Immunity (see flow charts for full processes of specific and non-specific immune responses)

Clonal selection

A B lymphocyte is stimulated by a helper T cell (by the binding of a complementary T cell receptor to the B cell’s processed antigen) to divide by mitosis to form identical clones, which become memory cells or plasma cells

What happens after a helper T cell binds to an antigen, displayed by an APC, complementary to its receptor

This stimulates the helper T cell to divide by mitosis, forming identical clones. These develop into memory T cells, stimulate B cells displaying antigens complementary to the T cell’s receptors to divide by mitosis to form plasma and memory cells (clonal selection) stimulate phagocytosis, activate cytotoxic T cells

Cell-mediated vs humoral response

Cell-mediated involves helper T cells stimulating cytotoxic T cells to kill infected cells (by releasing perforin). Humoral involves B cells producing complementary antibodies to foreign antigens.

Antigen variability

Antigens present on pathogens change shape frequently due to genetic mutations, so they are no longer complementary to the antibodies, so antigen-antibody complexes can no longer form

Active vs passive immunity

• Active produces antibodies, secreted by plasma/memory cells;

• passive has antibodies transferred into the body from an outside source.

• Active produces memory cells, so leads to long term immunity, since the antibody is produced in response to an antigen;

• passive doesn’t so only gives short term immunity as antibodies are broken down in the body.

• Active can take time to develop;

• Passive fast-acting

4 types of immunity

• natural active (from previous exposure to pathogen)

• natural passive (e.g. maternal antibodies to foetus across placenta, or to baby in colostrum (initial breast milk)

• artificial active (from vaccine containing harmless pathogen or its antigens) 

• artificial passive (e.g. injection of antidote for snake venom)

What is an attenuated pathogen

A weakened version of the pathogen, used in vaccines. Cannot cause serious sickness.

toxoid

inactivated toxin

herd immunity

• When a sufficiently large proportion of the population has been vaccinated

• Pathogen cannot spread within population

• Protects those that cannot be vaccinated (e.g. babies, those with compromised immune systems), as if most people are immune, the chances of coming into contact with an infected person are low

What is needed for a vaccination programme to be successful

• Vaccine must be economically available in sufficient quantities to vaccinate most of the population

• Vast majority of population must be vaccinated to ensure herd immunity

• Few/no side effects

• Available means of producing, storing and transporting vaccine

• Sufficient and widely distributed staff trained to deliver vaccine

Why might a vaccination programme not eradicate a disease

• Vaccination can’t induce immunity in those with defective immune systems

• People can get infected with the pathogen immediately after being vaccinated - immunity levels are not high enough to prevent the disease, or to prevent it spreading

• Antigenic variability - frequent mutations, leading to sudden changed in the antigens, so they can no longer be recognised by the immune system

• Varieties of pathogens - a vaccine cannot be effective against them all

• Pathogens can ‘hide’ from immune system and avoid immune cells, by concealing themselves inside cells or in places out of reach, e.g. intestines (cholera)

• Some may refuse to be vaccinated for religious, ethical or medical reasons

vaccine ethics

• Animal testing

• Long-term adverse side effects - may be more harmful than disease vaccinated against

• Clinical trials - risks for individuals for public health gains

• Compulsory?

• Individual health risks from side effects against good for population

• Expensive vaccination programmes in a country where disease is almost eradicated

Infection and replication of HIV

• HIV enters bloodstream and circulates

• Attachment proteins bind to CD4 molecule on helper T cells

• Capsid fuses with cell-surface membrane of helper T cell, so RNA and reverse transcriptase enzymes enter helper T cell

• Reverse transcriptase converts HIV’s RNA into DNA, which is inserted into helper T cell’s chromosomes

• (In the nucleus) DNA is transcribed into RNA which passes out of nucleus and is translated

• So new HIV proteins are made

• HIV virus particles break away from helper T cell

• By budding, so form lipid envelope

Why does HIV cause AIDS

• Much fewer helper T cells (down to 200 per mm3 blood)

• B cells not stimulated —> antibodies not produced

• Cytotoxic T cells not stimulated

Why do antibiotics not work against viruses

• Viruses don’t contain their own metabolic pathways, so antibiotics cannot disrupt pathways

• Viruses have a protein coat and not a murein cell wall So there are no sites for the antibiotics to work

• Viruses are within the organism’s host cells, so antibiotics cannot reach them

How does a vaccine result in production of antibodies against the pathogen

• The vaccine contains the pathogen’s antigens

• These antigens are presented on the surface (cell membrane) a macrophage

• Helper T cell with a complementary receptor binds to this displayed antigen

• Clones itself by mitosis

• These helper T cells stimulate B cells that have antibodies complementary to their antigens on their surface, by binding

• The B cell is stimulated to clone itself by mitosis to form memory cells

• The memory cells secrete large quantities of the antibody

Why does an antibody only bind to a specific antigen

It has a VARIABLE REGION that has a specific tertiary structure, which gives it a specific 3D shape (so it will only form antigen-antibody complexes with a specific antigen)

How does the ELIZA test work to test for antibodies against a disease

• The antigens of the disease being tested for are attached to a test well

• A sample of blood plasma is added to the well. If the antibodies are present, they bind to the antigen

• The well is washed to remove unattached antibodies

• Monoclonal antibodies, complementary to the antibody being tested for, and attached to an enzyme, are added

• Well is washed again

• Solution is added containing a substrate which changes colour if the enzyme is present

Ethics of monoclonal antibodies

• Use of animals - uses mice to produce the hybridoma cells that produce the monoclonal antibodies, which also involves inducing cancers in the mice

• Patients must give informed consent - there are some risks associated

• Risks associated with clinical trials