Lecture 1: Introduction Flashcards
What is the most significant disease to be eradicated from vaccination immunological development?
Smallpox 1980
What are some examples of successful immunisation campaigns?
Diptheria
Polio
Measles
Describe the types of immunological memory;
Genetic
or
Epigenetic
Describe immunological memory in terms of genetic causation;
Primary response can result in;
Gene rearrangement
Clonal expansion
Memory population
Rechallenge leads to antigen dependant memory population protection
Describe immunological memory in terms of epigenetic causation;
Primary response can result in;
Epigenetic modification of genes encoding immunological and inflammatory products
Rechallenge leads to antigen dependent protection
What are the three phases of an immune response?
Pre-existing innate immunity
Induced innate immunity
Induced adaptive immunity
What is innate immunity?
Defences that exist to protect the body to prevent infection i.e skin, mucous
or
defences that are activated following an event i.e trauma that may have led to infection. I.e innate immune cells are directed to a skin lesion regardless if infection is present or not, to prevent infection.
Describe the evolution of innate immunity;
- Fundamental defensive weapon for multicellular organisms.
- Must be versatile against a spectrum of pathogens
- Molecular mechanisms are highly conserved across species.
Describe the nature of the immune response;
If homeostasis is disturbed i.e trauma, cancer, infection then the immune system responds to help restore balance.
Describe some pathogens;
Range of shapes and sizes; worms protozoa fungi bacteria viruses
What is the function of the immune system?
To protect us from pathogens, it is ubiquitous.
Why did the immune system evolve?
Pathogens are everywhere in the environment and can reproduce in humans therefore if left unchecked then they can cause permanent damage or be lethal
What is the immune system an example of in biology?
An exploratory system mediated by chemical variations (signalling)
How does the environment influence pathogen development?
Environmental pressures lead to the selection of traits in pathogen development that favour reproduction in tissues, therefore the immune system must continually evolve to fight the evolving pathogens
What are the types of mammalian immune responses?
Innate and adaptive.
These systems are extensively interconnected and form a continuum that is known as the immune response
Describe the interplay of adaptive and innate immunity?
innate and adaptive immunity can activate and potentiate one another.
Innate immunity holds pathogens in check until adaptive is ready to function
How does innate immunity achieve its response?
non-specifically and broadly specific response
How does adaptive immunity function?
Through humoral (antibodies) and cell mediated uniquely specific responses
What is an example of innate immunity?
Physical barriers
What are the examples of external physical barriers?
Lysozyme in tears mucous and cilia in bronchi acids and rapid pH change in gut Commensals in gut (microflora) Skin fatty acids and commensals
What will largely determine which immune response will be effective?
The site of infection and type of pathogen
i.e intracellular vs extracellular invasive pathogens
Give some examples of pathogens that invade differently;
- Influenza must invade cells to reproduce
- Mycobacteria i.e TB can divide extracellularly or in macrophages
What is PAMPS?
Pathogen Associated Molecular Recognition Patterns
Whats the difference between PAMPS and Antigens
The innate immune system will recognise PAMPS and they are non-specific and found on a number of cells
Antigens are recognised by the adaptive immune system and are pathogen specific
Whats are DAMPS?
Damage Associate Molecular Patterns
Whats the difference between DAMPS and PAMPS?
Cell damage of death releases DAMPS and can cause inflammation and is often recogised by the same receptors for PAMPS
Pathogen or damage can lead to both DAMPS and PAMPS
What are the features of the pre-existing non-specific immune response;
- Skin
- Mucosal barrier
- pH, silivia, proteases etc
What are the features of the induced innate immunity broad recognition system;
- Compliment activation
- Phagocytosis
- Target Cell Lysis
- Inflammation
What are the features of the adaptive specific immune response?
- B Cells (antibodies)
- Th cells (cytokines)
- Tc Cells (cytosis)
What is a specific immune response?
A specific immune response such as the production of antibodies is known as an adaptive immune response because it results in adaptation of the person to the pathogen
Results in lifelong protective immunity
How is adaptive immunity distinguished from innate immunity?
Innate immunity is where pathogens are recognised, engulfed, and digested by phagocytic cells (macrophages). These are immediately available as part of the early phase of the host response to pathogens without prior exposure
What is part of the innate response?
Pre-existing barriers and induced mechanisms
How do innate mechanisms identify cells?
pattern recognition molecules (PRM) identify DAMPS or PAMPS
Number of responding cells is always large so no proliferation is required (response is short lived so repeated exposure has similar responses)
In an adaptive response, what mechanisms are activated?
All mechanisms are induced
Describe adaptive immune cell receptors and ligands
Infinite number of antigen receptor combinations, each is specific.
Response is triggered by antigen receptor binding.
Describe adaptive immune cells response;
Small number of cells respond and thus must proliferate (these survive), repeated exposure has much larger responses
Describe the immune system role in health;
- Clearance of dead cells and damaged cells
- Destruction of infectious organisms
- Destruction of cancer cells
Describe the role of the immune system in disease;p
- Immunodeficiency
- Transplant rejection
- Autoimmune disease
- Hypersensitivity and allergy
- Chronic Inflammation
Edward Jenner
- Smallpox immunization by Edward Jenner 1796
- First controlled demonstration of the immune response
- Took pus from lesions from milk maid who had cow pox. Inculated James Phipps. He did not catch small pox when exposed.
Louis Pasteur
- Coined the term of vaccination
Elie Metchnikoff
- Characterised the process of phagocytosis by leukocytes
- Defined 2 types of phagocytes, the macrophage and the microphage (neutrophils)
Jules Hoffman
- Discovered Drosophila with a mutation in the toll gene died because they could not mount an effective defence
- Toll was involved in sensing pathogenic microorganisms (a PRR)
Bruce Beutler
- Discovered that mice resistant to LPS had a mutation in a gene that was quite similar to the fly toll gene
- This TLR was the elusive LPS receptor
Ralph Steinman
-Demonstrated that dendritic cells have a unique capacity to activate T cells
- The prototypic antigen presenting cell (couples innate and adaptive immunity)
