Lecture 38 - immune responses to viruses

Question 1

Adaptive immune response

Answer 1

Slow response (days)
Highly specific
Memory
Essential in the fight against intracellular pathogens such as viruses

Question 2

What is adaptive immunity particularly important for?

Answer 2

Essential in the fight against intracellular pathogens such as viruses

Question 3

Adaptive immunity best deals with what stage/s of pathogenesis?

Answer 3

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

Question 4

Stages of microbial pathogenesis

Answer 4

Adherence to host cells - invasion of host tissues - replication within host tissues - disease causing damage to host tissues (pathology)

Question 5

Viruses are found in two ways

Answer 5

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

Question 6

Phases of adaptive immune responses

Answer 6

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)

Question 7

Capturing the virus and presenting it to the adaptive immune system

Answer 7

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.

Question 8

Capsid

Answer 8

Viral peptides come from the capsid which is the protein structure that makes up most of the viral particle

Question 9

APCs have…

Answer 9

Both MHC-I and MHC-II

Question 10

All cells have…

Answer 10

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

Question 11

Native antigens

Answer 11

Unprocessed antigens

Question 12

Clonal selection/expansion

Answer 12

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

Question 13

T cell differentiation

Answer 13

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

Question 14

Cytokines

Answer 14

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).

Question 15

What does the combination of ______ and _____ to CD8 T cells cause?

Answer 15

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

Question 16

Cytotoxic T cells

Answer 16

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

Question 17

How does a virally infected host cell let a cytotoxic T cell that it is infected?

Answer 17

The infected host cell lets the cytotoxic T cell know its infected by present the viral antigen on the cell surface using MHC-I

Question 18

Perforin and granzyme

Answer 18

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

Question 19

Cytotoxic T cells process

Answer 19

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

Question 20

How does the body deal with viruses floating around?

Answer 20

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.

Question 21

B cells differentiation

Answer 21

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.

Question 22

Plasma cell

Answer 22

Antibody producing cell that develops from B cells

Question 23

What are the antibodies we need to know for this course?

Answer 23

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

Question 24

How does IgM and IgG deal with the viruses that are floating around?

Answer 24

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

Question 25

Primary infection vs subsequent infections - IgG and IgM

Answer 25

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

Question 26

Neutralisation

Answer 26

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

Question 27

Opsonisation

Answer 27

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)

Question 28

Complement activation

Answer 28

3- Complement activation - Antibodies are involved in activating the classical pathway which leads to the complement cascade

Question 29

Specificity and memory the adaptive immune system

Answer 29

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.

Question 30

What aspect of the immune response if important when we talk about immunisations?

Answer 30

The memory aspect of the immune response is utilised in vaccinations/immunisations

Question 31

Vaccines purpose

Answer 31

Vaccines help to prime the immune response for future exposure to a viral pathogen

Question 32

Two components of vaccine

Answer 32

Antigen and adjuvant

Question 33

Antigen in vaccine

Answer 33

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)

Question 34

Attenuation of antigen

Answer 34

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.

Question 35

Adjuvant in vaccine

Answer 35

Helps to enhance the immune response against the antigen (adjuvants help vaccines work better)

Question 36

Bacterial pathogen vs viral pathogen

Answer 36

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