7 immunity

THE BODY’S DEFENSES-IMMUNITY

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THE NATURE OF DISEASE

• Pathogenic OrganismsPathogenic Organisms• Genetic DisordersGenetic Disorders• Toxic ChemicalsToxic Chemicals• Other Environmental FactorsOther Environmental Factors• Physical Damage to OrgansPhysical Damage to Organs• Nutritional DisordersNutritional Disorders

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TYPES OF PATHOGENIC ORGANISMS

• VirusesViruses• BacteriaBacteria• ProtozoanProtozoan• FungiFungi• AnimalAnimal• ParasitesParasites

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MECHANISMS OF DISEASE BY PATHOGENS

• Utilization of host nutritional Utilization of host nutritional resourcesresources

• Physical damage to host tissuesPhysical damage to host tissues• Production of toxic substancesProduction of toxic substances• Chromosomal and gene damageChromosomal and gene damage• Body cells behave abnormallyBody cells behave abnormally

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VIRUSES

nucleic acid

capsid

envelope

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BACTERIA

cell wall

plasma membrane

cytoplasm

circular DNA6

Defense Mechanisms

1. External defense2. Internal Defense3. Immune Defense

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• Skin acts as barrier to microbes and viruses- sweat has a low pH

• Mucus traps foreign particles• Tears

- Lysozyme has antimicrobial action• Gastric stomach acid

1st Line of Defense

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BODY COVERINGS: THE SKIN

sebaceous glands

sweat gland

epidermis

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BODY COVERINGS: MUCOUS MEMBRANES

mucus

cilia

columnar epithelium

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• Phagocytic cells (WBCs)- N L M E B- Natural Killer (NK) Cells: attack virus

infected cells• Inflammatory Response• Antimicrobial proteins

- Lysozyme- Interferon- Antibodies

2nd Line of Defense

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NONSPECIFIC PHAGOCYTOSIS

NeutrophilsMonocytesEosinophils

NeutrophilsMonocytesEosinophils

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MECHANISM OF PHAGOCYTOSIS

Mechanism of PhagocytosisMechanism of Phagocytosis

MacrophageMacrophage

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Lymphatic System

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Inflammatory Response

Histamine & prostaglandins released

Capillaries dilateClotting begins

Chemotactic factors attract phagocytic cells

Phagocytes consume pathogens & cell debris

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3RD LINE OF DEFENCE

Immunity: It is the ability of body to resist almost

all type of foreign organism (bacteria, virus, fungi) or toxins that tend to damage the tissue and organs

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CHARACTERISTICS OF IMMUNITY

• Recognition of self versus non-self• Response is specific• Retains a “memory” allowing an

accelerated second response• Can respond to many different

materials• Involves lymphocytes and antibodies

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Type:

1.Innate immunity2.Acquired / Adaptive immunity

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Innate immunity: Immunity that develops from general processes rather than from process directed at specific disease organism is called innate immunity. It include

1.Phagocytosis of bacteria and other invaders by WBC and cells of tissue macrophage system2.Destruction by acid secretion of stomach and digestive enzyme of organisms swallowed into the stomach3.Resistance of the skin to invasion by organisms4.Presence of certain chemical compounds in blood that attach to foreign organism or toxins and destroy

them some of these compounds area.Lysozyme: Causes bacteria to dissoluteb.Basic polypeptide: Which react with certain type of gram positive bacteria and inactivate

themc.Complement complex: These have various functionsd.Natural killer lymphocytes: These can recognize and destroy foreign cells, tumor cell, and

even some infected cells.

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Acquired immunity: Immunity that develops against individual invading agents such as bacteria, virus, toxins and even foreign tissue from other animal

Acquired immunity is caused by a special immune system that forms antibodies and activated lymphocytes that attack and destroy the specific organisms or toxins Types of acquire immunity:Two basic but closely allied types of acquired immunity occur in body

1.Humoral immunity or B-cell immunity2.Cell-mediated immunity or T-cell immunity

 Humoral immunity: In this body develops antibodies, which are globulin molecules in blood that are capable of attacking the invading agents. B-lymphocyte produces the antibodies.

Cell-mediated immunity: In this immunity is achieved through the formation of large number of activated lymphocytes that are specifically designed to destroy the foreign agent. Activated lymphocytes are T lymphocyte

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TYPES OF IMMUNITY

• Active Immunity- Naturally-Acquired Active Immunity- Artificially-Acquired Active Immunity

• Passive Immunity- Naturally-Acquired Passive Immunity- Artificially-Acquired Passive Immunity

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TYPES OF ACQUIRED IMMUNITY

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The production of antibodies against a specific disease by the immune system.

Naturally acquired through disease Artificially acquired through vaccination

Vaccines include inactivated toxins, killed microbes, parts of microbes, and viable but weakened microbes.

Active immunity is usually permanent

ACTIVE IMMUNITY

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A vaccinated person has a secondary response based on memory cells when encountering the specific pathogen. Routine immunization against infectious diseases such as

measles and whooping cough, and has led to the eradication of smallpox, a viral disease.

Unfortunately, not all infectious agents are easily managed by vaccination.

HIV vaccine in the works

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Passive Immunity- Protection against disease through antibodies produced by another human being or animal.

Effective, but temporaryEx. Maternal antibodiesColostrum.

PASSIVE IMMUNITY

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Passive immunity can be transferred artificially by injecting antibodies from an animal that is already immune to a disease into another animal. Rabies treatment: injection with antibodies against rabies virus

that are both passive immunizations (the immediate fight) and active immunizations (longer term defense).

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IMMUNE SYSTEM RESPONSE TO ANTIGENS

Humoral Immunity• Involves antibodies (secreted from B

cells) dissolved in the blood plasma.• Demonstrated as a immune response

using only the blood serum.• Defense against bacteria, bacterial toxins,

& viruses.27

Cell-Mediated Immunity• Involves the activities of specific white

blood cells (T cells).• Defense against cancer cells, virus-

infected cells, fungi, animal parasites, & foreign cells from transplants.

IMMUNE SYSTEM RESPONSE TO ANTIGENS

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Lymphocyte Formation

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B CELLS

• Mature in bone marrow• Involved in humoral immunity• Once activated by antigen, proliferate

into two clones of cells: plasma cells that secrete antibodies and memory cells that may be converted into plasma cells at a later time

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B CELLS

antibodies

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B CELLSB Cells

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ACTIVATION OF B CELLS BY ANTIGEN

antigen

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CLONAL SELECTION

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CLONAL SELECTION

plasma cells memory cells

antibodies

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Antibodies constitute a group of globular serum proteins called immunoglobins (Igs). A typical antibody molecule has two identical antigen-binding

sites specific for the epitope that provokes its production.

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ANTIBODY MOLECULE

antigen binding sites

antigen

light chains heavy chains37

MECHANISMS ON ANTIBODY ACTION

• Precipitation of soluble antigens• Agglutination of foreign cells• Neutralization• Enhanced phagocytosis• Complement activation leading to cell lysis• Stimulates inflammation

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Direct actions of antibodies on invading agents:

Antibodies can inactivate the invading agent in one of several ways

1.Agglutination: In which multiple large particles with antigen on their surfaces, such as bacteria or red cells, are bound together into a clump

2.Precipitation: In which the molecular complex of soluble antigen (such as tetanus toxin) and antibody becomes so large that it is rendered and precipitates

3.Neutralization: In which antibodies cover the toxic sites of antigenic agent

4.Lysis: In which some potent antibodies are occasionally capable of directly attacking membrane of cellular agents and thereby causing rupture of cell •These direct actions of antibodies attacking the antigenic invades probably, under normal conditions, are not strong enough to play a major role in protecting the body against the invaders. Most of protection comes through the amplifying effects of complement system.

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The binding of antibodies to antigens to form antigen-antibody complexes is the basis of several antigen disposal mechanisms.

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The classical complimentary pathway, resulting in lysis of a target cell

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Complement system:

Complement system consists of 20 heat liable plasma proteins that are functionally inactive i.e. the components of complement system circulate in blood in an inactive form

•These plasma proteins are enzyme in its inactive form •There are 20 plasma protein, out of which the principal actors in this system are 11 proteins designated as C1 to C9, B and D•Synthesis of complement proteins occurs mostly in the liver and some by macrophages•Complement system plays a role in host defense and inflammatory process

•The complement protein (enzyme) are usually inactive but can be activated in two pathways1.Classical pathway2.Alternate pathway

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Classical pathway:

The classical pathway is activated by antigen-antibody reaction 

When antibody binds with an antigen

Specific reactive site on constant portion of antibody become uncovered or activated

This activated specific reactive site binds directly with C1 molecule of complement system, setting into motion and cascade of sequential reaction

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Note:Cleaved fragments are designated with small letter (e.g. C3a, C3b)A horizontal bar over numberal component (e.g. C1) indicates that it has acquired enzymatic activityA horizontal bar over numberal of complex (e.g. C9b67) indicates an activated state 44

Alternate pathway

Sometime complement system is activated without the intermediation of an antigen-antibody reaction through alternate pathway

The alternate pathway can be triggered by 1.Large polysaccharide molecule in cell surface of some invading microorganism 2.Endotoxins of gram-negative bacteria3.Teichoic acids of gram-positive bacteria4.Aggregated IgA5.Cobra venom

•These substances react with complement factors B and D forming an activation products that activates factor C3 setting off the remainder of complement cascade beyond C3 level same as classical pathway. ** MAC= Membrane attack complex

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Importance of Complement system:

Multiple end products are formed and several of these cause important effects that help to prevent damage by the invading organism or toxins. Among these more important effects are the following:

1.Opsonization and phagocytosis: C3b strongly activated phagocytosis by neutrophil and macrophage causing them to engulf the

bacteria to which antigen-antibody complexes are attached. This process is called opsonization.

•It often enhances the number of bacteria that can be destroyed by many hundred folds.

2. Lysis:Lytic complex (C5b6789) can directly rupture the cell membrane of bacteria and other invading

organism  3.Agglutination

The complement products also change the surfaces of the invading organism, causing them to adhere to one another, thus promoting agglutination 4. Neutralization of viruses

Complement enzyme and other complement products can attack the structure of some viruses and thereby render them nonvirulent

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5.ChemotaxisC5a causes chemotaxis of neutrophil and macrophage thus causing migration of large number of

phagocytes into the local region of antigenic agent 6.Activation of mast cells and basophils:

Fragment C3a, C4a, and C5a all activate mast cell and basophils causing them to release histamine, heparin, and several other substance into local fluids• These substances in turn cause

a..Increased local blood flowb.Increased leakage of fluid and plasma protein in tissuec.Cause other local tissue reaction that help to inactivate or immobilse the antigenic agent

These factors play major role in inflammation. 7.Inflammatory effects:

Several other complement products in addition to inflammatory effect caused by activation of mast cells and basophils contribute to local inflammation

These products causea.Already increased blood flow to increase still furtherb.More increase in capillary leakage of protein and coagulation of protein in tissue

spaces Thus preventing movement of invading organism through the tissue

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Lymphocyte:

Lymphocyte is one of the type of white blood cells •Lymphocyte originate from multipotent hemopoietic stem cells of bone marrow •Lymphoid stem cell in bone marrow mature into B lymphocytes•Lymphoid stem cell which migrate in thymus mature into T lymphocytes•During development each B cell or T cell becomes immunologically committed to a specific epitope of an antigen There is continual recirculation of lymphocytes between the blood and lymphoid tissue B cells have a shorter life span of 5 to 7 days and T cells have a long life span of months or years Classification of lymphocytes:

According to size1.Small lymphocyte 2.Large lymphocyte

 Immunologically/functionally

1.T lymphocyte2.B lymphocyte

3. NK cells 49

All lymphocytes originate in the bone marrow, but while T- lymphocyte mature further in thymus, B-lymphocyte leave the bone marrow as mature cells. For this reason none marrow and thymus are called central lymphoid organ 

Lymphocyte migrate from these organs to blood and peripheral lymphoid organs (Spleen, lymph nodes, solitary nodule, tonsil, appendix and Peyer’s patch of ileum) where they proliferate and complete their differentiation

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B lymphocyte (B cells)

•These are responsible for humoral immune response due to synthesis and secretion of antibody•B cells originate from stem cell in bone marrow and differentiate in fetal life in liver then in bone marrow in adult•The letter “B” was derived from the first letter of “Bursa of febricius” in birds where they were first found•When B cells are activated by specific antigen it lead to proliferation and differentiation of B cell into plasma cell •Plasma cells synthesize and secrete antibodies

# derive from bone marrow, migrate to non-thymic lymphoid structure where they nest, proliferate when activated and differentiate into antibody secreting plasma cell

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T lymphocytes (T cells)

•T cells are responsible for cell mediated immune response•T cells develop and differentiate within thymus from migrating stem cell and thus called T cells•T cells leave the thymus as mature T lymphocytes and are found in blood, secondary lymphoid organ like lymph node, spleen, tonsil and elsewhere throughout the body Type of T lymphocytes:

On basis of functional properties T cells are:1.Helper T cells2.Suppressor T cells3.Cytotoxic T cells

T cells originate in bone marrow

Migrate to thymus, where they proliferate and produce cells that colonize # These call then Migrate to non-thymic lymphoid tissue where they mature # Here in non-thymic lymphoid tissue they also differentiate further into subpopulation T Helper cell, T cytotoxic cell. T Suppressor cell and T memory cell

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NK cells

In addition to B and T lymphocytes , there is a natural killer or NK, lymphocyte, which lacks the marker molecules characteristic of B and T cells

Function of NK cells 1. Main function is to kill virus infected cells 2.It is also believed that NK cells kills malignant cells and thus take part in Immunologic

defense against cancer cell   

In peripheral blood T cell are 70 –80% B cell is 10-15% NK cell are 10-15%

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Memory B-cell/T-cells

Responsible for accelerated response to second exposure to same antigen

Suppressor T-cells

Decrease immune response of T and B-cells.

Deficiency may cause autoimmune disease

Cytotoxic T-cells (Killer cells or T8 cells)

Destroy transplanted and other foreign cell

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Helper T cells

The Helper T cells form about 65% of total lymphocyte count in peripheral blood.They help in function of immune system Function:They serve as major regulator of all immune function by forming a series of protein mediator called lymphokines. These lymphokines act on cells of immune system as well as on bone marrow cell

Important lymphokines secreted by helper T cells1.Interleukin – 2, 3, 4, 5, 62.Granulocyte-monocyte colony stimulating factor3.Interferon

 So function of T Helper cell (lymphokines)

1.Stimulation of growth an proliferation of cytotoxic T cells and suppressor T cells2.Stimulation of B cells growth and differentiation to form plasma cell so ultimately help in formation of antibody3.Activation of macrophage system: They increase efficiency of phagocytosis done by macrophage so that they can attack and destroy greatly increased number of invading organisms.4.Feedback, stimulatory effect on Helper cells themselves: Some lymphokines produced by Helper T cells can stimulate Helper T cells directly thus act as an amplifier in further enhancing the helper cell response as well as the entire immune response to an invading antigen.

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Cytotoxic T cells

Cytotoxic T cell is a direct attack cell that is capable of killing microorganisms and at times even some of body’s own cells so they are also called killer cells. 

The receptor proteins on surface of cytotoxic cell cause theses cells to bind tightly to those organisms or cells that contain their binding specific antigen

After binding, cytotoxic T cells secrete hole-forming proteins called Perforins

These Perforins punch large round holes in membrane of attacked cells

Then fluid rapidly flow into the cell They also release cytotoxic substance directly into the attacked cellFrom interstitial space

Kills the cell

Cells become swollen

Cells burst

These effect destroys the attacked cell

Functions:They directly attack the microorganisms and kill themThey also play important role in destroying cancer cells, heart transplant cell, or other types of cells that are foreign to person’s own body.

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Suppressor T cells:

•They suppress the function of both cytotoxic and helper T cells•Suppressor function done by suppressor T cells regulates the activities of other cells, keeping them from causing excessive immune reactions that might be severely damaging to the body

It is also probable that the suppressor T cells play an important role in limiting the ability of immune system to attack a person’s own body tissue

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Types of T cells

On the basis of surface marker on lymphocyte cell surface they are:

1.CD4 lymphocyte: Helper T cells (Th or T H cells)

2.CD8 lymphocyte: Cytotoxic T cell (Tc)Suppressor T cell (Ts)

 •CD4 cells form about 65% and CD8 cells form about 35% of T cells in peripheral blood •Normal ratio of CD4 to CD8 cells is greater than 1.5•In AIDS the ratio is lost as CD4 cells are destroyed by HIV and the ratio of CD4:CD8 is less than 1. •In absence of lymphokines from the helper T cells, the remainder of immune system is almost paralyzed

•So in AIDS, it is the helper T cells that are inactivated or destroyed by HIV, which leads body almost totally unprotected against infectious disease.

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