2.4 cell recognition and the immune system

What is an antigen

• foreign molecule/ protein/ glycoprotein/ glycolipid

• That stimulates an immune response leading to the production of antibodies

How are cells identified by the immune system

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

• Often proteins so have a specific tertiary structure

What types of cells and molecules can the immune system identity

1. Pathogens - disease causing microorganisms

2. Cells from other organisms of the same species - organ transplants

3. Abnormal body cells - tumour or virus infected cells

4. Toxins - released by some bacteria

3 examples of pathogens

Viruses, fungi, bacteria

Describe phagocytosis of pathogens (non-specific immune response)

1. Phagocyte attracted by chemical/ recognises foreign antigen on pathogen

2. Phagocyte engulfs pathogen by surrounding it with its cell membrane

3. Pathogen contained in vesicle/ phagosome in cytoplasm of phagocyte

4. Lysosome fuses with phagosome and releases lysozymes (hydrolytic enzymes)

5. Lysozymes hydrolyse/ digest pathogen

What occurs after phagocytosis

Leads to presentation of antigens where antigens are displayed on the phagocyte cell surface membrane, stimulating the specific immune response

What are the 2 aspects of the specific immune response

• cellular and humoral response

What types of antigens do T-lymphocytes recognise

• antigen presenting cells

• E.g infected cells, phagocytes presenting antigens, transplanted cells, tumour cells

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

• Specific helper T cells with complementary receptors on cell surface bind to antigen on antigen-presenting cell

• Activated and divides by mitosis to form clones with stimulate:

• Cytotoxic T cells - kill infected cells/ tumour cells by producing perforin

• Specific B cells - humoral response

• Phagocytes - engulf pathogens by phagocytosis

What type of antigens do B lymphocytes recognise

• recognise free antigens, in blood or tissues

Describe the response of B-lymphocytes to a foreign antigen (the humoural response)

Clonal selection:

• specific B lymphocyte with complementary receptor (antibody with cell surface) binds to antigen

• This is then stimulated by helper T cells (which releases cytokines)

• So divides rapidly by mitosis to form clones

Some differentiate into B plasma cells which secretes large amounts of antibodies.

Some differentiate into B memory cells which remain in blood for the secondary immune response

What are antibodies

• quaternary structure proteins (4 polypeptide chains)

• Secreted by B lymphocytes (e.g plasma cells in response to specific antigens)

• Bind specifically to antigens forming antigen-antibody complexes

Draw the structure of an antibody

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Explain how antibodies lead to the destruction of pathogens

• antibodies bind to antigens on pathogens forming antigen-antibody complex

• Has a specific tertiary structure so binding site/variable region binds to complementary active site

• 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

What is the primary immune response

• first exposure to antigen

• Antibodies are produced slowly and at a lower conc

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

• Memory cells produced

What is the secondary immune response

• 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

• injection of antigens from attenuated (dead or weakened) pathogens

• Stimulating formation of memory cells

How do vaccines provide protection for individuals against disease

1. Specific B lymphocytes with complementary receptor binds to antigen, specific T helper cells bind to antigen presenting cell and stimulate B cell

2. B lymphocyte divides by mitosis to form clones

3. Some differentiate into B plasma which release antibodies, some differentiated into B memory cells

4. On secondary exposure, B memory cells rapidly divide by mitosis to produce B plasma cells

5. Antibodies released faster and at a higher concentration

How do vaccines provide protection for populations against disease

• herd immunity - Large proportions of population are vaccinated, reducing spread of pathogen

• So large proportion are immune, so do not become ill

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

What is active immunity

• initial exposure to antigen through vaccine or primary infection

• Memory cells involved

• Antibody produced and secreted by B plasma cells

• Slow, takes longer to develop

• Long term immunity as antibody can be produced in response to a specific antigen again

What is passive immunity

• no exposure to antigen

• No memory cells involved

• Antibody introduced from another organism (e.g breast milk/ placenta from mother)

• Faster acting

• Short term immunity as antibody hydrolysed (endo/exo/dipeptidases)

Explain the effect of antigen variability on disease and disease prevention

• antigens on pathogens change shape/ tertiary structure due to gene mutations (creating new strains)

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

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

• Specific antibodies not complementary/ cannot bind to changed antigen

Describe the structure of a HIV particle

• lipid envelope

• RNA

• Reverse transcriptase

• Capsid

• Attachment protein

Draw a HIV particle

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Describe the replication of HIV in helper T cells

1. HIV attachment proteins attach to receptors on helper T cells

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 inserted/ incorporated into helper T cell DNA (may remain latent)

6. Viral protein/ capsid/ enzymes are produced. So DNA transcribed into HIV mRNA and HIV mRNA translated into new HIV proteins

7. Virus particles assembles and released from cell via budding

Explain how HIV causes the symptoms of acquired immune deficiency syndrome

• HIV infects and kills helpers T cells (host cell) as it multiplies rapidly

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

• So plasma B cells can’t release as many antibodies for agglutination and destruction of pathogens

• Immune system deteriorates, more susceptible to opportunistic infections

• Pathogens reproduce, release toxins and damage cells

What are antibodies ineffective against viruses

• viruses do not have metabolic processes/ ribosomes (do not make protein)

• Viruses do not have bacterial enzymes/ murein 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

• have a specific tertiary structure/ binding site/ variable region

• Complementary to receptor/ protein/ antigen found on a specific cell type

• The therapeutic drug is attached to antibody

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

What’s a use for SOME monoclonal antibodies in medical treatments

• some are 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/protein/antigen associated with diagnosis

• Dye/stain/fluorescent marker attached to antibody

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

Explain the use of antibodies in the ELISA test to detect antigens (direct)

1. Attach sample with potential antigens to well

2. Add complementary monoclonal antibodies with enzyme attached, they bind to antigen if present

3. Wash well to remove unbound antibodies, to prevent false positive

4. Add substrate, enzymes create products that cause a colour change (positive result)

Explain the use of antibodies in the ELISA test to detect antigens (sandwich)

1. Attach specific monoclonal antibodies to well

2. Add sample with potential antigens, then wash well

3. Add complementary monoclonal antibodies with enzymes attached, bind to antigens if present

4. Wash well to remove unbound antibodies, to prevent false positive

5. Add substrate, enzymes create products that cause a colour change (positive result)

Explain the use of antibodies in the ELISA test to detect antibodies (Indirect)

1. Attach specific antigens to well

2. Add sample with potential antibodies, wash well

3. Add complementary monoclonal antibodies with enzymes attached, bind to antibodies if present

4. Wash well to remove unbound antibodies

5. Add substrate, enzymes create products that cause a colour change (positive result)

Suggest the purpose of a control well in the ELIZA test

• compare to test to show only enzyme causes colour change

• Compare to test to show all unbound antibodies have been washed away

Ethical issues with using vaccines and monoclonal antibodies

• preclinical testing/ use of animals, means potential stress/ harm to animals. However animals are not killed and it helps reduce human suffering

• Clinical trials on humans, potential harm/ side effects

• Vaccines, may continue high risk activities and still develop/ pass on pathogen

• Use of drug, potentially dangerous side effects