Innate Immunity

http://www.stanford.edu/class/mi104/

Innate Immunity

Microbiology and Immunology 104/204 (Immunology 204)

Spring Quarter 2005

Lectures:  David Schneider

Discussion: 

Lectures Mondays, discussions Wednesdays (mostly) 11:00 am-12:00 noon.  Class starts April 4.

D300 Fairchild 

Syllabus

Reading List

Summary

Immunologists divide your immune system into 2 parts:  the adaptive immune response and the innate.  The adaptive immune response is the subject of most immunology courses and includes B cell and T cell biology and those responses that are generated in immune cells by recombination events; everything else is your innate immune system.  When you are wounded, the immediate response that follows is your innate response and its job is to fight infections and excite the adaptive immune response. 

The innate immune system is ancient and recognizable pieces are found conserved in humans, insects and plants.  We will cover all of these systems in class.  We will cover core topics such as Toll signaling and complement fixation but will range to topics concerning the role our body’s flora plays in controlling infection and immune reactions that take place in communities, not just individuals.

The goal of the class is for you to be able to recognize innate immune responses in a large variety of organisms and to learn to design experiments to dissect these responses.  It is important to cover many organisms because this gives a deeper understanding of what comprises innate immunity. 

Grading

The goal of this class is to introduce you to the many aspects innate immune system both in humans and other organisms.  Three problem sets will be assigned and these will account for 50% of the grade.  These will be problem-solving exercises to guide you through designing experiments in innate immunity.  The problem set questions will mostly involve papers we cover in discussion section, making the discussion sections even more important.  The problem sets can be worked on in groups.  The final assignment is a research proposal (5 page, double space 12 point font) due June 9 at 5 pm.  The final assignment is the responsibility of the student alone. 

DateActivity/Topic
4/4Lecture 1: Introduction, Human mutations leading to disease resistance
4/9Lecture 2: Strangers, Dangers and Guards. Drosophila Toll signaling
4/11Lecture 3: Tlr signaling in vertebrates
4/16Discussion
4/18Lecture 4: Plant Immunity
4/23Discussion
4/25Lecture 5: Microflora and immunity
4/30Discussion
5/2Lecture 6: Barrier defenses, antimicrobial peptides and native flora
5/7Discussion
5/9Lecture 7: Adaptation in the innate immune system
5/14Discussion
5/16Lecture 8: Community Level Immunity
5/21Discussion
5/23Lecture 9: Macrophages and dendritic cells
5/28No class: Memorial Day
5/30Lecture 10: Neuroimmunity
6/4Discussion
6/6Lecture 11: Inflammation

Point form lecture notes, a bibliography and a PDF of each class presentation is available for downloading. The PDFs contain full copies of all the photos and movies used in class and thus can run to 30 Mb. All lectures were prepared using Adobe Indesign and were presented as PDFs using an Acrobat viewer. Viewing will be best with Acrobat 7.

Lecture 1: Introduction and Evolution of infection resistance:

In this lecture we review the topics we will discuss over the quarter. The second half of the lecture will concern loss-of-function mutations that result in reduced sensitivity to infection. These are inborn mechanism of fighting infectious diseases and can be considered part of innate immune defense.

Lecture 1 Notes, Lecture 1 Slides, Lecture 1 Bibliography

Lecture 2: Dangers, Strangers and Guards, Introduction to Toll

At least three recent theories describe how the innate immune system is activated. The first model suggests the innate immune system has evolved to see pathogen associated patterns and recognizes these with germline encoded receptors. A second model suggests the innate immune system has developed to recognize pathology. In the plant community a model has been put forward suggesting the innate immune system monitors cellular physiologies that are targeted by pathogens. We will compare and contrast these models and discuss what experiments you do based upon which model you hold to be true.

We will also discuss the roll the Toll gene plays in Drosophila development and immunity. The Toll signaling pathway was first studied in flies to dissect its role in dorsal-ventral patterning. Toll was later found to play a role in the activation of the innate immune system. In flies, Toll clearly is not a pattern recognition receptor. We will discuss how Toll and related pathways affect fly immunity.

Lecture 2 NotesLecture 2 SlidesLecture 2 Bibliography

Lecture 3: Vertebrate Toll and pattern recognition receptors

Several independent routes led to the discovery that Toll like receptors (Tlrs) played a role in innate immune recognition in vertebrates. The 11 Toll molecules are required to signal responses to a large array of agonists. Originally many Tlrs were described as pattern recognition receptors but this description has not held up for all them. We will discuss the roles Tlrs play in innate immunity in vertebrates and discuss some other molecules that might direct pattern recognition receptors.

Lecture 3 notesLecture 3 SlidesLecture Bibliography

Lecture 4: Plant immune responses

Plants have a variety of methods of fighting infection including: PAMP recognition that initiates a basal response; the HR or hypersensitive response, which induces apoptosis at the site of infection; the SAR or systemic required immunity that protects unifected leaves once an infection has been initiated elsewhere on the plant; and a jasmonic acid stimulated response that is induced in part by leaves damaged by insects. The JA response can make leaves inedible to insects. Plant pathogenesis is a well developed field in which the interactions between bacterial virulence proteins and the host cell metabolism are becoming well understood. This field has much to teach us about the way pathogens intereact with their hosts.

Lecture 4 notesLecture 4 SlidesLecture 4 Bibliography

Lecture 5: Barrier Epithelia and Antimicrobial Peptides

Our external surfaces are protected by innate immune responses. Our lungs keep a mucus escalator in continous motion to sweep particles out of the bronchi. Small particles that travel to the alveoli can be removed by macrophages or disarmed by IgA and complement. Of course pathogens have developed a number of methods of overcoming these immune responses and this is why we still suffer lung infections. An important part of the barrier epithelial response and innate immune responses in general is the antimicrobial peptide. These are most often described as pore producing molecules that kill bacteria but these peptides have many other modes of action. For example Salmonella uses AMPs as a signal to turn on its own virulence genes and Helicobacter pylori makes its own antimicrobial peptide. In humans, these peptides can act as mitosis inducing signals as well as chemoattractants. Clinical use of these peptides will be complicated because these molecules serve so many different functions in the body.

Lecture 5 NotesLecture 5 SlidesLecture 5 Bibliography

Lecture 6: Chocolate, Vaginas and Maggoty wounds: the role of native microbiota in innate immunity

We contain up to 10 times more microbes than we do human cells and these have a significant impact on our immunity. We are an ecosystem and pathogens are invaders in this ecosystem. Our native microbiota can help us fight infections. The chocolate producing plant Theobroma cacao uses endophytic fungi as protection against other fungal invaders. Vaginal pH inhumans is maintained by the native flora and helps protect against diseases such as HIV/AIDS. Insect infected wounds can be co-infected with bacteria that act as kairomones to attract more insects and our native flora controls our body smells, which in turn alter our attractiveness to mosquitoes. Finally we will look at how signaling in the gut between bacteria and the gut epithelium is required for normal development and function.

Lecture 6 NotesLecture 6 Slides,

Lecture 7: Adaptive-Innate Immunity

We typically divide immune responses into adaptive and innate. The adaptive response refers to the immune response found in vertebrates that involves RAG dependent recombination and B and T cells. "Adaptive" however is a perfectly fine adjective that can be applied to innate immune responses as well but these adapting innate immune responses are not often discussed because they fall outside of the normal definition of immune responses.

Lecture 7 Slides

Neural immunity

When you get sick, you feel that illness and this obviously involves your nervous system. Our nervous systems both respond to the innate immune system and regulate it. We will look at fever in invertebrates and vertebrates as well as the role the vagal nerve plays in responding to and modifying inflammatory responses.

Lecture 8: Adaptive-Innate Immunity

We typically divide immune responses into adaptive and innate. The adaptive response refers to the immune response found in vertebrates that involves RAG dependent recombination and B and T cells. "Adaptive" however is a perfectly fine adjective that can be applied to innate immune responses as well but these adapting innate immune responses are not often discussed because they fall outside of the normal definition of immune responses.

Lecture 7 Notes, Lecture 7 Slides, Lecture 7 Bibliography

Lecture 8: Phagocytes

Lecture 8 Notes, Lecture 8 Slides, Lecture 8 Bibliography

Lecture 9: NK Cells

Lecture 9 Notes, Lecture 9 Slides, Lecture 9 Bibliography

Lecture 10 Notes, Lecture 10 Slides, Lecture 10 Bibliography

Lecture 11: Inflammation and Shock

A local innate immune response can trigger inflammation during which cells and fluids flow into the affected tissues. Though it would appear this is something that could happen only in an organism with a closed circulatory system, similar types of events occur during infections in insects. We will also look at systemic inflammatory responeses that lead to shock and discuss methods of interfering with the progress of shock.

Lecture 11 Notes, Lecture 11 Slides, Lecture 11 Bibliography

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