Immune Tolerance Flashcards
What is the definition of immune regulation
Control of the immune response to prevent inappropriate reactions
Why is immune regulation needed
Avoid excessive lymphocyte activation and tissue damage during normal protective responses against infections
Prevent inappropriate reactions against self antigens
What is the definition of autoimmunity
Immune response against self antigen leading to a pathologic disease
What are some examples of auto-immune disease
Rheumatoid Arthritis, Irritable Bowl Disease, Multiple Scelorosis, psoriasis
What are the features of autoimmune disease
Imbalance between immune activation and control
Failure of control mechaniscs
Underlying causative factos: susceptibility genes + influences
More prevalent in women
Immune mechanism of autoimmunity
Result from immune response against self antigens or microbial antigens
Immune response is inappropriately directed or controlled
May be caused by T cells and antibodies
Many immunological disease are chronic and self-perpetuating
Immune mechanism of allergy
Harmful immune response to non-infectious antigens that cause tissue damage
Mediated by antibody IgE and mast cells
Or T cells - delayed type hypersensitivity
What are acute condition of immune regulation
Hypercytokinemia and sepsis
Too much immune repsonse
Positive feedback loop
Triggered by pathogens entering wrong compartment (sepsis) or failure to regulate response to correct level
What is a self-limiting response of the immune system
All immune responses are self limiting, manifested by decline of immune response
Immuen response eliminates antigen that initiated response
First signal for lymphocyte activation is eliminated
What are the 3 signal model of licensing a response
Antigen Recognition
Co-stimulation
Cytokine release
Why does the response against pathogens decline as the infection is eliminated
Apoptosis of lymphocytes that lose their survival signals (antigens)
Memory cells are the survivors
What is the basis of cancer immunotherapy
Active control mechanisms function to limit responses to persistent antigens (self antigens)
Three possibel outcomes of an infection
Resolution - no tissue damage, returns to normal, damage due to phagocytosis
Repair - healing with scar tissue and regenration. Fibroblast and collagen synthesis
Chronic inflammation - active inflammation and attempts to repair damage
What is immune tolerance
Specific unresponsiveness to an antigen that is induced by the exposure of lymphocytes to that antigen
What is the significance of immunological tolerance
All individuals are tolerant of their own antigens (self-tolerance); breakdown of self-tolerance results in autoimmunity
What are the two times tolerance can happen
Before T or B cells ever enter the circulation
Once in the circulation
What is Central tolerance
Destroy self-reactive T or B cells before they enter the circulation
Lymphocytes that recognise self antigens are eliminated or made harmless as part of maturation process
How is B cell central tolerance carried out
B cells mature in bone marrow
If immature B cell encounter antigen which can crosslink IgM, apoptosis is triggered
How is T cell central tolerance controlled
Doesnt bind to any self-MHC - apoptosis due to death by neglet
Is T cell dangerous - binds to MHC too strongly, apoptosis triggered, negative selection
Is T cell useful - binds to self MHC weakly, signal to survive - postivie selection
What is the autoimmune regulator
Transcription factor that allows the expression of antigen in the peripheral to be expressed in the thymus
Promotes self tolerance by allowign the thymic expression of genes from other tissue
Mutations have multi-organ autoimmunity
What are the ways in which the shape of the B cell can change once activated
Affinity maturation - self reactive B cell can made here
Where change shape of antibody to better bind it
How do you break tolerance with B cells
Somatic hyper mutations
Could become less tolerogenic and more reactogenic
Anti-streptococcus pyogenes - antigen that look like heart antigen
Peripheral tolerance - anergy
T cells need co-stimulatory signals
Most cells lack co-stimulatory proteins and MHC
Becomes anergic, lack energy and higher activation energy
Less likely to be stimulated in the future
Peripheral tolerance - ignorance
Antigen may be present in too low concentration to reach treshold for T cell triggering
Normally in eye and brain - T cell don’t really see antigen
Comparmentalisaiton of cells and antigens
Peripheral tolerance - antigen induced cell death
Activation of T cell receptor results in apoptosis
Caused by interaction of other moelcules such as Fas ligand. death ligand
What do Tregs do
Inhibit other T cells and other cells
Role of T regs
Block T cell acitvation
Inhibit effector functions of T cells
What does transcription factor FoxP3 syndrome
Have go Immune dysregulation, Polyendocrinopathy, Enterpathy X-linked syndrome (IPEX)
What is the main way Treg regulate immune tolerance
IL-10 cytokine
Anti-inflammatory cytokine
Multifucntional
Acts on a range of cells
Blocks proinflammatory cytokine synthesis including TNF, IL-6, IL-8, IFNy
Down regulates Macrophage functions
Why does T regs only exist in mammals
Mother is exposed to foreign MHC
Half from mum half from dad
What is the natural regulatory T cells
Development in thymus requires
Recognise self antigen, begin to shut down harmful reactions against self
What are inducible regulatory T cells
Develop in periphery - from mature CD4 T cells
Generate during immune response to limit collateral damage
What are cytokines
Cytokines program immune response
Focus it for the right kind of response
Inflammatory
Anti-inflammatory
Interferon gamma, IL2, IL10
What are cehmokines
Drive movement around the body
Act like address labels
Receptors profiles change with activation state of cell
How is T cell help cross regulated
Different classes perpetuate themselves
They cross neutralise other T classes
What does IL-21 in T cell do
Activates B cell and improves quality of B cell response
How is the constant region of the antibody important
Differnet antibody classes have different constant regions
Differences in function reflect the different types of responses required to clear pathogens
How do CD4 cells use cytokines on B cells
Cytokines to B cell to control gene editing and drop in and drop out different constant regions
Program B cells to make different antibodies
