Immune regulation Flashcards
What are the three main reasons for immune regulation?
1) To avoid excessive lymphocyte activation and tissue damage, during normal protective responses against infections.
2) To prevent inappropriate reactions against self-antigens (tolerance)
3) Failure of control mechanisms is the underlying cause of immune-mediated inflammatory diseases. Immune regulation is the control of immune response to prevent inappropriate reactions
What is autoimmunity?
The stimulated immune response against self-antigens, pathologic .
Disorders are classified under immune-mediated inflammatory diseases
What are the general principles in the pathogenesis of autoimmunity?
Susceptibility genes + environmental triggers; systemic or organ-specific (autoimmunity against specific antigenic. proteins presented by discrete cells)
B and T cell receptor repertoires and MHC genes are genetically distinct, self-antigens may be compatible with TCR to predispose for susceptibility infection activates an autoimmune response.
Why do immune-mediated inflammatory diseases occur?
Chronic disease with prominent inflammation, caused by a failure of tolerance or regulation. The inflammatory disease may be attributed n response to self-antigens (autoimmunity), however, others concerned with microbial antigens
Main causes: T cells and autoantibodies
Systemic or organ-specific
What is Crohns disease?
An inflammatory bowel disease, enhanced recruitment, and retention of effector macrophages, neutrophils, and T cells into the inflamed intestine whereby they are activated, releasing proinflammatory cytokines.
Microbiota of gut flora can activate immune response via PAMPs.
Which antibodies are responsible for allergic reactions?
IgE
How is an anaphylactic shock stimulated?
Deleterious immune response to non-infectious antigens that cause tissue damage and disease.
Mediated by antibody (IgE), and mast cells
B cell-driven
How is sepsis stimulated?
Pathogens stimulate excessive immune response through a positive-feedback loop. Triggered by pathogens, entering the wrong compartment.
This activates non-specific cytokines leads to systemic response; or a failure to regulate response to correct level Hypercytoinemia
What are the 3 phases in the 3-signal model?
Antigen recognition
Co-stimulation
Cytokine release
What happens during antigen recognition in the 3-signal model?
T/B cells activation occurs when presented with cognate antigen bound to complementary TCR/BCRs binding to MHC-II APCs.
What happens during co-stimulation?
Cell-cell communication is required through dendritic and antigen-presenting cells, by engaging with CD28 with B7 on APC. This adopts a spatial mechanism as activating molecules provides an immune synapse on the T cell- results in converges of TCRs to enable interaction and activation of signaling cascade.
TCR includes 1/2 signaling molecules (2 required)
Co stimulation molecules clear space in cell surface membrane to traffic TCRs
The signal from APC to the T cell informs the T cell to express CD28 on the surface to have interacted with B7
Activates T cell
Which molecules form an immune synapse?
CD28-B7 interacting molecules
What happens during the cytokine release phase of the 3-signal model?
The interaction produces a series of downstream signals which promote the target T cells survival and activation
What is a self-limiting response?
The Cardinal feature of all immune responses is self-limitation, manifested by the decline of immune responses. The principal mechanisms involve elimination of antigen that initiated the response
First signal for lymphocyte activation is eliminated
Autoimmune disease occurs considering the inhibition of antigen removal
What is the induction phase of immunity?
Antigen-presenting cells (dendritic cells) phagocytose antigen, internalization, and fragmentation at the endoplasmic reticulum results in peptide epitope being presented at the cell surface membrane at MHC molecules
T-cell activation due to peptide-TCR interaction, facilitated by B7-CD28 as costimulatory signals - specific antigen recognize, inducing a response, releasing cytokines
What happens during the effector stage of immunity?
Naive T-cells specializes in an effector: Autocrine communication with cytokines (Interleukin-2) causes cellular proliferation.
Effector T-cells recognize further MHC: peptide complexes on infected cells and performs the function
What happens during the memory phase of immunity?
Effect pool contracts to memory
What are the four main stages of cell immunity?
Induction phase
Effector stage
Memory phase
Resolution and repair
What happens during the resolution and repair phase?
Resolution: No tissue damage, returns to normal. Phagocytosis of debris by macrophages
Repair: Healing with scar tissue and regeneration. Fibroblasts and collagen synthesis
Chronic inflammation: Active inflammation and attempt to repair damage ongoing.
How are lymphocytes removed once a pathogenic threat has been eliminated?
Responses against pathogens decline as the infection is eliminated, therefore resulting in reduced presenting antigens.
Apoptosis of lymphocytes is stimulated due to a reduction in survival signals (Absence of antigen-stimulated signaling)
Specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen (Tolerogen v immunogen)
What is the role performed by costimulatory factors in immunological tolerance?
PDL-1 synthesized by T-cells and presented on cell surface membrane become inert to activation
Active control mechanisms may function to limit response to persistent antigen, adopting inhibitory signals.
What is the significance of immunological tolerance?
Individuals are tolerant of their own antigens (self-tolerance), breakdown of self-tolerance results in autoimmunity
Inducing tolerance exploited to prevent graft rejections treat autoimmune and allergic disease
What is central tolerance?
Destroys self-reactive T/B cells before they enter circulation. Lymphocytes that recognize self-antigens before maturation in the generative organs are eliminated (apoptosis) - concept of negative selection.
Receptor binding editing, B-cells to reduce receptor affinity
