Lec 1: Self vs Non-Self

Question 1

Primary Immunodeficiency

Answer 1

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

Question 2

What are the FIve stages of Immunity

Answer 2

1 recognition
2 response
3 destruction
4 repair
5 reset

Question 3

Adjuvants

Answer 3

foreign chemicals that drive infection

Question 4

Dysbiosis

Answer 4

Microbial imbalance impairs and disrupts immune homeostasis

changes composition of the microbiota

• can alter metabolic activity
• disrupt communities of microbes

Question 5

Levels of Tolerance

Answer 5

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

Question 6

The problem with cross reactive epitopes

Answer 6

antibodies produced by the body may react with your own cells and cause tissue damage

Question 7

Which homeostatic systems is the immune system integrated with?

Answer 7

Endocrine
Nervous
Metabolic

Question 8

which foreign substances affect us

Answer 8

toxins
chemicals
allergens
self-antigens
cancercells

Question 9

New terminology for the Human “Self”

Answer 9

humans as “supraorganisms”

Complicated self: human body plus microbiome

Host-microb interactions

Question 10

How does the immune system determine whether a microbe is harmful or not?

Answer 10

PAMPS and DAMPS

also, how disimilar their antigens are from antigens normally encounters in the hosts microbiome

Question 11

Immunogen

Answer 11

molecule that stimulates an immune response (peanut)

Question 12

Antigen

Answer 12

molecule that binds antibodies, BcRs, TcRs (peanut protein)

Question 13

Epitope

Answer 13

The part of the antigen (generally the peptide) that is recognized by the immune system

antigenic determinant

(recognition of peanut allergen)

Question 14

Continuity

Answer 14

a better description of immune phenomena

response appropriate for level of threat
distinguish between infection and colonization
minimal collateral tissue damage

Question 15

can you define a human as a supra organism?

Answer 15

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

Question 16

can you discuss how to apply (or not) the concept of self in immunology?

Answer 16

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

Question 17

could you compare and contrast the following terms?

• immunogen
• antigen
• epitope
• PAMP
• allergen

Answer 17

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

Question 18

Can you explain dysbiois as it pertains to ageing?

Answer 18

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.

Question 19

negative selection of lymphocytes

Answer 19

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

Question 20

Which is the currently accepted model of immunity

Answer 20

The Continuity Hypothesis

Question 21

The Continuity Hypothesis

Answer 21

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

Question 22

Why is the Self// non-self model no longer adequate?

Answer 22

“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

Question 23

Treg

Answer 23

stop or slow down immune rxns

these are self cells that react to other self cells

Question 24

What two observations does the continuity hypothesis rely on

Answer 24

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

Question 25

When does an immune response occur

Answer 25

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

Question 26

Evolution of tolerance

Answer 26

evolution of tolerance may be induced by a lack of inflammatory response and or a lack of tissue damage

Question 27

Contrary to the self hypothesis, what doe the continuity hypothesis allow?

Answer 27

The continuity hypothesis allows the self to induce and immune response

(break of continuity depending)

It also allows regulation