C 3.2

C3.2.1—Pathogens as the cause of infectious diseases

• Pathogens are organisms that cause infectious diseases.

• The organism that is infected and develops the disease is the host.

• A broad range of pathogens can cause diseases in humans. The main groups are viruses, bacteria, fungi and protists. 

• The bacteria that cause diseases in humans are all eubacteria.

• Archaea, which are the other domain of bacteria, are not known to cause infectious diseases in humans. 

C3.2.2—Skin and mucous membranes as a primary defence

SURFACE BARRIERS TO INFECTION:

1. SKIN

1. Dead waterproof surface layer, which is tough and elastic and forms a physical barrier;

2. Sebaceous glands in the skin secrete a chemical called sebum ( lactic acid and fatty acids), which makes the surface of the skin acidic and maintains skin moisture;

3. This prevents the growth of most pathogenic bacteria and therefore acts as a chemical barrier.

2. MUCOUS MEMBRANES

1. Mucus membranes are thin and soft areas of skin that are kept moist with mucus;

2. Mucous membranes are found in the nose, trachea, head of the penis, vagina and urethra;

3. Although they do not form a strong physical barrier, many bacteria are killed by lysozyme, an enzyme in the mucus;

4. So it acts as a chemical barrier.

C3.2.3—Sealing of cuts in skin by blood clotting

• Cuts in the skin are sealed by blood clotting and prevent entry of pathogens;

• Platelets have an important role in clotting;

• Platelets are small cell fragments that circulate with red and white blood cells in blood plasma;

• At the start of the clotting process, platelets are attracted to the wounded tissues, where they release clotting factors.

• These clotting factors initiate a cascade of reactions in which the product of each reaction is the catalyst of the next reaction.

• The cascade results in the rapid conversion of inactive prothrombin to active thrombin;

• Thrombin converts the fibrinogen which is a soluble plasma protein to long protein fibres called fibrin (insoluble);

• Fibrinogen is altered by the removal of sections of peptide that have many negative charges;

• Fibrin forms a mesh of fibres across wounds;

• Blood cells are caught in the mesh and soon form a semi-solid clot;

• If exposed to air the clot dries to form a protective scab, which remains until the wound has healed.

C3.2.4—Differences between the innate immune system and the adaptive immune system

The immune system has two main parts: 

1. Innate immune system: non-specific, as different pathogens are all responded to in the same way and the responses do not change during an organism's life.

Phagocytes are part of the innate immune system.

2. Adaptive immune system: specific, as each pathogen encountered elicits a new and different response and immune responses develop during an organism's life. 

Lymphocytes are part of the adaptive immune system.

C3.2.5—Infection control by phagocytes

• Ingestion of pathogens by phagocytic white blood cells gives non-specific immunity to diseases;

• This is because a phagocyte does not distinguish between pathogens, it ingests any pathogen;

• Phagocytes destroy pathogens in blood and tissue fluid;

• They can squeeze out through the walls of blood capillaries and move through tissues to the sites of infection;

• A large number of phagocytes at a site of infection form pus;

• The cell surface membrane of the phagocyte extends out and around the pathogen, engulfing it by endocytosis.

• Once the pathogen is inside a vacuole in the cytoplasm of the phagocyte,

• Lysosomes fuse with the vacuole, to add enzymes which digest and kill the pathogen.

• The remains of the foreign material are expelled from the phagocyte;

C3.2.6—Lymphocytes as cells in the adaptive immune system that cooperate to produce antibodies

• Lymphocytes have a rounded nucleus and until activated they only have a small amount of cytoplasm.

• Lymphocytes circulate in the blood. 

• There are also large numbers of them in lymph nodes of the lymphatic system. 

• This system consists of vessels that drain excess fluid from body tissues. 

• Lymph nodes are small bean-shaped structures that develop at intervals

along lymph vessels.

• Lymphocytes of different types ( B and T-helper lymphocytes) cooperate to

produce antibodies.

• Antibodies are large Y-shaped proteins. 

• The two arms are variable, with hypervariable parts 

• The part of an antibody that binds to the antigen is the hypervariable region. 

• As the name suggests, there is immense variation in the hypervariable regions of antibodies and the immune system can generate new versions

• However, one lymphocyte only produces antibodies with one type of hypervariable region.

• The stem of the Y helps the body to destroy the pathogen, for example, by making it more recognizable to phagocytes that then engulf it.

C3.2.7—Antigens as recognition molecules that trigger antibody production

• Lymphocytes have to distinguish between body cells ("self" cells) and "non-self" cells such as invading pathogens.

• Pathogens possess protein molecules or glycoproteins or large polysaccharides on their cell membranes called antigens.

• Antigens are foreign substances that stimulate the production of antibodies;

• When a lymphocyte is exposed to a specific foreign antigen, it will produce specific antibodies.

• They have a complimentary shape to the antigens on the pathogens;

• When a pathogen enters the body, its antigens bind to the antibodies in the cell surface membrane of one type of lymphocyte;

• It is similar to the binding of a ligand to a receptor, or the binding of a substrate to the active site of an enzyme.

• However, unlike the binding of ligands to receptors, antibody to antigen binding is irreversible. 

• Unlike the binding of substrates to enzymes, the antigen is not changed chemically.

• One lymphocyte only produces antibodies with one type of hypervariable region.

C3.2.8—Activation of B-lymphocytes by helper T-lymphocytes

C3.2.9—Multiplication of activated B-lymphocytes to form clones of antibody-secreting plasma cells

C3.2.10—Immunity as a consequence of retaining memory cells

Steps of specific immune response

The principle of ‘challenge and response’

Antigens on the surface of pathogens that have invaded the body are the ‘challenge’. The ‘response’ involves the following stages.

1. Activation of Helper T-cells

• There are many types of lymphocytes in the immune system. 

• Each type has antibody-like receptor proteins in their plasma membrane, to which one type of antigen can bind. 

• Pathogen that has infected is engulfed by macrophages ( a type of phagocyte);

• Antigens from the pathogen are then displayed/presented by MHCH proteins on the macrophage membrane;

• Specific helper T-lymphocytes that have antibody-like receptors that match the displayed antigens bind to the macrophages. 

• These bound helper T-cells are then activated by the macrophage.

• The activated helper T-lymphocytes bind to B-lymphocytes that have the same antibody-like receptor. 

• The helper T-lymphocytes activate these B-lymphocytes, both by means of the binding and by release of a signalling protein.

2. Activation of B-lymphocytes by Helper T-lymphocytes

• The activated helper T-lymphocytes bind to B-lymphocytes that have the same antibody-like receptor. 

• The helper T-lymphocytes activate these B-lymphocytes, both by means of the binding and by release of a signalling protein.

1. Clonal expansion of activated B-cells

• Activated B-lymphocytes cells start to divide by mitosis to form a clone of cells, that all produce the same type of antibody;

• These B-lymphocytes grow in size and develop an extensive endoplasmic reticulum with many ribosomes attached to it, along with a large Golgi apparatus. 

• This allows rapid production of antibodies by protein synthesis.

• The cells that have grown and differentiated for antibody production are plasma B-cells.

Figure: Activated B cells with antibodies specific to a particular antigen are selected by clonal selection. They then multiply via mitosis in a process called clonal expansion.

2. Production of memory cells

• Immunity is the ability to eliminate an infectious disease from the body.

• Antibodies can give us immunity to a disease but they only persist in the body for a few weeks or months.

• The plasma B-lymphocytes that secrete antibodies are also gradually lost after an infection has been overcome.

• However, immunity can last for much longer and in many cases for the rest of our lives. 

• This is due to memory B-lymphocytes.

• Most B-lymphocytes in a clone become active plasma B-cells. 

• A smaller number of the cells do not actively secrete antibodies but persist for a long time after the infection. 

• These memory B-lymphocytes remain inactive unless the same pathogen reinfects the body.

• They then are activated and respond very rapidly.

• Immunity to an infectious disease is thus due to having either antibodies against the pathogen or memory cells that allow rapid production of the antibody.

• Memory cells ensure that the second time an antigen is encountered, the body is ready to respond rapidly by producing more antibodies at a faster rate. 

• Memory cells give long-term immunity to a disease. This is a secondary immune response.

C3.2.11—Transmission of HIV in body fluids

HIV can be transmitted in the following ways:

• Sex without a condom

• transfusion of infected blood or blood products

• Sharing of needles used by intravenous drug users

• childbirth and breastfeeding.

C3.2.12—Infection of lymphocytes by HIV with AIDS as a consequence

• AIDS is caused by HIV (human immunodeficiency virus);

• HIV is a retrovirus;

• It is made up of several key components including RNA and the enzyme, reverse transcriptase, which is used to produce DNA in the host cell.

• HIV attacks Helper T- T-lymphocyte cells;

• It inserts its RNA into the host cell, which then incorporates the RNA in its DNA;

• Transcription now includes the HIV’s code, resulting in an output of more viral RNA;

• The number of T lymphocytes is reduced over the years;

• The activation of the B lymphocytes requires Helper T cells;

• Thus B lymphocytes are not activated and cannot divide to form a clone of antibody-producing cells;

• Antibodies are not produced and the pathogen survives to cause an infection;

• This results in lower immunity;

• This renders the immune system unable to fight off other pathogens and so the individual becomes prone to infection from other opportunistic pathogens

• When the HIV individual is suffering from several diseases or conditions at the same time, they are said to have acquired immune deficiency syndrome (AIDS)

• A syndrome is a group of diseases or conditions that occur together. 

C3.2.13—Antibiotics are chemicals that block processes occurring in bacteria but not in eukaryotic cells

• Antibiotics are chemicals produced by microorganisms to kill or inhibit the growth of microorganisms;

• Most antibiotics are antibacterial. 

• They block processes that occur in prokaryotes but not in eukaryotes.

• Antibiotics target vital bacterial processes such as DNA replication, protein synthesis and cell wall formation.

• Antibiotics can also be made synthetically (in a laboratory)

• For example, Penicillium fungus produces penicillin to kill bacteria when they compete for the dead organic matter on which they both feed.;

• Antibiotics block processes in bacteria and not humans as there are many differences between bacterial and human cells;

• They do not protect against viruses as viruses have no metabolism of their own as they use the host cell’s mechanisms for transcription, translation and other metabolic pathways.

• Drugs that would target these processes would damage the host cells and cause even more harm.

• Antivirals are drugs that target viral enzymes without harming the host cell

C3.2.14—Evolution of resistance to several antibiotics in strains of pathogenic bacteria

• Within a bacterial population, there is variation caused by mutations (as occurs in populations of all species)

• A chance mutation might cause some bacteria to become resistant to an antibiotic (eg. penicillin)

• When the population is treated with this antibiotic, the resistant bacteria do not die

• This means the resistant bacteria can continue to reproduce with less competition from the non-resistant bacteria, which are now dead

• Therefore the genes for antibiotic resistance are passed on with a much greater frequency to the next generation.

• As bacteria only have one copy of each gene, a mutant gene will have an immediate effect on any bacterium possessing it

• Over time, the whole population of bacteria becomes antibiotic-resistant because the antibiotic-resistant bacteria are best suited to their environment

• This is an example of evolution by natural selection

• Some pathogenic bacteria have become resistant to penicillin as they have acquired genes that code for the production of the enzyme penicillinase, which breaks down penicillin.

• For example, MRSA (methicillin-resistant Staphylococcus aureus) can infect the blood or surgical wounds of hospital patients and resists all commonly used antibiotics.

Measures to avoid antibiotic resistance

• Antibiotic resistance in bacteria is an example of natural selection that humans have helped to develop through incorrect use or overuse of antibiotics

• Implementation of certain measures can help to avoid antibiotic resistance. These measures may include:

  • Avoiding prescription of antibiotics for non-serious or non-bacterial infections

  • Completing the full prescribed course of antibiotics to ensure the infection is completely cleared

  • Maintaining high standards of hygiene in the hospital environment by hospital staff.

  • Minimising the use of antibiotics for routine treatment of animals in agriculture

  • Development of new types of antibiotic by pharmaceutical companies

C3.2.15—Zoonoses as infectious diseases that can transfer from other species to humans

• Some pathogens can use more than one species as a host.

• Mycobacterium bovis causes tuberculosis in cattle but can also infect a wide variety of other animal species.

• Milk produced by infected cattle may contain live cells of the bacterium which transmit the tuberculosis to humans if the milk is drunk. 

• This is an example of a zoonosis—a disease that can be transmitted to humans

from other animals in natural circumstances.

• Rabies is also a zoonosis. 

• The lyssavirus that causes rabies can be transmitted from infected dogs to humans by a bite or scratch or if saliva from the dog comes into contact with the eye, mouth or nose of a human.

• Japanese encephalitis is a zoonosis that can be transmitted from infected pigs or birds by mosquito bites.

• COVID-19 infection is a disease that has recently transferred from another species, with profound consequences for humans.

C3.2.16—Vaccines and immunization

The principle of vaccination

1. Immunization is the use of a vaccine to trigger immunity.

2. The vaccines are given intramuscularly, subcutaneously ( under the skin), or by mouth.

3. Three types of material can be used in a vaccine:

1. pathogens that are either killed or live but attenuated so they carry the antigens but do not cause the disease.

2. antigens from the pathogen (usually proteins)

3. mRNA or DNA coding for a protein that acts as an antigen

4. The principle of vaccination is that antigens in the vaccine cause the production of the antibodies needed to control the disease;

5. Sometimes two or more vaccinations are needed to stimulate the production of enough antibodies;

6. The first vaccination/ antigens stimulate a specific immune response called the primary immune response;

7. This response includes the antigens stimulating the Helper T-lymphocytes & B-lymphocytes; 

8. This stimulates the production of plasma cells and then specific antibodies.

9. If memory cells are also produced, long-lasting immunity develops. 

10. The second vaccination, sometimes called a booster shot, causes a response from the memory cells and therefore there is a faster and greater production of antibodies;

11. Memory cells bring about a rapid secondary response;

12. Sometimes a series of vaccinations is needed to stimulate the production of sufficient memory cells;

13. This is an example of active or artificial immunity.

C3.2.17—Herd immunity and the prevention of epidemics

• Herd immunity is achieved when a significant proportion of a population has already contracted a disease or been vaccinated. 

• As a result, the spread of a virus or other pathogen is impeded, because it repeatedly encounters people who are already immune. 

• With herd immunity, any new outbreak of the disease will decline and disappear.

• Not everyone in the population has to be immune for herd immunity to develop. 

• The following formula can be used to estimate the percentage of people

who must be immune for the population as a whole to be protected.

• R is the average number of people that an infected person infects. 

• Measles is highly infectious and has an R-value of 15, so (1 - 1/15) x 100% = 93% of the population must be vaccinated to reach herd immunity.

C3.2.18—Evaluation of data related to the COVID-19 pandemic

During the COVID-19 pandemic, huge amounts of data were collected. 

This data is being analysed and evaluated by epidemiologists to find out how to

prevent or control future pandemics.

The formula for percentage change= Final -initial/initial X 100

The formula for percentage difference = (Value 1-value 2) / average of value 1 & 2 X100

1. The World Health Organization has published data for individual countries and six regions. The data shows a series of waves of infection. The table below gives the numbers of cases and deaths in each week that was the peak of a wave in the Americas region.

1. Calculate deaths as a percentage of cases for each of the peak weeks, to identify trends in mortality

2. Suggest reasons for the waves of infection and changes in mortality rate.