Lecture 6: Self and Non-self Discrimination Flashcards by Calum Macindoe

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)

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What can inappropriate immune recognition lead to?

Inappropriate immune recognition and response can be damaging (bad)

Immunopathology = when things go wrong

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What is hypersensitivity?

Heightened or persistent response to exogenous antigen or innocuous antigen

eg allergy

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What are some examples of immunopathology?

Hypersensitivity
Autoimmune disease
Transplant rejection
Immunodeficiency

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Write some notes on autoimmune disease:

◦Breakdown in mechanisms that control self tolerance
◦Hypersensitivity to autoimmune antigens

Failure of self tolerance

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Write some notes on transplant rejection;

Antigens on the donor graft provoke a severe host reaction

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Write some notes on immunodeficiency;

◦Inadequate functioning immune system
◦persistent infection

I.e HIV results in common injections becoming lethal

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Describe the Response to Ag and deficient response to an infectious agent;

Antigen: Infectious Agent

Response to Ag: Protective immunity

Deficient Response: RECURRENT INFECTION

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Describe the Response to Ag and deficient response to an innocuous substance;

Antigen: Innocuous substance

Response to Ag: ALLERGY / HYPERSENSITIVITY

‘Deficient’ Response: No symptoms

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Describe the Response to Ag and deficient response to an organ graft;

Antigen: Organ Graft

Response to Ag: REJECTION

Deficient Response: Acceptance

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Describe the Response to Ag and deficient response to an self organ;

Antigen: Self Organ

Response to Ag: AUTOIMMUNITY

Deficient Response: Self Tolerance

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Describe the Response to Ag and deficient response to an tumour;

Antigen: Tumour

Response to Ag: Tumour Rejection

Deficient Response: CANCER

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Whats three examples of autoimmunity?

Chrons
Pernicious Anemia
Systemic Lupus Erythrmoamtus

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Write some notes on chrons;

Autoreactive T-cells cause intestinal inflammation and scarring

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Write some notes of pernicious anemia;

◦Antibodies damage to parietal cellsin stomach

◦Compromised vitamin B12 absorptionresulting in anaemia

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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