Topic 6.3 Response to Infection Flashcards
Leucocytes
- White blood cells
- There are two types:
Granulocytes- contain granules
-neutrophil
-eosinophil
-basophil
Agranulocytes- do not contain granules
-lymphocyte
-monocyte
Non-specific responses
- Physical, chemical and mechanical barriers are non-specific (innate immunity- born with).
- They attempt to prevent entry of all pathogens.
- Some are part of biological responses in the blood, such as inflammation.
Inflammation
- Activates the second line of defence.
- Leucocytes (such as macrophages, neutrophils and the compliment system) are drawn to the infected area:
-fight and eliminate the pathogen
-initiate tissue repair
—> Inflammation causes fever, heat and swelling often during infections- its often a sign the immune system is working.
Fever
- Normal body temperature is around 37°C.
- When infected by a pathogen, the hypothalamus raises your body temperature which inhibits bacterial growth.
- Prolonged temperatures above 40°C can be damaging to your tissues and extensive water loss can be deadly.
Compliment System
- Involves a number of proteins produced in the liver.
- They target and coat invading pathogens.
- Triggers inflammation which recruits extra immune cells to the area.
- Extra immune cells carry out phagocytosis and kill the pathogens.
Cells of the Innate Immune System: Mast Cell
- Cells involved in allergic responses, releasing histamine and other inflammatory molecules.
- Sit within skin and muscle tissue.
(Activate when come into contact with foreign antigens).
Cells of the Innate Immune System: Natural Kill (NK) Cell
- Kill pathogen-infected cells and cancer cells.
- Release chemicals called cytokines, which alert and attract other immune cells.
Cells of the Innate Immune System: Macrophage
Antigen Presenting Cells that destroy foreign substances by phagocytosis (engulfing them) and activate other immune cells.
Cells of the Innate Immune System: Neutrophil
Fast-acting phagocytes that flock to the site of inflammation.
Cells of the Innate Immune System: Basophil
- Involved in allergic and inflammatory responses.
- Releases histamine like mast cells (but unlike mast cells they circulate the blood).
Cells of the Innate Immune System: Dendritic Cell
Phagocytic Antigen Presenting Cells with and important role in altering T cells to new pathogens.
Cells of the Innate Immune System: Eosinophil
Phagocytes that also produce enzymes to counteract inflammatory molecules released by mast cells.
Cells of the Innate Immune System: Complement
- A set of around 30 proteins in the blood plasma that can be activated by the presence of microbes or antibody-antigen complexes.
- Can destroy pathogens and activate phagocytic cells.
The Non-Specific Immune Response
The non-specific immune response aims to stop any pathogens getting in regardless of what they are.
(Cells such as neutrophils or macrophages are non-specific).
The specific Immune Response
- A specific response of the immune system to the pathogens.
- Each T cell and B cell is tailored toward a specific pathogen and is not effective against any others.
Four Key Features of a Specific Immune Response
- It can distinguish self form non-self.
- It is specific to each foreign in cell.
- It is diverse- can recognise potentially any foreign antigen.
- Immunological memory- the secondary response to a pathogen is rapid.
Humoral Response
- Humoral: bodily fluid.
- The immune response to pathogens (and their antigens) free in the tissues and bloodstream.
—> Involves specific antibodies
1) Complimentary TH lymphocytes bind to foreign antigen on antigen-presenting T cells.
2) Release cytokines that stimulate clonal expansion (rapid mitosis) of complementary B lymphocytes.
3) B cells secrete antibodies with complementary variable region to antigen.
Cell Mediated Response
- The response to your own body cells that have altered self-antigen.
(eg. cells that have become infected by a virus, or have become -cancerous).
1) Complementary TH lymphocytes bind to foreign antigen on APC.
2) Stimulates:
-Clonal expansion of complementary TH cells (rapid mitosis): become memory cells or trigger humeral response.
-Clonal expansion of cytotoxic T cells: secrete enzyme perforin to destroy infected cells.
MHC
- MHC: Major Histocompatibility Complex
- A molecule found on the surface membrane of all cells and is used to present antigens, both self and non-self.
—> MHC molecule in the membrane of a normal cell presents ‘self-antigen’ and leave these cells alone.
Antigen Presenting Cell
- The phagocytic cells are known as antigen presenting cells.
- After they engulf and digest pathogens they will present parts of the pathogen (antigens) on their surface attach to MHC molecules.
How do Antigen Presenting Cells work?
- Phagocytic cells (eg. macrophages) engulf and digest pathogens.
- They then present antigens of these pathogens on their surface.
- Antigens are presented to T cells and their T cell receptors; this then activates those cells.
- Activated T cells divide by mitosis, creating many more identical copies of each specific cell T cell.
How do Helper T Cells work?
- T cells are made in bone marrow, but mature in the thymus gland (hence ‘T’).
- Each different helper T cell has a unique T cell receptor on its surface that fits a specific antigen.
- T cells can only recognise antigen presented to them on MHC from antigen presenting cells.
- Activated T cells divide rapidly mitosis, creating many clones.
- These helper cells will activate other cells in the cell mediated response.
-Develop memory cells
-Stimulate phagocytes
-Stimulate B cells
Plasma B Cell (definition)
Short lived cells whose main function is to produce large amounts of antibodies against a particular antigen.
Helper T cell (CD4+) (definition)
They help to activate:
- B cells to secrete antibodies.
- Macrophages to destroy microbes.
- Cytotoxic T cells to kill infected target cells.
Memory B Cell (definition)
- Mainly involved in the secondary response.
- They rapidly differentiate into plasma B cells (and divide rapidly by mitosis) in order to quickly produce antibodies against the pathogen.
Cytotoxic T cell (CD8+) (definition)
Effector cells that destroy virus-infected cells, etc that exist in the cytosol, or contiguous nuclear compartment.
Antibodies (definition)
Antibodies can combine with viruses and toxins of pathogens to block them from entering or damaging cells.
Antigens (definition)
Proteins on the surface of cells which trigger an immune response.
They are specific to particular cells.
Perforins (definition)
They bind to the cell surface membrane of the target cell and pierce holes (perforate) in the membrane.
B Cells Explanation
- B cells are made and matured in the bone marrow (hence ‘B’).
- Mature B cells circulate in the bloodstream and are concentrated in the lymph glands where lymph fluid drains back into the blood.
—>They produce antibodies that target specific pathogens.
What do B cells produce?
- Antibodies.
- These can be attached to the B cell plasma membrane, or released free into the cell.
Steps in humeral response (?)
1) Clonal Selection: Activation of specific B cell with complimentary antibodies to the pathogens antigen.
2) Clonal Expansion: Mitosis (proliferation) so more cells have correct antibodies.
3) Differentiation: Plasma cells, B Memory cells.
Antibodies explanation
As antibodies recognise antigens outside of cell, B cells and antibodies are involved in the humoral response.
1) Agglutination: When the antibodies bind to the antigens on the pathogen.
2) Opsonisation: When a pathogen is marked for phagocytosis. A chemical which makes an antigen or pathogen more recognised by phagocytes.
3) Neutralisation: Antibodies bind to and neutralise/inactivate viruses and toxins.
B Cell Activation
Before B cells can produce their antibodies on mass, they must become activated.
T Cell Independent Activation: Activation without the T cells
- A B cell and its membrane-bound antibodies recognises and attaches to antigens.
- The B cell becomes activated, divides by mitosis and produces antibodies.
T Cell Dependent Activation: Activation with T cells
1) A B cell antibody receptor matches with it s complimentary antigen. A B cell internalised the antigen and presents it on its surface (like APCs).
2) An activated T cell (by the same pathogen) binds to the B cell, via this presented antigen.
3) The T cell produces cytokines which activate the B cell. After activation, the B cell divides by mitosis to produce memory B cells and B effectors cells. B effectors cells eventually differentiate into antibody producing plasma cells.
Killer T Cells (cytotoxic- CD8+) Explanation
- Activated in a very similar way to Helper T cells (cytokines from activated T Helper cells are required).
- They can attack body cells which have been anti-genetically altered by viruses or cancer cells.
-They destroy the pathogen by punching holes through their cell surface membranes so the cell contents spill out (lysis).
Killer T Cell Activation
1) An APC (eg. macrophage) digests and engulfs the pathogen and presents the antigen on its surface via MHC.
2) Killer T cell with complimentary T cell receptors bind to the antigen on the APC.
3) Killer T cells becomes activated by release of cytokines from activated helper T cells (Killer T Memory cells are also formed).
4) Active T killer cells release perforin chemicals. These punch holes in the membrane of infected cells and cause them to burst (lysis).
Primary Response
(First exposure to antigen: vaccine, infection)
—>Slow, weak
- Helper T cells activated
- Cause lysis
- B cells activated and divide
- Form plasma cells
- Produce antibodies
- Memory B+T cells left behind
Secondary Response
(second exposure to antigen: long interval between primary + secondary)
—> Quicker, stronger
- Use of memory cells
- No symptoms
- Shorter time lag between exposure and antibody production
- Pathogen usually destroyed before any symptoms
Passive immunity
When antibodies are introduced from outside the body; you don’t have to make them yourself.
Artificial Passive Immunity
Can be used if there isn’t a vaccine ready yet or if someone requires a tetanus injection or requires antibodies for a snakebite.
Artificial Passive Immunity: Advantage
Immediate- don’t need to wait for antibodies to be made.
Artificial Passive Immunity: Disadvantage
Short term- the person will not have a long lasting protection.
Natural Passive Immunity
An example is when an infant receives a mothers antibodies through the placenta or breast milk.
Active Immunity
Active immunity involves exposure to a pathogen/antigen.
-Either though natural exposure (natural active)
-Or through vaccination (artificial active)
Vaccination
Vaccination aims to stimulate a primary immune response, without actually causing the disease like a normal infection would.
This allows people to safely develop memory cells against a pathogen.
1) Vaccine contains dead/inactive form of a pathogen or antigen
2) Triggers primary immune response
3) Memory are produced and remain in the bloodstream, so secondary response is rapid & produced higher concentration of antibodies
4) Pathogen os destroyed before it causes symptoms.
Phagocytosis (version 2- better)
1) Phagocyte moves towards pathogen via chemotaxis.
2) Phagocyte engulfs pathogen via endocytosis to form a phagosome.
3) Phagosome fuses with lysosome (phagolysosome).
4) Lysozymes digest pathogen.
5) Phagocyte absorbs the products from pathogen hydrolysis.
(Antigen presenting occurs at end).
How do antibodies lead to the destruction of a pathogen?
- Formation of antigen-antibody complex results in agglutination.
- Activation of complement.
- Opsonisation (marks microbes for phagocytes).
- Precipitation/ neutralisation (makes toxins insoluble).
Examples of passive and active immunity
- Passive natural: antibodies in breast milk/ across placenta.
- Passive artificial: anti-venom, needle stick injections.
- Active natural: humeral response to infection.
- Active artificial: vaccination.
