Flashcards in Week 11 - Disease causing immune responses Deck (27)
What are two reasons hypersensitivity reactions may arise?
-Dysregulated/uncontrolled immune responses to foreign antigens
-Immune responses directed against self-antigens
When do immediate hypersensitivity reactions occur, and what cells/molecules do they involve?
Rapidly, within minutes after exposure
They involves allergens, IgE antibodies and Mast cells
IgE production requires Th-cells. How are These regulated?
Regulated by T-cell derived cytokines
Stimulatory: IL-4 & IL-13
Is hypersensitivity evident on first exposure to an allergen?
No, usually appears on repeated contact
What leads to mast-cell degranulation and mediator release?
Mast cell's IgEs cross linking by the antigen
What are the four most common allergic disorders?
Atopic eczema, food allergy, allergic rhinitis and asthma
How do allergic disease patterns change with age?
Food allergy and atopic dermatitis are the first signs. These move to persistent asthma and allergic rhinitis, which usually persist into later childhood
Which antibodies are involved in Antibody mediated hypersensitivity reactions (T2)?
IgM and IgG
What are three mechanisms of immune system action involved in Type 2 HS reactions?
Phagocytosis by neutrophils and macrophages
Cytotoxic action by killer cells
Lysis mediated by the complement system
What are two diseases manifesting Type 2 HS ?
Myasthenia gravis, rheumatic heart disease, autoimmune haemolytic anaemia
What do the antibodies of Type 2 HS reactions, react with?
They react against antigens that are components of the cell membrane, and may deposit on any tissue expressing that antigen. This is why they cause diseases specific for a particular tissue
What causes autoimmune haemolysis?
IgG or IgM auto-antibodies against RBC antigens are generated, which either causes agglutination and complement destruction of RBCs, or splenic macrophages binding the IgG coated RBCs, gradually destroying them
What is allo-immune haemolysis?
ABO blood group incompatibility leading to complement activation. This causes opsonization and phagocytosis, or RBC lysis
What is haemolytic disease of new born caused by?
Second onwards pregnancies where the mother is Rh- but the baby is Rh+
What does Immune-complex mediated hypersensitivity (T3) involve?
Immune complexes: usually antigen+IgG or IgM
Polymorphonuclear cells (PMNs), which cause local tissue damage and inflammation
What are the causes of T3 HS diseases, such as polyarteritis nodosa?
Immune complexes are normally broken down by complement components like C3b coating them and allowing them to be phagocytosed by the liver and spleen macophages.
If this fails to happen, immune complexes are deposited on blood vessels, especially in kidneys and synovium.
This leads to systemic disease, which often manifests with vasculitis, arthritis and renal disease
What does T-cell mediated Hypersensitivity (Type 4) reactions involve?
T cells, lymphokines, antibodies, antigens and macrophages.
What are the two major causes of T-cell mediated hypersensitivity reactions?
T-cell mediated autoimmune diseases - usually limited to a few organs and not systematic
T cell mediated hypersensitivity reactions to environmental antigens - including contact sensitivity to chemicals
Which type of hypersensitivity reaction is granuloma formation in an infection with Mycobacterium tuberculosis?
Type 4 - T-cell mediated hypersensitivity.
What are the mechanisms of tissue injury in T4 HS reactions?
Inflammation induced by cytokines produced by CD4+ T-cells
Killing of host cells by CD8+ cytotoxic lymphocytes
Th1 production of IFN-y, principal macrophage activator
Th17 cells recruit leukocytes, including neutrophils
--- macrophages and neutrophils are a major cause of tissue injury
What are the principal antigenic barriers to transplantation?
Major Histocompatibility complex (MHC) and human leukocyte antigen (HLA)
Why does transplantation rejection occur?
Inflammatory reactions damage transplanted tissues. This is mediated by the adaptive immune system, and MHC antigens contribute most to the rejection
What are the two forms of recognition in transplant rejection?
Direct - T-cells recognise allogeneic MHC molecules in the graft, displayed by donor dendritic cells in the graft
Indirect - graft alloantigens may be processed and presented by the recipients dendritic cells
What happens in hyperacute transplant rejection and why does it occur?
Occurs within minutes, there is thrombosis of graft vessels and ischaemic necrosis of transplant
This is due to the presence of preformed antibodies specific for antigens on graft endothelial cells
What happens in acute transplant rejection and why does it occur?
This occurs within days or weeks of transplant, as a result of active immune response of recipient, stimulated by alloantigens in the graft. CD8+ cells destroy the graft cells directly
How does chronic transplant rejection occur?
Progressive loss of graft function, that may be associated with graft fibrosis, T-cells reacting against graft alloantigens, and some effects from alloantibodies