Lecture 12: T cells and Adaptive Immunity Flashcards
Tuesday 5th November
What does the adaptive immune system do?
Adaptive immune systems destroy/eliminate invading organisms and any toxins that they produce.
Describe the features of the adaptive immune system
- Adaptive immune systems destroy/eliminate invading organisms and any toxins that they produce.
- The adaptive immune system can raise immune responses against pathogens that have never been encountered before by the host organism.
- The adaptive responses are highly specific to a particular pathogen.
- They provide long-lasting protection (they have immunological memory).
- Any substance capable of generating an adaptive immune response is called an ANTIGEN (antibody generator)
- The adaptive immune system is recruited and trained by the innate immune system (more later).
What are the 3 features of the adaptive immune system
- Immunisation
- Instruction
- Attack
What is most of what we know about the adaptive immune system derived from?
Most of what we know about the adaptive immune system is derived from immunisation experiments in laboratory animals, typically mice.
what is the adpative immune system trained and recruited by?
Trained and recruited by the innate immune system
Describe immunisations
① An antigen, a harmless molecule (typically a foreign protein), is injected into a mouse in the form of a suspension containing adjuvant.
② Adjuvant activates innate immunity responses
It comprises:
immunological stimulants such as inactivated mycobacterial proteins
irritants such as aluminium hydroxide.
③ The activated innate response also responds to the antigen in the vaccine
④ This innate immune response then trains the adaptive immune response.
How specific are the responses of the adaptive immune system?
Remarkably, the ability to generate adaptive responses is very specific: immune responses can be generated that can distinguish between very similar molecules such as single amino acid alterations or isomers.
Is it true that immune responses can distinguish between amino acids?
Yes
What is the R number?
The number of secondary responses produced by a primary response
What is the R number for the measles?
Between 12 and 16
Who published a paper falsely inking MMR vaccine (measles, mumps, rubella) with autism?
Andrew Wakefield in 1998
What are the adaptive responses performed by?
The lymphocytes
Where do the lymphocytes develop?
Lymphocytes develop in CENTRAL or PRIMARY LYMPHOID ORGANS :
- bone marrow
- thymus
What happens after lymphocytes develop in primary lymphoid organs?
They migrate to the PERIPHERAL or SECONDARY LYMPHOID ORGANS
What are the PERIPHERAL or SECONDARY LYMPHOID ORGANS that lymphocytes migrate to ?
Adenoids
Tonsils
Lymph nodes
Spleen
Peyer’s patches
Appendix
Skin
Respiratory tract
Where do lymphcyes occur in large numbers?
Lymphocytes occur in large numbers in the blood and lymph - the colourless fluid in the lymphatic vessels green.
Apart from the blood and lymph, where else are lymphocytes concentrated?
They are also concentrated in the lymphoid organs such as the thymus, lymph nodes (lymph glands), spleen and appendix.
How many lymphocytes are there in the human body?
There are 2 x 1012 lymphocytes in the human body: together this makes our lymphocytes comparable in cell mass to our brain or liver!
Describe the experiments from the 1950s that established lymphocytes as being responsible for the adaptive immune response
- Mice/rats were heavily irradiated: they were then unable to mount ADAPTIVE immune responses, but could still react via some INNATE responses.
- The assumption was that the radiation treatment had destroyed the cells of the adaptive system.
- Various types of cells were then transferred into these animals, which were then examined for gain of adaptive responses
- Transfer of LYMPHOCYTES into these irradiated rodents restored ADAPTIVE immunity, establishing that lymphocytes were responsible for adaptive immune responses.
Which cells link the adaptive and innate immune systems?
Dendritic cells
Where are dendritic cells widely distributed?
In tissues and organs
What do dendrtic cells display?
They display a wide variety of TLRs and other pattern receptors.
What are dendritic cells activated by ?
Dendritic Cells are activated by binding of pathogen to any of these receptors.
Is it true that dendritic cells digest and display their pepti
What do dendritic cells display?
They display a wide variety of TLRs and other pattern receptors.
Is it true that dendritic cells digest and display peptides/groove proteins on the cell surface?
Yes.
How are dendritic cells activated?
DC are activated by binding of pathogen to any of these receptors.
Is it true that dendritic cells mature from antigen capturing DC to mature antigen-presenting cell (APC)?
Yes, this happens in lymphoid organs and the peptides will be presented to t cells
What do dendritic cells do after displaying peptides on their cell surface?
DC then migrate and travel to a nearby lymphoid organ such as a lymph node, where they ACTIVATE ADAPTIVE IMMUNE responses, training them to recognise the peptide fragments that are carried.
These peptides are presented to T cells.
What do activated dendritic cells do?
Activated dendritic cells phagocytose and degrade invading microorganisms.
Where do T cells develop ?
develop in thymus tissue from thymocytes derived from common lymphoid progenitor cells, which are themselves derived from a haemopoietic stem cell originating in the liver (foetuses) or bone marrow (adults).
“T cells migrate from the bone marrow to the thymus, differntiate to thymocytes, migrate to lymphoid organs, and become T cells”. Is this true?
Yes
Describe in detail how dendritic cells activate T cells?
① DC present peptides to T cells in the lymphoid organ.
② T cell TCR recognises ‘self’ antigen: no action taken.
③ T cell TCR recognises no antigen: no action taken
④ T cell TCR recognises ‘non-self ‘ antigen: activation, mitosis and clonal expansion of SPECIFIC T cells
Why do antigen presenting cells only present to T cells?
① Co-stimulatory molecules on APC ‘dock’ with T-cell specific co-stimulatory molecules
② Peptide is held in the groove of an APC presenting protein and is ‘scanned’ by the TCR
③ No recognition: no action. Cells undock.
Recognition: T cell activated.
Is it true that there are differnt effector T cells for each pathogen?
Yes
This activation and clonal expansion takes time: this is why we need the innate immune system to protect us over the first few critical hours and days after encountering pathogens.
Clonal expansion also explains why lymph glands swell after infection.
This activation and clonal expansion takes time: this is why we need the innate immune system to protect us over the first few critical hours and days after encountering pathogens.
Clonal expansion also explains why lymph glands swell after infection.
What are the 3 classes of T cell?
Regulatory (or suppressor)
Cytotoxic
Helper
Does clonal expansion affect all 3 types of T cell?
Yes
What do activated T cells do?
They migrate to the site of infection and act locally
Do T cells act locally?
Yes
What to T Helper cells do?
Helper T cells activate macrophages, dendritic cells, B cells and maintain cytotoxic T cell activity by secreting a variety of cytokines
What do T regulatory cells do?
Regulatory (or suppressor) T cells inhibit the function of helper T cells, cytotoxic T cells and dendritic cells
What do cytotoxic T cells do?
Cytotoxic T cells kill infected host cells by persuading them to commit suicide apoptotically
How do cytotoxic T cells kill?
The TC cell recognises the antigens that were used to activate it on the target cell membrane, and so binds specifically to a target cell. The contact points form an immunological synapse.
The TC cell secretes perforins ( ), which assemble and form a channel in the target cell wall. The T cell then secretes specific proteases ( ), which enter the target cell, and activate CASPASES, the effector proteins of apoptosis. (NK cells also use this process)
The TC cell binds receptors on the target cell that send a signal that activates CASPASES, the effector proteins of apoptosis.
The apoptotic bodies are phagocytosed by antigen-presenting cells (mostly DC but also macrophages) and can therefore be used to retrain T cells: it’s an amplifying process. That’s why Treg suppressor T cells are needed.
What do caspases induce?
Apoptosis
