5: Cell recognition and the immune system Flashcards
What is an infection?
Interaction between a pathogen and the body’s various defence mechanisms
What is a pathogen?
Disease causing organism
What type of cells form the responses of the body to pathogens?
Lymphocytes
What type of lymphocytes and responses are there?
T lymphocytes - cause cell-mediated responses
B lymphocytes - cause humoral responses
Why is it important a cell can be recognised as the body’s own cells?
To prevent the lymphocytes from destroying their own cells
What molecules allow lymphocytes to recognise cells?
Proteins - as there is a variety of specific 3D tertiary structure
What can the immune system identify?
Pathogens
Non-self materials from other organisms
Toxins produced by pathogens
Abnormal body cells such as cancer cells
How is the identification of non-self cells disadvantageous?
Organ transplants as immune system wants to destroy these cells
This causes rejection of the tissue
What is done to prevent tissue rejection?
Donor tissue normally matched as close to recipient
Immunosuppressant drugs lowering the response
What are the best matches of tissues?
Relatives that are genetically close
What are the two different types of defence mechanism?
Non-specific - response is immediate and same for all pathogens
Specific - response is slower and specific to each pathogen
Why is there a good chance that there is a specific lymphocyte for a pathogen?
10 million different types of lymphocytes - good chance one will have the complementary protein shape
Are the lymphocytes produced in response to pathogens?
Not in response, they are already there
How do lymphocytes recognise the body’s cells?
In the fetus, lymphocytes constantly collide with different cells
Lymphocytes that have complementary shapes with the body’s cells die or are suppressed
Only ones left fight non-self materials
Where are lymphocytes produced?
Bone marrow
What happens in adult cells to prevent the destruction of self cells?
If lymphocytes show an immune response to self cells they undergo apoptosis (cell death)
This prevents them maturing and means no more of this type will form
What is a self-antigen?
Antigens found on the surface of a self cell
What is apoptosis?
Programmed cell death
What are the two types of non-specific defence mechanisms?
Physical barrier
Phagocytosis
What are the two types of specific defence mechanisms?
Cell-mediated response (T lymphocytes) Humoral response (B lymphocytes)
What are some examples of physical barriers?
Skin - prevents entry of some pathogens
Nose/throat/digestive tract - membrane lining secretes sticky mucus trapping microbes
What is the first line of defence?
Physical and chemical barriers
What are some examples of chemical barriers?
Eyes - tears have lysozyme enzyme kills bacteria
Ear - wax has antimicrobial properties
Stomach - hydrochloric acid kills bacteria
What are the two types of white blood cell?
Lymphocytes and Phagocytes
What is the function of phagocytes?
Ingest and destroy pathogens before it can cause harm (phagocytosis)
What is the second line of defence?
Phagocytosis
Explain the process of phagocytosis
Phagocytes attracted to pathogen by their chemical products
Receptors on phagocytes recognise and attach to chemicals on the surface of the pathogen
They engulf the pathogen to form a vesicle (phagosome)
Lysosomes fuse with vesicle and release lysozymes which destroy the pathogen
Soluble products are assimilated into cytoplasm of phagocyte
How do lysozymes affect pathogens?
Hydrolysis of cell wall, means it produces small soluble products
What is an Erythrocyte?
Red blood cell
What is a leukocyte?
White blood cell
What is an autoimmune disease?
When lymphocytes think self cells are pathogens and attack them
E.g. Type 1 diabetes
What is the innate system?
Physical barriers
Inflammation
Innate leukocytes (phagocytes)
What is the advantage of the non-specific response?
Immediate response
What is the advantage of a specific response?
Specific to each epitope
What is an epitope?
Specific area on a specific antigen
What are the two branches of the acquired immune system?
Natural
Artificial
What are the two types of artificial acquired responses?
Active - immunisation/vaccination
Passive - antibody transfer
What are the two types of natural acquired immune responses?
Active - cell mediated or humoral
Passive - maternal
How is an element of the acquired immune system maternal?
Antibodies through placenta and milk
Same environment makes it effective
What is immunity?
Ability to resist an infection from pathogen or toxins
What is an antigen?
Molecule that is recognised by the adaptive immune system via antigen receptors such as antibodies
What is assimilation?
Broken down products are used in the cell
Where are lymphocytes made and matured?
Made in bone marrow
B - matured in bone marrow
T - matured in thymus gland
Where is the thymus gland?
Behind the sternum
What are the two types of B lymphocytes?
Plasma cells
B memory cells
What are the two major types of T lymphocytes?
T helper
T cytotoxic
What are the types of T cytotoxic cells?
Active
Memory
What are the types of T helper cells?
Active
Memory
What is the humoral response?
Production of antibodies by B lymphocytes
How is T helper cell activated?
Presented antigen on self cells
Non-self non-pathogenic cells
Cancerous cells which present abnormal antigens
What happens when a T helper cell is activated?
Mitotic cloning & cytokine released
Activate: cytotoxic T cells, phagoytes, B lymphocytes
Produces some T Helper memory cells
How do cytotoxic T cells work?
They bind to the pathogenic cell and release perforin in to the cell
This ruptures the cell wall, causing water to rush in and cause cell bursting
What process causes the creation of different lymphocytes?
Haemotopeosis
Where can antibodies travel in the human body?
Anywhere in bodily fluid
Except spinal cord & brain
What is the specificity of B lymphocytes?
Specific for epitope & antigen
Releases specific antibody
Multiple for each pathogen as many epitopes
How do B lymphocytes activate?
Interacts with antigen by B cell receptor
Endocytosis of antibody-antigen complex
Antigen presentation
T Helper interacts and stimulates mitosis of specific B cell
Plasma & B Memory produced
What is the process whereby T Helper cells cause the mitosis of specific cells?
Clonal selection
What is a plasma cell?
Cell that produces many antibodies
2000 antibodies / second
Only alive for a few days
What does a B memory cell do?
Doesn’t produce antibodies
Can identify and cause secondary immune response
Survives for decades
What is the advantage of the secondary immune response?
Response is larger and faster
How do B memory cells cause the secondary immune response?
When activated, they divide rapidly and produce plasma cells
What organelles are required for plasma cells and why?
Mitochondria - energy for protein synthesis
Rough Endoplasmic reticulum - needed for protein synthesis
Golgi body - provides vesicles for exocytosis
What type of molecules are antibodies?
Glycoproteins synthesised by B cells
What is an antibody made up of?
4 polypeptide chains - 2x Heavy chain
2x Light chain
How do antibodies cause pathogen death?
Do not kill cells, enhances phagocytosis by
Viral neutralisation
Agglutination
Precipitation of soluble antigens
What is viral netralisation?
Blocks antigen binding sites
Cannot bind to host
What is agglutination?
Forms clumps of the pathogen
What is precipitation of soluble antigens?
Antibodies bind to soluble antigens making them insoluble
What is formed when an antibody binds to an antigen?
An antigen-antibody complex
What are the two regions of antibodies?
Variable region
Constant region
What are the binding sites of antibodies?
Antigen binding sites located in the variable region
What does the binding site consist of?
Sequence of amino acids, specific 3-D shape
Binds to specific antigen epitope
What is HER2 and where is it found?
Receptor over-expressed on breast cancer cells
What is the treatment for breast cancer cells with over-expressed HER2?
HER2 antibody produced in lab (herceptin)
Neutralises growth receptor
Flags cell for destruction
What is an antibody-drug conjugate?
Many molecules of a drug bonded to the constant region of an antibody
How is using an antibody-drug conjugate advantageous?
Drug is more specific
What do the drugs in antibody-drug conjugates typically do to destroy the target cells?
Prevents microtubule formation in mitosis
What is the drug called in an antibody-drug conjugate?
Cytotoxic agent
What does the cytotoxic agent have to be in an antibody-drug conjugate?
Non-immunogenic (immune system won’t destroy)
Non-toxic to self cells
Highly potent in small quantities
What does the Ab have to be in an antibody-drug conjugate?
Maintains characteristics
Targets well known antigen on target cell
Minimises non-specific binding
What is a linker?
The bond between the drug and the antibody in an antibody-drug conjugate
What is the properties of the linker?
Stable so the antibody-drug conjugate remains intact
Ensures cytotoxic agent is functional
What does ELISA stand for?
Enzyme Linked Immunosorobant Assay
What is an assay?
Biochemical test
What are the two types of ELISA test?
Indirect ELISA - tests for antibodies (Ebola Ab)
Sandwich/direct ELISA - tests for antigen (Insulin)
What is the process of a Sandwich/Direct ELISA?
Antibody bound to well
Sample added
Wash with distilled water to leave specific antigen
Secondary antibody with enzyme added
Washed & substrate added
Colour change caused by enzyme on secondary antibody
Colour measured
What is the process of a Indirect ELISA?
Antigen bound to well
Sample added
Washed with distilled water to leave specific Ab
Secondary antibody with enzyme attaches to 1st antibody
Washed & substrate added
Colour change caused by enzyme on secondary antibody
Colour measured
What is a monoclonal antibody production?
Antibodies which bind to a specific epitope
What is the process of monoclonal antibody production?
Inject specific antigen into mouse
Plasma cells stimulated & isolated from spleen
Cultured with myeloma cells induced in mouse (immortal)
Hybridoma cells formed (B cell, myeloma cell + polyethylene glycol)
Cells are separated & cloned under microscope
Harvest antibodies & humanised for human cells
What are the ethical issues of monoclonal antibody production?
Production involves use of mice, causing cancer in their cells. Reservations on animal testing
Deaths associated with treatments, risks & benefits so patient permission required
Testing caused near death of trial patients, concerns of conduct in drug trials
Why are myeloma cells used in antibody production?
Plasma cells only live for 3-4 days
Myeloma cells are immortal
What type of response does vaccination cause?
Acquired –> Artificial –> Active
What does a vaccine contain?
Inactivated or attenuated pathogen/toxins
Response against antigen caused
What does a vaccine cause?
Memory (T&B) cells produced
Triggers primary immune response, boosters trigger secondary
Why are vaccines used?
Economically viable
Limited side affects
Ease to produce, store & transport
Potential to produce herd immunity
What is herd immunity?
Reduced transmission by high proportion of population being immune due to vaccination
Protects those who are not immunised
Who does herd immunity protect?
Those who are not immunised
E.g babies/very young
When is herd immunity ineffective?
Patient develops illness following vaccination
Patient has defective immune system
Antigenic variability (mutation)
Pathogen species variability
Pathogens concealed inside cells/ outside body
Patient objects to vaccination
What are the ethical concerns of vaccines?
Development: use of animals, human trials, insufficiently tested
Side effects
Expense: spending money on this instead or something else
What is the pregnancy testing for?
Human chorionic gonadotrophin (hCG)
Produced by women during fetal development
What is the process for pregnancy testing?
Free monoclonal antibodies specific to hCG are conjugated to enzyme on the reaction site
Fixed antibodies which traps hCG are found on the test site, and that which traps the free antibody at the control site
hCG binds to free antibodies and causes colour change at test site
Free antibodies cause colour change at control site
What does HIV stand for?
Human Immunodeficiency Virus
What does AIDS stand for?
Acquired Immune Deficiency Syndrome
What is AIDS?
A condition whereby the immune system deteriorates and fails
Makes them more vulnerable to other infections
Develops when T-helper cell numbers reach a critically low number, by HIV
What does HIV do to the body?
Infects & kills T-helper cells which are host cells
Without T-helper cells it is difficult to mount an effective immune response
What is the structure of HIV?
Core than contains RNA and proteins (reverse transcriptase & intergrase)
Coating called a capsid (around core)
Outer layer called envelope made of membrane from host cell
Attachment proteins sticking out from envelope
What is an attachment protein?
Protein that attaches to a receptor molecule on the cell membrane on T-helper cell (CD4)
Why does HIV & other viruses need host cells to replicate?
They have no ribosomes or other organelles required for reproduction
What is the process of HIV replication?
Attachment protein attaches to receptor molecule on T-helper cell membrane
Capsid released into the cell, uncoats and releases contents
Reverse transcriptase converts ssRNA -> ssDNA -> dsDNA
Intergrase inserts viral DNA into the host DNA
Host cell makes viral proteins from viral DNA
Viral proteins assemble new viruses, which bud from the host and form new viral cells
What is the latency period?
Time whereby HIV replication drops to a lower level after initally diving rapidly
Why does HIV kill T-helper cells?
They undergo apoptosis
How long does HIV take to cause AIDS to develop?
10 years without treatment
What are the initial symptoms of AIDS?
Minor infection of mucous membranes & recurring respiratory infects
What are the mid-stage symptoms of AIDS?
Immune system cells decreases
More susceptible to more serious infections
What are the late stage symptoms of AIDS?
Range of serious infections that can kill the patient
What drugs are used for HIV?
No cure/vaccine for HIV
Antiviral drugs slow down the progression of HIV infection
What is the best way to control HIV infection?
Reducing the spread via unprotected sex, or from mother to fetus
How do antibiotics kill bacteria?
Interfering in their metabolic reactions by targeting their bacterial enzyme & ribosomes
Why can antibiotics not kill viruses?
They use human ribosomes & enzymes which antibiotics don’t harm
What are antiviral drugs?
Drugs which target virus-specific enzymes
E.g HIV has the enzyme reverse transcriptase
