Indiscriminatory Immune System 1

Question 1

Immunological Tolerance

Answer 1

Specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen implying antigen specificity
Significance - all people are tolerant of self-antigens (self-tolerance) - breakdown of self-tolerance causes autoimmunity
therapeutic potential: inducing tolerance can be exploited to prevent graft rejection, treat autoimmune/allergic diseases, and prevent immune responses in gene therapy and maybe stem cell transplantation.

Question 2

Immunoregulation

Answer 2

balance between activation and supression without damaging the host. Over-activation (immunitiy) causes auto immune disease and supression (tolerance) causes immuno supression
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Question 3

Why induce tolerance?

Answer 3

to prevent graft rejection
to treat auto immune and allergic diseases
to prevent immune responses in certain types of gene therapy

Question 4

Immunogenic and non-immunogenic resposnes ot antigenic stimuli

Answer 4

both types of responses happen due to tissue inflammation. tissue inflammation is caused by antigenic stimulus. some are benefitical responses and some are apthologic:
Immunogenic responses: Elimination of pathogenic microorganisms, autoimmunity, allergy and/or asthma, fetal rejection, transplant rejection, pathogen clearance, tumour clearance.
Non-immunogenic response: persistence of commensal microoranisms
self antigens
innocuous antigens
normal pregnancy
transplant survival
pathogen persistance
cancer
immunotherapeutic intervention via therapies can induce a response.

Question 5

T-cell activation by Anitgen Presenting cells

Answer 5

Signal 1: Recognition of peptide/MHC complex
Signal 2: Co-stimulation, provided by ligation of CD28 on T cells by B7 molecules on APCs
Signal 3: Production of polarising cytokines by APCs
Co-stimulation through CD28 contributes to IL-2 production, promoting proliferation and survival.
T cells differentiate into effector cells (5-7 days)

Question 6

Experimental demonstration of tolerance

Answer 6

1. Mouse fetuses from CBA strain injected in utero with live adult tissue cells from genetically disparate mouse strain (strain A).
2. CBA mice challenged with skin grafts from adult A-strain donor 8 weeks after birth
3. majority of recipients dont mount a rejection response - become tolerant
4. same mice rejected skin grafts from 3rd party donot (strain AU)

Showed that they didnt reject the strian as they had already been exposed to antigen in utero - Showed tolerance is specific - tolerant only to antigens related to in utero and childhood development.

Question 7

How to induce experimental tolerance

Answer 7

Administration of Ag to very immature animals
Administration of very large or very small
Administraon of treated Ag that cant be processed properly

Question 8

Central and peripheral tolerance

Answer 8

Central tolerance: Happens before immune system starts to react
Peripheral tolerance: Happens after the immune system reacts - continuous development of the immmune system?

Question 9

Central and peripheral tolerance - Role of Lymphocytes

Answer 9

Lymphocytes prevent self-cells/antigens from causing an immune reaction. Their principle fae is to recognise self-antigens and kill them (deletion/apoptosis) but:
Some B cells change their specificity (receptor editing)
some T cells differentiate into regulatory (suppressor) T lymphocytes.

Question 10

T cell Tolerance - Immature T cells -

Answer 10

T cells express no TCR before arrival to Thymus
express y/d (gamma delta) or a/B (alpha beta) - peptides which form the TCR receptors
Immature T cells posses only 10% of receptors seen in mature T cells - cannot recognise anything
Immature T cells form the bone marrow may express CD4 and CD8 - dont know their type yet.
This happens in the Thymus