02/10/2015 obrienmp@cf.ac.uk immunity and immunological response mo o’brien lecturer (adult...

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Immunity and Immunological Response

Mo O’Brien

Lecturer (Adult Nursing Studies)

3.18b Ty Dewi Sant

X 3415

obrienmp@cf.ac.uk

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What we will cover today

Session One:The role of the immune system and innate (non specific) immunity.Session Two: Adaptive (specific) ImmunitySession Three: Vaccination and immunisation

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First Session Aims

Review what is immunology.

The Inflammatory response.

Non specific (innate) immunity.

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Session ObjectivesDefine the term: immunology. Describe the two key functions of the immune systemDescribe the three stages of the inflammatory response Define non-specific immunity and describe the various defense mechanismsDescribe briefly the role of white cells: phagocytes, eosinophils, natural killer cells and killer cells

Second session will address Adaptive (specific) immunity and

the third session will address Immunisation and Vaccination

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Immunology

This is the study of the way in which individuals fight off disease (produced by microorganisms) and how they distinguish between that material which is ‘foreign’ and that which is not ‘self’ (i.e. belonging to that individual).All animals have mechanisms whereby they can prevent the entry of and destroy invading microorgansims (this is true of any foreign material). These mechanisms are termed ‘immune response’.

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“The battle for supremacy – between the human immune system ( the defences)

and microorganisms (the invaders)”Humans and microorganisms (e.g. viruses, bacteria etc) live in a complex relationship with one another.

Some bacteria (i.e. normal or indigenous flora) colonise specific areas of the human body, and providing that they remain at these sites, they may be beneficial to the individual, (e.g. by preventing colonisation of these areas by other microorganisms which produce disease)

Virus

Bacteria

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Two key functions of the immune system

1. To distinguish between that which is self and non-self (This comparison is made by comparing ‘histocompatibilty’ of cells.)

Cells (with the exception of red blood cells) have identification markers on their surface. These have a class of proteins on them which we call Major Histocompatibility Complex (MHC) and this allows the body to distinguish between cells that belong to that person only and those that are ‘foreign’.

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Two key functions of the immune system2.2. The second function is for the immune system to (i)respond

rapidly and appropriately to the non-self material in an attempt to (ii) isolate and (iii) eradicate from the body.

BUT:

The immune system can also act inappropriately at times i.e. an ‘auto-immune disease’ e.g. rheumatoid arthritis – there is a problem in distinguishing between ‘self’ and ‘non-self’ – this may be genetic.

Because the immune system malfunctions there is an inflammatory response produced (e.g rheumatism)

The immune system can become ‘hypersensitive’ to proteins and pollens and may respond inappropriately ( e.g. asthma, hayfever, eczema), e.g. cilia do not operate, goblet cells produce mucous, bronchioles become inflammed and narrow in diameter …..

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NON SPECIFIC & SPECIFIC immune responses

Given certain circumstance most types of micro- organisms (that are that are capable of infecting humans) can invade, colonise and produce tissue damage in humans (i.e. produce infection)Humans have evolved NON-SPECIFIC and SPECIFIC immune systems responses to defend themselves from invading micro-organisms Although useful to divide immunity into non specific and specific responses, it is important to recognise that they both work closely together, each making the other more effective.

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NON – SPECIFIC IMMUNITYNon-specific immunity is normally present from birth (often referred to as innate or inborn immunity)

Immune responses are the same for all foreign material (e.g the same response shown to a splinter of wood or a bacterium each time it is presented)

Non-specific response is evoked immediately on contact with foreign material.

BUT if the foreign material / bacterium etc is contacted again the non-specific response is NOT INVOKED to a greater extent than on the first occasion – it will be the same, (the specific immune response [adaptive or acquired immunity] however involves a degree of memory, and if the same immunogen is presented again it will remember how it was dealt with the last time it was presented.)

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The inflammatory response

This is the process of non-specific defense to tissue damage or infection. The term inflammation comes from the latin word ‘inflammare’, meaning to burn.Four classical signs of inflammation:

1. Redness (rubor)

2. Heat (calor)

3. Swelling (tumor)

4. Pain (dolor)

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Three stages to the inflammatory response

1. Vasodilation and increased permeability of blood vessels

2. Phagocytosis

3. Repair

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Vasodilation and increased permeability of blood vessels

Following entry of an irritant or microorganism through body surfaces there is a brief constriction of arterioles followed by prolonged dilatation.This leads to flushing of the capillary network with blood and the characteristic redness of inflammation.At the same time the leucocytes (which normally occupy the centre of the bloodstream) move to the periphery and line the inside of the blood vessels, a process known as ‘margination.’This acts as a prelude to the migration of leucocytes through the vessel wall into adjacent tissues

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The inflammatory responseContraction of vascular endothelium and

escape of vascular contents.Under the influence of a type of antibody molecule called IgE, Basophils (which circulate in the blood) and Mast Cells (which remain stationery in connective tissue) release chemical mediators including histamine.Histamine causes the cells of local blood vessels to contract, become leaky and allow plasma, plasma proteins, fibrin, red cells and leucocytes to flood out.The escaped vascular components are termed ‘exudate’ and results in the characteristic swelling and pain of inflammation.The white blood cells are now out into the area where the bacteria are and neutrophils rush to the area. Neutrophils release ‘hydrochlorus acid’ to destroy foreign materials.

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NON – SPECIFIC IMMUNITYThis forms the first line of defense via :

1. Physical barriers (e.g. skin and mucous membranes)

2. Chemicals (e.g.lysozyme, spermine)

3. Phagocytes (neutrophils, monocytes and macrophages)

4. Complement (i.e. a group of proteins in the blood that attract phagocytes to invading organisms)

5. Eosinophils (cytotoxic white blood cells that inflict damage on multicellular parasites)

6. Natural killer cells (large lymphocytes which are non phagocytic and spontaneously kill some tumour cells, virus infected cells and cells of bone marrow origin)

7. Killer cells (similar to natural killer cells but requires the coating of target cells with antibody to function)

8. Interferons (a family of proteins secreted by white cells, which inhibit replication of viruses in uninfected cells)

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Physical barriersSkin provides:

a physical barrier,

has low pH due to lactic and fatty acids

Epidermis; the thin outer layer that contains tightly packed epidermal cells and keratin provides water proofing – this is completely renewed every 15-30 days.

The dermis – the thicker inner layer, contains sebacious glands associated with hair follicles - these produce sebum which consists of lactic and fatty acids maintaining a pH of 3-5

Mucous membranes including ciliated epithelial cells, saliva, tears and mucous secretions, (in gastrointestinal, urogenital and respiratory tracts – thus a huge surface area is defended)Temperature: Normal body temperature inhibits growth of most microorganisms. Elevated body temperature can have a direct effect on pathogenic organisms.

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Chemicals – a huge number of factors – here are some examples.

Low pH of skin, stomach and vagina inhibits microbial growth.Fatty acids and lactic acid: maintaining a pH of 3-5 of skin.Pepsin: a digestive enzyme which hydrolyzes proteinsLysozyme: a hydrolytic enzyme found in mucous secretions – these cleave the peptidoglycan layer of the bacterial cell wall.Antimicrobial substances that directly destroy microorganisms by damaging cell membranes.(e.g. cryptidins and -defensins, produced in the base of crypts in small intestine; b-defensins, produced within the skin, respiratory tract) Surfactant proteins A and D which are present in the lungs function as opsonins which enhance the efficiency of phagocytosis.Interferons – a group of proteins produced by cells following viral infection. These are secreted by cells and then bind to nearby cells and induces the mechanisms which inhibit viral replication.Compliment – see further on…

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Leucocytes. The types and functions of the blood-borne white cells. Numbers vary and are indicative of state of health. Platelets are

fragments of megakaryocytes, which are found in bone marrow. .

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PhagocytesPhagocytes

Phagocytosis involves the ingestion of pathogenic microorganisms. The plasma membrane expands around the particulate material to form large vesicles called phagosomes.Only specialised cells are capable of phagocytosis – the main ones are monocytes, macrophages and neutrophils.Phagocytosis is accompanied by increased O2 consumption, increased activity of metabolic pathways, generation of hydrogen peroxide and increased glycolysis – all this generates heat and contributes to the characteristic heat in inflammation.

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NeutrophilsComprise 50-70% of total white cell count10-12 microns in diameterCirculate for < 48 hours in the blood prior to migrating into the tissues where they phagocytose unwanted or foreign materials and then they die due to huge energy loss – “suicide packets”Neutrophils leave the bone marrow where they are generated and enter the blood stream and then need to be directed to:(i) cross the capillary wall closest to the infection site(ii) Migrate towards the source of infection through local tissues(iii) Recognise and then phagocytose (eat) the invading organism(iv) Kill the microbe

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Neutrophils

Neutrophils rely on the compliment system to direct them toward the invading organism.

When the compliment system is activated it (i) attracts neutrophils across local blood vessels in to the tissues. (ii) Directs them to the infection site (iii) coats the microbes with molecules (opsonins) called C3b for which neutrophils and macrophages have receptors for.

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Monocytes and Macrophages

Comprise 3 - 8% of the total white cell count.14-19 microns in diameter (largest of the white cells)Horse-shoe shapedMonocytes circulate in the bloodMacrophages are highly mobile cells that migrate through connective tissue and are widely distributed throughout the bodytissues especially found close to the basement membrane of blood vessels, lymph nodes, lungs and genital tract.

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Monocytes and Macrophages

Their role is to phagocytose LARGE bacteria and dead body cells.Phagocytosis is accompanied by the secretion of lysozyme (an enzyme found in most external secretions – sweat, tears, saliva) but this is principally secreted by the macrophages.Lysozyme splits bonds between amino sugars in peptidoglycans (only found in bacterial cell walls) and this then punctures the bacterial cell wall leading to it’s death.Macrophages also have receptors that recognise cell debris (‘scavenger receptors’) and a range of molecules that are expressed by other dying cells that need to be cleared out of the system.

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ComplimentThe 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])

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Compliment Cascade

Activation 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 moleculeand 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.

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EosinophilsForm 2 - 4% of the total white cell count.10-12 microns in diameter.Possess numerous granules containing enzymes which are directed out of the cell and perforate target cell membranes.Opsonins (including antibody molecules) assist the adherence of the eosinophils to target cells, but they can also function independently of them.Their major role in non-specific immunity is to inflict damage on multicellular parasites such as hookworms, round worms, tapeworms, that are too large to be phagocytosed.Following infection with these parasites, the eosinophil count, which is usually very low, rises dramatically.

Eosinophils are also found in increased numbers in some allergic conditions such as asthma in response to innocuous substances that are mistakenly recognised by the hosts immune system as parasite-like antigens

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Natural Killer [NK] CellsNK cells form less than 1% of the total white cell count and appear as large granular lymphocytes.They kill a range of virally infected cells by binding to viral glycoproteins that appear on the surface of infected body cells.Once the NK cell adhers to the virus infected cell it then releases an active protein called perforin (a cylindrical shaped molecule) that is inserted into the wall of the target cell.This creates a pore to the outside and the cell bursts due to the change in osmotic pressure.

NK cell activity is non-specific in that the same cell can kill a range of host cells infected with different viruses.

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Killer [K] cellsLike natural killer cells they come from the large granular lymphocyte population and kill virally infected cells in the same way.However their recognition of and adherence to target cells is dependent upon those target cells being coated with antibody.This type of cytotoxicity is non-specific in that K cells can kill any cell that has any type of antibody bound to it.This is a typical example of how non-specific immune responses and specific (adaptive) responses (i.e. the production of antibodies) work together to overcome an infection.

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Repair

This is the last stage of inflammation when ‘pus’ (dead neutrophils and bacteria) is formed.This may appear as an abscess, a boil or carbuncle.The inflammatory process is usually self limiting and tissue healing normally occurs spontaneously

Wound Healing Flow Chart

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