IB 6.3 Defence against infectious disease

6.3 Defence against infectious disease

Plan

1 Skin and mucous membranes as barriers to infection

2 Cuts, platelets and blood clotting

3 Coronary thrombosis

4 Phagocytes and Lymphocytes

5 HIV/AIDS

6 Antibiotics

2

3

4

1

Xavier DANIEL, Ph.D. IB

5


Introduction

Disease: A pathological condition of a part, organ, or system of an organism

resulting from infection, genetic defect, or environmental stress, and

characterized by an identifiable group of signs or symptoms.

Ex.: Cholera, Malaria, Tuberculosis, HIV/AIDS, Smallpox, Measles

Pathogen: An agent that causes disease by infection, e.g. a living

microorganism such as a bacterium, a fungus or a virus.

Ex.: Vibrio cholerae, Plasmodium, Mycobacterium tuberculosis, HIV virus,

Variola viruses, Measles virus


Introduction

Pathogen = an organism or virus that causes a disease

Animals have internal defence mechanisms to protect them against pathogens


Introduction

Animals have three lines of defence to protect them against pathogens

If pathogen is successful in crossing a line of defence, it will face the next one


Plan





5 HIV/AIDS

6 Antibiotics

2

3

4

1


5




Skin and mucous membranes as barriers to infection 1

1


Skin and mucous membranes as barriers to infection

sweat

1


Skin and mucous membranes as barriers to infection

1. Skin = physical barrier against infection

Impermeable

Outer epidermal layer constantly replaced

removes parasites and other pathogens

Acidic pH inhibits growth of pathogens

Sebaceous glands secrete sebum: low pH and moisture

2. Sweat contains lysozyme that prevents bacterial growth

Lysozyme destroys bacterial cell walls

3. Mucous membranes Secrete a lining of sticky mucus that trap microorganisms

Also secrete lysozyme

Have ciliated cells, cilia push mucus containing bacteria out

Airways

Ears

Foreskin

Vagina

Identity of pathogen not determined at this

stage: non-specific response


Plan





5 HIV/AIDS

6 Antibiotics

2

3

4

1


5


Cuts, platelets and blood clotting 2

Thromboplastin

Blood clotting to stop bleeding

Fibrinogen soluble

Fibrin insoluble


Plan





5 HIV/AIDS

6 Antibiotics

2

3

4

1


5


Coronary thrombosis 3

Atherosclerosis = progressive degeneration of artery walls

1.Endothelial damage

2.Plaque formation

3.Raised blood pressure

4.Rupture of lining

5.Inflammatory response in lumen

6.Thrombus

7.Embolus

8.Death of cells downstream blood clot



1. Endothelial damage 2. Plaque formation 3. Raised blood pressure

Artery wall is elastic and smooth

Wide lumen

Lesion of endothelium

LDL Cholesterol deposits under endothelium

Plaque

Plaque builds up over decades

Artery wall less elastic + Blood flow impeded

Blood pressure rises



2. Plaque formation

White blood cells invade plaque

Inflammation under endothelium

Atherosclerotic plaque

Fibers + Fat + Cells



4. Rupture of lining 5. Inflammatory response in lumen 6. Thrombus

Lining about to break

under plaque pressure

Plaque invades lumen

Platelets trigger Inflammatory response

Formation of blood clot = Thrombus in lumen



6. Thrombus 7. Embolus 8. Death of cells downstream blood clot

A part of thrombus breaks away

= Embolus

Carried away by blood flow



6. Thrombus 7. Embolus 8. Death of cells downstream blood clot

A part of thrombus break away

= Embolus

Carried away by blood flow

Embolus or thrombus

If bigger than lumen

Block blood flow

Cells downstream deprived of O2

Death of tissue



If artery blocked is coronary artery



Main factors increasing risks of coronary thrombosis

Smoking

High blood cholesterol concentration

High blood pressure

Diabetes I and II

Obesity

Lack of exercise



Main terms in cardiovascular diseases (CVD)


Plan





5 HIV/AIDS

6 Antibiotics

2

3

4

1


5




Phagocytes and Lymphocytes 4



Pathogen crosses the first line of defence

Pathogen enters the body

Second line of defence = white blood cells

Many kinds of WBC, i.e. Macrophages (= Phagocytes) and Lymphocytes

All cells have specific proteins on their surface

Cells of the body have self proteins on their surface

Pathogens have non-self proteins on their surface

Phagocytes recognize non-self

Change shape to engulf pathogen: phagocytosis

Identity of pathogen not determined at this

stage: non-specific response

Macrophages and Neutrophils

Same for dead tissue cells and cell debris Xavier DANIEL, Ph.D. IB

Pseudopodia

surround

microbes.

1

Microbes

are engulfed

into cell.

2

Vacuole

containing

microbes

forms.

3

Vacuole

and lysosome

fuse.

4

Toxic

compounds

and lysosomal

enzymes

destroy microbes.

5

Microbial

debris is

released by

exocytosis.

6

Microbes

MACROPHAGE

Vacuole Lysosome

containing

enzymes

Phagocytosis


• Attack, learn & remember pathogens circulating in

blood & lymph

• Produce specific antibodies

against specific antigen

• Types of B cells

– Plasma cells • immediate production of antibodies

• rapid response, short term release

– Memory cells • continued circulation in body

• long term immunity



Antigen = antibody-generating substance

Antibody for epitope A

Antigen

Antibody for epitope B

Antibody for epitope C

Three Epitopes

of the Antigen

• Antigen = any foreign molecule

• An antibody recognizes and binds to a small,

accessible portion of the antigen = epitope

• One given antigen can have more than one

different epitopes

A

B

C



s s

s s

s s

s s

s s

s s

s s

s s

s s

s s

s

s s

s s

s

s s

s s

s s

s s

s s

Structure of antibodies

light chains

antigen-binding site

heavy chains


light chain

B cell membrane

heavy chains

light chain

hypervariable region


Constant region

S

S

Disulfide bridges

(intra- and inter-molecules)



1. Among all Ab present,

Antibody anti-X recognizes Antigen X

2. THE B lymphocyte with

Ab anti-X activated

3. Proliferates

Makes a clone

Each B lymphocyte of

this clone presents Ab anti-X

4. Response specific to Ag X

B lymphocytes activation

No need to produce all B lymphocytes all the time

Just produce the one(s) that are needed now



Loose antibodies Antibodies bound

to B lymphocyte

membrane

Plasma cells Memory cells

Die after a few days

In blood for various

lengths of time

In blood for years to life




Identity of pathogen determined at this stage:

specific immune response

• “Anti-self” B lymphocytes are destroyed

before Clonal Selection

– This has to occur since the antigen receptors are

formed from RANDOM gene rearrangements

– Could accidentally produce a receptor that

recognizes a body cell/molecule

– Autoimmune diseases result when clonal

selection fails

B lymphocytes activation



Neutralization

Loose antibodies

Plasma cells

production

Agglutination Precipitation Cell lysis




Plan





5 HIV/AIDS

6 Antibiotics

2

3

4

1


5


HIV / AIDS 5

HIV = Human Immunodeficiency Virus

AIDS = Acquired Immunodeficiency Syndrome

1. HIV invades and destroys T-Helper cells

2. Capacity to produce antibodies eventually lost

3. Susceptibility to "opportunistic" pathogens

4. Syndrome = more sensitive to

multiple concomitant diseases

some are typical of latter stages

of AIDS, i.e. Kaposi's sarcoma

Early infection: body produces anti-HIV antibodies

Detection of antibodies: "HIV-positive"


HIV / AIDS 5

Most efficient drugs against

HIV are antiretroviral drugs

Anti-fusion

Anti-integrase

Anti-maturation

Reverse transcriptase inhibitors


HIV / AIDS 5

Transmission of HIV:

Sexual intercourse: abrasions mucous membranes penis/vagina causing minor bleeding

Transfusion of contaminated blood

Placenta/childbirth/breastfeeding

Sharing hypodermic contaminated needles

Rare minorities of individuals do not have cell receptors for HIV on their Helper T-cells

and do not develop AIDS


Plan





5 HIV/AIDS

6 Antibiotics

2

3

4

1


5


Antibiotics

Antibiotics can be

Antibiotic : anti life

Only living organisms are affected by ATB

Viruses are NOT targets of ATB

Most ATB target bacterial pathogens

Prokaryotes (bacteria) and eukaryotes show differences in metabolism

ATB take advantages of these differences

ATB are specific for prokaryotic metabolic processes

Antibiotics = chemicals that can kill or damage prokaryotic cells but not eukaryotic cells

bactericidal (kill bacteria)

bacteriostatic (making bacteria inactive)


Antibiotics

Targets of Antibiotics


Antibiotics

Many antibiotics discovered in saprotrophic fungi

In nature, they compete with bacteria for nutrients

Excrete antibacterial antibiotics

Culture the fungi + extract ATB

Some are extracted from bacteria or chemically synthesized

One ATB-producing fungi

Penicillium

Penicillin Discovery attributed

to Alexander Fleming

Scotland

Nobel prize 1928

Sources of Antibiotics


Antibiotics

Testing Penicillin

Stage 1:Growing the penicillin

This was a combination of the latest freeze-drying technology and some much more traditional equipment: thousands of milk bottles (in which to grow the bacteria), milk churns, a dog bath and a

hand pump! From this, the team were able to gather a few grams of pure penicillin.

Stage 2: Testing penicillin on animals

There was enough penicillin to test it on eight mice. They were injected with a deadly bacteria (streptococci). Four of the mice were then given penicillin. 24 hours later the mice which had not

been injected with penicillin were dead. Those who had been injected were healthy.

Stage 3: The first human trial of penicillin

By 1941 the team had enough penicillin to test it on a human. The patient had terrible abscesses which had spread from his mouth to his scalp, eyes, arm and even his lung. He was going to die –

there was nothing to lose by trying penicillin. After four days of treatment he was much improved and was sitting up in bed – penicillin worked. However, they did not have enough, and after five days the

supply ran out – the patient relapsed and died.


Antibiotics

Resistance to Antibiotics


Antibiotics

Resistance to Antibiotics

Required measures

Doctors prescribe ATB only for serious bacterial infections

Patients complete full courses of ATB to eliminate the infections completely

High hygiene standards maintained in hospitals to prevent cross-infections

Farmers not using ATB in animals feeding

Develop new ATB

IB 6.3 Defence against infectious disease

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Transcript of IB 6.3 Defence against infectious disease