Lec 1: Self vs Non-Self Flashcards
Primary Immunodeficiency
Genetic, a good example of this would be bubble boy disease in which David Vetter was incapable of producing B or T cells. He dies from an epstien bar diease infection after a bone marrow transplant
What are the FIve stages of Immunity
1 recognition 2 response 3 destruction 4 repair 5 reset
Adjuvants
foreign chemicals that drive infection
Dysbiosis
Microbial imbalance impairs and disrupts immune homeostasis
changes composition of the microbiota
- can alter metabolic activity
- disrupt communities of microbes
Levels of Tolerance
Pathogenic microbes harbor epitopes that are stong immunogens
microbe epitopes that are most similar to self-antigens show lower immunogenicity
poor recognition of epitopes associated with the commensal microbiome
The problem with cross reactive epitopes
antibodies produced by the body may react with your own cells and cause tissue damage
Which homeostatic systems is the immune system integrated with?
Endocrine
Nervous
Metabolic
which foreign substances affect us
toxins chemicals allergens self-antigens cancercells
New terminology for the Human “Self”
humans as “supraorganisms”
Complicated self: human body plus microbiome
Host-microb interactions
How does the immune system determine whether a microbe is harmful or not?
PAMPS and DAMPS
also, how disimilar their antigens are from antigens normally encounters in the hosts microbiome
Immunogen
molecule that stimulates an immune response (peanut)
Antigen
molecule that binds antibodies, BcRs, TcRs (peanut protein)
Epitope
The part of the antigen (generally the peptide) that is recognized by the immune system
antigenic determinant
(recognition of peanut allergen)
Continuity
a better description of immune phenomena
response appropriate for level of threat
distinguish between infection and colonization
minimal collateral tissue damage
can you define a human as a supra organism?
Yes!
Humans are walking biomes with more bacterial cells that eukaryotic cells.
Moreover, this symbiosis is a two way street in which our immune system drives the ratios of our microbiota and our microbiota drives our immune system
can you discuss how to apply (or not) the concept of self in immunology?
in classical immunology the term “self” was used to describe anything that wasn’t our own cells.
This can be very difficult to use nowadays with increasing knowledge our our microbiota and out immune system.
The term Self would nowadays be an umbrella term for any cells which express epitopes that are common and similar to our own cells, are not harmful to our homeostasis, and our immune survalence system encounters regularly
could you compare and contrast the following terms?
- immunogen
- antigen
- epitope
- PAMP
- allergen
Immunogen = a molecule that drives a immune reaction
Antigen = a molceule that binds an antibodies ie// Bcr, and TcR
Epitope = The part of the antigen (generally the peptide) that is recognized by the immune system
PAMP = an immunogen which can also can be processed into an antigen. Common in pathogenic microbes
Allergen = Antigen that drives an abnormally strong immune response
Can you explain dysbiois as it pertains to ageing?
As we age we undergo immunosenescence, which is the gradual reduction our immune cells over our lifetime.
With less regulation of our microbiota as we get older due to the smaller “police force” the ratios of microbes, as well as jsut a change of microbial flora in general will change. This can in turn lead to dysbiosis.
negative selection of lymphocytes
Lymphocytes bearing receptors specific for an antigen are deleted if the genes codes for that antigen are present with in the gemone of that organism
Which is the currently accepted model of immunity
The Continuity Hypothesis
The Continuity Hypothesis
The immune self in defined in the process of selection of immune competent cells. Im comparison to the non-self model, cells foreign to the host can be tolerated when introduced in early development
immune self is based on the genomic self
similar code to the molecular self will not elicit an immune response
Why is the Self// non-self model no longer adequate?
“Self” compounds can elicit an immune response
Non-self compounds do no elicit an immune response
Tumour and apoptotic cells belong to non-self
commensals and the fetus belong to the self
For selection of lymphocytes, lymphocytes only survive if and only they react weakly to the “self” components
- does not survive if they do not react at all
- selection is cts
- immune rxn to self is nessecery
- maintenece
- immune cell activation
Treg
stop or slow down immune rxns
these are self cells that react to other self cells
What two observations does the continuity hypothesis rely on
immunne system is aquired and not inate. that is, everything in lymphatic selection will not trigger an immune reaction later. furthermore, everystrong discontinuity in the interactions between immune receptors and their targets triggers an immune response
autoreactivity is constant and necessary
When does an immune response occur
entry of an epitope that breaks continuity of immune survalance
entry is significant in size
many entry ways are activated
entry triggers stress and pro-inflamatory signals
Evolution of tolerance
evolution of tolerance may be induced by a lack of inflammatory response and or a lack of tissue damage
Contrary to the self hypothesis, what doe the continuity hypothesis allow?
The continuity hypothesis allows the self to induce and immune response
(break of continuity depending)
It also allows regulation
