Immune tolerance Flashcards
What is the definition of immune regulation?
Control of the immune response to prevent inappropriate reactions
What can decreased immune function lead to?
Leads to removal of unwanted cells or pathogens
Immunocompromised patients (AIDs, leukaemia, genetic diseases)
Opportunistic infections
Cancer (cells evade apoptosis)
What can increased immune response (hypersensitivity) be caused by?
Infection Environmental factors Genetic factors (family Hx) Female predisposition Hygiene hypothesis theory
What are some examples of diseases caused by an increased immune function?
Rheumatoid arthritis
Type 1 diabetes
Systemic lupus erythematosus SLE
Psoriasis
What is immune regulation required for?
Avoiding excessive lymphocyte action and tissue damage during normal protective responses against infection
Prevent inappropriate reactions against self-antigens
What are complications of an exaggerated immune response?
Sepsis- immune cells entering the wrong part of the body and causing organ dysfunction
this can be caused by…
hypercytokinaemia (cytokine storm) where there are so many cytokines produced that it leads to organ dysfunction
Direct organ damage - Type 1 diabetes, Hashimoto’s thyroiditis
Fatal damage to tissues - multiple sclerosis, ALS
What are the three signals that a T cell needs to be activated?
Antigen to which it is specific
Co-stimulation via receptors on the APC
Cytokines to be released
Define auto-immunity?
immune response against self antigen - pathologic
aka immune-mediated inflammatory diseases
What is tolerance in immunity?
Specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen
What two levels can tolerance occur at?
Before lymphocytes enter circulation - central tolerance
After lymphocytes enter circulation - peripheral tolerance
What is the mechanism for autoimmune diseases?
Immune response against self antigens (autoimmunity) or microbial agents (crohns disease)
Immune response is inappropriately directed or controlled; mechanisms of injury are the same
What are the three possible outcomes to inflammation?
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 repair attempts ongoing
Where does central tolerance occur?
Thymus for T cells and bone marrow for B cells
How does central B cell tolerance occurs?
Immature B cells express IgM antibodies on cell membranes
If these immature B cells bind to stromal cells in the bone marrow they are auto reactive and undergo apoptosis
What are the 3 steps to central T cell tolerance?
Useless - Doesn’t bind to any self-MHC at all; Death by neglect (apoptosis)
Dangerous - Binds to self-MHC too strongly; Apoptosis triggered - negative selection
Useful - Binds to self-MHC weakly → Signal to survive - positive selection
Give the steps of cell-mediated immunity
Induction - Cell infected DC collects material
MHC-peptide TCR interaction
Effector- Naïve T cell becomes effector
Effector cell sees MHC-peptide on infected cell performs function
Memory - Effector pool contracts to memory
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