Research assignment question

Instruction

1-To answer these questions students are required to primarily use pre-lecture material and lecture material, but students can also do their own research (and for some questions this is a requirement; 1-2 independent research sources is sufficient), which should be appropriately referenced (as should any pre-lecture literature).

2- The word limit for each question is 500 words (excluding reference list), but students can elect to write less or to not attempt all questions. The word count should be provided for each question; for example: ‘Question 1 (xxxx words)’

QUESTION 1

The interactions between pathogens and their mammalian hosts are played out on coevolutionary battlegrounds.

Discuss this statement by explaining:

1. a) Why humans are constantly susceptible to infection despite the evolution of complex

innate and adaptive immune responses and,

1. b) How pathogens, and the molecules they produce, interact with macrophages to cause

disease and can sometimes be exploited for therapeutic benefit.

You should use examples from the pre-lecture and lecture material and you should also

source another example from the literature. Include a reference list (not included in word count).

QUESTION 2

Diversity in the B cell and T cell repertoire.

1. a) As a member of a research team studying a tribe found in a remote region of New

Guinea, you make the astonishing discovery that they have only two variable (V) genes

for the light (L) chain and three V genes for the heavy (H) chain of immunoglobulins.

Nevertheless, they seem healthy and able to resist the diversity of pathogenic organisms

endemic to the area. Suggest how this might be accomplished.

1. b) Individuals frequently harbour auto-reactive B cells (i.e. B cells that express receptors

that recognise self-antigen), but do not develop autoimmune disease. Explain how this

situation can occur.

QUESTION 3

"All disease begins in the gut"

- Hippocrates.

The gut microbiome is crucial for health and homeostasis. In fact, it is so important that our bodies revere the gut microbiome, allowing it special immune privilege.

Discuss:

1. a) how tolerance may be induced to the gut microbiome, with reference to B cells and T

cells

1. b) the role of the gut microbiome in health and disease, and how our understanding of this might lead to therapies for immune disorders, including examples of early attempts to target the microbiome for therapy (hint: i) refer to the regulation exerted by bacterial

products ii) the evidence for the influence of the gut microbiome on immune disorders,

both in humans and mice).

Refer to lecture material, publications discussed during lectures, and 1-2 publications of your own finding. Include a reference list (not included in word count).

QUESTION 4

Exploiting our understanding of the immune system for therapeutic gain.

Our understanding of the immune system has increased in leaps and bounds over the past few decades. This has allowed us to exploit this knowledge to treat immune-related disorders such as cancer and autoimmune disease. However, our understanding of the complexities of the immune system is still relatively limited, so it is crucial to tread carefully when manipulating the immune response.

Discuss:

1. a) The role of T cells in preventing cancer (how T cells recognise and kill cancer cells),

how regulatory T cells are detrimental in the control of tumour growth (including how

Tregs function) and an example(s) of a mechanism used by cancer cells to evade the T

cell response

1. b) T cell-targeted therapies for the treatment of cancer. Include examples of clinically

available and pipeline therapeutics and briefly their mechanisms of action. Choose one

therapy to describe in more detail (a few sentences) their mechanism.

1. c) The uncertainty and potential pit falls/dangers of manipulating the immune system for

therapy, particularly with reference to T cell responses. Explain examples of currently

used therapeutics (e.g. CTLA-4 inhibitors) and past failures.

QUESTION 5

Development of HIV vaccines and boosting innate immunity.

None of the clinical trials of vaccines against HIV have proven to have sufficient sensitivity or specificity to progress into the general population. Researchers have suggested that incorporating molecules that stimulate innate immune responses like ligands for toll like receptors with the HIV antigens may enhance immunity and improve the vaccine efficacy.

1. a) What is it about HIV that makes developing a new vaccine so challenging?
2. b) How might targeting the innate immune response improve the adaptive response and boost vaccine efficiency?