11.1 Antibody production and vaccination Flashcards
What is referred to as an antigen?
Any foreign molecule that can trigger an immune response
What are antigens recognized by?
- Lymphocytes which bind to and detect the characteristic shape of an exposed portion (epitode)
What do lymphocytes do when they detect an antigen?
- Lymphocutes trigger antibody production (adaptive immunity) which specifically bind to epitopes via complementary paratopes
What are some antigenic determinants?
- Surface markers present on foreign bodies in the blood and tissues - including bacterial, fungal, viral and parasitic markers
- The self markers of cells from a different organism (this is why transplantation often results in graft rejection)
- Even proteins from food may be rejected unless they are first broen down into component parts by the digestive system
What is MHC? What is the opposite?
A self marker that lebels the body’s cells as a ‘friend’ and are tolerated by the immune system
An antigen is non self and is recognised as foreign by the immune system
Where are self markers (MHC class I) present on?
On surfaces of all nucleated body cells and identify the cell as part of the organism
* Different organisms have distinct self markers which prevent transplantation of tissues (unless a very close genetic match)
Why do red blood cells not possess the same distinctive and unique self markers as all other body cells?
Because they are not nucleated
* This means that red blood cells can be transferred between individuals without automatically causing immune rejection
What do red blood cells possess that limit the capacity for transfusion?
- Possess basic antigenic markers
- May possess surface glycoproteins (A and B antigens) either independently (A or B) or in combinatino (AB)
- Alternatively, red blood cells may possess neither surface glycoprotein (denoted as O)
In what ways if blood transfussion limited?
- AB blood groups can only recieve blood from any other type (as they already possess both antigenic variants on their cells)
- A blood groups cannot recieve B blood or AB blood (as the B isoantigen is foreign and will stimulate antibody production)
- B blood groups cannot receive A blood or AB blood (as the A isoantigen is foreign and will stimulate antibody producition)
- O blood groups can only recieive transfusions from other O blood donor (both antigenic variants are foreign)
What reaults in positive or negative blood groups?
An additional glycoprotein (Rhesus factor) is either present or absent, resulting in positive or negative blood groups
What results in positive or negative blood groups?
An additional glycoprotein (Rhesus factor) is either present or absent, resulting in positive or negative blood groups
What are the 2 most important antigen systems in blood transfusions?
The ABO blood group and the Rhesus (Rh) blood group are the two most important antigen systems in blood transfusion as mismatches between donor and recipient can lead to an immune response
What are the 2 most important antigen systems in blood transfusions?
The ABO blood group and the Rhesus (Rh) blood group are the two most important antigen systems in blood transfusion as mismatches between donor and recipient can lead to an immune response
What basic antigen sequence do all three alleles of the A, B, and O phenotypes have?
Antigen H
* Antigen H is modified by the addition of an additional molecule
* If the additional molecule is galacose, antigen B results etc.
What happens when a recippient is given a transfusion involving the wrong type of blood?
Agglutination followed by hemolysis where red blood cells are destroyed and blood may coagulate in the vessels
What does mixing the wrong type of blood with its anti A+B serum produce?
Red dots that are produced from agglutination
What is a pathogen?
An agent that causes disease - either a microorganism (bacteria, protist, fungi or parasite), virus or prion
* Are generally species-specific in that their capacity to cause disease (pathogenesis) is limited to a particular species (i.e. polio specifically affect human hosts)
What is a disease and illness?
- A disease is any condition that disturbs the normal functioning of the body (i.e. the body can no longer maintain homeostasis)
- An illness is a deterioration in the normal state of health of an organism (a disease may cause an illness)
What are zoonotic diseases?
Diseases from animals that can be transmitted to humans are called zoonotic diseases (or zoonoses) because certain pathogens may cross the species barrier and be able to infect and cause disease in a range of hosts.
e.g. rabies
What is the name of the pathogen that can cross a species barrier?
A zoonosis
What are the ways in which infectious diseases can be transmitted?
- Direct contact
- Exchange of fluids - sex, beastfeeding
- Contamination - food
- Airborne - transferred in the air
- Vectors - intermediary organisms that transfer pathogens without developing disease symptoms themselves
What is the name of the pathogen that can cross a species barrier?
A zoonosis
What is the major factor contributing to the increased appearance of zoonotic diseases?
Growth of contact between **animals and humans by such means as humans living in close contact with livestock or disruption of habitats.**
What does the body respond with when challenged by a foreign pathogen?
Respond with both a non-specific and a specific immune reaction
What are non-specific immune cells called and what do they do?
- Non-specific immune cells called macrophages will engulf pathogens non-selectively and break them down internally
- A proportion of macrophages (dendritic cells) will present the antigenic fragments of the pathogen to specific lymphocytes
How is the body able to recognize each single, specific antigen?
The body contained millions of different T lymphocytes and B lymphocytes that can recognize each
What activates B lymphocytes in mammals?
T lymphocytes
What do macrophages do with pathogens and their antigens?
- Pathogens are ingested by macrophages
- Antigens are displayed in the plasma membrane of macrophages
- Lymphocytes called helper T cells bind to antigens being displayed because they have an antibody-like receptor protein in their plasma membranes
- Helper T cells bind and are activated by the macrophage
- The activated helper T cells then bind to lymphocytes called B cells
- Selected B cells are activated by bindings to the helper T cell
- Release a signally protein after binding
Pathogens are ingested by macrophages, and antigens from them are displayed in the plasma membrane of the macrophages.Lymphocytes called helper T cells each have an antibody-like receptor protein in their plasma membranes, which can biind to antigens displayed by macrophages. Of the many types of helper T cells, only a few have receptor proteins that fit the antigen. These helper T cells bind and are activated by the macrophages.
The activated helper T cells then bind to lymphocytes called B cells. Again, only B cells that have a receptor protein to which the antigen binds are selected and undergo the binding process. The helper T cell activates the selected B cells, both by means of the binding and by release of a signally protein.
What is the overall process of how clones of a specific antibody is made and how does it provide long-term immunity?
- Antigenic fragments are presented to specifc helpter T lymphocytes that, when activated, release cytokines
- The cytokines stimulate a specific B cell that produces antibodies to the antigen to divide and form clones (clonal selection)
- Most of the clones will develop into short-lived plasma cells that produce large quantities of specific antibody
- A small proportion of clones will differentiate into long-lived memory cells that funciton to provide long-term immunity
What is polyclonal activation?
When several different T and B lymphocytes are stimulated to produce a variety of specific antibodies because pathogens typically contain multiple distinct antigenic fragments on their surface.
What do macrophages do with pathogens and their antigens?
- Pathogens are ingested by macrophages
- Antigens are displayed in the plasma membrane of macrophages
- Lymphocytes called helper T cells bind to antigens being displayed because they have an antibody-like receptor protein in their plasma membranes
- Helper T cells bind and are activated by the macrophage
Pathogens are ingested by macrophages, and antigens from them are displayed in the plasma membrane of the macrophages.Lymphocytes called helper T cells each have an antibody-like receptor protein in their plasma membranes, which can biind to antigens displayed by macrophages. Of the many types of helper T cells, only a few have receptor proteins that fit the antigen. These helper T cells bind and are activated by the macrophages.
The activated helper T cells then bind to lymphocytes called B cells. Again, only B cells that have a receptor protein to which the antigen binds are selected and undergo the binding process. The helper T cell activates the selected B cells, both by means of the binding and by release of a signally protein.
What are the roles of plasma cells?
- Plasma cells secrete anibodies
- They are mature B lymphocytes (white blood cells) tha produce and secrete a large number of antibodies during an immune response
Which part of a plasma cell helps in the production of antibodies?
The plasma cell’s cytoplasm (orange) contains an unsually extensive network of rough endoplasmic reticulum (rER). rER manufactures, modies and transport proteins, in this case, the antibodies. The cell produces a lot of the same type of protein meaning that the range of genes expressed is lower than a typical cell. This explains the staining pattern of the nucleus where dark staining indicates** unexpressed genes**.
What does activated B cells multiply to form?
A clone of plasma cells and memory cells
How does activated B cells divide?
Mitosis -> generating a clone of plasma cells that all produce the same antibody type
What is clonal selection?
The generation of large numbers of plasma cells that produce one specific antibody type is known as clonal selection
What happens to antibodies, plasma ells and the antigens after the infection has been overcomed?
- Antibodies only persist in the body for a few weeks or months
- Plasma cells that produce them are also gradually lost
- Antigens associated with it are no longer present
What do the clones of B cells become?
- Most become active plasma cells
- A smaller number become memory cells, which remain long after the infection
What determines the memory cells activity?
- Memory cells remain inactive unless the same pathogen infects the body again, in which case they become active and respond very rapidly.
What does immunity to an infectious disease involve?
Either having antibodiesagainst the pathogen, or memory cells that allow rapid production of the antibody
What do antibodies do?
They aid the destruction of pathogens
* Opsonization
* Neutralization of viruses and bacteria
* Neutralization of toxins
* Activation of complement
* Agglutination
What is opsonization?
They make a pathogen more recognizable to phagocytes so they are more readily engulfed. Once bound, they can link the pathogen to phagocytes
What is neutralization of viruses and bacteria?
Antibodies can prevent viruses from docking to host cells so that they cannot enter the cells
What is neutralization of toxins?
Some antibodies can bind to toxins produced by pathogens, preventing them from affecting susceptible cells
What is activation of complement?
The complement systemm is a collection of proteins which ultimately lead to the perforation of the membranes of pathogens. Antibodies bound to the surface of a pathogen activate a complement cascade which leads to the formation of a “membrane attack complex” that forms a pore in the membrane of the pathogen allowing water and ions to enter into the cell ultimately causing the cell to lyse.
What is agglutination?
Antibodies can cause sticking together or “agglutination” of pathogens so they are prevented from entering cells and are easier for phagocytes to ingest. The large agglutinated mass can be **filtered by the lymphatic system **and then phagocytized. The agglutination process can be dangerous if it occurs as a result of an incorrect blood transfusion
What does immunity depend on?
Persistance of memory cells
How does immunity develop?
When the immune system is challenged by a specific antigen and produces antibodies and memory cells in response
How does immunity develop?
When the immune system is challenged by a specific antigen and produces antibodies and memory cells in response
What do memory cells ensure?
That the second time an antigen is encountered, the body is ready to respond rapidly by producing more antibodies at a faster rate
What do vaccines contain?
- Antigens that trigger immunity but do not cause the disease
- May contain a live attenuated (weakened) version of the pathogen, or some derivative of it that contains antigens from the pathogen
What does the antigen in vaccines stimulate?
A primary immune response
After vaccination, what happens if the actual microorganism enters the body as a result of infection?
It will be destroyed by the antibodies in a secondary immune response
What was the first infectious disease of humans that have been eradicated by vaccination?
Smallpox
Why was the campaign to eradicate smallpox successfull?
- Only humans can catch and transmit small pox. There is no nimal reseroir where the disease could be maintained and re-emerge
- Symptoms of infection emerge quite quickly and are readily visible allowing teams to “ring vaccinate” all of the people who might have come in contact with the afflicted person.
- Immunity to smallpox is long-lasting
Why was the campaign to eradicate smallpox successfull?
- Only humans can catch and transmit small pox. There is no nimal reseroir where the disease could be maintained and re-emerge
- Symptoms of infection emerge quite quickly and are readily visible allowing teams to “ring vaccinate” all of the people who might have come in contact with the afflicted person.
- Immunity to smallpox is long-lasting
What is the study of epidemiology?
The study of the distribution, patterns and causes of disease in a population.
What is the study of epidemiology?
The study of the distribution, patterns and causes of disease in a population.
What produces histamines in response to what?
- The immune system
- White cells release histamines in response to allergens
- Basophils also release histamines which circulate in the blood
What are mast cells?
Immune cells found in connective tissue that secrete histamine in response to infection
What does histamine cause in response to infection?
Dilation of the small blood vessels in the infected area causing the vessels to become leaky. This increases the flow of fluid containing immune components to the infected area and it allows some of the immune components to leave the blood vessels resulting in both specific and non-specific responses
What contributes to a number of symptoms of allergic reactions?
Histamine
* Cells in a variety of tissues have membrane-bound histamine receptors
* Histamin eplays a role in bringing on the symptoms of allergy in the nose (itching, fluid build-up, sneezing, mucus secretion and inflammation).
* Also plays a role in formation of allergic rashes and in the dangerous swelling known as anaphylaxis
How can be taken to lessen the effects of allergic responses?
Anti-histamines
What 2 things fuse to create a hybridoma cell?
Fusion of a tumour cell with an antibody-producing plasma cell creates a hybridoma cell
What 2 things fuse to create a hybridoma cell?
Fusion of a tumour cell with an antibody-producing plasma cell creates a hybridoma cell
What is a monoclonal antibody?
Monoclonal antibodies ae highly specific, purified antibodies that are produced by a clone of cells, derived from a single cell. They recognize only one antigen.
What is the monoclonal antibody production like?
- Antigens that correspond to desired antibody are injected into an animal (usually a mous)
- B cells are produce by the above animal and the antibodies produced by B cells are removed by removing the spleen to obtain them
- Tumour cells are obtained. These cells grow and divide endlessly
- B cells from above animals are fused with tumour cells, producing a cell called a hybridoma
- These hybridoma divide endlessly and produce a lot of antibodies
- The hybridoma cells are cultured and the antibodies they produce are purified and extracted
Why are monoclonal antibody used in medicine?
- They are stable molecules
- They can be used over a long period of time
How are hybridoma cells cultured?
They can be cutured in a fermenter where they will secrete huge amonts of monoclonal antinody
* The cell is multiplied in the fermenter to produce large numbers of genetically identical copies, each secreting the antibody produced by the original lymphocyte
What are the uses of monoclonal antibodies?
- Cancer treatment and diagnosis
- Pregnancy test
- Diagnosis of disease
- Locate blood clot
- Screen blood for HIV
What are the pros and cons about monoclonal antibodies?
Pros
* Target specific
* Cancer therapy
* Dianose disease
Con
* Expensive, time consuming
* Side effects
* Too specific
What is the process of herceptin production?
- The membrane protein HER2 is injected into a mouse
- Harvest B lymphocyte that make HER2 B lymphocytes
- Fuse HER2 B lymphocytes from mouse with tumour cells to produce a hybridoma HER2 cell
- HER2 hybridoma cells divide and produce a lot of the desired antibodies
- Antibodies are purified and extracted
- Modify the antibodies for the specific treatment/diagnosis
Describe the antibodies on the pregancy test
Pregancy tests detect hCG which is uniquely produced during pregnancy. The urine of a pregant women contains detectable levels of hCG
Point C - antibodies to hCG are immobilized in the strip
Point B - free antibodies to hCG are attached to a dye
Point D - there are immobilized antibodies that bind to the dye-bearing antibodies
Urine is applied at the end of the strip and washes antibodies down the strip
