Lecture 38 - immune responses to viruses Flashcards
Adaptive immune response
Slow response (days)
Highly specific
Memory
Essential in the fight against intracellular pathogens such as viruses
What is adaptive immunity particularly important for?
Essential in the fight against intracellular pathogens such as viruses
Adaptive immunity best deals with what stage/s of pathogenesis?
Adaptive immunity is best at dealing with most stages of pathogenesis - and some effect early stages of replication (innate immunity works better earlier on in pathogenesis
Stages of microbial pathogenesis
Adherence to host cells - invasion of host tissues - replication within host tissues - disease causing damage to host tissues (pathology)
Viruses are found in two ways
The body has to deal with both intracellular and extracellular forms of virus
Intracellular - virus enters cell, replicate in the cell and turn into viral factories
Extracellular - viruses burst out of the cell usually killing the cell and this is the phase by which it moves around the body
Phases of adaptive immune responses
Adaptive immune response consist of sequential phases: recognition of antigen by specific lymphocytes, activation of lymphocytes (consisting of their proliferation and differentiation into effector cells), and the effector phase (elimination of antigen). The response declines as the antigen is eliminated and most of the antigen stimulated lymphocytes die by apoptosis. The antigen-specific cells that survive are responsible for memory. The duration of each phase may vary in different immune responses. The y-axis represents an arbitrary measure of the magnitude of the response. Thes principles apply to humoral immunity (mediated by B lymphocytes) and cell-mediated immunity (mediated by T lymphocytes)
Capturing the virus and presenting it to the adaptive immune system
Viral peptides binded to the MHC-II (uses digested proteins from the captured virus)
MHC-I bind unprocessed antigens (native antigens) from cytoplasm which leaked out of the phagolysosome for example.
Capsid
Viral peptides come from the capsid which is the protein structure that makes up most of the viral particle
APCs have…
Both MHC-I and MHC-II
All cells have…
MHC-I (APCs use it differently) - in cells they are used to pick up antigen and then acts as a signpost for the immune system
Native antigens
Unprocessed antigens
Clonal selection/expansion
Mature lymphocytes with receptors for many antigens develop before they encounter with these antigens
The viral peptide (antigen) presented on MHC is used like a key by the dendritic cell and it hunts around until it finds the matching lock (rreceptor on T cell)
Expansion of T and B lymphocytes expressing the same antigen receptor
T cell differentiation
T cells differentiate into memory T cells and effector T cells
Effector cells …
CD4 T cells are helper T cells and they don’t particularly attack the virus head on instead they help another type of T cell known as the CD8 T cells/cytotoxic T cell
Cytotoxic T cells/CD8 T cells are the killer T cells and go and tackle the virus head on
Cytokines
Cytokines are Soluble proteins released from a variety of cells. They are involved in a variety of immune functions, including fever production, cell activation and differentiation (e.g. B cell -> plasma cell).
What does the combination of ______ and _____ to CD8 T cells cause?
The combination of presentation to CD8 T cells by APC on MHC-1 and the cytokines makes these CD8 T cells cytotoxic. They will now be ready to go out and find the MHC-1 on cells that are infected and kill these cells
APC has presented the peptide on MHC-II which connects onto CD4 T cells/helper T cells which cause CD4 T cells to release a Buch of helper molecules known as cytokines. Cytokines get cells excited and ready for a killing fest.
At the same time, the APC is also presenting the specific peptide on MHC-I to the CD8 T cell
Cytokines produced by CD4 T cells help CD8 T cells become activated
Cytotoxic T cells
Differentiated CD8+ T cells, which kill virally infected cells or tumour cells, normally through the perforin and granzyme pathway.
Cytotoxic T cells synthesise special proteins that specifically kill the virally infected host cell - The infected host cell lets the cytotoxic T cell know its infected by present the viral antigen on the cell surface using MHC-I
How does a virally infected host cell let a cytotoxic T cell that it is infected?
The infected host cell lets the cytotoxic T cell know its infected by present the viral antigen on the cell surface using MHC-I
Perforin and granzyme
Perforins cause a hole in the infected cell and granzyme is released shortly after and causes apoptosis (kills the cell along with the virus)
Use the perforin/granzyme pathway to kill virally infected cells and tumor cells
Cytotoxic T cells process
The cytotoxic T cell hunts around the body looked for the infected cells that is expressing the viral antigen on MHC-I on the cell surface. When it finds this cell the CD8 molecule starts releasing two very important chemicals - perforin, which punctures a hole through the infected cell, and this is quickly followed by the release of granzyme which makes its way through the puncture and into the infected cell and completely destroys the cell along with all of the virus. This infected cell has died in its service to protect all the other cells. This is how the adaptive immune response uses the cellular adaptive immune response to kill intracellular pathogens such as viruses like the rhinovirus
How does the body deal with viruses floating around?
The body deals with these viruses that are floating around and free to infect another new epithelial cell is through our humoral immune system, the system that uses antibodies to deal with viruses.
B cells differentiation
Form memory cells and effector cells
For the antibody producing plasma cells to develop from B cells …
1- Unprocessed antigen (native antigen) must attach to the B cell receptor
2- Helper T cell to attach to processed antigens. Presented by the APC cell MHC-II (this causes cytokines to be released from the helper cell)
These two things cause mature B cells to become a plasma cell, the cell that actually produces the antibody that the reacting/original antibody receptor was.
Plasma cell
Antibody producing cell that develops from B cells
What are the antibodies we need to know for this course?
IgG - long term immunity, memory antibodies, neutralises, opsonises and fixes complement
IgA - Secretory antibody; on mucous membranes
IgM - Produced at first response to antigen, can serve as a B cell receptor
IgD - Receptor on B cells
IgE - Antibody of allergy, worm infections
How does IgM and IgG deal with the viruses that are floating around?
IgM is the first to appear followed by IgG in a primary infection, on subsequent infections IgG is one that pops ups first with relatively slow IgM
1- Neutralisation - neutralises the virus by the antibodies attaching themselves all over the surface of the virus and basically the virus is unable to attach to anything because it is covered in all kinds of antibodies which stops it getting into cells or attaching therefore neutralising it
2- Opsonisation - Antibodies attach to viral particle (opsonisation). After antibody binds to the membrane, phagocytes are attracted to the pathogen. The Fab portion of the antibody binds to the antigen, whereas the Fc portion of the antibody binds to an Fc receptor on the phagocyte, facilitating phagocytosis (very tasty to phagocytes now)
3- Complement activation - Antibodies are involved in activating the classical pathway which leads to the complement cascade
Primary infection vs subsequent infections - IgG and IgM
Lots of IgM relative to IgG indicates that the infection has just occurred
Lots of IgG relative to IgM usually means that the patient has seen the virus sometime before
Neutralisation
1- Neutralisation - neutralises the virus by the antibodies attaching themselves all over the surface of the virus and basically the virus is unable to attach to anything because it is covered in all kinds of antibodies which stops it getting into cells or attaching therefore neutralising it
Opsonisation
2- Opsonisation - Antibodies attach to viral particle (opsonisation). After antibody binds to the membrane, phagocytes are attracted to the pathogen. The Fab portion of the antibody binds to the antigen, whereas the Fc portion of the antibody binds to an Fc receptor on the phagocyte, facilitating phagocytosis (very tasty to phagocytes now)
Complement activation
3- Complement activation - Antibodies are involved in activating the classical pathway which leads to the complement cascade
Specificity and memory the adaptive immune system
Exposure to antigen A and B - induces the production of different antibodies (specificty). The secondary response to antigen A will be more rapid and larger than the primary response (memory) and is different from the primary response of antigen B (again reflecting specificity). Antibody levels decline with time after each immunisation.
First response to antigens is going to be relatively slow because it will take some time for the antigen to be selected, expanded, for there to be maturation and differentiation in the various types of T and B cells. Memory cells enable the immune system a quick way to go directly and respond, these memory cells reside in large numbers in the lymph node so the next time you see that particular viral particle instead of having to search for one particular T or B cell there will be many of them and the chances of them connecting with them and causing further clonal expansion will occur far quicker.
What aspect of the immune response if important when we talk about immunisations?
The memory aspect of the immune response is utilised in vaccinations/immunisations
Vaccines purpose
Vaccines help to prime the immune response for future exposure to a viral pathogen
Two components of vaccine
Antigen and adjuvant
Antigen in vaccine
The specific molecule that the immune system may recognise. It is a preview of the molecule that you want the body to fight against
Made using heat killed, attenuated (makes virus/toxin/bacteria less deadly - repeated culture/passage or recombinant viral proteins)
Attenuation of antigen
An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or “live”).
Pathogenic virus isolated from patients, grown in human cells. Infect monkey cells with cultured virus. Virus acquires many mutations that allow it to grow well in monkey cells. Mutations make the virus unable to grow well in human cells and this creates a vaccine candidate.
Adjuvant in vaccine
Helps to enhance the immune response against the antigen (adjuvants help vaccines work better)
Bacterial pathogen vs viral pathogen
Bacterial pathogen MHC II Helper/CD4 T cell Release cytokines B cells becomes activated as long as it also sees native antigen
Viral pathogen
APC + antigen on MHC-I
Helper/CD4 T cell releases cytokines as a result of MHC-1 peptide complex
Cytotoxic/CD8 T cells
