chapter 8 - defence against disease1 defence against disease chapter 8 pages 245-284 rbc leukocyte...

Chapter 8 - Defence Against Disease 1

Defence Against Disease

Chapter 8

Pages 245-284

RBC

Leukocyte (WBC)

Leukocyte (WBC)

2

ImmunityImmunityInfection:Defn: entry of a pathogen into the body of

a organism (host) that might cause disease.

ImmunityDefn: reactions that occur in a person in

response to an infection

The immune system• The immune system is able to

distinguish foreign material from material that is made by the body.

• The immune system has two kinds of responses to the entry of foreign material.

1. Non- Specific Immunity: involves a natural immunity that is non-specific.

2. Specific Immunity (adaptive immunity): the action of specific white blood cells (lymphocytes) to a specific antigen (pathogen or part of) which acts to neutralize the pathogen (also invokes production of memory cells)

Self and Non-self• All cells have marker proteins on their plasma

membrane

• These proteins are the products of the MHC genes. Each person has different MHC genes.

• Therefore marker proteins are specific to each person/organism

• Cells with the body's own marker proteins are accepted as “self”. These proteins are not antigenic to our own immune system.

• Cells with foreign markers are recognised as “non-self”. These marker proteins are antigenic for us.

How Does The Body Know What Cells To Attack

Antigens• The term “antigen” originates from “antibody

generator”

• Defined as a substance that, when it invades the body, will stimulate the formation of a specific type of antibody

• Usually protein or polysaccharide

• May be free e.g. in the bloodstream, or attached to the cell surface of a pathogen

• Critical in differentiating “self” and “non-self”

• Self antigens on the cell membranes are called “markers”.

• Those markers critical to the success of transplantation form the MHC (major histocompatability complex)

• An antigen is typically a large complex molecule, not normally present in the body, that is capable of producing an immune response

How Does The Body Know What Cells To Attack

IMMUNE SYSTEMIMMUNE SYSTEM

Consists of Three Lines of Consists of Three Lines of DefenceDefence


Pathogen invades Tissue/ Cell

Non Specific DefenceSpecific Defenceacquired

resistanceBarrie

rs

1

Physiological

Mechanisms

ChemicalMechanis

ms

Phagocytes and

NK Cells

Inflammation

BasophilsMast Cells

and platelets

Histamines &

phagocytosis

B Cells

T Cells

Memory Cells

Antibodies

Humoral Immunity

Cell Mediated Immunity

32


Non-Specific Immunity

reading: 246 – 250 Quick Check:1-7 Biozone: 147-148

Non-specific mechanisms

• Part of body’s natural immunity

• Provide protection

• Are present at birth

• Either prevent entry of pathogens or destroy them

• Limit the onset and development of infection

• Directed against a wide range of pathogens

9

Non-specific mechanisms:

Barriers: 1st line of defence


1. The First Line of Defence

‘The Wall”• The best action against micro-

organisms is to prevent their entry into the body altogether.

• The first line of defence against infection takes place at the body surfaces.

Skin

• An intact skin acts as a barrier against entry by micro-organisms. A cut or abrasion will allow entry of bacteria or viruses.

– Hardening of outer layers• Provides a physical barrier

– Anti-bacterial and anti-fungal secretions• Produced by sweat glands, sebaceous

(oil) glands, bacterial flora of the skin– Lack of moisture

• Limits growth of microorganisms

12

The First Line of Defence continued….continued….

Mucous Membranes

• secreted by the cells lining your respiratory tract

• traps bacteria which are then swept upwards to the back of the throat by the action of cilia.

• some of the mucus and bacteria is then swallowed, coughed or sneezed out, or blown out through the nose.

• promote growth of natural flora whose secretions limit pathogen growth


Natural Secretions

• Many secretions of the body contain bactericidal agents. Tears and saliva contain lysozyme, an enzyme that cause bacteria to lyse or burst. Acid in the stomach also kills many bacteria.

Peristalsis Diarrhoea eliminates pathogens by

movement towards the anus for elimination

Vomiting also results in removal of pathogens from body


14

Enzymes– Lysozyme in tears, saliva, sweat, nasal

secretions and tissue fluids breaks up (lyses) the cell wall of certain bacteria

Natural Flora

• Many different bacteria are normally found on the skin, gut and in the vagina. These bacteria are harmless to the body and occur naturally.

• The presence of these bacteria can inhibit the growth of pathogenic bacteria as they compete for nutrients and space.


Gastro-intestinal secretions

– HCl in stomach, alkaline fluids e.g. bile in duodenum• Are of a pH which is outside the

range of tolerance for many microorganisms

Hairs and cilia

– Filter inhaled air– Remove micro-organisms and other

antigenic material (e.g. pollen)



16

Non-specific mechanisms:

2nd Line of defence

17

The Second Line of Defence

“The Dumb Soldiers”

PHAGOCYTES

Phagocytes (group of cells)

• (particular) white blood cells• formed in the bone marrow• very motile and can move between

cells• engulf and destroy micro-organisms

and foreign materials through phagocytosis

• include the following groups:

1.Neutrophils

2.Monocytes/ Macrophages

3.Eosinophils


The Second Line of Defence continued …

(a) SEM (4300x) : macrophage pulling rod-shaped E.coli towards it with long cytoplasmic extensions. Several bacteria on the macrophage’s surface are being engulfed

(b) Events of phagocytosis

Monocytes • Largest of the white blood cells• become macrophages when they leave the

bloodstream

Macrophages • gather in various tissues such as the lungs, liver,

kidneys and brain.• are particularly active against micro-organisms that

can live inside the cells of the person they infect.• engulf bacterium

Neutrophils• The most numerous of the phagocytotic cells• Granulated nucleus• Attacks bacteria• Die after engulfing bacterial pathogen• Their dead cells become the bulk of • ‘pus’ at wounds


Macrophage destroying bacterial cells

Eosinophils • can be phagocytotic.• secrete enzymes to kill parasitic worms

among other pathogins


Non-phagocytic leucocytes -

Basophil - contain granules of toxic chemicals

that can digest foreign microorganisms. These are cells involved in an allergic response

Mast Cells- similar to basophils, mast cells contain

a variety of inflammatory chemicals including histamine and seratonin. Cause blood vessels near wound to dilate! and increase permeability of the capillaries

a large connective tissue cell that contains histamine and heparin and serotonin which are released in allergic reactions or in response to injury ...

Basophils are a type of white blood cell (leukocyte). These cells help you fight infections by releasing histamine and other chemicals like heparin (antocoagulant)

LEUKOCYTES

LEUKOCYTES

All produced in the Bone Marrow from Stem Cells

Granular Leukocytes

Have large, lobbed nuclei and distinctive granules in their

cytoplasm

Agranular Leukocytes

Cytoplasm usually lacks granules and the

nucleus is more rounded

Neutrophils

•Most numerous WBC•Main phagocytotic cell•Ingest bacteria and phagocytize dead cells

Eosinophils

•Produce enzymes which detoxify foreign proteins and fight parasatistic infection

Basophils

•Produce and release heparin and histamine in response to injury or infection

Lymphocytes

(T and B)

•Some produce antibodies (B Cells) and others attack invading cells directly (T Cells)

Monocytes/ Macrophag

es

•Largest WBC• monocytes grow into macrophages•Phagocytotic cells that don’t usually die after consuming pathogen

23


Complement Proteins

Phagocytes are able to recognise foreign bodies with the aid of complement proteins.

Complement proteins help phagocytes by:

1. Sticking to invading microorganisms to become more readily identifiable by phagocytes.

2. Some stimulate phagocytes to become more active.

3. Some attract phagocytes to the site of infection.

4. Some complement proteins destroy the membranes of invading micro-organisms.


Compliment Proteins continued …

Consequences of complement fixation

Membrane attack complex results in lesions/holes in foreign cell. These result in death

Amplifies inflammatory response because fixation causes the release of vasodilators and chemotaxis chemicals

Foreign cell is made sticky and easier to

phagocytise

OPSONIZATION

Complement: at least 20 different types of plasma proteinsUsually in inactive formBind to sugars or protein on foreign cell “complement fixation”

Natural killer cells (NK cells)

• are a type of lymphocyte (like macrophages)

• police the body in blood and lymph

• lyse and kill cancer cells and virus-infected cells

• act against any such target (i.e. non-specific)

• recognise certain sugars on invader’s surface

• are not phagocytic: attack membrane of target cell and cause it, and its nucleus, to disintegrate


28

Interferons.

• are a group of antiviral chemicals

• are secreted by some cells when they are infected by virus particles.

• act on uninfected cells making them more resistant to the virus.

• interfer with virus replication

• stimulate macrophages to destroy virus infected cells

• are produced very early during viral infection.

• if a person develops a cold or flu, then the interferons have failed.



Fever


30

The Cause of Fever

Biozone– Fever p152

Inflammatory response

Four signs of Inflammation

1. Redness1. Increased blood flow to area brings

chemical and cellular agents to the site of injury and potential infection

2. Heat 1. Results from increased blood flow

3. Swelling1. Because blood vessels become

more permeable and “leak” more fluid into surrounding tissues

2. This encourages lymphatic return past stationary lymphocytes in lymph nodes

4. Pain• Adaptive because we protect area

and prevent further damage


Inflammatory response continued …

Prevents spread of damaging agents to nearby tissues

Disposes of cell debris and pathogens

Sets the stage for repair


Inflammation


Key Elements of the 2nd Line of Defence

FEATURE PRODUCED/

FOUND

FUNCTION KEY FEATURES

Leokocyte

Monocytes

Macrophages

Neutrophils

Basophils

Eosinophils

Nk Cells

Mast Cells

Stem Cells

Interferons

Compliment Proteins

Vasodilation

Inflammation

Fever

Interleukin-1

Prostaglandins

Pyrexia -

Cytokines

Histamines

Seratonin Chapter 8 - Defence Against Disease 36

37

Specific Immunity 3nd Line of defence

Chapter 8 - Defence Against Disease

The Lymphatic System

Function:

• 1. take up excess tissue fluid and return it to the bloodstream

• 2. absorb fats at the intestinal villi and transport to the circulatory system

• 3. defend against disease


The Lymphatic System

Components include:– Bone Marrow (stem cells differentiate into

lymphocytes

– Lymphocytes: T and B (plasma & memory) Cells, Macrophages & NK cells

– Lymph vessels

– Lymph organs: Thymus, spleen,

– Lymph nodes: tonsils, adenoids, armpits, groin etc

– Lymph: fluid of the vessels containing cells of the lymph and foreign material (antigens) that have drained into it!


Lymph Nodes

• Biozone– The Lymphatic System p153

43

Specific ImmunityThe Third Line of

Defence

Once a pathogen or other foreign material has entered the body, it is

not only bombarded with your non-specific defences but is subject to attack by cells of

immune system, the T and B Lymphocytes.

This system is slower to take action but is more specific in its attack.

T and B Cells are the bodies special forces

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Specific ImmunityThe Third Line of Defence


• This line of defence requires a specific response to a particular infection by the immune system and results in adapted or acquired immunity.

• The specific immunity acquired is generally long lasting, often for life.

• This third line of defence involves special white blood cells known as lymphocytes.

• Lymphocytes attack the particular invader, but also remember the attack (memory cells) so that a latter infection may be stopped more rapidly.



Two main groups of lymphocytes are involved in specific immunity:

B Cells

T Cells

• B Cells mature in the bone marrow to produce

• T Cells leave the bone marrow and mature in the thymus gland, where they turn into T-lymphocytes or T-cells.

• B and T Cells work together and help each other!!



B Cells & theHumoral (Antibody

Mediated) Immunity

Ballistics

B Cells & theHumoral (Antibody

Mediated) Immunity

• B Cells provide - Humoral (Antibody Mediated) Immunity

• they can produce large quantities of antibodies in response to a foreign antigen

• Must recognise ‘non-self’ antigen by binding to it to its receptor site

• Requires a helper T- Cell to activate the B Cell

• Once activated by a Helper T Cell, it divides madly producing two types of daughter cells including:

• Plasma B cells• Memory B Cells

• These cells are clones of the original activated cell and thuis produce the same antibody. This is known as the Clonal Selection Theory (see page 255) 48


B-CellsB-Cells


B-Cells in Action


B-memory Cells

• When the plasma cells produce new antibodies and B-cells, some produced differentiate into other cells called B-memory cells.

• B-memory cells have the same antigen-antibody specificity as the original parent B-cell.

• Memory cells can survive for many years or even life.

• If a second infection ever occurs, the B-memory cells react faster and more vigorously than the initial infection.

• Remain in circulation, producing small quantities of antibody


B-Plasma Cells

• Produce and secrete huge quantities of antibody molecules

• These antibodies bind with antigens forming an antibody-Antigen complex

• Plasma cells are relatively short living & broken down following infection


Antibodies- Antibodies- “immunoglobulins

” • B-cells have immunoglobulins on their surfaces.

• Immunoglobulins are proteins that identify antigens.

• Immunoglobulins are also called antibodies.

• The immunoglobulins of each B-cell have a specific structure and recognise only one kind of antigen.

• There are millions of antigens that the body must be able to respond. In response to this millions of different B-cells are produced with different immunoglobulins on their surfaces.

• Self – tolerance is the ability of the immune system to recognise and ignore its own tissues early in development

• Auto-immune disorder is the condition occuring when the body attacks its own tissues


The Structure of The Structure of AntibodiesAntibodies


Action of Antibodies

• immunoglobulins – ig for short

• Whenon the surface of a Lymphocyte – they are receptor sites. Off, they are antibodies!

• both t and b cells have immunoglobulins on their surface

• secreted immunoglobulins are called antibodies

• it is the binding of antigen to receptor which triggers the specific immune response

• during maturation, the genes that determine ig structure are continually being rearranged. this leads to new combinations of shape and charge in the antigen binding site

• antibodies can combine with two antigens at once. this can cause clumping, or agglutination

• the antigen – antibdy complex promotes phagocytosis

• activates complement proteins

• neutralizes the binding site of an antigenChapter 8 - Defence

Against Disease 58

“immunoglobulins

”more facts!

Clonal selection Theory

When an antigen enters the body it probably passes many B cells before it meets one

with the immunoglobulan with which it can combine. In effect the antigen ‘selects’ the

B cell that will lead to its death

• Antigen ‘selects’ B Cell and its immunoglobulan

• B cell rapidly reproduces (mitosis) to produce identical daughter cells

• Each of these reproduces rapidly to produce a large clone of cells

• Cell cloned in this way will have exactly the same DNA and antibodies

• Most will differentiate into in plasma B cells, others into memory cells



T-CellsT-Cells

• When T-cells mature in the thymus, many different types of T-cells are produced which recognise many different antigens.

Types of T - Cells

Helper T-cells (Th)

• Release chemicals which attract phagocytes

• Stimulate cell division in B-Cells• Produce chemicals that stimulate other

T Cells

Helper T - Cells

Cytotoxic (Killer) T

Cells

Memory T Cells


T-CellsT-Cells

Cytotoxic T-Cells (Tc)

• Another type of T-cell, cytotoxic T-cells (Tc), kills body cells that have been infected with a virus.

• Tc cells kill the infected cell by secreting proteins that punch holes in the membrane of the cell and the contents ooze out.

• Tc cells can only kill a virus when it is inside a cell.

• Some Tc cells also destroy cancer cells.

Suppressor T Cells (Tsc)

• regulates immune response by turning it off when the infection passes


T-CellsT-Cells

Cytotoxic T-Cells (Tc)

• Another type of T-cell, cytotoxic T-cells (Tc), kills body cells that have been infected with a virus.

• Tc cells kill the infected cell by secreting proteins that punch holes in the membrane of the cell and the contents ooze out.

• Tc cells can only kill a virus when it is inside a cell.

• Some Tc cells also destroy cancer cells.

Memory T Cells (Tm)

• Remain in circulation (spleen) for many years after infection


Allergies and Hypersensitivity


IgE binds with mast cells which are now sensitised to the allergen- producing histamines – inflammatory response – increase blood volume; permeability of vessels,



Blood Groups – Blood Antigens

• A red blood cell antigen, the rhesus factor is present on the red blood cells of a majority of people. Such people are rhesus positive (RH+). If the antigen is absent a person is rhesus negative (Rh-). If a person who is Rh- and comes into contact with RH+ blood will respond by producing antibodies against the antigen. This can become critical in pregnancy


Rhesus Incompatibility


Rhesus Incompatibility


Acquiring Specific Immunity

• Acquired Immunity is the term used to describe when antibodies are required to form immunity from a specific antigen.

• Passive Immunity is when antibodies are received by an outside source (vaccination).

• Passive naturally occuring Passive induced

• Active Immunity is when antibodies are produced within a person (B-cells and T-cells).).

• Active naturally occuring Active induced


Acquiring Specific Acquiring Specific ImmunityImmunity

Classification of BacteriaGram Stains pages 214-215

• 1984, bacteriologist, Joachim Gram developed the gram stain

• Gram stain distinguishes between two main groups of bacteria

• Important stain to help identify which drugs are useful

• Gram Positive bacteria take up the violet colour of the stain– Gram + have a cell wall layer of teichoic acid– Are particularly susceptible to penicillin and

sulphonamide drugs• Gram Negative bacteria fail to take up the stain and by

default stain pink– Gram – have no teichoic acid in their walls and

smaller amounts of disaccharides and amino acids– Outer layer of lipid compounds enables these

bacteria to resist penicillin and other drugs– Also makes phagocytosis of the bacteria very difficult– Effective drugs include streptomycin, tetracycline

– S. empidermis: gram negative (susceptible to penicillin)

– S. ecoli: gram negative (resistant to penicillin)75

chapter 8 - defence against disease1 defence against disease chapter 8 pages 245-284 rbc leukocyte...

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