12 ATAR Human Bio: Immune System

Pathogens

• disease causing organisms (Eg. Bacteria, viruses, parasites etc.)

• Vectors: host of a pathogen

• these foreign organisms that invade the body + multiply cause communicable/infectious diseases

Bacteria

• Single-celled organisms; 0.5 - 2 micrometers

• found all over body, particularly on skin and in the alimentary canal.

• Mostly harmless, some beneficial, some harmful

• Classified by their cell shape

• enter body through sites of entry (nose, mouth, open wounds) where they reproduce + colonise area

• they then produce toxins which breakdown surrounding tissue cells

• Disease symptoms often allergic responses to products of bacterium

• diseases it cause= Anthrax, Gastroenteritis, Pneumonia, Tetanus, Tuberculosis (TB)

• bacterial infections can be treated by antibiotics

Bacteria structures

• Slime layer- around outside of some bacteria

• Cell Membrane- similar to other cells

• Flagella- for movement; may have 1 or many but not found on all bacteria

• Cytoplasm- appears granular due to presence of ribosomes, bacteria don’t have membrane bound organelles

• Capsule- formed of complex carbohydrate by some bacteria; for protection

• DNA- no nuclear membrane so DNA forms a tangle inside cell; some of DNA is in form of loops called PLASMIDS that can be exchanged during reproduction

• Cell Wall- composition varies but often made of peptidoglycan; a combined carb-protein

Viruses

• Seen under electron microscopes

• Distinctive structures containing DNA OR RNA, surrounded by a protein coat and lipid envelope, some have additional lipid envelopes.

• Infect cells by introducing it’s own DNA (through host cell), so the cell manufactures virus particles.

• diseases it causes= HIV/AIDS, chickenpox, colds, COVID-19, influenza, measles

• TREATMENT; some drugs (anti-virals) can control infections, no drugs known to kill them, antibiotics cannot be used to treat viral infections (no cell wall)

Bacteriophages, Fungi + Parasites

• Bacteriophages: Bacteria infected by a virus

• Fungi: eg. ring worm, tinea

• Parasites: eg. Malaria, Tapeworms, Lice, Scabies, Ticks

Transmission of Pathogens

• Contact- direct + indirect

• Body fluids

• Droplets

• Airborne Transmission (Aerosols)

• Ingestion

• Vectors

• Contact- direct + indirect

DIRECT; Touching an infected person (skin infections and some STDs)

INDIRECT: Touching an object that has been touched by an infected person (drinking from the same cup)

• Body Fluids

• Blood/ other body fluids from an infected person come into contact with another person. (with mucous membranes (In nose/ mouth/genitals))

• EG. being pricked by an infected needle. Hepatitis B & C are transmitted in this way.

• Droplets

• Tiny droplets of moisture may contain pathogenic organisms.

• emitted when you breath, talk, sneeze or cough.

• Droplets may be breathed in by another person or settle on food and then ingested.

• EG. Cold and flu are spread by droplets.

• Airborne Transmission

• When airbourne moisture evaporates, some bacteria and viruses are able to survive (viable) as spores.

• can be inhaled and can cause infection.

• EG. Anthrax Spores, COVID-19

• Ingestion

• Contaminated food or drink may result in disease.

• EG. Food poisoning (salmonella), dysentery and typhoid are transmitted this way.

• Vectors

• Transfer of pathogens by other animals. (spread pathogen to food and then it is ingested)

• EG. Insects, ticks, mites, mosquitoes (malaria) and flies

Non-specific defences

• work against all pathogens

• body’s first line of defence

• stop pathogens entering the body and limit their effect

  1. External defenses: prevent pathogens entering the body

  2. Protective reflexes: ejecting pathogens from the body

  3. Inflammatory response: reduce the spread of pathogens

  4. Fever response

External Defences

External Defences- skin

SKIN:

• An IMPERVIOUS BARRIER, prevents entry of microorganisms, provided it is not broken by cuts.

• Large numbers of bacteria live on the skin naturally, so new bacteria often find it hard to become established.

• Sebaceous glands secrete SEBUM an oily substance that contains antibacterial substances that kill pathogenic bacteria

• Sweat glands produce lysozyme (sweat- salts + fatty acids) that prevents growth of microorganisms.

External Defences- mucous membranes

• line body cavities that open to the exterior.

• Traps microorganisms and inhibits entry.

• Digestive, Urinary and Reproductive tracts- Trachea + Bronchi, Nasal Cavity, Mouth Cavity , Anus, Stomach

External defences- hairs + cilia

• Hairs – nose cavity and ears, traps any foreign particles.

• Cilia – tiny hair like projections from cells, lines nose and trachea + bronchi

  • Beating motion moves mucous containing trapped particles upwards towards throat where they can be coughed up or swallowed

External defences- lysozyme + acids

• Lysozome- enzyme found in tears, saliva, sweat and secretions from nose and tissue fluid that kills bacteria.

• Acids –

  • HCl in stomach is concentrated enough to kill bacteria that has been ingested/those contained in mucous swallowed from nose + windpipe

  • Vagina also has acidic secretions that reduces growth of microorganisms.

  • Sweat is slightly acidic

External defences- cerumen + flushing

• Cerumen (ear wax) – inhibits bacterial growth, protects outer ear against infections, slightly acidic and contains lysozyme.

• Flushing action – urine flowing through urethra has a cleansing action which prevents bacterial growth. Women have a shorter urethra than men so tend to suffer from more bladder infections. Tears, saliva and sweat also have flushing action.

Protective Reflexes

• reflex is an automatic, involuntary response to a stimulus.

• 4 reflexes that help to protect against infection:

  • Sneezing

  • Coughing

  • Vomiting

  • Diarrhoea

• Sneezing

• forceful expulsion of air from the lungs to eject air, mucous, foreign particles and/or irritating gases.

• Stimulus= irritation of the walls of the nasal cavity.

• Coughing

• Caused by irritation to the lower respiratory tract. (Bronchi & bronchioles)

• Air and mucous is forced from the lungs out, via the mouth.

• Vommiting

• Response to excess stretching of the stomach or to bacterial toxins.

• results in contraction of the abdominal muscles & diaphragm to expel the stomach contents.

• Diarrhoea

• Caused by irritation of the intestines

• response is increased contractions of the muscles of the intestinal walls, so irritant is removed quickly.

• As most of the water is absorbed from within the large intestine, the swiftness of the contents moving through this area does not allow for the water to be removed

Internal non-specific defences

• PHAGOCYTES: Engulf and digest microorganisms and cell debris

• LEUCOCYTES (WBCs): Able to leave blood capillaries and migrate through tissues to site of infection or injury; Some secrete substances that destroy bacteria before engulfing it, others engulf live bacteria and then digest them.

• MACROPHAGES: Large phagocytic cells that develop from leucocytes, wandering or fixed, engulf, digest or release chemicals to destroy other cells

Purpose of Inflammation

• Reduce the spread of pathogens

• Destroy pathogens

• Remove damaged tissues & cells

• Repair damaged tissue

  • ‘-itis’ refers to inflammation, e.g. tonsilitis

Inflammatory response

1) Damage to cells causes mast cells to release histamine & heparin

• Histamine increases blood flow (redness) & permeability of capillaries (swelling)

• Heparin prevents clotting

• These abnormal conditions cause pain

2) These chemicals attract phagocytes to consume debris & micro-organisms

• The micro-organisms & phagocytes die and form pus

3) New cells are produced by mitosis

Lymphatic system

Lymph Vessels- more fluid will leak out of arterioles due to HP than will return to capillaries + veins, diameter larger than capillary=more volume collected

Lymph Nodes- each surrounded by CT that extends into the node, mass of lymphoid tissue; containing- lymphocyte, macrophages and plasma cells

ROLE-

• trap large particles (bacteria)

• macrophages destroy these particles- usually within 10-30 mins of being trapped

• when infections occur= increase production of lymphocytes

• specific immunity

Fever Response

• During infection (the inflammatory response) WBCs (or pathogens) release pyrogens= stimulus

• Hypothalamus responds to the pyrogens to reset the body’s thermostat.

• body “feels” cold and responds by shivering and vasoconstriction of arterioles in the skin.

• Body temp rises

• Macrophages drawn to the area and engulf the pathogen, then stimulated to release interleukins/cytokines (enhance the pyrogens= increase fever)

• Eventually fever breaks, with sweating and vasodilation and body temp returns to normal.

Benefits of a fever

1. Inhibit growth of some bacteria and viruses

2. Speeds up chemical reactions in the body: promotes cells repair

• enhance WBC function

• enhance presentation of antigens to macrophages

• increase production of antibodies

Specific defences

• directed at a particular pathogen,

• Only work on one particular disease

• 2 parts to immune response:

  1. Antibody mediated/humoral- involves the production of special proteins= antibodies, which circulate around the body (blood + lymph) and attack invading agents

  2. Cell mediated- involves formation of special lymphocytes (cells) that destroy invading pathogens. (inside cells)

Lymphocytes

Both these cells are produced in the bone marrow, and end in the lymphoid tissue:

• About half the cells go to the thymus where they mature into T cells.

• The other half of the cells mature in the bone marrow to become B cells.

Lymphoid tissue contains thousands of different types of B cells- each capable of responding to a specific antigen

Antigens

Both antibody-mediated and cell-mediated immunity are triggered by antigens.

• any substance capable of causing a specific immune response, (generally causes the body to produce specific antibodies).

• can be:

  • large molecules.

  • proteins, carbohydrates, lipids or nucleic acids.

  • a whole micro-organism, (virus particle/bacterial cell)

  • part of a bacterium- flagella, cell wall or capsule.

  • toxins produced by bacteria.

  • contained within tissues transplanted from another person, such as blood cells of a foreign blood group, and such things as pollen grains and egg white

Antibodies

• a specialised protein that is produced in response to a non-self-antigen.

• can combine with that antigen to form an antigen–antibody complex.

• Antigen molecules have specific active sites and at these sites the antibody can combine with the antigen.

Antibody-mediated immunity (humoral response)

• involves the production and release of antibodies into the blood and lymph.

• provides resistance to viruses, bacteria and bacterial toxins before these micro-organisms or substances enter the body’s cells.

Humoral response process

1. Pathogen invades the body

2. An antigen (pathogen) is detected by a macrophage.

3. Macrophage engulfs the pathogen (breaks it apart) & presents antigen to B cells/B lymphocytes by displaying it on its cell membrane.

4. antigen activates B cells, they enlarge and divide into a group of cells called a clone.

5. Most of the clones become plasma cells, which secrete the specific antibody capable of attaching to the active site of the antigen.

6. antibodies circulate in the blood, lymph and extracellular fluid to reach the site of the invasion of microorganisms or foreign material.

7. B cells of the clone that did not differentiate into plasma cells remain as memory cells.

8. These memory cells spread to all body tissues to allow the response to occur more rapidly should the antigen enter the body again.

How do antibodies work to provide resistance to infection?

• combine with foreign enzymes or bacterial toxins, or inactivate them by inhibiting reaction with other cells or compounds.

• bind to the surface of viruses and prevent the viruses from entering cells coat bacteria so that the bacteria are more easily consumed by phagocytes.

• cause particles such as bacteria, viruses or foreign blood cells to clump together — agglutination.

• dissolve organisms.

• react with soluble substances to make them insoluble and thus more easily consumed by phagocytes.

Primary vs Secondary Response

• first exposure to an antigen the immune reaction= primary response.

• body’s immune system usually responds fairly slowly, often taking several days to build up large amounts of antibodies

• takes time for the B cells to multiply + differentiate into plasma cells.

• However, primary response leaves immune system with a memory of that particular antigen.

• second/subsequent exposure to same antigen= much faster response because of activity of memory cells.

• plasma cells are able to form very quickly, with antibody levels in the blood plasma rising rapidly

• Often response is so quick that the antigen has little opportunity to exert any noticeable effect on the body and no illness results.

Cell-mediated immunity

• provides resistance to the intracellular phase of bacterial and viral infections

• also important in providing resistance to fungi and parasites

• involved in the rejection of transplants of foreign tissue

• also appears to be important in fighting cancer cells.

Cell-mediated immunity process

1. T lymphocytes are responsible for cellular immunity, but it starts in the same way as antibody-mediated.

2. A macrophage (APC)/B cell encounters the foreign antigen, travels to the nearest lymph node and presents it to the T cells (Helper T-cells secrete cytokines to enhance this process)

3. antigen activates more T cells to become sensitised

4. The sensitised T cells enlarge and divide, each giving rise to a clone, a group of identical T cells.

5. Some cells of the clone remain in the lymphoid tissue as memory cells- able to recognise the original invading antigen.

6. If infection w/ same antigen should occur again, these memory cells can initiate a much faster response to the second and subsequent infections.

7. The T cells that don’t become memory cells develop further, producing 3 different types of T cells: Killer, Helper + Suppressor

Killer T-cells

• migrate to the site of infection and deal with the invading antigen.

• attach themselves to the invading cells and secrete + inject a substance that will destroy the cell, and then go off in search of more infected cells.

Helper T-cells

• secrete cytokines (substances) that:

  • cause more lymphocytes at the infection site to become sensitised= intensifying response.

  • attract macrophages to the place of infection so that the macrophages can destroy the antigens by phagocytosis.

  • intensify the phagocytic activity of macrophages

Suppressor T-cells

• act when the immune activity becomes excessive/when the infection has been dealt with successfully.

• release substances that inhibit T and B cell activity, thus slowing down the immune response.

Antibody-mediated VS Cell-mediated Immunity DIFFERENCES

1. Works against bacteria, toxins + viruses before they enter the body’s cells; also against RBCs of a different blood group than the person — Works against transplanted tissues and organs, cancer cells and cells that have been infected by viruses/bacteria; also provides resistance to fungi + parasites.

2. Most new B cells develop into plasma cells, which produce antibodies + release them into blood and lymph — Most new T cells develop into killer/helper T cells, which migrate to the site of the infection.

3. Antibodies combine w/ specific antigen and inactivate/destroy it — Killer T cells destroy the antigen, while helper T cells promote phagocytosis by macrophages.

Antibody-mediated VS Cell-mediated Immunity SIMILARITIES

1. Foreign antigen reaches lymphoid tissue

2. Certain B/T Lymphocytes stimulated to undergo rapid cell division

3. Some of the new B cells / sensitised T-cells form memory cells.

Types of immunity- Natural vs Artificial

NATURAL – occurs without any human intervention ARTIFICIAL – results from giving people an injection of an antibody or antigen that triggers an immune response so they will make their own antibodies (requires human intervention)

Types of Immunity- Passive vs Active

PASSIVE – person is given antibodies produced entirely by someone else; short-lived (lasts only as long as the antibodies are in the body); No memory cells produced- person’s own immune system is never activated= permanent immunity cannot occur + may get ill on subsequent exposures.

ACTIVE- results when the body is exposed to a foreign antigen + manufactures their own antibodies; long-term, due to the manufacture of memory cells, should a subsequent infection occur involving the same antigen, the appropriate antibodies can be produced very quickly→avoid the worst symptoms/may not develop any symptoms at all

Herd Immunity

• Vaccinating a large enough proportion of the population to stop the transmission of a pathogen amongst the community.

• By vaccinating enough individuals it:

  • Stops the chain of transmission

  • Does not give the pathogen a host so it can die out.

Types of Vaccines

1. Live attenuated- contain weakened micro-organisms (reduced virulence: reduced ability to produce disease symptoms) Eg. Polio, TB, MMR

2. Dead/inactivated micro-organism- not as long lasting. Eg. whooping cough

3. Toxoid - if bacteria/virus produces a toxin, toxin can be filtered + used as antigen in a vaccine to initiate immune response Eg. Tetanus

4. Sub-unit- Instead of using whole pathogen, fragment of microorganism used to provoke an immune response. Eg. HPV

5. Biosynthetic- Using recombinant DNA (mRNA): bacterial/viral DNA can be manipulated to become harmless. Eg. COVID-19

Vaccine delivery

• Injections: using a syringe into the body

• Oral: a syrup that is swallowed

• Aerosol spray: nasal spray (for flu’s)

• In development: Skin patches Food

Vaccination schedule

• WHO has set a schedule to vaccinate infants; starts at 2 months old which gives enough time for a baby’s immune system to begin to develop.Then continues throughout childhood: 2, 4, 6, 12, 18 months etc.

• timing of boosters after the initial vaccination are important:

  • Too soon: antibodies present in the blood will destroy the antigen

  • Too late: not enough memory cells are left for the booster to be effective

Risks of Vaccines

• Most common side effects:  Redness, swelling, heat & pain (all at injection site)  Fever

• Allergic reaction: Generally not from the vaccine but the medium they are cultured in.

• Cross-species disease: not from the vaccine but the medium they are cultured in: animal tissue

• Use of chemical preservatives- Concerns about health risks of chemicals, Side effects, Misinformation

Ethical concerns of Vaccines

• Manufacturing:

  • vaccines require a host to be developed for viruses to reproduce- Chicken embryos/mice used to culture vaccines (Animal welfare)

  • Sometimes human tissue needs to be used, so cells initially created in the IVF process are used- people unhappy with origin of these cells

• Testing of vaccines:

  • Before clinical trials: drugs are tested on animals

  • People who volunteer need to be well informed of risks. Often volunteers from underdeveloped nations w/ less education- concern they may not understand risks adequately/fairly.

• Decisions:

  • Parents making decisions on behalf of their children – but risk of a side effect may affect the child for life

  • children too young to understand + make informed decisions

Antibiotics

• A substance that kills or inhibits the growth of bacteria

• Egs. Penicillin, Streptomycin, Cephalosporin

• Can be broad spectrum/affect a wide range of bacteria or can narrow spectrum/effective only against specific types of bacteria

• Bacteriostatic antibiotics inhibit growth of bacteria by interfering with protein synthesis

• Bactericidal antibiotics destroy bacterial pathogens by targeting cell walls, cell membranes or metabolic pathways/action of enzymes found inside bacteria.

Antibiotic resistance (timing)

• 4 years for resistance to occur, more consideration before prescribing

• Multiple drug resistant: resistant to many types of antibiotics.

• prescribed antibiotics- advised to take full course (typically 10 days), even if feeling better earlier, as resistant bacteria survive the antibiotic treatment & reproduce to pass on the resistant trait= Reinfection + sickness occurs again

• Natural selection:

  • Some bacteria may be more resistant to an antibiotic, therefore take longer to be killed.

  • Stopping the antibiotic early, means the bacteria with resistance, live & reproduce + go on to infect others with an antibiotic resistant strain of bacteria.

Antivirals

• Viruses enter a host cell & the DNA or RNA induces the cell to produce new virus particles.

• These particles leave the cell and infect others.

• Scientists attempting to find viral proteins that that can be disabled.

• Any drug that interferes with the replication process is likely to be toxic to the host cell.

• many antiviral drugs available and more being developed

Hygiene Hypothesis

• increased incidence of children w/ allergies (that can lead to greatly increased susceptibility to disease) is due to improved hygiene practices and living standard

  • less exposure to bacteria and virus

  • no immune response to pathogens triggered

  • decrease immunity for wide range infections (no natural immunity/memory cells)

  • increased chance of being infected

  • over-production of histamine—> allergies

Genetic engineering

• the introduction of foreign/modified DNA into another cell

• Uses:

  • identify mutated genes + replace faulty genes with healthy ones (therefore treat disorders like cancers)

  • Producing synthetic hormones: Insulin for Diabetics, hGH, Factor VIII for people with Haemophillia

  • Producing Vaccines

TRANSGENIC ORGANISMS

• an organism whose genome has been altered by adding gene/genes from another organism.

• introduced genes become part of the organisms DNA and can thus be passed on from one generation to the next

Enzymes within Genetic Engineering

• RESTRICTION ENZYMES (in bacteria)- used to cut (viral) DNA at RECOGNITION SITE (specific sequence of bases), restricting duplication of viruses

• DNA LIGASE – enzyme that can join or recombine separate pieces of DNA by forming bonds between last nucleotides in process called LIGATION

Straight vs Staggered Cuts

• Some restriction enzymes produce a STRAIGHT CUT= produces BLUNT ENDS

• Others produce STAGGERED CUTS= produce bits that overhang called STICKY ENDS

• Sticky ends are useful because the single-stranded overhang can combine with any other fragment of DNA that has a complimentary ending - corresponding sequence (Including ones from different organisms)

Producing organisms w/ recombinant DNA OVERVIEW

1. Isolate the gene

2. Insert gene into a plasmid (vector) and clone

3. Insert large quantities of the vectors into host cells to produce the foreign protein using instructions in the recombinant DNA

EG. Bacteria- the gene from insulin production has been introduced, are used to manufacture insulin for treatment of diabetes

Recombinant DNA- STEP 1

STEP 1 – Isolate Gene and cut using restriction enzyme

• Isolate the gene of interest (stated in question)

• Then use restriction enzymes to cut DNA on either side of required gene at restriction sites.

Recombinant DNA- STEP 2

STEP 2 – Isolate a plasmid and cut with same restriction enzyme

• Cut the plasmid with the same restriction enzyme used in cutting the gene to be inserted

Vector + Plasmids

• Vector- molecule of DNA that can transfer genetic material

  • undergoes replication

  • common vectors= bacterial plasmids (recombinant tech) & viral phages- virus that infects bacteria (gene therapy)

• Plasmids= usually circular, double-stranded unit of cytoplasmic DNA, found in bacteria that are capable of replicating within a cell independent of chromosomal DNA (mitosis)

Recombinant DNA- STEP 3

STEP 3 – Splice the Human DNA into the Plasmid using DNA ligase

• The sticky ends of the Human and Plasmid DNA anneal to each other and are spliced together by ligase

• The gene foreign to the vector (ie. The human gene) is now referred to as RECOMBINANT DNA (it has recombined)

Recombinant DNA- STEP 4

STEP 4 – Bacteria takes up recombinant plasmid and then multiplies

• Copies of the recombinant plasmid/vector are made

• Copies are placed into host cells (ie. bacterial cells)

• The host cells then produce the protein that the gene codes for