Immune System - Cell Biology Semester 2
How are humans attacked by pathogens
In every breath for 1 mins we collect 10,000 pathogens + 5000 virus and 1/2 fungi
Plus everything we eat and drink will contain pathogens as well
What are the 3 types of pathogens
Bacteria - Invade rapidly and can rapidly cause illness that can be varied and be in or out of the cell as well
Viruses - They invade rapidly and cause quick illness, they are able to mutate in the human to prevent antibody destroying them and can also cause repeat illness so the immjne system memory is important
Parasites - There are many that are all highly varied and can survivce for years in the body and recrudescense may occur
How is the immune system developed
A large investement of energy and are made up of cells that can move in and out of any tissue in the body.
T cells can live in the blood for up mto 9 years that are then able to make antibodies
How is Saliva a physical barrier
It is made in the salivary gland, subligual and submandibular and parotid glands
It will comtain many antimicrobial proteins such as lactoferrin lysozyme and smaller active peptidases
H2O2 will prevent from gum disease and mucins prevent bacteria getting a grib of gum or teeth by making the surface slippy so bacteria cant stick
Saliva also will help to promote wound healing so cuts repair quicker in the mouth
How is ear wax a physical barrier
It is made in the glands of the ear canal and move into the ear
It will help to trap bacteria dust and other small particles that try to enter the ear
It also contain antimicrobial proteins that kill a large variety of bacteria
How is the skin a physical barrier
The skin is antimicrobila and is good at killing stuff trying to the enter the body
There is commensal bacteria on the surface of the skin that can kill other bacteria that may arrive
The layers below are held tightly together by tight junctions and the layer below contain langerhan cells and cytotoxics T cells
How is mucus a physical barrier
Is found in every body site that has open access to the outside of the body
It is made by goblet cells ands is important for the health of tissues that intercat with the outside
It is major made of mucin and large glycosylated proteins
It is very dense so bacteria can be trapped and also is slippery so they cant get a grip of any tissues
Contain antimicrobial proteins that kill pathogen directly
Due to the sticky nature can trap pathogens that are then exreted via sneezing and coughing
What is cilia
It is contained on the bronchi and are cells that are coated with small hairs
They are able to beat in coordinated manner to shift water, mucus and pathogens from the surface of cells so can be coughed out of the lungs = Mucocillary clearance
Cilia can be shortened by smoking
What is rapid, indiscrimmate defence = Innate immunity
These are non antigen specific antibodies and there is no long term memoryu
They work quickly and indiscrimajte fo the pathigen type and have a very short life span
How does Innate immunity work - the first cell step for all pathogens
The first cell tha hit the pathogen will be the epithelial cells and they will produce antimicrobial proteins after forming a barrier of epithelial cells
This work due to proteins are inserted to pathogen membrane and disrupt osmotic balance so then the cells will die
What are primary lymphoid organs
This is where the immune cells will be made and secreted from to then be used:
Thymus - Site of T cell differentiation and maturation but switch off when get older
Bone Marrow - Where most immune cells are produced and where they divide
What are secondary immune organs
This is where innate immune cells are stored and activated to then be used for immune response:
Lymph nodes - Multiplication of T and B cells
Spleen-T and B cells are stores and then filter to the blood in upper left abdomen
Peyers Patch - Generate a response to the gut pathogens in the small intestine
Tonsils - In the throat and lots of B cells and important for nose and throat pathogens
What are epithelial cells and how do they work
Involved in the recognition of viruses and send out signals in the form of chemokines and cytokines in the recognition stage of the pathogen
There is then recruitment of innate immune cells in the acute infection phase and modulation of immune cells in the late infection phase
Whart are cytokines
These are key signalling molecules that are small peptides but they dont enter cells but bind to membran receptors and induce singals in the cell
They have to attract migration of other cells such as chemokines, need to activate other immune cells and thnen cause proliferation of cells and cell survival
What are monocytes and macrophages
Monocytes are released from the bone marrow and then circulate in the blood and are the largest cell in the blood
Aftyer 1-3 days rhen move to tissues and then diffferentiate to dendritic cells or macrophages
They can kill pathogens by phagacytosis and kill host cell of a virus directly by antibody dependent cellular cytotoxicity
What are macrophages
These are cells that stay in the tissues
Each organs has own population:
Brain - Microglia , Skin- Langerhans and Liver - Kupffer cells
If a tissue gets infected they act rapidly to kill pathogesn by phagacytosis and also activate T cells in adaptive immune respone
They can also remove dead cells to stop them triggering immune response
What is Phagacytosis
It is the digestion of foreign molecules in the body
The foreign pathogens are recognised by PAMp - Pathogen associated molecule patterns
The particels are injesyed by a phagocyte and then inside are then moved into a phagosome that then fuse with lysozymes that have hydrolytic enzymes so digest the pathogen and then the products are released and the antigen are displayed so get an antigen displaying cell
What are DAMP + PAMP
DAMP - Damage associated molecule patterns that are released from host cell when they die or under stress to trigger sterile inflammatory immune response for an injury or wound
PAMP will form micro-organsium during an infection via a pathogen and are needed for phagacytosis and recoginsing the pathogen
What are Neutrophills
Thye most abundan type of white blood cell in the body from bone marrow and have a lobed nucleus and large granules number
They live for 3 days and first incoming responders for an immune response
They can carry out phagacytosis for an immune response
Can also do degranulation: there are ready made granuoles that have antimicrobial proteins that can be released quickly rather than wait for gene epxression to make new proteins
Can also do Netosis: They shoot out DNA that will stick to cells all around including bacteria, the traps have antimicrobial proteins that can kill the pathogens
What are Eosinophils + Basophils
They both have acidic granules that can kill parasites but may then cause damage to host cells
They are vital for imme response to large parasites as they can release the granules and also DNA to trap the parasites
They can make reactive oxygen species and release enzymes to then break down the parasites
What are mast cells
These are granulocytes and are similar to the basophils and can be differentiated by the mast cell nuclei that are round not lobed
They are found in the mucosal sites and have large number of granules with inflammatory and antimicrobial proteins
They are activated by antibodies + DAMP + PAMP and their main role is to release histamine as it is a signal mediator that can cause blood vessels to then dilate and bring other cells to the area
What are complement cells
Used to complete another type of cells that will then enhance its performance of other cells in the innate immune system
They can be recruited by antibodies generated by the adaptive immune system
They will consist of 30 liver derived globular proteins and will start as an inactive precursor protein that are then activated
3 casacdes caused by this: Lectin , Classical and Alternative and all lead to culmination in the opsonisatio and formation of membrane attack complex to then go to the pathogen
What are dendritic cells
These are the bridges between the innate and adaptive immune system and have long dendrites like neurons
They can collect large amount of material from the environment and then digest it and present the info the to the T cells
They can patrol certain areas and collect antigens to then take to lypmh nodes and show them to T cells
What is an antigen and how are they presented
It is a non self substance that can trigger an immune response
They are presented by MHC molecules where there ate Type 1 amd Type 2:
The dendritic cells swallw everything that they come across and then put them into class 1 or class 2 MHC
The CD8 cell bind to class 1 and CD4 bind to class 2
They bind for 24hrs and the T cell can then bind to the MHC as long as anitgen is specific for T cell and the trigger an immune response
What are T cells
These are the cellualr arm of the adaptive immune system
They move from the bone marrow to the thymus to develop there and when they are releaed they pass through the luymp nodes and if they bind to a specific antigen on a dendritic cell then they rapidly proligerate and cause immune response
What are the 2 types of T cell
There are Cytotoxic T cells that will release cytokines and granzymes to then kill infected cells
They will be the T cells that bind to the MHC 1 cell
There are T helper cells that produce cytokines to attract and activate other immune cells and they are used to help B cells produce antibodies for long term immunity, they bind to MHC 2 cell
How are T cells generated
Dendritic cells will patrol and swallow antigens by phagacytosis, the dendritic cells then move to the T cell zonez of the nearest Lymph nodes and T cells can intercat with them and when the specifc T cell is there it bind to the dendritic cell
The Specific T cell stay proliferated for 48 hours and activate functions like cytokine production when the activated ones go the inflammed tissue along inflammatoery signal gradients
Once the infection is cleared the T cells are killed off and few become memory cells
How do T cells start an immune respone
T cells are mobilsied when they encouter a dendritiuc cell or B cell that has digested an antigen and is displaying the antigen fragments bound to MHC molcule
There are then cytokines that will mature the T cells and the MHC antigen complex actave the T cell receptor so T cell release Cytokines, that then can either cause growth of more T cells
Or there can be some T cells that then become helper T cells and secret cytokines to attract new macrophages and more lymphocyte cells and other T cells may become Cytotoxic T cells and track down and kill infected cells
Killer T cells are from CD8 MHC and Helper T cell from CD$ MHC
What do memory T cells do
They can stay in the blood for a long time so give longter term immunity
They will react very quickly when their specific antigen is detetced in the body and proliferate rapidly and can then turn direct to Cytotoxic T cells quicker so get a quicker immune response
What do B cells do
They are generated in the bone marrow and ther role is to produce many antibodies, this is done due to have specific cell bound antibdoy receptor on their surface that then respond to antigens that bind on the B cell gto then activate it to the turn to plasma cells that wilol secrete the antibodies or to turn them to memory cells that then can turn to Killer T cells or stay as memory cells for future infection
What do B cells respond to
They can repsond to specific antigens to then make antibodies very quickly
They can then move to lymph nodes to interact with the T helper cells to fully activate the B cells so then antibodies can start to be secreted
B cells after this move the germinal centres and rapidly proliferate and mature to plasma cells that then change to the antibodies
What is the structure of an antibody
There is a constant region that is the heavy chain and is the same on all antibodies, there is also a smaller chain that is the variable chain that will differentiate each specific antibody
The 2 chains are held together by disulphide bridges
At the end of the variable chain there is antigen binding site on the N terminus at the end of both variable chains, each antibody can hold 2 antigens
End of the constant regions are the C terminus
What are the types of antigens
IgA are found in mucus, saliva, tears and breats milk and proect against pathogens
IgD- Part of the B cell receptor and will activate basophils and mast cells
IgE- Protect and parasites worms and responsible for allergic responses
IgG- Secreted by plasma cells in the blood and able to cross the placenta into the foetus
IgM- Attached to the surface of B cells or secreted into the blood and are responsible for the early stages of immunity
What is Opsonisation
This is one of the ways that antibodies will remove pathogens, it wokrs by coating the membrane of the pathogen membrane with antibodies so then there is a greater chance of the pathogen being destroyed by phagacytosis as the macrophage can engulf the whole thing
What is neutralisation
This is where the 2 antibody come together and trap 2 pathogenic cells between their anitgen receptors
This can then antibody-antigen compex that is then injested by a macrophage for phagacytosis
How are B and T cell different to each other
B cells are used for humoral immunity and T cells are for cellular immunity
B cell will bind to B cell receptor and T cell to T cell receptors
B cells will make antibodies unlike T cells and both are able to make memory cells
What is the response time of different immune responses
Phagacytosis is the quickesy form of response due to being immediate
Then is cytokines followed by T cells and then finally antibodies due to need to make them, but then they stay in the body for long time so then have very rapid secondary response for future infection
How are B memory cells made
In the germinal centre of some activated B cells there can be differentiation to Plasma cells to then make antibodies
In some other B cells they become memory cells and can live for very long time for future infection where they can change to plasma cells and make lots of antibodies very quickly
What is Immunopathology
This is where the immune system will overreact to a challenge
There are many checkpoints in the immune system and then balamces built to the responses to switch them off but they can ligger so then release unneeded cytokines that cause major inflammation
What is Autoimmunity
This is where the immune system will attack its own self tissue and cells of the body
This makes an autoimmune disease but can be treated with drugs or by supressing T/B cells