4.6 - Immunology and Disease

Pathogenic

An organism that causes a disease, damaging its host

Infectious

A disease that may be passed or transmitted from one individual to another

Carrier

A person who shows no symptoms when infected by the disease organism but can pass the disease to another individual

Disease reservoir

Where a pathogen is normally found. This may be in humans or another animal and may be a source of infection

Endemic

A disease which is always present in the area but at low levels

Epidemic

A significant increase in the usual number of cases of a disease, often associated with a rapid spread

Pandemic

A global epidemic occurring worldwide or in multiple countries, usually affecting a large number of people

Vaccine

Uses non-pathogenic forms, products or antigens of microorganisms to stimulate an immune response which confers protection against subsequent infection

Antibiotic

Substances produced by microorganisms that affect the growth of other microorganisms

Antibiotic resistance

Where a microorganism, which should be affected by an antibiotic, is normally found longer susceptible to it

Vector

A living organism which transfers a disease from one individual to another

Toxin

A chemical produced by a microorganism, which causes damage to its host

Anitgenic types/serotypes

Organisms with the same or very similar antigens on the surface. Such types are sub-groups or strains of a microbial species which may be used to trace infections. They are usually identified by using antibodies from serum

The human body as a host

• Many organisms live in or on the human body in symbiotic or parasitic relationships

• Some species are pathogenic or parasitic;

  • Have the potential to cause disease if they secrete toxins or if their numbers increase too much

• Help to defend against disease or cause disease

Tuberculosis: type of organism

Bacteria

Tuberculosis: source of infection

Bacterial (Mycobacterium tuberculosis) disease currently on the rise due to the link with the HIV epidemic

Tuberculosis: tissues affected

Lungs and neck lymph nodes

Tuberculosis: mode of transmission

• Spread rapidly in overcrowded conditions

• Airborne droplets when infected people cough, sneeze and spit

Tuberculosis: symptoms

• Coughing

• Chest pain

• Coughing up blood

Tuberculosis: prevention

BCG vaccination programme for children

Tuberculosis: control methods and treatment

Long course of antibiotics

Examples of bacterial infections

• Cholera

• Tuberculosis

Examples of viral infections

• Smallpox

• Influenza

Examples of Protoctistan infections

• Malaria

Cholera: type of organism

Gram negative bacterium which is endemic in some areas of the world

Cholera: source of infection

Grab negative bacteria. Endemic in some areas of the world

Cholera: tissues affected

Gut lining

Cholera: mode of transmission

Water borne

Toxins affect the gut lining

Cholera: mode of transmission

Water borne. Humans act as reservoirs or carriers and contaminate water supplies in which the organism is transmitted, although it multiples in the human host

Cholera: symptoms

Watery diarrhoea —> severe dehydration and frequently death

Cholera: prevention

• Treatment of contaminated or dirty water

• Good hygiene

• Provision of clean drinking water

Cholera: control methods and treatment

Vaccine (made from killed organism or possible genetically engineered) may provide temporary protection

Smallpox; types of organism

Virus Variola Major

Smallpox: source of infection:

Virus

Only organism that humans have intentionally made extinct outside specialist laboratories

Smallpox: tissues affected

• Mouth

• Throat

• Lymph nodes

• Blood stream

Smallpox: mode of transmission

• Inhaled or transmitted by saliva

• Close contact with infected people

• Person to person or from contaminated objects

Smallpox: symptoms

• Fever

• Fluid-filled blisters all over the body

• 30 to 60% fatality rate

Smallpox: prevention

• Successful immunisation program was based on its low rates of antigenic variation/mutation and the highly immunogenicity nature of its component antigens

• So the vaccine was highly effective

• No animal reservoir and people were keen to be immunised because of the devastating effects of the disease

Smallpox: control methods and treatment

• Fluids and drugs to reduce fever

• Vaccination

Influenza: types of organism

Virus of which there are three main sub-groups. Within each sub-group there are many different antigenic types

Influenza: source of infection

Virus

When a new strain appears, there is not immunity in the population and epidemics and, sometimes, pandemics occur

Influenza: tissues affected

Cells lining the upper respiratory tract

Influenza: mode of transmission

• Sufferers spread by droplet infection

Influenza: symptoms

• Sore throat

• Coughing

• Fever

Influenza: prevention

• Quarantine

• Hygiene

Mode of spread is difficult to control

Influenza: control methods and treatment

• Antibiotics are ineffective against influenza and are only used to treat the symptoms of secondary bacterial infection

• Annual vaccination programmes are available but due to the number of types, together with the emergence of new types, they are not always effective

Malaria: type of organism

Caused by Plasmodium spp, a protoctistan parasite

Malaria: source of infection

• Protoctistan parasite; Plasmodium spp.

• Endemic in some sub-tropical regions

• Disease is mainly caused by 2 species that have amny antigenic types

Malaria: tissues affected

• Liver

• Red blood cells

Malaria: mode of transmission

• Female Anopheles mosquitoes, through feeding on blood taken, act as vectors to transmit the parasite to new victims

Malaria: symptoms

Organism initially invades liver cells and then multiplies in red blood cells which burst, releasing more parasites an causing severe bouts of fever

Malaria: prevention

• Relies on knowledge of the life cycle of both the vector and the parasite in order to exploit their weak points

• Prevention transmission

  • Prevent biting by use of nets, clothing, insect repellent

• Destroy populations of the vector

• Mosquito larvae are aquatic and can be eaten by introduced fish, killed by draining breeding sites, or spraying oil on the water’s surface

• Adults are killed with insecticides, bacterial infection or by sterilisation

• Each of these has advantages and disadvantages

Malaria: control methods and treatment

• Treatment targets the parasite while it is in the blood rather than in the cells. Quinine has been used but it is now less effective as the Plasmodium has developed resistance. Artermisinin is also used, often combined with other drugs to reduce the possibility of resistance.

• Drug treatment is available but mainly to reduce the chances of infection

• Vaccines prove difficult to develop as the malarial parasite mutates and there are different antigenic types

• Plasmodium is affected by drugs when outside the cells in the blood but these have limited effectiveness and have side effects

  • Resistance is an increasing problem

• Antibodies are only effective against the parasite when outside body cells so limiting the target stages of a vaccine

Virus

Intracellular parasites that use a cell’s metabolic pathways to produce more virus particles

Structure of virus

• Core of nucleic acid (DNA or RNA) surrounded by a protein coat or capsid

• Capsid; repeating subunits of protein (capsomeres)

• Some surrounded by a lipid coating - often derived from cell membrane of host

  • Can contain antigens

    • Different types in combination give a number of different strains

Explain why viruses are not able to reproduce without a host cell

No ‘cellular machinery’ organelles or cytoplasm

Describe the life cycle of a virus

1. Gain entry to host cell (attaches to receptors on the host and enters the cell often by phagocytosis)

2. Viral DNA inserts itself into host DNA + instructs the cell to make new virus particles. If virus NA = RNA, reverse transcription takes place to make a DNA copy of virus genome

3. Host cell fills up with virus particles

4. Host cell ruptures by lysis

5. Cell dies

6. New virus can infect new cells

Ways in which viruses can be pathogenic

• Cell lysis when they escape from cells to infect other cells/organisms (shedding)

• Production of toxic substances

• Cell transformation where they can trigger cells to become cancerous - activate oncogenes which can subsequently lead to cancer formation

• Suppress the immune system (e.g. HIV) if the virus is specific to an immune cell

• Any treatment for viral diseases would damage host cells as virus is inside them

Antibiotic

Chemical produced by a microorganism that kills/inhibits the replication or growth of bacteria

Broad spectrum antibiotics

Affect both Gram positive and Gram negative bacteria

Narrow spectrum antibiotics

Only act on certain bacteria

Bactericidal antibiotics

Kill bacteria

Bacteriostatic antibiotics

Prevents/inhibits growth or bacterial replication

Explain what factor determines which type of antibiotic is used

Aspect of of bacterial metabolism affected

Explain how antibiotics used medically work

Affect bacterial metabolism but do not interfere with the host cell metabolism

Ways to assess the effectiveness of different strengths/types of antibiotic

• making a lawn plate of the bacteria

• placing discs of different strengths of one antibiotic or different antibiotics on the surface

• measuring the clear zone where the bacteria have not grown or have been killed. The larger the area of the clear zone, the more bacteria have been killed, so the more effective the antibiotic is.

Describe the structure of the bacterial cell wall

• Contains peptidoglycan (murein) consisting of molecules of polysaccharide cross linked by amino acid side chains. The cross linking provides strength and the wall protects against osmotic lysis.

• It is surrounded by an outer layer of lipoprotein and lipopolysaccharide.

• The Gram reaction reflects the more complex structure of Gram negative cell walls

• The presence of the extra layers protects the cells from the action of some antibacterial agents such as lysozyme and penicillin.

Explain the advantage of extra layers on bacterial cell walls

Protects the cells from the action of some antibacterial agents such as lysozyme and penicillin

Gram positive bacteria

• Thick peptidoglycan layer - retain crystal violet stain

• Appear purple after Gram staining

Gram negative bacteria

• Thin peptidoglycan layer - alc used in the procedure washes cv stain out

• Counterstaining with safranin stains the cells red

• Extra layer of lipopolysaccharide which protects the cells from lysozyme and the action of penicillin

Cell wall of Gram positive bacteria

Thick peptidoglycan/murein layer

Cell wall of Gram negative bacteria

Thin peptidoglycan layer

Extra layers of lipopolysaccharide which protects the cells from lysozyme and the action of penicillin

Colour of stain of Gram positive bacteria

Purple

Colour of stain of Gram negative bacteria

Pink/red

Explain how penicillin affects bacteria

• Affects formation of cross linkages in the cell wall during growth and division of bacterial cells

• Binding to and inhibiting the enzyme responsible for formation of cross-links between molecules of peptidoglycan

• Wall is weakened

• Osmotic changes occur

• Cells lyse/burst

Which class of bacteria is penicillin more effective against?

Gram positive due to difference in structure of cell wall

Explain how tetracycline affects bacteria

• Affects protein synthesis (process common to all bacteria)

• Effective against a broader range of bacteria

• Acts as a competitive inhibitor of the second anticodon-binding site on the 30S subunit of bacterial ribosomes

• Prevents binding of a tRNA molecule to its complementary codon

• Inhibits the translation stage of protein synthesis

Which class of bacteria is tetracyline more effective against?

Neither. Broader range. Broader spectrum antibiotic

Explain why viruses are not effected by antibiotics

No/absence of metabolic pathways

Explain how antibiotic resistance is caused

Overuse of antibiotics

Explain the process of development of antibiotic resistance

1. Bacteria divide rapidly under optimum conditions - high mutation rate

2. Naturally occurring mutations that confer resistance to antibiotics have given these bacteria a selective advantage in the presence of antibiotics

3. Natural selection of bacterial strain that are completely unaffected by some antibiotics

4. In the absence of antibiotics, they not longer have an advantage over non-mutated but if they cause an infection, they are increasingly difficult to control

5. Numbers of resistant strain increase —> infections more difficult to treat with the usual antibiotics

Purpose of natural barriers

Reduce the risk of infection

Examples of natural barriers

• Skin

• Skin flora

• Blood clotting

• Inflammation (localised)

• Phagocytosis

• Mucus

• Ciliated epithelium

• Lyzozyme

Purpose of the skin as a natural barrier

• Tough barrier

• Vitamin C is needed to maintain strong connective tissue —> prevents microbes entering the body

Purpose of the skin flora as a natural barrier

• Protection

• Compete with pathogenic bacteria and unlike these bacteria, the flora is not easily removed by washing

Purpose of blood clotting as a natural barrier

Seal wounds in skin quickly to prevent infection

Purpose of inflammation as a natural barrier

• Localise breaks in the barrier

• Raised temperature is unfavourable to microbes

• Increase in blood flow delivers phagocytes to the area

Purpose of phagocytosis as a natural barrier

Destroy invading microbes

Purpose of mucus/cilitated epithelia/mucous membranes

• Trap microbes in inhaled air

• Mucus traps the microbes and the cilia on the cells brush/sweep the mucus away from the lungs

Purpose of lyzozyme as a natural barriers

• In tears, saliva and stomach acid

• Kills bacteria

  • hydrolyses peptidoglycan in bacterial cell walls

  • Weakened cell wall breaks as water from the tears and saliva enters the microbe by osmosis

  • Cause the cells to lyse/burst

Purpose of stomach acid as a natural barrier

Contains lysozyme to kill ingested bacteria

Innate immunity

Non-specific, natural responses to microbes. Natural barriers in the body to reduce the risk of infection

Adaptive immunity

• Specific to the antigen

• Develops as a result of antigens being recognised as foreign to the body

Antibodies

• Proteins (globulins) which are specific to the antigen with which they bind to form an antigen-antibody complex

• Y - shaped

Structure of an antibody

Y-shaped, formed from 4 polypeptide chains and have 2 binding sites

Explain how an antigen-antibody complex renders the antigen inactive

• Agglutination which increases the rate of engulfment by phagocytes. If viruses.toxins are joined together by agglutination, it can mean that they are too large to enter a cell

• Marking for phagocytosis

Describe the process of the humoral immune response

• Stem cells in the bone marrow make B lymphocytes

• Specific receptors detect specific antigen —> B lymphocyte is activated

• Activation of B lymphocytes by a corresponding antigen (clonal selection)

• Stimulates proliferation of antibody- secreting/producing cells (plasma cells and memory cells) (clonal expansion)

• Divide rapidly, forming antibody secreting plasma cells

• This clonal expansion is increased by the cytokines from the cell mediated response

• Memory cells produced remain in the bloodstream/circulation ready to divide rapidly if the same antigen is encountered again

Where B lymphocytes originate from

Stem cells in the bone marrow

Where B lymphocytes mature

In the spleen and lymph nodes