Adaptive Immune Response Flashcards
What is the adaptive immune system important in?
- important in memory immune responses or later in novel infection
How long can it take the adaptive immune system to respond to a new pathogen?
- > 96
What do B lymphocytes do?
- Secrete antibodies (immunoglobulins)
What are the two major T lymphocytes
- CD4+ T lymphocytes = Helper T lymphocytes
- CD8+ T lymphocytes = Cytotoxic T lymphocytes
What do B cell receptors interact with?
- interact directly with antigen
How many BCR receptors does a B cell have on its surface?
- Each B cell has 200-500,000 identical BCRs on its surface
Where can B cell receptors be shed?
- can shed into the blood and tissue fluid as antibodies
What are antibodies?
- Antibodies are simply soluble BCRs
What do antibody monomers consist of?
- 2 heavy and 2 light polypeptide chains
How much do heavy chains weight on an antibody?
- 50 kDa
How much do light chains weight on an antibody?
- 25 kDa
What type of bonds link heavy and light chains together in an antibodies structure?
- Disulphide bonds which are formed between two cysteine acids
Describe antibody formation?
- initially each pre-B cell has the same light chain and heavy chain genes (bases are the options they can choose at random)
- theses genes have multiple options
- this creates cast diversity - 100 billion
- leads to different shapes of binding site at top of antibodies
What crates the diversity within antibody formation?
- it is the gene rearrangement of these V, D and J segments in pre-B cells that creates the diversity
- this means each B cell has a different receptor for the heavy chain
Describe how DNA is involved in antibody formation:
- DNA is cut by recombinase = RAG1 and RAG2 (these cause issue in animals producing B and T cells)
- removes non-selected segments
- when re-joining, a few additional nucleotides added randomly to heavy chain gene
- base deletion is also possible
- introduces more diversity
What do T cell receptors interact with?
- Antigenic peptides in major histocompatibility complex (MHC) molecules
- they will always recognise antigen if its showing MHC
How do T -cells work (e.g., can they shed like B cell receptors)?
- TCRs cannot shed
- function by recognising antigens close to it
There are two types of MHC molecule - MHC1 and MHC2
What does MHC1 do?
- presents mostly intracellular antigens (present in every nucleated cell)
- helps detect and kill infected cell (e.g., viral or intracellular infection)
What does MHC2 do and where are they found?
- found on antigen presenting cells
- presents mostly extracellular antigens
- helps respond to extracellular and intracellular infections
What do MHC class 1 molecules recognised by?
- Recognised by CD8+ T cells (only interact with MHC class 1)
- TCR and CD8 are the molecules that interact
MHC is presented in nearly all cells - What is the function?
- Function is T cell mediated killing
- Killing intracellularly infected cells
What helps to stabilise the interaction between a Cytotoxic T cells and MHC class 1 and peptide ?
- CD8
What molecule only every interacts with MHC class 2?
- CD4+ T cells only interact with MHC class 2
- TCR and CD4 are the molecules that interact
What is MHC class 2 present on?
- dendritic cells
- macrophages
- B cells
What is MHC class 2 molecules function?
- Function is T-cell mediated help cytokine release activating B cells
What helps stabilise the interaction of the helper T cell with MHC class 2?
- CD4
What does a T cell receptor resemble?
- resembles a membrane bound antibody FAB fragment
What are TCRs composed of?
- composed of 2 transmembrane glycoprotein chains (alpha and beta)
How do T cell receptors form?
- in a similar way to the B cell receptor
- gene rearrangement
What are the 4 main ways that antibodies effect pathogens?
- neutralisation
- opsonisation
- antibody-dependent cell-mediated cytotoxicity
- activation of complement
What is neutralisation of pathogen entry?
- High affinity (bind strongly) neutralising antibodies can block viruses and bacteria from bringing the receptor by which they enter the host cell
- e.g. antibody can block binding of a virus by blocking fusion event
- can also stop toxins binding to the cell receptors by which they have their effect
What is opsonisation?
- coating pathogen surfaces and facilitating recognition and phagocytosis
- In addition to innate molecules like complement antibodies can also enhance phagocytosis vis Fc receptors (Bind to bottom of Y antibody) on phagocytes cell surface making it up to 100 times more effective
Give an example of how opsonisation works:
- macrophages and neutrophils posses surface Fc receptors to bind Ab to activate phagocytosis
What is Antibody-dependent cell-mediated cytotoxicity (ADCC)?
- antibodies bind non-self antigens on host cell
- Fc receptors on immune cells bind to these antibodies
- cells such as neutrophils, macrophages eosinophils and NK cells
In ADCC why are cross-linking of Fc factors important?
- they are key to apoptosis/ release of perforins etc.
Activation of complement can be through innate mechanisms - how does it do this and what is another way it can be activated?
- lectin pathways = innate
- classical pathways = antibodies
What does activation of complement lead to?
- leads to same outcomes
- optimisation, inflammation, MAC formation
In the classical pathway of activation of complement what happens?
- C1q interacts with pathogen surface or with antibodies bound to surface
What are Cytotoxic T lymphocytes (CTL)?
- major effector cell of adaptive immune system
What do cytotoxic T lymphocytes require before they can do their job?
- requires activation first in lymphoid tissues via MHC class 1/TCR interaction
Where do CTL migrate to?
- migrate to infection site
What do CTL do?
- recognise infected cells showing off infected pepotided via MHC class 1
CTL cells can cause two methods of killing - what are these?
- perforin/granzyme killing
- FAS mediated Killing
- both leas to apoptosis of the target cell
- Apoptosis by these mechanisms far more rapid than death due to factor withdrawal or other apoptotic stimuli
How do CTL cells know what cells to kill and what cells not to kill?
- all the cells in a tissue are susceptible to the induction of apoptosis by the cytotoxins or armed CD8 T cells but only infected cell are killed
- specific recognition by the T cell receptor identifies which target cell to kill, and the polarised release of cytotoxic granules ensures that neighbouring cells are spared
What do T helper cells do?
- main importance in activating other cells
T helper cells release cytokines involved in what?
- increasing antibody production
- increasing phagocyte activity and NK cell activity
- increase antigen presentation
- can also release anti-inflammatory cytokines
What is memory response critical to?
- critical to most immunity
Memory - during an infection activated T and B cells do what?
- divide via mitosis - as you want more of these
Memory - what happens after T and B cells have divided?
- cytokine interleukin (IL_-2 released and IL-2 receptor expressed
- IL-2 drives T-cell proliferation
Memory - what happens at the resolution of the immune response?
- vast majority of these specific T and B cells die
- some cells can remain as memory T cells, memory B cells and plasma cells (secrete Abs continuously)
- these can survive in an individual for a lifetime
Memory - what are plasma cells?
- differentiated B cell
- constant release of antibodies
What are the locations of plasma cells?
- medullary cords of lymph nodes (lymph)
- bone marrow (blood)
- MALT (mucosa)
Where can memory B and T cells be found?
- some tissue resident, some in circulation
Memory B and T cells allow immune response in a 2nd exposure to be what?
- Faster (easier to activate memory cells)
- Larger (more antibodies)
- More efficient ( high affinity BCR and TCR)
- More effective (different antibody sub-classes)
