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Immunology of Infection 4A Course Information 2023-2024

Introduction

Welcome to the final year of your programme. One of the aims of the final year is to prepare you for the years ahead. The teaching will be structured differently, and you will be encouraged to work independently. We expect you to develop a breadth to your thinking and writing. This is the time to bring together knowledge gained during the past three years, looking for general principles which can be used productively. This mature approach should be expressed in your coursework, project report and examination answers. The key to success in final year is good time-management.

We recommend that you read this Course Information Document at the start of your final year.

In addition, there is important information about regulations, assessment and progression in the Life Sciences Handbook: Regulations & Advice; again, you should read this document at the start of the year and you must refer to it as necessary.

Please keep this Course Information Document for future reference after you graduate; you may need to provide course details for further study or other training.

While the information contained in the document is correct at the time of printing, it may be necessary to make changes. Check your online timetable, Moodle and your email messages regularly.

Course Contacts

Course Coordinators

Professor Tom Evans, Tom.Evans@glasgow.ac.uk

Deputy: Professor Pasquale Maffia, Pasquale.Maffia@glasgow.ac.uk

Programme Coordinator for Final Year

Professor Simon Milling, Simon.Milling@glasgow.ac.uk

Teaching Staff

Teaching staff names can be found on your online timetable and contact details can be found on the University website Staff A-Z

External Examiner

Dr Janine Coombes, Robert Gordon University

Life Sciences Office

The Life Sciences Office is located in Room 353 of the Sir James Black Building. Opening hours for enquiries are: Monday to Friday: 9:30am to 4:30pm.

Course Summaries

Course Code

BIOL4189

Course Title

Immunology of Infection 4A option

Academic Session

2023-24

Short Description of the Course

This course focuses on the mechanisms of immune protection against infectious agents (including bacteria, viruses and parasites), and the immune evasion strategies employed by these pathogens.

The course includes an optional 3-day field trip. There is no cost to the student for the field trip.

Requirements of Entry

Normally, only available to final-year Life Sciences students in a Infection & Immunology programme. Visiting students may be allowed to enrol, at the discretion of the Life Sciences Chief Adviser and the Course Coordinator.

Associated Programmes

This course is offered by the Immunology programme.

Available to visiting students

Yes

Available to Erasmus students

Yes

Typically offered

Semester 2

Timetable

This option is assigned to block S2-A. Normally, there are 3 hours of teaching on Mondays, which may be split over more than one session.

Course Aims

The aims of this course are to develop:

in depth knowledge of immune responses to infectious agents, and of mechanisms used by pathogens to avoid immune detection and attack;

understanding of current controversies and emerging questions in vaccination;

the ability to synthesise the research literature and present it to other scientists.

Intended Learning Outcomes of Course

By the end of this course, students will be able to:

discuss the molecular and cellular interactions that occur between bacteria and their hosts, and immune mechanisms underpinning bacterial protection;

appraise how immune responses against parasites and viruses are initiated and regulated;

interpret and present information from relevant literature.

Minimum Requirements for Award of Credits

Students must submit at least 75% by weight of the components (including examinations) of the course’s summative assessment.

Description of Summative Assessment

The course will be assessed by a 2-hour examination (75%) and in-course assessment consisting of a poster presentation (25%).

Are reassessment opportunities normally available for all summative assessments in this course

Not applicable for Honours courses

Formative Assessment and Feedback

During the course, students will be guided through the process of preparing a poster presentation. They will produce draft posters and will receive individual verbal feedback on their drafts both from their peers and from staff.

The synoptic session at the end of the course is designed to be primarily ‘student-led’, and an opportunity for the student to ask, and answer, questions on the topics covered, which will help prepare the students for the examination.

Examination Diet

April/May

Total Exam Duration

120 minutes

In-Course Assessment: Poster Presentation

Session Summaries

Session 1: Option Introduction & Techniques to Study the Immunology of Infection

Professor Tom Evans

Synopsis

Review of the option content. Diversity of microbial life. Animal and other models of infection. Virulence and virulence genes. Data interpretation.

Intended Learning Outcomes

Understand the overall philosophy of the course.

Appreciate and be able to recall the major features characterising the different forms of microbial infectious agents.

Be able to discuss the different kinds of models used to investigate the immunology of infection.

Understand and be able to give examples of what constitutes virulence in an infectious agent and its genetic basis.

An ability critically to appraise experimental evidence.

Reading

Medical Microbiology, 4th edition Edited by Samuel Baron.

University of Texas Medical Branch at Galveston, Galveston, Texas

Galveston (TX): University of Texas Medical Branch at Galveston; 1996.

ISBN-10: 0-9631172-1-1. This is a bit old but you can read it for free via PubMed “Books” Has useful chapters on microbial structure.

Mice, microbes and models of infection

Nature Reviews Genetics 4, 195-205 (March 2003) | doi:10.1038/nrg1019

Jan Buer & Rudi Balling

Trolling for the ideal model host: zebrafish take the bait.

Allen JP, Neely MN.

Future Microbiol. 2010 Apr;5(4):563-9. Review.


Session 2: Intestinal Helminth Infections

Prof Rick Maizels

Synopsis

The aim of this session is to discuss the how the helminth parasite infections drive a protective Type 2 immune response which engages both the innate and adaptive arms of the immune system, and to consider how parasites can interfere with host immunity by inhibiting innate immunity and promoting immune regulatory networks. Taken together, these aspects allow us to define how protective immunity may be enhanced, and also to take advantage of natural anti-inflammatory mechanisms evolved by parasites, to find new routes to dampen immunological disorders.

Intended Learning Outcomes

By the end of the session, you should be able to:

Summarise the biological features of helminths

Describe the types of innate and adaptive immune responses induced by helminths.

Identify how protective immunity to principal helminth parasites may operate

Discuss how helminths may modulate host immunity to maintain infection

Reading

Patel N, Kreider T, Urban JF Jr, Gause WC. Characterisation of effector mechanisms at the host:parasite interface during the immune response to tissue-dwelling intestinal nematode parasites. Int J Parasitol. 2009 Jan;39(1):13-21.

Grencis RK: Immunity to helminths: resistance, regulation, and susceptibility to gastrointestinal nematodes. Annu Rev Immunol 2015, 33:201-25.

McSorley HJ, Maizels RM: Helminth infections and host immune regulation. Clin Micro Rev 2012, 25:585-608

Maizels RM, Hewitson JP, Smith KA: Susceptibility and immunity to helminth parasites. Curr Opin Immunol 2012, 25:459-66.

 DOI: 10.1146/annurev.immunol.17.1.657


Session 3: Immune Response to Influenza Virus

Dr Megan Macleod

Synopsis

Influenza virus is a RNA virus from the Orthomyxoviridae family. It causes an acute respiratory infection in mammals and birds following infection of respiratory tract epithelial cells. In this lecture we will discuss the innate and adaptive immune response induced by the virus highlighting how influenza virus subverts these responses, mechanisms of protective immunological memory, and vaccine strategies.

Intended Learning Outcomes

At the end of the session you should have an understanding of:

The molecular basis of how influenza virus triggers the innate immune response.

How influenza specific B and T cells are primed and their contribution to viral clearance.

How influenza virus subverts the innate and adaptive immune response.

Mechanisms of protection to influenza virus offered by immunological memory and how this relates to current and experimental influenza virus vaccines.

Reading

A reading list will be made available prior to the session.

 

Session 4: Human Herpes Viruses

Professor Tom Evans

Synopsis

This session will consider the immune defences against this very important group of human pathogens and how the viruses have evolved strategies to evade immune clearance.

Intended Learning Outcomes

Understand and recall the life cycle and diseases caused by these viruses.

Understand and recall the detailed molecular mechanisms employed by these viruses to evade clearance by elements of the innate and acquired immune system.

Understand the ability of these viruses to establish a dormant state within humans and how this is maintained in the face of immune defence and what precipitates reactivation.

Reading

Virol J. 2016 Mar 8;13:38. doi: 10.1186/s12985-016-0495-5.

Evasion of host antiviral innate immunity by HSV-1, an update.

Curr Top Microbiol Immunol. 2015;391:355-81. doi: 10.1007/978-3-319-22834-1_12.

Immune Evasion by Epstein-Barr Virus.

Ressing MEvan Gent MGram AM1, Hooykaas MJPiersma SJWiertz EJ.

Su C1, Zhan G2, Zheng C3,4.

Recognition of herpesviruses by the innate immune system

Søren R. Paludan, Andrew G. Bowie, Kristy A. Horan & Katherine A. Fitzgerald

Nature Reviews Immunology 11, 143-154 doi:10.1038/nri2937


Session 5: HIV

Professor Tom Evans

Synopsis

Entry of HIV to the host. Immune response to this chronic viral infection. Virus evasion. Vaccine development.

Intended Learning Outcomes

Appreciate the life cycle of HIV and how this influences its effects on the host immune system.

Understand and recall how the HIV virus uses components of the immune system to reach its target cells following mucosal infection.

Understand and recall how HIV enters CD4 cells and the role of co-receptors.

Understand and recall how HIV evokes an immune response but this fails to clear the virus.

Appreciate the progress towards developing a vaccine for HIV.

Reading

The immune response during acute HIV-1 infection: clues for vaccine development

Andrew J. McMichael, Persephone Borrow, Georgia D. Tomaras, Nilu Goonetilleke & Barton F. Haynes

Nature Reviews Immunology 10, 11-23 doi:10.1038/nri2674

DCs and NK cells: critical effectors in the immune response to HIV-1

Marcus Altfeld, Lena Fadda, Davor Frleta & Nina Bhardwaj

Nature Reviews Immunology 11, 176-186 doi:10.1038/nri2935 (2011)

Immunology and the elusive AIDS vaccine

Herbert W. Virgin & Bruce D. Walker

Nature 464, 224—231 (11 March 2010) doi:10.1038/nature08898

CHEMOKINE RECEPTORS AS HIV-1 CORECEPTORS: Roles in Viral Entry, Tropism, and Disease

Edward A. Berger, Philip M. Murphy and Joshua M. Farber

Annual Review of Immunology

Vol. 17: 657-700 (Volume publication date April 1999)


Session 6: Malaria

Professor Jim Brewer

Synopsis

In 2008, malaria caused nearly one million deaths, mostly among African children. Malaria is caused by protozoan parasites of the genus Plasmodium. The best current vaccine available (less than 40% effective) targets the sporozoite stage of the parasite, which travels from the skin to the liver following an infected mosquito bite. However, it is the subsequent blood stage of infection, where parasites invade, replicate and burst out of erythrocytes, that exclusively causes disease pathology ranging from mild fever to life threatening cerebral malaria. Natural immunity to malaria requires a number of exposures to infection and is frequently anti-disease rather than providing sterile immunity to parasites.

In the current session, we will review host-parasite interactions during the sporozoite and blood stages of malaria infection. We will also discuss how the immune response contributes to disease pathology, with emphasis on cerebral malaria and severe malarial anaemia.

Intended Learning Outcomes

At the end of this session, you should be able to:

Describe the processes involved in induction of sporozoite immunity.

Describe the evidence for immunosuppression during malaria infection.

Review current theories to explain cerebral malaria, based on sequestration of blood stage parasites and the host’s immune response.

Discuss theories to explain severe anaemia in malaria, where the loss of red blood cells exceeds that attributable to parasite multiplication.

Reading

Chakravarty, Sumana, Ian A Cockburn, Salih Kuk, Michael G Overstreet, John B Sacci, and Fidel Zavala. 2007. CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes. Nat Med 13, no. 9: 1035-1041. doi:10.1038/nm1628.

Engwerda, Christian R, and Michael F Good. 2005. Interactions between malaria parasites and the host immune system. Current Opinion in Immunology 17, no. 4 (August): 381-387. doi:10.1016/j.coi.2005.05.010.

Good, Michael F., Huji Xu, Michelle Wykes, and Christian R. Engwerda. 2005. DEVELOPMENT AND REGULATION OF CELL-MEDIATED IMMUNE RESPONSES TO THE BLOOD STAGES OF MALARIA: Implications for Vaccine Research. Annual Review of Immunology 23, no. 1 (4): 69-99. doi:10.1146/annurev.immunol.23.021704.115638.

Millington, Owain R, Caterina Di Lorenzo, R Stephen Phillips, Paul Garside, and James M Brewer. 2006. Suppression of adaptive immunity to heterologous antigens during Plasmodium infection through hemozoin-induced failure of dendritic cell function. Journal of biology 5, no. 2: 5.

Nie, Catherine Q., Nicholas J. Bernard, M. Ursula Norman, Fiona H. Amante, Rachel J. Lundie, Brendan S. Crabb, William R. Heath, et al. 2009. IP-10-Mediated T Cell Homing Promotes Cerebral Inflammation over Splenic Immunity to Malaria Infection. PLoS Pathog 5, no. 4 (April 3): e1000369. doi:10.1371%2Fjournal.ppat.1000369.

Schofield, Louis, and Georges E. Grau. 2005. IMMUNOLOGICAL PROCESSES IN MALARIA PATHOGENESIS. Nature Reviews Immunology 5, no. 9: 722.

Wykes, Michelle N., and Michael F. Good. 2008. What really happens to dendritic cells during malaria? Nat Rev Micro 6, no. 11 (November): 864-870. doi:10.1038/nrmicro1988.


Session 7: Tuberculosis

Professor Tom Evans

Synopsis

How tuberculosis bacilli infect and interact with the immune system. The role of Th1 mediated immunity and the cytokines that orchestrate this response. Pathogen evasion of immunity. Use of immune response to detect latent infection.

Intended Learning Outcomes

Understand and recall how Mycobacterium tuberculosis interacts with the host and establishes infection.

Understand and recall how M. tb survives within cells and evokes a Th1 response.

Appreciate the cytokines that orchestrate the Th1 response to TB.

Use of technology to detect latent TB infection.

Reading

Nat Immunol. 2015 Jan;16(1):57-63. doi: 10.1038/ni.3048.

The balance between protective and pathogenic immune responses in the TB-infected lung.

Orme IMRobinson RTCooper AM.

Mycobacterium tuberculosis and the intimate discourse of a chronic infection.

Russell DG.

Immunol Rev. 2011 Mar;240(1):252-68. doi: 10.1111/j.1600-065X.2010.00984.x. Review.

For better or for worse: the immune response against Mycobacterium tuberculosis balances pathology and protection.

Dorhoi A, Reece ST, Kaufmann SH.

Immunol Rev. 2011 Mar;240(1):235-51. doi: 10.1111/j.1600-065X.2010.00994.x. Review.

Innate immune effectors in mycobacterial infection.

Saiga H, Shimada Y, Takeda K.

Clin Dev Immunol. 2011;2011:347594. Epub 2011 Jan 12. Review.

Cell-mediated immune responses in tuberculosis.

Cooper AM.

Annu Rev Immunol. 2009;27:393-422. Review.


Session 8: Vaccination

Professor Jim Brewer

Synopsis

Vaccines have probably been the most effective medical intervention against infectious diseases. However, vaccine development has mainly occurred through progress in microbiology, biochemistry and more recently molecular biology, while immunology has historically played little role. With increasing demand for vaccines against HIV, Malaria and Tuberculosis, immunological understanding of what the protective immune response against these agents looks like, together with rational application of adjuvants/immunomodulators to replicate these responses means that immunology will play an increasing role in the development of vaccines in the future. In this session we will review our current understanding and controversies of how vaccine adjuvants/immunomodulators work.

Intended Learning Outcomes

At the end of the session you should be able to:

Review current theories to explain immune activation in response to microbial adjuvants (PAMPs).

Review current theories on the role of endogenous danger signals in immune activation by non-microbial adjuvants.

Discuss interactions between cells of the innate and adaptive immune systems during the responses to vaccine adjuvants.

Discuss evidence that vaccine adjuvants (e.g. Alum) can control the magnitude and duration of antigen presentation and the impact of this on the development of immune responses.

 

Session 9: Pathogen Recognition by the Immune System

Professor Tom Evans

Synopsis

This session will integrate with innate immune signalling and elements of acquired immune responses but will focus on the pathogen molecules that are important in initiating immune responses.

Intended Learning Outcomes

Understand and recall the members of the Toll-like receptor family, their ligands and the intracellular responses they evoke.

Appreciate the members of the intracellular nucleotide binding domain, leucine rich containing (NLR) protein family, the ligands that they recognise and their role in host defence.

Understand and recall the structure and function of the inflammasome.

Understand and recall the innate immune receptors involved in anti-fungal immunity.

Understand and recall the structure and function of retinoic acid inducible gene I like (RIG) receptors in antiviral immunity.

Reading

Immunity to fungal infections

Luigina Romani

Nature Reviews Immunology 11, 275-288 doi:10.1038/nri2939

Central roles of NLRs and inflammasomes in viral infection

Thirumala-Devi Kanneganti

Nature Reviews Immunology 10, 688-698 doi:10.1038/nri2851

A cell biological view of Toll-like receptor function: regulation through compartmentalization

Gregory M. Barton & Jonathan C. Kagan

Nature Reviews Immunology 9, 535-542 (August 2009) | doi:10.1038/nri2587

NLRs at the intersection of cell death and immunity

Jenny P.-Y. Ting, Stephen B. Willingham & Daniel T. Bergstralh

Nature Reviews Immunology 8, 372-379 doi:10.1038/nri2296

Inferences, questions and possibilities in Toll-like receptor signalling

Bruce Beutler

Nature 430, 257-263 (8 July 2004) | doi:10.1038/nature02761; Published online 8 July 2004

Pathogen recognition by the innate immune system.

Kumar HKawai TAkira S.

Int Rev Immunol. 2011 Feb;30(1):16-34.

The inflammasome NLRs in immunity, inflammation, and associated diseases.

Davis BKWen HTing JP.

Annu Rev Immunol. 2011 Apr 23;29:707-35.


Session 10: Immunology of SARs-CoV-2

Professor Tom Evans

Synopsis

In the lecture, we will discuss how the SARs-Cov2 virus infects the host and interacts with the immune system. How a natural immune response is generated towards the virus and how this can be supplemented by vaccines. Finally, how various co-morbidities, disease states (i.e., immunocompromised) and treatments can alter the efficacy of vaccines to SARs-Cov-2.

We will also discuss how clinical studies can be designed to evaluate the efficacy of vaccine to SARs-CoV-2 in different immunological states

Intended Learning Outcomes

To understand how SARs-Cov2 interacts with host cells to establish infection.

To understand how the immune system generates an anti-viral response to SARs-CoV-2.

To understand the current vaccine approaches and the extent of these protective responses in health and immunocompromised individuals.

Reading

Siddigi &Mehra https://www.jhltonline.org/article/S1053-2498(20)31473-X/fulltext

Vardhana &Wolchok  https://rupress.org/jem/article/217/6/e20200678/151725/The-many-faces-of-the-anti-COVID-immune-responseA

Jackson et.al., https://www.nature.com/articles/s41580-021-00418-x

Hippiseley-Cox et.al., https://www.bmj.com/content/374/bmj.n2244

Kearns et.al., https://doi.org/10.2139/ssrn.3910058

 

Session 11: Synoptic Summary of Option Content

Professor Tom Evans

This session will provide a look back at the content of the course and will emphasise themes that occur in different lectures. This will provide an essential framework for synthesising the information provided as at this level we expect students not just to be able to recall factual accounts of specific host/pathogen interaction but also to appreciate more global themes and problems in this field. There will also be an opportunity to bring up any points that have puzzled you and for your knowledge to be tested.