A9- Immune system and HIV ✅

what is an antigen?

• foreign molecule / protein

• stimulates an immune response leading to production of antibody

how are cells identified by the immune system?

• each type of cell has specific molecules on its surface that identify it

• often proteins→ have a specific tertiary structure

what types of cells and molecules can the immune system identify?

1. pathogens

2. cells from other organisms of same species (e.g. organ transplants)

3. abnormal body cells e.g. tumour cells or virus infected cells

4. toxins released by some bacteria

describe phagocytosis of pathogens (non specific immune response)

1. phagocyte recognises foreign antigens on pathogen /(is attracted by chemicals)

2. phagocyte engulfs pathogen by surrounding it will its cell membrane

3. pathogen contained in phagosome vesicle in cytoplasm of phagocyte

4. lysosome fuses with phagosome and releases hydrolytic enzymes called lysozymes

5. lysozymes hydrolyse pathogen

what does phagocytosis lead to…

• presentation of antigens where antigens are displayed on the phagocyte cell-surface membrane

• stimulating specific immune response ( cellular or humoral )

give 4 examples of antigen presenting cells

1. infected cells

2. phagocytes presenting antigens

3. transplanted cells

4. tumour cells

describe the response of T lymphocytes to a foreign antigen ( the cellular response )

T lymphocytes recognise (antigens on surface of) antigen presenting cells

Specific helper T cells with complementary receptors bind to antigen on antigen-presenting cell → activated and divides by mitosis to form clones which stimulate:

• cytotoxic T cells → kill infected cells

• specific B cells → humoral response

• phagocytes → engulfs pathogen by phagocytosis

describe the response of B lymphocytes to a foreign antigen (the humoral response)

1. clonal selection:

• specific B lymphocyte with complementary receptor binds to antigen

• this is then stimulated by T helper cells ( which release cytokines )

• so divides ( rapidly ) by mitosis to form clones

2. some differentiate into B plasma cells → secrete large amounts of monoclonal antibody

3. some differentiate into B memory cells → remain in blood for secondary immune response

what do B lymphocytes recognise?

free antigens eg. in blood or tissues, not just antigen presenting cells

what are antibodies?

• quaternary structure proteins ( 4 polypeptide chains )

• secreted by B lymphocytes eg. plasma cells in response to specific antigens

• bind specifically to antigens forming antigen-antibody complexes

describe the structure of an antibody

explain how antibodies lead to the destruction of pathogens

• Antibodies bind to antigens on pathogens forming an antigen-antibody complex

• Specific tertiary structure so binding site / variable region binds to complementary antigen

• Each antibody binds to 2 pathogens at a time causing agglutination (clumping) of pathogens

• Antibodies attract phagocytes

• Phagocytes bind to the antibodies and phagocytose many pathogens at once

explain the difference between the primary and secondary immune response

Primary:

• first exposure to antigen

• antibodies produced slowly and at a lower concentration

• takes time for specific B plasma cells to be stimulated to produce specific antibodies

• memory cells produced

Secondary:

• second exposure to antigen

• antibodies produced faster and at a higher concentration

• B memory cells rapidly undergo mitosis to produce many plasma cells which produce specific antibodies

what is a vaccine?

• introduction of antigens → could be from attenuated pathogens

• stimulating formation of memory cells

explain how vaccines provide protection to individuals against disease

1. specific B lymphocyte with complementary receptor binds to antigen

2. specific T helper cell binds to antigen presenting cell and stimulates B cell

3. B lymphocyte divides by mitosis to form clones

4. some differentiate into B plasma cells which release antibodies

5. some differentiate into B memory cells

6. on secondary exposure to antigen, B memory cells rapidly divide by mitosis to produce B plasma cells

7. these release antibodies faster and at a higher concentration

Explain how vaccines provide protections for populations against disease

• Herd immunity - large proportion of population vaccinated, reducing spread of pathogen

→ large proportion of population immune so do not become ill from infection

→ fewer infected people to pass pathogen on / unvaccinated people less likely to come in contact with someone with disease

1. when does active immunity occur?

2. how can it be stimulated?

1. when the immune system is stimulated by an antigen to produce antibodies and memory cells

2. Naturally- from an infection or Artificially- from a vaccination

does active immunity create long or short term immunity and why?

long term immunity

due to memory cell formation

what is passive immunity?

when a person receives ready-made antibodies without producing them

why does passive immunity result in short term immunity?

• ready-made antibodies injected

• no immune response triggered

• no memory cells formed

describe 5 differences between active and passive immunity

explain the effect of antigen variability on disease and disease prevention

• antigens on pathogens change shape / tertiary structure due to gene mutations

• so no longer immune ( from vaccine or prior infection )

• B memory cell receptors cannot bind to changed antigen on secondary exposure

• specific antibodies not complementary so cant bind to changed antigen

give 3 example applciations of how disease and disease prevention is affected by antigen variability

yearly new flu vaccines developed

no vaccine for HIV

can catch a cold many times

describe the structure of a HIV particle

describe the replication of HIV in helper T cells

1. HIV attachment proteins bing to receptors on helper T cell

2. lipid envelope fuses with cell surface membrane, releasing capsid into cell

3. capsid uncoats, releasing RNA and reverse transcriptase

4. reverse transcriptase converts viral RNA to DNA

5. viral DNA is incorporated into T helper cell DNA

6. viral protein / capsid / enzymes are produced

• DNA transcribed into HIV mRNA

• HIV mRNA translated into new HIV proteins

7. virus particles assembled and released from cell

explain how HIV causes the symptoms of acquired immune deficiency syndrome (AIDS)

1. HIV infects and kills T helper cells (host cell) as it multiplies rapidly

• so T helper cells can’t stimulate cytotoxic T cells, B cells and phagocytes

• so B plasma cells cant’ release as many antibodies for agglutination and destruction of pathogens

2. immune system deteriorates → more susceptible to infections

3. pathogens reproduce, release toxins and damage cells

explain why antibodies are ineffective against viruses

• viruses do not have metabolic processes eg don’t make proteins

• viruses do not have bacterial enzymes / murrain cell wall

what is a monoclonal antibody

• Antibody produced from genetically identical / cloned B lymphocytes / plasma cells

• So have same tertiary structure

Explain how monoclonal antibodies can be used in medical treatments

• Monoclonal antibody has a specific tertiary structure / binding site / variable region

• Complementary to receptor / antigen found only on a specific cell type (eg. cancer cell)

• Therapeutic drug attached to antibody

• Antibody binds to specific cell, forming antigen-antibody complex, delivering drug

Some monoclonal antibodies are also designed to block antigens / receptors on cells.

Explain how monoclonal antibodies can be used in medical diagnosis

• Monoclonal antibody has a specific tertiary structure / binding site / variable region

• Complementary to specific receptor / antigen associated with diagnosis

• Dye / stain / fluorescent marker attached to antibody

• Antibody binds to receptor / antigen, forming antigen-antibody complex

Examples vary, eg. pregnancy tests

use of antibodies in ELISA test to detect antigens

• describe the method for the direct ELISA test

(uses a single antibody that is complementary for the antigen you’re testing for:)

1. Attach sample with potential antigens to well

2. add complementary monoclonal antibodies with enzymes attacked → bind to antigen of interest if present

3. Wash well → remove unbound antibodies (to prevent false positive)

4. Add substrate → if antigen present/ positive result→ enzymes converts substrate into coloured product → colour change = positive result

use of antibodies in ELISA test to detect antibodies

• describe the method for the indirect ELISA test

(uses two different antibodies- used to detect pathogenic infection eg. HIV)

1. attach specific antigens to well

2. add sample of blood plasma with potential antibodies, if specific antibodies are present these will bind to antigens at bottom of well

3. wash well to remove unbound antibodies

4. add secondary complementary monoclonal antibodies with enzyme attached

5. secondary antibodies bind to primary antibody

6. wash well→ remove unbound antibodies

7. add substrate→ enzymes create products that causes a colour change (positive result)

suggest the purpose of a control well in the ELISA test ( contains now target antigen)

• compare to show only enzyme causes colour change

• compare to show all unbound antibodies have been washed away

suggest why failure to thoroughly wash the well can result in a false positive in the ELISA test

• antibody with enzyme remains even if it hasn’t bound to antigen

• so substrate converted into colour product

Suggest some general ethical issues associated with the use of vaccines and monoclonal antibodies

1. Pre-clinical testing on / use of animals → potential stress / harm / mistreatment

○ But animals not killed & helps produce new drugs to reduce human suffering

2. Clinical trials on humans → potential harm / side-effects

3. Vaccines → may continue high risk activities and still develop / pass on pathogen

4. Use of drug → potentially dangerous side effects

Suggest some points to consider when evaluating methodology relating to the use of vaccines and monoclonal antibodies

1. Was the sample size large enough to be representative?

2. Were participants diverse in terms of age, sex, ethnicity and health status?

3. Were placebo / control groups used for comparison

4. Was the duration of the study long enough to show long-term effects?

5. Was the trial double-blind (neither doctor / patient knew who was given drug or placebo) to reduce bias?

Suggest some points to consider when evaluating evidence and data relating to the use of vaccines and monoclonal antibodies

1. What side effects were observed, and how frequently did they occur?

2. Was a statistical test used to see if there was a significant difference between start & final results?

3. Was the standard deviation of final results large, showing some people did not benefit?

4. Did standard deviations of start & final results overlap, showing there may not be a significant difference?

5. What dosage was optimum? Does increasing dose increase effectiveness enough to justify extra cost?

6. Was the cost of production & distribution low enough?