucus entraps foreign microorganisms. Cilia propel microorganisms out of body.Physiologic barriers

Temperature Normal body temperature inhibits growth of some pathogens. Fever response inhibits growth of some pathogens. Low

pH Acidityof stomach contents kills most ingested microorganisms.

Physical Barriers

Chemical mediators

Lysozyme cleaves bacterial cell wall. Interferon induces antiviral state in uninfected cells. Collectins disrupt cell wall of pathogen

These are alsoEnzymes contained in tears SweatMucus in the digestive, respiratory, and reproductive tracts which neutralize potential

invaders.

Together, these barriers work to prevent most foreign objects from entering the body.

Occasionally, the physical barriers can be compromised -for example through a cut or injury to the skin and antigens can enter the body.

Innate Immune System Innate immunity, provides the first line of defence against

infection. Most components of innate immunity are present before the onset

of infection And constitute a set of disease-resistance mechanisms that are not specific to a particular pathogen but that include cellular and molecular components that recognize

classes of molecules peculiar to frequently encountered pathogens Innate immune system, which consist Phagocytic cells include

macrophages, Dendritic cells, Mast cells, Monocytes, and Neutrophils. Of these, macrophages and neutrophils are the most important.

• Phagocytosis.

• Another important innate defence mechanism is the ingestion of extracellular particulate material by phagocytosis.

• Phagocytosis is one type of endocytosis, the general term for the uptake by a cell of material from its environment.

• In phagocytosis, a cell’s plasma membrane expands around the particulate material, which may include whole pathogenic, to form large vesicles called phagosomes

• Most phagocytosis is conducted by specialized cells, such as blood monocytes, neutrophils, and tissue Macrophages.

• Most phagocytosis is conducted by specialized cells monocytes, neutrophils, and tissue macrophages

Inflammation One of the key mechanism of innate

immunity is the body’s ability to focus these innate defence mechanisms on sites of microbial invasion. This focused defensive response is called is inflammation

During inflammation changes in tissues brought about by microbial invasion or tissue damage result in increased blood flow and the local accumulation of the cells that can attack and destroy the invaders.

These cells called neutrophils and macrophages

Macrophages

Like other white blood cells, they are produced by stem cells in the bone marrow.

When bacteria or other foreign objects enter the body nearby macrophages are alerted to the presence of foreign matter by, a chemical reaction with the receptors on their surface

The macrophages then proceed to move towards the pathogen where they surround the invading antigen with a pouch called a phagosome

Neutrophils Neutrophils make up the majority of white blood

cells in the body. These cells generally are the first to arrive at a site of

inflammation after detecting chemical signals in the blood.

By Phagocytosis,Neutrophils is similar to that described for Macrophages

Among the chemical signals that Neutrophils can receive are:Interleukin-8

Cytokines   Chemokines  Are cell-signaling proteins which facilitate

communication between immune system cells.

Complement proteins The complement proteins are a group of proteins that assist in eliminating

foreign pathogens and in promoting the ensuing inflammatory reaction. The major site of synthesis of complement proteins is the liver, although

these proteins are also produced in macrophages They interact with antigens in one of several ways Either marking (opsonizing) them for ingestion by other immune cells, Sending out chemical signals to bring additional immune cells to join the

fight, Combining together with one another and killing the invaders directly by

punching holes them

Natural Killer Cells Natural killer (or NK) cells are lymphocytes which attack tumors and body

cells infected by viruses.. Once they arrive at such a site, natural killer cells give off the interferon-

gamma cytokine in order to prime additional macrophages They also evaluate body cells to determine whether they have been infected

by a virus. When they find infected cells, the NK cells either inject those cells with

enzymes that cause the body cells to self-destruct, or they signal the cell to commit suicide, destroying the viruses contained inside in the process.

.

Toll-like Receptors Toll-like Receptors (TLRs) are

transmembrane proteins found in a variety of cells, most notably on the surface of mast cells, macro-phages, and dendritic cells.

TLRs can recognize a broad spectrum of pathogens and, as a result, are instrumental in initiating both innate and adaptive immune responses

Adaptive immune systemThe body's third line of defense is the adaptive immune system, also called the acquierd immune system because we are not born with it, but acquire it through contact with specific pathogens during our lifetime. Its primary job is to protect us against reinfection.They key components of the adaptive immune system are B-cells, T-cells, Memory cells, antibodies, and the secondary lymphoid organs.Microbes like bacteria and viruses continually mutate, over time they become resistant to particular drugs as well as to the effects of the immune system. To counter that, the adaptive immune system, as the name implies, can adapt itself to target very specific mutations of antigens as they are encountered.

B-cells B-cells (for bursa cells) are small white blood cells, also

called lymphocytes, whose primary job is to make antibodies that attack bacteria and toxins.

Each B-cell is covered on its surface by thousands of B-cell receptors (BCRs), which look for matching (or cognate) antigens in the body.

When a B-cell receptor comes in contact with its cognate antigen, the receptor binds to it.

The B-cell then begins repeatedly dividing in a process called proliferation, differentiate into memory B cells and effector B cells called plasma cells..

Plasma cells live for only a few days, they secrete enormous amounts of antibody during this time.

Antibodies • Antibodies are Y-shaped glyco proteins that

consist of two identical heavy polypeptide chains and two identical light polypeptide

chains.• Molecules which bind to various types of

antigens such as bacteria and viruses, and mark them for destruction by phagocytes and other cells of the immune system.

• The "hands" at the top of the two arms of the antibody attach themselves to selected antigens, while the tail of the antibody attaches to a receptor on the surface of a phagocyte such as a macrophage.

• In that way, the antibody acts like a bridge from the macrophage to the antigen, drawing the antigen closer while simultaneously stimulating the appetite of the phagocyte.

• Some antibodies also have the ability to neutralize viruses, binding with the virus and preventing it from entering a body cell.

T-cells T-cells (for thymus cells) attack , those cells which have become infected by viruses

or which have become cancerous. They can determine whether a body cell has been infected and, if so, signal it to self-

destruct, also killing the viruses inside in the process. Like B-cells, T-cells also display molecular receptors on their surface which will

bind to their cognate antigens. But, unlike B-cells which can release its receptors as antibodies, the T-cell receptors

(TCRs) remain on the surface of the cell. TCRs specialize in recognizing protein antigens.

Once the TCRs are activated by a specific antigen, they also begin to replicate the way that B-cells do, building up a clone of T-cells specifically programmed to react to the particular antigen.

A variant of the T-cell which does not attack infected cells directly is the T-helper (Th) cell.

When activated, the T-helper cell begins secreting cytokines which draw other immune cells to the site of the infection.

A cytokine is a cell-signaling protein molecule.

TC & TH cells T helper and T cytotoxic cells can be distinguished from one another by the

presence of either CD4 or CD8 membrane glycoproteins on their surfaces T cells displaying CD4 generally function as TH cells, whereas those displaying

CD8 generally function as TC Cells TH cell recognizes and interacts with an antigen– MHC class II molecule

complex, TH cell is activated—it becomes an effector cell, that secretes various growth factors collectively known as cytokines

TC cell that recognizes an antigen–MHC class I molecule complex Proliferates and differentiates into an effector cell called a cytotoxic T

lymphocyte (CTL). The CTL has a vital function in monitoring the cells of the body and eliminating

any that display antigen, such as virus-infected cells, tumor cells, and cells of a foreign tissue graft.

Secondary lymphoid organs The secondary lymphoid organs, consisting primarily of the lymph nodes, spleen,

tonsils, and adenoids, play a crucial role in activating the adaptive immune system.

The lymph also carries with it bacteria and viruses from the tissues. The lymph nodes essentially act like filters and the foreign matter contained in the lymph is deposited in the lymph nodes

In contrast to the secondary lymphoid organs, the primary lymphoid organs include the thymus, bone marrow, and the foetal liver.

The critical function of the thymusis to "educate" T-cells not to attack normal body cells, or to eliminate those T-cells that do.

Bone marrow contains stem cells which produce red blood cells that carry oxygen, white blood cells that fight infection, and platelets that help with blood clotting.

B cell divides repeatedly and differentiates generating a population of plasma cells and memory cells

Memory B cells have a longer life span than plasma cells, and they express the same membrane-bound antibody as their parent B cell

Memory cells are cells that have already been programmed to respond to a certain antigen help to generate required antibodies during an immune response

Memory cells