Immunopathology Flashcards
Which wing of the immune system is involved in hypersensitivity reactions?
Adaptive immune system
Why can hypersensitivity reactions not occur on the first exposure to a pathogen?
Sensitisation must occur first
Which cell / antibody principally mediates type 1 hypersensitivity?
IgE
Which cell / antibody principally mediates type 2 hypersensitivity?
IgM or IgG bound to a cell or antigen matrix
Which cell / antibody principally mediates type 3 hypersensitivity?
IgM or IgG bound to soluble antigen
Which cell / antibody principally mediates type 4 hypersensitivity?
T cells
How quickly do type 1 hypersensitivity reactions occur?
Immediately
Type 1 hypersensitivity reactions increase in severity with repeated challenges. T/F?
True
What type of hypersensitivity is responsible for most allergies?
Type 1
Describe the pathophysiology of type 1 hypersensitivity.
Sensitisation where there is priming of mast cells as IgE binds to the mast cells
Re-exposure to the antigen causes binding of the antigen to the IgE resulting in degranulation of mast cells
Resultant release of toxins, tryptase, pro-inflammatory cytokines, chemokine, prostaglandins and leukotrienes
How are future type 1 hypersensitivity reactions amplified?
Each reaction is a pro-inflammatory process in which the inflammation caused by the rection increases production of IgE and mast cells leading to a bigger response in the next reaction
There is often an initial period of recovery followed by further worsening of symptoms in type 1 hypersensitivity reactions. T/F?
True
Type 1 hypersensitive reactions cause smooth muscle contraction and increased vascular permeability. The release of which substance is largely responsible for this?
Histamine
Severe type 1 hypersensitive reactions cause massively increased vascular permeability. What are the implications of this?
Anaphylaxis:
soft tissue swelling which threatens the airway
loss of circulatory volume causing shock
Describe the pathophysiology of type 2 hypersensitivity reactions.
Type II hypersensitivity binds with sensitization which causes opsonisation of cells, this leads to cytotoxicity where there is complement activation, inflammation and tissue destruction
In type 3 hypersensitivity reactions large immune complexes bound to a soluble antigen form. These complexes are large and aggregate in small blood vessels. What are the implications of this?
direct occlusion of vessels
complement activation
perivascular inflammation
In what type of hypersensitivity is the reaction delayed?
Type 4
Describe the pathophysiology of a type 4 hypersensitivity reaction where there is a contract-sensitising agent
The contact sensitising agent penetrates the skin and binds to self-proteins, altering these proteins in such a way that they are then taken up by langerhans cells (APCs) and presented to lymphocytes in lymph nodes, initiating an immune response
What is autoimmune disease?
A harmful inflammatory response directed against ‘self’ tissue by the adaptive immune system
Autoimmune diseases usually encompass several types of hypersensitivity. T/F?
True
Several organ-specific autoimmune diseases rarely co-exist within the same patient. T/F?
False - Organ specific autoimmune diseases often co-exist within the same patient
Type 1 diabetes is a selective autoimmune destruction of the beta cells of the pancreas. What types of hypersensitivity reactions are at play here?
Type 2 and 4
Myasthenia gravis is a syndrome of fatiguable muscle weakness, Which parts of the body are particularly affected by this?
Limbs
Respiratory tract
Head and neck
What is the cause of myasthenia gravis?
IgG antibodies target the ACh receptor of the neuromuscular junction, blocking the receptor and preventing signal transduction
Give examples of systemic autoimmune diseases.
Rheumatoid arthritis systemic lucid erythematosus inflammatory bowel disease connective tissue disease systemic vasculitis
What are some of the characteristic systemic signs of rheumatoid arthritis?
Pulmonary nodules and fibrosis pericarditis and valvular inflammation small vessel vasculitis soft tissue nodules skin inflammation weight loss anaemia
What is rheumatoid factor?
A large immune complex formed by the targeting of IgG antibodies by IgM and IgA antibodies
In which area of the body can rheumatoid factor be found in high concentrations in RA patients?
Synovial fluid
The presence of rheumatoid factor is not specific to RA. The presence of what other protein is more specific to RA?
Anti-Citrullinated protein antibodies
Historically, autoimmune disease has been treated by systemic immunosuppression. What types of drugs are used for this?
Steroids
inhibitors of metabolism
inhibitors of T cell function
Biologic therapy in RA has many benefits, however there is an increased risk of infection particularly…?
Tuberculosis
Describe the general pathogenesis of autoimmune disease
The pathogenesis of autoimmune disease involves a combination of genetic predisposition and environmental factors leading to a recognition of self antigens by the immune system as foreign and a persistence of the inflammatory response leading to chronic disease
Describe the genes commonly involved in genetic predisposition for autoimmune diseases
MHC 1 AND 2 genes
Cytokines and cytokine receptor genes
transcription factors and cell adhesion molecules
Give examples of environmental factors which could influence the development of autoimmune disease.
Infection resulting in Molecular mimicry or tissue damage exposing self antigens
geographical factors (e.g. vit D and MS)
Modifiable personal risk factors such as smoking
