22/10/[email protected] Adaptive (Specific) Immunity Mo O’Brien Lecturer (Adult Nursing Studies) 3.18b Ty Dewi Sant 02920 743415 [email protected]

21/04/23 [email protected] 1

Adaptive (Specific) Immunity

Mo O’BrienLecturer (Adult Nursing Studies)

3.18b Ty Dewi Sant

02920 743415

[email protected]


Overview• The immune system includes all of the

structures and processes that provide a defense against potential pathogens (disease causing agents) .

• These defenses can be classified as INNATE (NON-SPECIFIC / INBORN) immunity or ADAPTIVE (SPECIFIC / ACQUIRED) immunity.

• Although the two categories refer to different defense mechanisms there are areas in which they overlap.


Innate (non specific) immunityIncludes both external and internal defensesDefenses are always present in the bodyRepresent the first line of defense against

invasion by potential pathogensAct fast but show low specificity in both

recognition and disposal of invading organisms.

Do not show memoryIf these defenses are not sufficient to destroy

the pathogens, lymphocytes may be recruited and their specific actions used to reinformce the non-specific immune defenses.


Innate (non specific) immunity

The innate immune system distinguishes between the body’s own tissue cells (‘self’) and microorganisms.

Invading organisms are then ‘flagged’ for phagocytic attack

• See notes of previous lecture for more on all of this


Structures and defense mechanisms of non-specific (innate) immunity

Structure Mechanisms

External Digestive tract Physical barrier; Lysozyme (enzyme that destroys bacteria)

Skin High stomach acidity; normal bacteria of colon offer protection

Respiratory Tract

Secretion of mucus; cilia; alveolar macrophages

Genitourinary tract

Acidity of urine and vaginal lactic acid

Internal Phagocytic cells

Ingest and destroy bacteria, cellular debris, denatured proteins, toxins.

Interferons Inhibit the replication of viruses

Compliment proteins

Promote destruction of bacteria; enhance inflmmatory response

Endogenous pyrogen

Secreted by leucocytes and other cells; produces fever



Is more complex than non-specfic (innate) immune response

Is highly specificIt is induced and requires time to

develop It shows memory (the secondary

response)It is restricted to vertebrates.



o Cells are recognised by the body as being either self or non-self, each carrying ‘markers’ on their membranes that similarly are referred to as self-antigens and non-self antigens.

o The body should not normally attack self-antigens but will respond to the presence of non-self antigens.


Macrophages (‘the big eaters’), which are mature monocytes found in tissues throughout the body offer a ‘first up’ defense while waiting for the body’s adaptive defense mechanisms to fully engage.

The macrophages engulf the non-self antigen by a process of phagocytosis i.e. the cells ability to wrap around the antigen.

The fully active adaptive mechanism can destroy the non-self antigen, the remnant material being phagocytosed by macrophages, assisted by neutrophils



Adaptive (Specific) ImmunityThe adaptive defense is the ability of the body to recognise and distinguish between offending agents and to develop specific responses against them.

The basis for these defenses lies in the blood


Antigens• Antigens are molecules that stimulate the

production of specific antibodies and combine specifically with the antibodies produced. (Antibodies are also referred to as immunoglogulins)

• They invoke an immune response.• Most antigens are large molecules (such as

proteins) and most are foreign to the blood and other body fluids.

• They can enter the body from the environment or can be generated within the body.


Environmental antigens…includeInhaled macromolecules (e.g. proteins on cat hairs can trigger an asthma attack in susceptible people)Ingested macromolecules (e.g. shellfish proteins that trigger an allergic response in susceptible people)Molecules that are introduced beneath the skin (e.g. on a splinter or in an injected vaccine)


Antigens generated within the cells of the body …

include

Proteins encoded by the genes of viruses that have infected a cell.

Abberrant proteins that are encoded by mutant genes e.g. mutated genes in cancer cells


AntigensThe ability of a molecule to function as an antigen depends not only upon it’s size but also upon the complexity of it’s structure.

A large and complex molecule can have a number of different antigenic determinant sites which are areas of the molecule that stimulate production of, and combine with different antibodies.

Most naturally occurring antigens have many antigenic determinant sites and stimulate the production of different antibodies with specificities for these sites.


Antigens – summary

An antigen (Ag) is any foreign substance that enters the body and induces an immune response

Antigens may be found on the surface of pathogenic organisms, on the surface of red blood cells and tissue cells, on pollens, in toxins and in foods.

The critical feature of any substance called an antigen is that it stimulates the activity of certain lymphocytes classified as T or B cells.


A pathogen, such as a bacterium, has many different antigens on its surface. Each of these antigens interacts with a specific B cell receptor protein, thereby activating those B cells that can produce antibodies against those specific antigens.


T & B Lymphocyte Cells Come from hemapoietic

(blood forming) stem cells in bone marrow (as do all blood cells)

T & B cells differ in their development and method of action

To maximize the chances of encountering antigens lymphocytes continually circulate between the blood and certain lymphiod tissues.

A given lymphocyte spends an average of 30 minutes perday in the blood and recirculates about 50 times a day between blood and lymphoid tissue

B LYMPHOCYTE

T LYMPHOCYTE




T CellsSome immature stem cells migrate to the thymus (hence ‘T’) and become T cells making up about 80% of the lymphocytes in the circulating blood.

Whlist in the thymus, these T lymphocytes multiply and become capable of combining with specific foreign (non-self) antigens.

They are then described as sensitised

Thymus derived cells produce an immunity that is said to be cell mediated immunity


Types of T cells and their functionsCytotoxic (Tc) (or ‘killer’) T cells; destroy foreign cells directly by speeding up the process of apoptosis (programmed cell death) by forming a pore that allows enzymes to enter the cell and bring about destruction of it’s lysosomes. [These are not to be confused with ‘natural killer cells’ – see innate immunity.]

Helper T cells (Th); release substances known as interleukins (IL) that stimulate other lymphocytes and macropghages and thereby assist in the destruction of foreign cells.

Regulatory T cells (Treg) suppress the immune response in order to prevent overactivity. These may inhibit or destroy active lymphocytes.Memory T cells remember an antigen and start a rapid response if that antigen is contacted again.



T Cells

The T cell portion of the immune system is generally responsible for defense against cancer cells, certain viruses and other pathogens that grow within cells (intracellular parasites), as well as for the rejection of tissue that has been transplanted from another person


The role of the Macrophages

Macrophages (“big eater”) are phagocytic white blood cells derived from monocytes that act as processing centres for non-self antigens.

They ingest foreign proteins and break them down within phagocytic vesicles and then insert fragments of the foreign antigen into their plasma membrane.

The T cell can then recognise the foreign antigens that have been presented to it by the macrophage.


The role of the Macrophages

However the T cell will only recognise these foreign antigens if there are also antigens present on the macrophage that the T cell can recognise as belonging to ‘self’.‘Self’ antigens are know as MHC (major histocompatibility complex) antigens because of their importance in cross matching for tissue transplantation



A special receptor on the T cell must bind with both the MHC protein and the foreign

antigen fragment. The activated T helper cell then produces interleukins which stimulate

other leukocytes, such as B cells.


B cells and antibodies An antibody (Ab), [also

known as an immunoglobulin (Ig)] is a substance produced in response to an antigen.

Antibodies are manufactured by B lymphocytes

These B cells must mature in the foetal liver or in lymphoid tissue before becoming active in the blood.


Activation of B cells

The B cell combines with a specific antigen. The cell divides to form plasma cells which then produce antibodies. Some of the cells will develop into memory cells which protect against infection.

B memory cells

Antibodies

Plasma cells

Activated B cell multiplies

B cell binds to antigen

B cell with specific antigen receptor


B cells and antibodies

• B cells have surface receptors that bind with a specific type of antigen

• Exposure to that antigen stimulates the cells to multiply rapidly and produce large numbers (clones) of plasma cells.

• Plasma cells produce antibodies against the original antigen and release these antibodies into the blood, providing the type of immunity known as humoral immunity (humoral refers to body fluids as opposed to cellular immunity which involves T cells i.e. takes place directly between the T cells and antigens).


B cells and antibodiesHumoral immunity generally protects against circulating antigens and bacteria that grow outside of cells (extracellular pathogens)All antibodies are contained in a portion of the blood plasma called the gamma globulin fractionSome antibodies produced by B cells remain in the blood to give long term immunity.Some of the activated B cells do not become plasma cells but like certain T cells they become memory cells. On repeated contact with an antigen these cells are ready to produce antibodies immediately.Because the plasma contains other globulins as well, antibodies have become known as immunoglobulins.


The Antigen – Antibody reaction

The antibody that is produced in response to a specific antigen, such as a bacterial cell or a toxin has a shape that matches some part of that antigen much in the same way that the shape of a key matches to the shape of its lock.

The antibody can bind specifically to the antigen that caused its production and thereby destroy or inactivate it.


B cells must be activated by

helper T cells before they

produce antibodies.


Complement

The destruction of foreign cells sometimes requires the enzymatic activity of a group of non-specific proteins in the blood, together called COMPLIMENT.Compliment proteins are always present in the blood but they must be activated by antigen-antibody complexes or by foreign cell surfaces.Compliment is so called as it assists with immune reactions.


Some of the actions of Complement are

It coats foreign cells to help phagocytes recognize and engulf them

It destroys cells by forming complexes that punch holes in plasma membranes

It promotes inflammation by increasing capillary permeability

It attracts phagocytes to an area of inflammation


The compliment system is directed to defend against bacterial invasion.The system consists of inactive precursors that are activated by proteolytic enzymes in a cascade, which like other cascade systems, multiplies the number of molecules involved at each step.The system can be activated by the specific immune system (the classical pathway) or the non-specific immune system (the alternative pathway).Both pathways end in the production of chemicals known as complement fragments and these promote phagocytosis and a structure known as a membrane attack complex (This is a ring of compliment fragments that inserts itself into the membrane of invading cells, forming a large pore that causes the cell to lyse [i.e. cell death])


Compliment CascadeActivation of the cascade can be by the classical specific immune system or by the non-specific production of a C3-stabilizing combination of a non-antigenic but non-self molecule and factors B and D.

Like all cascade systems, there is a multiplication of active molecules at each step, and these molecules cause inflammation, phagocytosis, chemotaxis and cell lysis.


The Immunoglobulins


lgG Main form of antibodies in

circulation (75%) and is termed the ‘work horse’ antibody.

It is important for opsonization because phagocytes have receptors which bind to the region of IgG molecules.

Production increased after immunization;

secreted during secondary response

Found in blood, lymph and intestines

Enhances phagocytosis, neutralizes toxins and activates compliment

Crosses the placenta and confers passive immunity from mother to foetus.


lgAMain antibody type in external secretions, such as saliva & mother’s milk. Also found in tears, sweat, mucus and digestive juices.

Comprises 15% of the immunoglobulins. May appear early in the course of infection and its detection has a role in the diagnosis of acute infection


lgM Forms the bodies natural

antibodies e.g. ABO blood groups.

Function as antigen receptors on lymphocyte surface prior to immunization

secreted during primary response – the first antibody to be secreted after infection.

Stimulates agglutination and activates compliment

Comprises 10% of the immunoglobulins


lgD• Function as antigen

receptors on lymphocyte surface prior to immunization

• Comprise < 1% (approx 0.2%) of the immunoglobulins

• Needed for B cell maturation and is located on the surface of B cells

• other functions unknown but may be related to the inhibition of autoimmune disease.


lgE

• Located on basophils, binds to mast cells and eosinophils and is therefore responsible for allergic symptoms in immediate hyper-sensitivity reactions (e.g. asthma, eczema, hay fever, anaphylaxis) and is also activated when parasitic infection present.

• < 0.1% (approx 0.004%) of the immunoglobulins




Naturally Acquired Immunity

Immunity may be acquired naturally through contact with a specific disease organism, in which case, antibodies manufactured by the infected persons cells act against the infecting agent or it’s toxins.

The infection that triggers the immunity may be so mild so as to cause no symptoms (subclinical)

Nonetheless it will stimulate the host’s cells to produce an active immunity.



Each time a person is invaded by disease organisms cells manufacture antibodies that provide immunity against infection.

Such immunity may last for years and in some cases for life.

Because the host is actively involved in the production of antibodies, this type of immunity is called active immunity.



Immunity also may be acquired naturally by the passage of antibodies from a mother to her foetus through the placenta.

Because these antibodies come from an outside source, this type of immunity is called passive immunity.

The antibodies obtained in this way do not last as long as actively produced antibodies, but they do help the infant for about 6 months, at which time the child’s own immune system begins to function.


Artificially Acquired Immunity

A person who has not been exposed to repeated small doses of a particular organism has no antibodies against that organism and may be defenseless against infection

Therefore artificial measures may be used to cause the person’s immune system to produce antibodies.

To administer virulent pathogens would be very dangerous so virulence is reduced in the laboratory setting before it is administered.


Artificially Acquired Immunity In this way the immune system is made to produce

antibodies without causing serious ill health – this protective process being referred to as vaccination or immunisation, whilst the substance administered is referred to as the vaccine.

A vaccine is generally administered as a preventative measure designed to provide protection in anticipation of invasion by a particular disease causing organism.

All vaccines carry a risk of adverse side effects and may be contraindicated in some cases e.g. vaccines that contain live virus should not be administered to individuals who are immunosuppressed (i.e. with a CD4 count of less than 200 / ml of blood) or to pregnant women as there is a risk that they may cross the placenta and harm the foetus.

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22/10/[email protected] Adaptive (Specific) Immunity Mo O’Brien Lecturer (Adult Nursing Studies) 3.18b Ty Dewi Sant 02920 743415 [email protected]