2.4 Cell recognition and the immune system

What is an antigen?

• A foreign molecule (e.g., protein, glycoprotein, glycolipid).

• It stimulates an immune response, leading to antibody production.

What are the specific surface features that allow cell identification?

• Specific molecules on the cell-surface membrane (or cell wall).

• These are often proteins (with a unique tertiary structure), glycoproteins, or glycolipids.

What is the first category of target identified by the immune system?

• Pathogens: disease-causing microorganisms like viruses, fungi, and bacteria.

What is the second category, relevant to transplants?

• Cells from other organisms of the same species (e.g., cells in a donated organ).

What is the third category involving the body's own cells?

• Abnormal body cells, such as tumour cells or virus-infected cells.

What is the fourth category involving non-cellular threats?

• Toxins (poisons) released by some bacteria.

How does a phagocyte initially detect a pathogen?

• It is attracted by chemical signals.

• It recognises foreign antigens on the pathogen's surface.

What is the physical action of engulfment?

• The phagocyte's cell membrane extends and surrounds the pathogen.

Where is the pathogen contained after engulfment?

• Inside a vesicle called a phagosome in the phagocyte's cytoplasm.

What organelle fuses with the phagosome, and what does it release?

• A lysosome fuses with the phagosome.

• This forms a phagolysosome and releases lysozymes (hydrolytic enzymes).

How is the pathogen destroyed?

• The lysozymes hydrolyse / digest the pathogen.

What crucial event for the specific immune response follows phagocytosis?

• The phagocyte presents the pathogen's antigens on its own cell-surface membrane.

• This stimulates the specific immune response (cellular and humoral).

What do T lymphocytes recognise to initiate the cellular response?

• Antigens presented on the surface of Antigen-Presenting Cells (APCs).

• APCs include infected cells, phagocytes that have engulfed pathogens, transplanted cells, and tumour cells.

What is the specific trigger for a helper T cell's activation?

• A specific helper T cell with a complementary receptor binds to the antigen on the APC.

What happens to the activated helper T cell?

• It is activated and divides by mitosis to produce a clone of genetically identical helper T cells.

What is one function of activated helper T cells?

• They stimulate cytotoxic T cells.

• Cytotoxic T cells kill infected or tumour cells (e.g., by releasing perforin).

What is a second function of activated helper T cells?

• They stimulate specific B lymphocytes, initiating the humoral response.

What is a third function of activated helper T cells?

• They stimulate phagocytes to increase phagocytosis of pathogens.

How do B lymphocytes differ from T lymphocytes in antigen recognition?

• B cells can recognise free, unprocessed antigens (e.g., in blood or tissue fluid), not just antigens presented on cells.

What is the first event in B cell activation?

• Clonal selection: A specific B cell with a complementary surface antibody (receptor) binds directly to the antigen.

What is required for the selected B cell to become fully activated?

• It must be stimulated by cytokines released from an activated helper T cell.

What happens to the activated B cell?

• It divides rapidly by mitosis to produce a clone of genetically identical B cells.

What do some of the cloned B cells differentiate into, and what is their function?

• They differentiate into B plasma cells.

• Plasma cells secrete large quantities of monoclonal antibodies specific to the antigen.

What do other cloned B cells differentiate into, and what is their function?

• They differentiate into B memory cells.

• Memory cells remain in the bloodstream to provide long-term immunity for a secondary immune response.

What are antibodies?

• Quaternary structure proteins (made of 4 polypeptide chains).

• They are secreted by B lymphocytes (specifically plasma cells) in response to a specific antigen.

• They bind specifically to antigens, forming antigen-antibody complexes.

What are the four polypeptide chains in an antibody?

• Two identical heavy (long) chains.

• Two identical light (short) chains.

• Held together by disulfide bridges.

What is the function of the variable region?

• It forms the antigen-binding site.

• Its specific tertiary structure is complementary to a specific antigen.

What is the function of the constant region?

• It is the same in all antibodies of the same class (e.g., IgG).

• It allows binding to phagocytes (e.g., macrophages) and complement proteins.

What is the role of the hinge region?

• It provides flexibility, allowing the antibody to bind to antigens at varying distances.

What is the first action of an antibody?

• It binds to specific antigens on a pathogen via its complementary variable region, forming an antigen-antibody complex.

How do antibodies cause agglutination, and what is its benefit?

• Each antibody can bind two pathogens at once (it is bivalent).

• This clumps (agglutinates) pathogens together.

How do antibodies ultimately lead to pathogen destruction?

• The constant region of the bound antibody attracts phagocytes.

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

What is the primary immune response?

• The first exposure of the immune system to a specific antigen.

Describe the speed and level of antibody production in the primary response.

• Antibodies are produced slowly and at a lower concentration.

• There is a lag phase while specific B cells are activated and cloned.

What key cells are produced during the primary response?

• B memory cells and T memory cells.

What is the secondary immune response?

• The second or subsequent exposure to the same antigen.

How does the secondary response occur so rapidly?

• B memory cells specific to the antigen rapidly undergo mitosis.

• They quickly produce a large clone of plasma cells.

Describe the speed and level of antibody production in the secondary response.

• Antibodies are produced much faster and at a much higher concentration.

What is a vaccine?

• The introduction (e.g., by injection) of antigens into the body.

• These antigens can be from attenuated (weakened), dead, or parts of pathogens.

• Their purpose is to stimulate the formation of memory cells without causing disease.

What are the first two cellular events following vaccination?

1. A specific B lymphocyte with a complementary surface antibody binds to the vaccine antigen.

2. A specific T helper cell binds to the antigen (presented on an APC) and stimulates the B cell with cytokines.

What happens to the activated B cell?

3. It divides by mitosis to form a clone.

4. Some cells differentiate into B plasma cells, which secrete specific antibodies.

What crucial long-term cells are also produced?

• Some cloned cells differentiate into B memory cells (and T memory cells).

What happens upon later exposure to the real pathogen?

• . B memory cells rapidly divide by mitosis to produce many plasma cells.

7. These plasma cells release specific antibodies faster and at a higher concentration, destroying the pathogen before it causes illness

What is herd immunity?

• When a large proportion of a population is vaccinated/immune, it reduces the overall spread of the pathogen.

How does herd immunity protect unvaccinated individuals?

• Immune people do not become ill or carry the pathogen.

• This means there are fewer infected people to transmit the pathogen to susceptible individuals.

How is active immunity acquired?

• Through exposure to antigens (via natural infection or vaccination).

What is the key cellular feature and duration of active immunity?

• It involves the production of memory cells.

• It provides long-term immunity.

How is passive immunity acquired?

• By receiving antibodies from another organism (e.g., from mother via placenta or breast milk, or via an antibody injection).

What is the key cellular limitation and duration of passive immunity?

• It does not involve memory cells.

• It provides only short-term, immediate protection as the foreign antibodies are broken down.

Why do pathogens like influenza show antigenic variation?

• Gene mutations in the pathogen change the amino acid sequence of its surface antigens.

• This alters the tertiary structure of the antigens, creating new strains.

Why does antigenic variation mean prior immunity may not work?

• Existing memory cells have receptors/antibodies complementary to the old antigen shape.

• They cannot recognise or bind to the new, changed antigen.

What are the practical consequences of antigenic variability?

• A person can be re-infected by the new strain (e.g., common cold).

• New vaccines must be developed regularly (e.g., annual flu vaccine).

• It makes creating effective vaccines for some pathogens very difficult (e.g., HIV).

Name the five key structural components of an HIV particle.

• Lipid envelope.

• Attachment proteins (embedded in the envelope).

• Capsid (protein coat).

• RNA (genetic material).

• Reverse transcriptase (enzyme).

What is the first step in HIV infecting a helper T cell?

• HIV attachment proteins bind to specific receptors (e.g., CD4) on the helper T cell's membrane.

How does the viral core enter the cell?

• The lipid envelope fuses with the helper T cell's cell-surface membrane.

• This releases the viral capsid into the cell's cytoplasm.

What is released from the capsid?

• The capsid uncoats, releasing viral RNA and the enzyme reverse transcriptase.

What unique step does reverse transcriptase catalyse?

• It uses the viral RNA as a template to produce complementary DNA (cDNA).

What happens to the viral DNA?

• The viral DNA is inserted / incorporated into the host cell's DNA.

• It may remain latent (inactive) for a period.

How are new viral components made?

• The integrated viral DNA is transcribed into HIV mRNA.

• HIV mRNA is translated by the host cell's ribosomes into new viral proteins (capsid, enzymes, etc.).

What are the final steps?

• New virus particles are assembled from the RNA and proteins.

• They are released from the cell by budding (acquiring their lipid envelope from the host cell membrane).

What is the direct cellular effect of HIV replication?

• HIV infects and kills helper T cells (its host cells) as new viruses bud out.

How does the loss of helper T cells impair the immune response?

• Fewer helper T cells means reduced stimulation of:

  • Cytotoxic T cells (cellular response).

  • B cells (humoral response).

  • Phagocytes.

• This leads to fewer antibodies being produced.

What is the ultimate result, defining AIDS?

• The immune system deteriorates.

• The individual becomes immunocompromised and highly susceptible to opportunistic infections (e.g., pneumonia, TB) that a healthy immune system would control.

Why don't antibiotics target viral metabolic processes?

• Viruses have no metabolism / independent metabolic pathways of their own.

• They use the host cell's metabolic machinery (e.g., ribosomes for protein synthesis).

Why don't antibiotics target viral cell walls or enzymes?

• Viruses do not have a murein (peptidoglycan) cell wall (a common antibiotic target in bacteria).

• They do not possess the specific bacterial enzymes that antibiotics inhibit.

What is a monoclonal antibody?

• An antibody produced from a single clone of genetically identical B lymphocytes / plasma cells.

• Therefore, all monoclonal antibodies are identical and have the same tertiary structure, binding to the same antigen.

What is the fundamental principle of using monoclonal antibodies (mAbs) for treatment?

• A mAb has a specific tertiary structure / binding site.

• It is complementary to an antigen found only on a specific target cell type (e.g., a cancer cell).

How can mAbs be used for targeted drug delivery?

• A therapeutic drug (or radioactive substance) is attached to the monoclonal antibody.

• The mAb binds to the target cell, forming an antigen-antibody complex, delivering the drug directly to that cell.

What is an alternative therapeutic use of mAbs that doesn't involve a drug?

• Some mAbs are designed to bind to and block specific antigens or receptors on cells.

• This can inhibit processes like cell signalling that promote disease (e.g., cancer growth).

What is the principle of using mAbs for diagnosis?

• A mAb has a specific tertiary structure / binding site.

• It is complementary to a specific antigen or protein associated with a disease or condition.

How are mAbs used to locate or identify this antigen in a sample?

• A detectable marker (e.g., fluorescent dye, enzyme, or radioactive label) is attached to the mAb.

• The mAb binds to its target, forming an antigen-antibody complex.

• The marker then allows detection (e.g., via colour, light, or radiation).

What is the first step in a direct ELISA to detect an antigen?

• The sample (potentially containing the antigen) is added to and attaches to the wells of a plate.

What is added next?

• Add monoclonal antibodies specific to the antigen. These antibodies have an enzyme attached to them.

What critical step follows to ensure accuracy?

• Wash the wells thoroughly.

• This removes any unbound antibodies, preventing a false positive result.

How is a positive result visualised?

• Add the substrate for the enzyme.

• If the enzyme-linked antibody is present (bound to antigen), it will catalyse a colour change in the substrate.

What is the first, different step in a sandwich ELISA?

• Monoclonal antibodies (without enzyme) are first attached to the wells of the plate. These are the capture antibodies.

What is done with the sample?

• Add the sample. If the antigen is present, it binds to the capture antibodies in the well.

• Then wash to remove unbound material.

What is added to detect the bound antigen?

• Add a different monoclonal antibody specific to the antigen, this time with an enzyme attached. This is the detection antibody.

What are the final two steps?

• Wash again to remove unbound detection antibody.

• Add the enzyme substrate; a colour change indicates the antigen was present.

What does an indirect ELISA test detect?

• The presence of specific antibodies in a blood sample (e.g., to diagnose a past infection).

What is immobilised in the well at the start of an indirect ELISA?

• Specific antigens (for the antibody being tested for) are attached to the well.

What is added from the patient?

• The patient's blood serum / sample is added.

• If present, the specific antibodies will bind to the immobilised antigens.

• The well is then washed.

What is added to detect the patient's bound antibodies?

• A secondary antibody is added. This is a monoclonal antibody with an enzyme attached, complementary to the human antibodies.

What are the final steps to get a result?

• Wash again to remove unbound secondary antibody.

• Add the enzyme substrate; a colour change indicates the patient's antibody was present.

What is one purpose of a control well in an ELISA?

• To confirm that the colour change is caused only by the enzyme on the bound antibody, and not by another component.

What is a second purpose of the control?

• To show that all unbound antibodies have been successfully washed away, validating the washing step.

Why can inadequate washing cause a false positive?

• If unbound enzyme-linked antibodies remain in the well.

• These enzymes will still convert the substrate, causing a colour change even if the target antigen/antibody is absent.

What is an ethical issue related to animal use in developing these treatments?

• Pre-clinical testing on animals can cause potential stress, harm, or mistreatment.

• Counter-argument: It is done to develop drugs that reduce human suffering, and regulations aim to minimise harm.

What is a key ethical issue in clinical trials?

• Clinical trials on human volunteers carry the risk of harm or unexpected side effects.

• This requires informed consent and rigorous safety oversight.

What are two other ethical or social considerations?

• Vaccines: Some argue they might encourage high-risk behaviours (false sense of security).

• Monoclonal Antibodies/Drugs: They can have potentially dangerous side effects.

What should you consider about the participants in a trial?

• Was the sample size large enough to be statistically significant?

• Were participants diverse in age, sex, ethnicity, and health status to ensure results are widely applicable?

What should you consider about the trial design?

• Was a placebo / control group used for a fair comparison?

• Was the trial double-blind (neither participant nor researcher knows who gets the treatment) to reduce bias?

What should you consider about the length of the study?

• Was the duration long enough to identify long-term effects or ensure lasting immunity?

What must be assessed regarding the safety data?

• The type and severity of side effects observed.

• The frequency / rate of occurrence of these side effects.

How can you determine if the treatment had a real effect?

• Check if a statistical test (e.g., t-test, chi-squared) was used.

• The test should determine if there is a significant difference between the results in the treatment group and the control group.

What does a large standard deviation in the final results indicate?

• It shows high variability in individual responses.

• It suggests that some people benefited much more than others, or that some did not benefit at all.

What does it suggest if the standard deviations of the start and final results overlap?

• It indicates that the apparent difference may not be statistically significant.

• The variation within each group might be greater than the change between them.

What should be considered about the dose and cost?

• Was the optimum / most effective dosage determined?

• Does increasing the dose lead to a significant enough increase in effectiveness to justify the higher cost and potential side effects?

What practical factor affects the availability of the treatment?

• Is the cost of production and distribution low enough to make the treatment widely accessible and affordable for healthcare systems?