Lecture 6: Self and Non-self Discrimination Flashcards
What is the major role of the immune system?
The immune system is designed to recognise and respond to pathogens
In this way the immune system is protective (good)
What can inappropriate immune recognition lead to?
Inappropriate immune recognition and response can be damaging (bad)
Immunopathology = when things go wrong
What is hypersensitivity?
Heightened or persistent response to exogenous antigen or innocuous antigen
eg allergy
What are some examples of immunopathology?
Hypersensitivity
Autoimmune disease
Transplant rejection
Immunodeficiency
Write some notes on autoimmune disease:
◦Breakdown in mechanisms that control self tolerance
◦Hypersensitivity to autoimmune antigens
Failure of self tolerance
Write some notes on transplant rejection;
Antigens on the donor graft provoke a severe host reaction
Write some notes on immunodeficiency;
◦Inadequate functioning immune system
◦persistent infection
I.e HIV results in common injections becoming lethal
Describe the Response to Ag and deficient response to an infectious agent;
Antigen: Infectious Agent
Response to Ag: Protective immunity
Deficient Response: RECURRENT INFECTION
Describe the Response to Ag and deficient response to an innocuous substance;
Antigen: Innocuous substance
Response to Ag: ALLERGY / HYPERSENSITIVITY
‘Deficient’ Response: No symptoms
Describe the Response to Ag and deficient response to an organ graft;
Antigen: Organ Graft
Response to Ag: REJECTION
Deficient Response: Acceptance
Describe the Response to Ag and deficient response to an self organ;
Antigen: Self Organ
Response to Ag: AUTOIMMUNITY
Deficient Response: Self Tolerance
Describe the Response to Ag and deficient response to an tumour;
Antigen: Tumour
Response to Ag: Tumour Rejection
Deficient Response: CANCER
Whats three examples of autoimmunity?
Chrons
Pernicious Anemia
Systemic Lupus Erythrmoamtus
Write some notes on chrons;
Autoreactive T-cells cause intestinal inflammation and scarring
Write some notes of pernicious anemia;
◦Antibodies damage to parietal cellsin stomach
◦Compromised vitamin B12 absorptionresulting in anaemia
Write some notes on SLE;
◦Antibodies against DNA and nuclear antigens
◦Immune complexes lodge in kidneys, joints, skin
◦Complement-mediated tissue damage
How does the immune system respond to antigens?
Immune system responds to antigens through activation of lymphocytes that bear specific receptors (sIg or TCR)
What influences the antigen response?
Context
Context of antigen recognition facilitates differential immune responses and functions
Describe that context factors that influence the antigen response;
The nature (protein, lipid etc) and concentration of the antigen
Site of entry/venue
How antigen is processed, presented to antigen-specific lymphocytes
Receptors class
The individual’s antigenic history
Associated soluble and cell-surface signalling events (Functional consequence)
What are the possible sites of entry for antigens?
◦mucosa
◦peripheral tissues
◦circulation
◦secondary lymphoid organs
What can result from antigen recognition?
Proliferation and differentiation
Effector functions
◦antibody production
◦cytotoxicity, inflammation
Recruitment of non-specific effectors(e.g. phagocytes)
Redistribution
Immunological memory
What is immunological tolerance?
Immunologic tolerance is defined as ‘unresponsiveness to an antigen that is induced by a previous exposure to that antigen
Why is immune system education necessary, where does it occur and what happens when it fails?
The immune system has to be “educated” not to recogniseself -in this way tolerance is “learned” i.e T and B cells
Immune system ”education” takes places in lymphoid tissue (primary and secondary tissue)
A failure of self tolerance results in autoimmunity
What does central tolerance achieve?
Central tolerance in the primary lymphoid organs eliminates clones that recognise self
What is peripheral tolerance?
It is a backup system that eliminates any cells that recognise self that have evaded central tolerance elimination
What can happen in central tolerance to cells hat recognise self?
Strong self recognition
1) Apoptosis - deletion
2) Change in receptors ( B cel editing (ONLY))
3) Development of regulatory T cells (CD4 + T cells only)
Self recognition
1) Anergy
2) Apoptosis
3) Deletion
What happens in peripheral tolerance?
Some self-reactive lymphocytes mature and enter peripheral tissues. There they may be inactivated or deleted by encounter with self antigens in these tissues, or are suppressed by the regulatory T cells (peripheral tolerance).
What is an antigen?
Antigen-molecule that binds TCR or an antibody
What do antibodies and TCR molecules recognise?
- Antibodies and TCR can only recognisestructures of a certain size and these are called epitopes
- An antigen is a ‘collection of epitopes’ on a single structure
- B cell and T cell epitopes often differ
Describe small protein antigen immunogenicity;
Decreased;
Small (<2500 Da)
Simple
Similar to self
Poor MHC binding
Describe large protein antigen immunogenicity;
Increased:
Large
Complex
Many differences
MHC binding
What are the types of epitopes?
Linear epitope
Conformational (assembled) Epitope
Write some notes on T cell epitopes;
T cell epitopes are linear and therefore the antigen must be first processed and presented before recognition can occur.
The peptide fragment then binds a MHC molecule before it can bind a TCR (t cell receptor)
Whats the ‘general scheme’ for dealing with foreign material?
Ingestion by phagocytic cells(egDCs)
Transport to secondary lymphoid organs
Processing and epitope presentation to lymphocytes
Specific lymphocyte activation
Immune response generation
What do dendritic cells do?
Dendritic cells recognisepathogens via invariant receptors, ingest and display antigens to lymphocytes
What is the purpose of DC?
The bridge the gap between innate and active immunity.
Act as APC
What is APC functions?
Antigen collection and transport Antigen concentration Antigen processing Antigen presentation Co-stimulation ◦Surface molecules ◦Pro-inflammatory cytokines
Tolerance Induction
