Disorders of the immune system Flashcards
What is the Coombes and Gell classification of type I hypersensitivity?
- immediate, atopic
- IgE mediated
What is the Coombes and Gell classification of type II hypersensitivity?
- Cytotoxic, antibody-dependent
- IgM or IgG bound to cell/matrix Ag
What is the Coombes and Gell classification of type III hypersensitivity?
- Immune complex
- IgM or IgG bound to soluble Ag
What is the Coombes and Gell classification of type IV hypersensitivity?
- Cell-mediated
- T cells (CD4 and CD8)
What is the Coombes and Gell classification of type V hypersensitivity?
Likely a subclass of type II
- Receptor-mediated
- IgM or IgG bound to receptors
What are the specific characteristics of type I hypersensitivity
- response to challenge occurs immediately
- tends to increase in severity with repeated challenge
- predominantly mediated by IgE bound to mast cells
What is the process of mast cell activation?
- sensitisation
- mast cells primed with IgE
- re-exposure to antigen
- antigen binds to IgE associated with mast cells
- mast cells degranulate
- pro-inflammatory process stimulates and amplifies future responses
What substances are released when mast cells degranulate?
- toxins (i.e. histamine)
- tryptase
- pro-inflammatory cytokines
- chemokines
- prostaglandins
- leukotrienes
What is the result of histamine release?
- in the skin: swelling and itching
- in the respiratory tract: bronchospasm and wheeze
What is the result of tryptase release?
- a type of proteinase
- degradation
Which substances released from mast cells encourage the immune system to mount an inflammatory response?
- pro inflammatory cytokines
- chemokines
- prostaglandins
- leukotrienes
What are the tissue effects of an early phase type 1 hypersensitivity reaction?
- occurs within minutes of exposure
- largely as a result of histamine and prostaglandin exposure
> smooth muscle constriction
increased vascular permeability
What are the tissue effects of an late phase type 1 hypersensitivity reaction?
- occurs over hours to days after exposure
- principally mediated through recruitment of T cells and other immune cells to site
> sustained smooth muscle contraction/hypertrophy
tissue remodeling
What is anaphylaxis?
Severe, systemic type 1 hypersensitivity reaction
What causes anaphylaxis?
widespread mast cell degranulation caused by systemic exposure to antigen
What is the principle danger in anaphylaxis?
vascular permeability causing:
- soft tissue swelling threatening airway
- loss of circulatory volume causing shock
Give examples of type 1 hypersensitivity
- asthma (although not true type 1)
- penicillin allergy
- hay-fever
What is the cause of type II hypersensitivity
caused by binding of antibodies directed against human cells
What are the characteristics of type II hypersensitivity?
- delayed - generally over days, weeks or months
- uncommon cause of drug allergy
- common cause of auto-immune disease
Name a type II hypersensitivity drug allergy
Drug associated haemolysis
- goes on to develop anaemia
- pretty rare
Name a type II hypersensitivity autoimmune disease
bullous pemphigoid
- characterised by development of deep blisters on the skin
- antibody found between the epridermis-dermis junction
What is the process of type II hypersensitivity reaction
- sensitisation
- opsonisation of cells
- cytotoxicity
- complement activation
- inflammation
- tissue destruction
What is the process of type V hypersensitivity?
- sensitisation
- opsonisation of cells
- cytotoxicity
- complement activation
- inflammation
- tissue destruction - direct biological activation with antigen
- Either through receptor activation (common) or receptor blocking (occasional)
What is a common autoimmune example of type V hypersensitivity?
Graves’ disease
What causes type III hypersensitivity?
Mediated by immune complexes bound to soluble antigen
- aggregates get stuck in small vessels, where they activate complement and cause inflammation around them
Name examples of type III hypersensitivity reactions
- SLE
- RA
- Post-strep glomerulonephritis
Which hypersensitivity reaction presents delayed from time of exposure?
- type II
- type III
- type IV
- type V
Name an example of type IV hypersensitivity reaction
contact dermatitis
What causes type IV hypersensitivity reaction?
- mediated by the action of lymphocytes infiltrating the area
N.B by definition, is delayed
How may nickel cause a type IV hypersensitivity reaction?
Nickel is too basic in structure to trigger a response.
It binds to human proteins, altering the shape. This is what is recognized by the immune system.
What is autoimmune disease?
harmful inflammatory response directed against ‘self’ tissue by the adaptive immune response
- organ specific
- systemic
What hypersensitivity reaction is seen in T1DM?
selective, autoimmune destruction of the pancreatic beta cells
- often mix of type II and type IV
What hypersensitivity reaction is seen in myasthenia gravis?
Classic example of type II(V) hypersensitivity
What causes myasthenia gravis?
IgG against the acetylcholine receptor
- antibody blocks the receptor, preventing signal transduction
What are the systemic effects of RA?
- pulmonary nodules and fibrosis
- pericarditis and valvular inflammation
- small vessel vasculitis
- soft tissue nodules
- skin inflammation
- weight loss, anaemia
Describe rheumatoid factor in relation to RA
- IgM and IgA directed against the Fc portion of IgG forming a large immune complex
- high conc. in synovial fluid
- also in other tissues
- not specific to RA
Describe the pathophysiology of RA
- Inflammation leads to the release of PAD from inflammatory cells
- alters proteins to citrulline
- allows immune system to recognise as foreign
- anti-citrullinated protein antibodies found in RA
Describe the immune response in RA
- loss of tolerance
- activation of macrophages and lymphocytes
- TNF alpha and IL1 produced
- amplification of inflammatory cascade occurs
etc.
What are the main treatment methods for autoimmune disorders?
- steroids
- inhibitors of metabolism
- inhibitors of T cell function
- biological therapies
What is the benefit of biological therapies in treating autoimmune disorders?
Neutralises a specific part of the immune system without significant side effects of other drugs
What is molecular mimicry?
- bacteria possesses an antigen that looks very similar to the human antigen
Name an example of molecular mimicry
Rheumatic fever
- caused by strep. which is similar to heart tissue
- cellular infiltrate into the myocardium and you get inflammation of the heart valves, called a rheumatic valve
What modifiable factors are linked with RA?
smoking - generates a lot of citrullinated proteins
