Chapter 7: Cellular response in defence. Higher Human Unit 1: Cell Function and Inheritance 12/10/2014 1 Mrs Smith.

Chapter 7: Cellular

response in defence.

Higher Human

Unit 1: Cell Function and Inheritance

11/04/23

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Mrs Smith

Learning Intentions

• You should be able to describe self and non-self antigens as in ABO blood group system.

• You should be able to explain the production of antibodies and the role of blood cells.

• Describe phagocytosis and the function of lysosomes.• Know the differences between innate, acquired, active and

passive immunity.• Describe what is meant by auto immunity and what causes

allergy in the body.11/04/23

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Mrs Smith

Previous knowledge

• Every body cell has a membrane

• There are proteins in and on this membrane (phospholipid bi-layer)

• What are the 6 functions of these proteins?

• What is an immune system?

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THE IMMUNE SYSTEM

We all get sick sometimes...but then we get

better.

What happens when we get sick?

Why do we get better?

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Cellular Defence

• We are constantly surrounded by an almost infinite number of micro-organisms – on surfaces, airborne, inside us, on our skin, in food, clothing. Everywhere.

BACTERIA FUNGI VIRUSES

Random facts about bacteria

• There are typically 40 million bacterial cells in a gram of soil and a million bacterial cells in a millilitre of fresh water; in all, there are approximately five nonillion (5×1030) bacteria on Earth, forming much of the world's biomass

• You can fit thousands upon thousands of bacteria on a pinhead.

• There are approximately ten times as many bacterial cells in the human flora of bacteria as there are human cells in the body, with large numbers of bacteria on the skin and as gut flora.

Random facts con’t

• One survey found 20,000 species of bacteria in a litre of seawater.

• The number of scientifically recognized species of animals is about 1,250,000 (most are insects). There are almost 300,000 recognized species of plants. There are an estimated 10-100 million different species of bacteria.

back to Cellular Defence….

• Most micro-organisms are actually harmless, but a few species can cause disease if they enter our bodies and grow to sufficient numbers.

• We call these microbes pathogens.• Of all the species of bacteria, only about

30% are pathogenic. And only a small percentage of that 30% can cause harm to human hosts.

So what is an immune system?

• Immunity is the ability of the body to resist infection by a disease causing organism (pathogen) o to overcome the organism if it succeeds in invading and infecting the body.

• Immunity can be – INNATE (non-specific) or – ACQUIRED (specific)

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IMMUNITY

INNATE (nonspecific)

PASSIVEACTIVE

NATURAL ARTIFICIAL ARTIFICIALNATURAL

ACQUIRED (Specific)Skin, HCl, cilia, mucus etc.

Antibodies self made after infection. E.g. Chickenpox, flu

Antibodies self made after vaccination. E.g. polio, measles.

Antibodies pre-made by mother – breastmilk, across placenta. Various antibodies.

Antibodies pre-made by other organism such as a horse. E.g. tetanus

11INNATE IMMUNITY: Nonspecific

Innate immunity consists of:

• Outer barriers• Cellular response

– phagocytosis– inflammatory reaction– NK (natural killer) and mast cells

• Soluble factors

When you were born, you brought with you several mechanisms to prevent illness. This type of immunity is also called nonspecific immunity.

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INNATE IMMUNITY – INBORN and UNCHANGING

• Nonspecific - the same response works against many pathogens.

• This type of response is the same no matter how often it is triggered.

• The types of cells involved are macrophages/neutrophils, natural killer cells, and mast cells.11/04/23 Mrs Smith

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INNATE IMMUNITY – The barriers

• Physical– skin– hair– mucous

• Chemical– sweat– tears– saliva– stomach acid– urine

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Inflammatory response

Step 1. Circulation to the site increases tissue warm, red and swollen

Step 2. WBCs leak into tissues phagocytes engulf and destroy bacteria

• chemical and cell response to injury or localized infection

• eliminates the source of infection

• promotes wound healing

INNATE IMMUNITY Cellular response

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Inflammatory response (cont’d)

POSITIVE

• indicate a reaction to infection

• stimulate phagocytosis

• slow bacterial growth

– increases body temperature beyond the tolerance of some bacteria

– decreases blood iron levels

NEGATIVE

• extreme heat enzyme denaturation and interruption of normal biochemical reactions

> 39° C (103°F) is dangerous

> 41°C (105°F) could be fatal and requires medical attention

Fevers have both positive and negative effects on infection and bodily functions

INNATE IMMUNITY Cellular response

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Phagocytosis – ‘Cell Eating’

• When foreign cells such as bacteria and viruses invade the human body the body will respond by attacking them.

• This is done by white blood cells.

• Types of phagocytic white blood cells are:– Monocytes

– Macrophages: engulf pathogens and dead cell remains.

– Neutrophils: release chemicals that kill nearby bacteria.

The reason for PUS

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During an infection hundreds of white cells migrate to the infected area and engulf the infected bacteria by phagocytosis. Phagocytes and and dead pathogens accumulate causing PUS

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Phagocyte migration

Neutrophils and macrophages recognise chemicals produced by bacteria in a cut or scratch and migrate "toward the smell". Here, neutrophils were placed in a gradient of a chemical that is produced by some bacteria. The cells charge out like a "posse" after the bad guys.

CELLS alive!

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Macrophages

• WBCs that ingest bacteria, viruses, dead cells, dust.

• Most circulate in the blood, lymph and extracellular fluid.

• They are attracted to the site of infection by chemicals given off by dying cells.

• After ingesting a foreign invader, they “wear” pieces of it called antigens on their cell membrane receptors – this tells other types of immune system cells what to look for.

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Macrophage and E. coli

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Macrophage ingesting yeast

This human macrophage, like the neutrophil, is a professional "phagocyte" or eating cell (phago = "eating", cyte = "cell"). Here, it envelops cells of a yeast, Candida albicans

CELLS alive!

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Neutrophils

• WBCs – are phagocytic, like macrophages

• neutrophils also release toxic chemicals that destroy everything in the area, including the neutrophils themselves

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Neutrophil phagocytosing S. pyogenes, the cause of strep throat

Human neutrophils are WBCs that arrive quickly at the site of a bacterial infection and whose primary function is to eat and kill bacteria. This neutrophil is ingesting Streptococcus pyogenes.

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Neutrophil killing yeast

One way that neutrophils kill is by producing an anti-bacterial compound called “superoxide anion“, a process called oxidative burst. Here, a neutrophil senses, moves toward and ingests a yeast. In the next two panels, oxidation can be seen by using a dye.

YEAST

NEUTROPHIL

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Phagocytosis – summary

• A phagocyte detects chemicals released by the bacterium and moves along a concentration gradient (low to high).

• The phagocyte attaches to the bacterium and engulfs it in a vacuole formed by an infolding cell membrane.

• The phagocyte has organelles called LYSOSOMES which contains digestive enzymes.

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Surround and attack!

• What happens when the bacteria is under attack?

1. White blood cells senses bacteria.

2. White blood cell moves towards bacteria.

3. White blood cell begins to surround bacteria.

4. White blood cell surrounds bacteria.

5. White blood cell kills bacteria.

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Mrs Smith

The stages of attack.

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IMMUNITY

INNATE (nonspecific)

PASSIVEACTIVE

NATURAL ARTIFICIAL ARTIFICIALNATURAL

ACQUIRED (Specific)Skin, HCl, cilia, mucus etc.

Antibodies self made after infection. E.g. Chickenpox, flu

Antibodies self made after vaccination. E.g. polio, measles.

Antibodies pre-made by mother – breastmilk, across placenta. Various antibodies.

Antibodies pre-made by other organism such as a horse. E.g. tetanus

Remember immunity can be:

• Immunity can be – INNATE (non-specific) we have just done

this so, ........... On to – – ACQUIRED (specific) IMMUNITY

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• Your mom’s antibodies were effective for just a short time at birth, but your innate immune system can be activated quickly. It is always your first line of defense during an infection, but it can’t always eliminate the germ.

• When this happens, your body initiates a focused attack against the specific pathogen that is causing the infection. This attack may lead to long-term protection against that pathogen.

• This type of immunity is called acquired immunity, the customized second line of defense.

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Acquired immunity: Depends on the action of antibodies to combat antigens

• Acquired immunity can be split into a further 2 groups:– PASSIVE (antibodies made by another

organisms i.e. mother, horse)– ACTIVE (self production of antibodies)

• Each with a natural and an artificial aspect to them.

Antigens

• An antigen is a complex molecule such as protein or polysaccharide which is recognised as alien by LYMPHOCYTES (type of wbc).

• The presence of an antigen stimulates WBC’s to produce special protein molecules called antibodies

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Antibodies• An antibody is a Y-shaped

molecule.• Each of its arms bears a receptor

‘binding’ site which is specific to a particular antigen.

• The body has 1000’s of different types of lymphocytes each capable of responding to one specific antigen and producing the appropriate antibody.

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IMMUNITY

INNATE (nonspecific)

PASSIVEACTIVE

NATURAL ARTIFICIAL ARTIFICIALNATURAL

ACQUIRED (Specific)Skin, HCl, cilia, mucus etc.

Antibodies self made after infection. E.g. Chickenpox, flu

Antibodies self made after vaccination. E.g. polio, measles.

Antibodies pre-made by mother – breastmilk, across placenta. Various antibodies.

Antibodies pre-made by other organism such as a horse. E.g. tetanus

Natural acquired immunity

• Acquired active natural.

• Acquired passive natural.

• Both of these types of immunity require antibodies which are produced by LYMPHOCYTES. These are made in bone marrow.

• There are two types of lymphocyte. – T-lymphocyte (T-cells) from the thymus– B-lymphocytes (B-cells) from other places.

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Acquired immunity : Natural - B lymphocytes

• The antibodies are made by B-lymphocytes.

• In the presence of antigens, the B-cells will multiply to produce many antibodies.

• After the infection some of these B-cells will remain to serve as ‘memory cells’ – ready to respond more quickly if body is exposed to same antigens.

• The production of extra-cellular molecules (antibodies) that deal with specific foreign material is called a HUMORAL RESPONSE.

• B-lymphocytes are matured in the bone marrow.

• Leukaemia.

• These do not kill pathogens directly.

• These cells patrol the body, and on recognising foreign antigens, the activate killer T cells, B cells and macrophages.

T-Lymphocytes – Helper T cells

Helper T-cell – the judge that identifies germs and orders their destruction

Acquired immunity : Natural - T lymphocytes

• The second type of Lymphocytes are T-Lymphocytes

• AKA killer T cells.

• A killer T cell will attack and destroy body cells (self antigen markers) that signal (by foreign antigens) that they have been invaded by a pathogen.

T-Lymphocytes – Killer T cells

• The T –cell releases a chemical to destroy the cell and the pathogen in it.

• This is called a CELL MEDIATED RESPONSE

Killer T-cell – Kills germs.

Immunological memoryPrimary and secondary esponse

• Primary response – after seeing a pathogen for the first time it takes a while before enough antibodies are found in the bloodstream. The infected person usually still gets sick.

• Secondary response – happens when there is another exposure to the same antigen. Antibody production is rapid, and a higher concentration is reached and maintained for a longer time. Here disease is usually prevented.

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Immunological memory -memory cells

• Following the first exposure to the antigen, some B- and T-lymphocytes specific to the antigen remain in the body as memory cells.

• If exposed to the pathogen again memory cells quickly produce clones of antibody forming B-cells and Killer T-cells

HERE THE PERSON HAS AQUIRED IMMUNITY IN A NATURAL WAY!

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43Immunological memory -memory cells

Essay Question – 2002

• Give an account of immunity under the following headings.– B-lymphocytes and T-

Lymphocytes (7)– Macrophages (3)

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IMMUNITY

INNATE (nonspecific)

PASSIVEACTIVE

NATURAL ARTIFICIAL ARTIFICIALNATURAL

ACQUIRED (Specific)Skin, HCl, cilia, mucus etc.

Antibodies self made after infection. E.g. Chickenpox, flu

Antibodies self made after vaccination. E.g. polio, measles.

Antibodies pre-made by mother – breastmilk, across placenta. Various antibodies.

Antibodies pre-made by other organism such as a horse. E.g. tetanus

46NATURAL PASSIVE IMMUNITY

Antibodies (Y) are also found in breast milk. The antibodies received through passive immunity last only several weeks.

While your immune system was developing, you were protected antibodies. These antibodies traveled across the placenta from the maternal blood to the fetal blood.

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Natural – Antibodies from mother passes into baby’s blood via breast milk or across the placenta. This is temporary until baby’s own immune system develops.

Essay Question – 2009

• 2. A. Describe how immunity is naturally acquired. (10).

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IMMUNITY

INNATE (nonspecific)

PASSIVEACTIVE

NATURAL ARTIFICIAL ARTIFICIALNATURAL

ACQUIRED (Specific)Skin, HCl, cilia, mucus etc.

Antibodies self made after infection. E.g. Chickenpox, flu

Antibodies self made after vaccination. E.g. polio, measles.

Antibodies pre-made by mother – breastmilk, across placenta. Various antibodies.

Antibodies pre-made by other organism such as a horse. E.g. tetanus

Artificial Aquired immunity.....Active

• Artificial – Vaccinations. Forced exposure to a “dead” pathogen. This exposure introduces the white blood cells to the antigens so they can produce antibodies. Memory cells remain, allowing a secondary response in needed.– Small pox vaccine is a harmless form of the pathogen– Polio vaccine is a weakened form of the vaccine.– Cholera vaccine is a dead microbe whose antigens are

unaltered.

Vaccines con’t

• No matter how the vaccine is made or what it contains, its job is to promote production of B and T cells and the formation of antibodies..... Then some will persist as memory cells.

HERE A PERSON ACQUIRED IMMUNITY BY ARTIFICIAL MEANS!

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IMMUNITY

INNATE (nonspecific)

PASSIVEACTIVE

NATURAL ARTIFICIAL ARTIFICIALNATURAL

ACQUIRED (Specific)Skin, HCl, cilia, mucus etc.

Antibodies self made after infection. E.g. Chickenpox, flu

Antibodies self made after vaccination. E.g. polio, measles.

Antibodies pre-made by mother – breastmilk, across placenta. Various antibodies.

Antibodies pre-made by other organism such as a horse. E.g. tetanus

Acquired immunity -Passive

• Artificial – antibodies made by a non related organism, usually a different species such as a horse, are injected into bloodstream. This only lasts a few years. E.g. tetanus.

Essay Question – 2001

• Give an account of immunisation under the following headings.– Artificial active immunity. (6)– Artificial passive immunity (2)– The impact of vaccination on

childhood diseases. (2)

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TASK – Testing you knowledge!

• Complete Torrance Pg 56 Questions 1-3

CO-OPERATIVE TASK:

Social goal: Equal participation

Academic goal: Describe what is meant by “active immunity” and “passive immunity” and give natural and artificial examples.

TASK: Essay question

• Give an account of specific immunity (10)

TASK: Essay question, on Scholar

• Give an account of the role of lymphocytes in the immune system.(10)

Expected Answer• B-lymphocytes (4 marks)

• B-lymphocytes mature in the bone marrow

• They produce specific antibodies

• to foreign (or non-self) antigens

• The response of B-lymphocytes is called the humoral response (because the antibodies have their effects away from the B-lymphocytes)

• (After the initial response) memory cells remain in the body

• The memory cells cause a faster/stronger secondary immune response (on subsequent exposure to the pathogen)

• T-lymphocytes (4 marks)

• T-lymphocytes mature in the thymus

• The antigens on infected cells are changed and recognised as foreign antigens by T-lymphocytes

• The T-lymphocytes destroy the infected cells directly

• This is known as the cell-mediated response

• (After the initial response) memory cells remain in the body

• The memory cells cause a faster/stronger secondary immune response (on subsequent exposure to the pathogen)

• Coherence (1 mark)

• One mark is given if sub-headings are used, or points placed correctly in two groups.

• Relevance (1 mark)

• One mark is deducted if macrophages are discussed.

• Marks for points 5. and 6. of T-lymphocytes cannot be given if they have already been given for points 5. and 6. in B-lymphocytes.

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What makes us sick?

• “Enemies” in the environment in the form of microbes and chemicals are constantly attacking our bodies, disrupting homeostasis

• Smetimes immune system homeostasis is disrupted on its own

it may over-react to antigens such as

with allergies

it may under-react as with human

immunodeficiency virus infection (HIV)

it may react to self proteins as with

autoimmune disease

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Allergies

• Allergies are basically an overreaction by the immune system to a harmless foreign material.

• There are several types of allergic reactions: sneezing, wheezing, watering, running nose, itching, coughing, swelling, anaphylaxis

• There are many substances that cause to these over reactions: pollen, dust, dust mites, foods, feather fibres, antibiotics, insect bites…

• Hayfever is an allergy. The allergen (pollen) causes the B cells to release antibodies which attach to tissues leading to the release of a chemical called histamine.

• Histamine is responsible for nasal congestion, running nose, constriction of airways etc.

Self and Non-self

• Membranes have a unique combination of surface proteins that are specific to an individual (except identical twins).

These proteins are called antigens.The immune system recognises this antigenic “signature” and so knows that these cells belong to ‘self’.

Non-self

• Cells that do not have this unique combination of antigens are recognised as “foreign” or non-self and will then be attacked by the immune system.

ABO Blood Grouping

• Blood is made from:– PLASMA (liquid part, clear)– RBC’s (carry oxygen, makes blood red, have no

nucleus but do have a membrane)– WBC’s (far fewer in number, part of immune system)

• Human blood is not as simple as just that.• There are different types and these variations

cannot be overlooked.

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Blood grouping

• RBC membranes, like all other cells, have a protein signature (antigens).

• There are 4 main blood groups:

Blood transfusions save many lives.

• However, the blood of the donor has to be compatible with that of the patients.

• For e.g. If a patient who has blood group A receives blood from a donor with blood group B then…

The patient’s anti-B . Antibodies in the plasma will attack the RBC’s (as they have B antigens).

The patient recognises the donors B antigens as non-self.

• Antibodies in the plasma will attack the RBC’s (as they have B antigens).

• This results in the blood clumping/thickening (agglutination) therefore clogging up blood vessels.

= AGGLUTINATON

of the blood

So when are groups compatible

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Antigens on RBC

Antibodies in plasma

35%

11%

3%

51%

Tissue Rejection

• When living organs/tissues are transplanted from one organism to another, they are recognised as foreign by the receiver.

• As a result their immune system will target these cells and destroy the new organ.

• This attempt to destroy the foreign tissue is called tissue rejection.

Tissue Rejection con’t

• Transplants can be successful if the donor is genetically very similar to the recipient.

• IMMUNOSPPRESSOR drugs are then administered. This will inhibit/weaken the patients immune system so it is less able to destroy the new tissue.

• This, however, puts the patient at a much higher risk of contracting diseases/infections such as pneumonia.

Tissue Rejection can be prevented with IMMUNOSUPPRESORS

Autoimmunity

• Autoimmunity is a malfunction of the immune system where it starts to attack cells with self antigens. In other words the body attacks it’s own cells.

• Examples of autoimmune diseases:– Rheumatoid Arthritis

– IS attacks cartilage tissue between joints. It is eventually replaced, but by fibrous tissue, making the joint immovable.

– Multiple Sclerosis– Nerve cells are attacked leading to poor transmission of nerve

impulses therefore various disabilities.

AUTOIMMUNITY: Why does the immune system attack the body that it’s

supposed to protect?

TASK – Testing you knowledge!

• Complete Torrance Pg 59 Questions 1-4

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Exercise and stress • Exercise has been shown to boost the immune

response– moderate exercise increases the immune response

in all age groups– intensive exercise can stress the immune system

• Lack of sleep and exhaustion decrease immune function

• Psychological stress has also been found to decrease immune function

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WHAT CAN YOU DO TO HELP YOUR IMMUNE SYTSEM?

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Diet

• A well-balanced diet is essential for good immune system health– fats are very important in the production of WBCs,

cytokines and natural killer cells– selenium, zinc, and copper are required in small

amounts, which you get if you eat a balanced diet– vitamin E has been shown to boost antibody

production in the elderly

– vitamin B6 aids in antibody synthesis

• But mega-dosing can be harmful, too!11/04/23 Mrs Smith

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Environment

• Chemicals

– dioxin

– pesticides

– solvents

• Sunlight

• Medication

• Viruses

• Bacteria

• Food

Exposure to certain things in their environment may activate the immune systems of some people

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77Acquired immunodeficiency

syndrome (AIDS)• First identified in 1981 - Caused by the human immunodeficiency virus (HIV)

and is spread by contact with body fluids.

• Infects CD4+ (helper) T cells, which decrease in number.

• Decreased numbers of CD4+ T cells lead to increased susceptibility to opportunistic infections.

• Treatments include drugs that inhibit the activity of HIV proteins, thereby preventing production of the virus

Worldwide HIV infection, 1999

HIV virus particle11/04/23 Mrs Smith