2 Pathology Flashcards
Characteristics of Type I hypersensitivity reaction
(classic allergy- asthma, eczema, hay fever, drug allergies)
mediated by IgE bound to mast cells
Immediate, atopic
tends to ↑ in severity with repeated challenge (first time death, next time death)
Characteristics of Type II hypersensitivity reaction
cytotoxic, antibody dependent IgG (or IgM) bound to cell/matrix Ag (antibodies directed against human cells) Uncommon cause of allergy Common cause of autoimmune disease
Characteristics of Type III hypersensitivity reaction
Mediated by immune complexes bound to soluble antigen
Cause of autoimmune disease and drug allergy
IgM or IgG bound to soluble Aggregate in small blood vessels:
> Direct occlusion
> Complement activation
> Perivascular inflammation
Characteristics of Type IV hypersensitivity reaction
(also known as Delayed type hypersensitivity)
Present several days after exposure
Mediated by T lymphocytes (CD4 + CD8) infiltrating area
Outline the process by which allergies occur
- Sensitisation
- Mast cells primed with IgE
- Re-exposure to antigen
- Antigen binds to IgE associated with mast cells
- Mast cell recognises, bu conformational change
- Mast cell degranulates, releasing:
-toxins (ie histamines)
-pro-inflammatory cytokines
-chemokines etc.
(causing inflammation, itch, smooth muscle contraction-wheeze) - Pro-inflammatory process stimulates and amplifies future responses
what is anaphylaxis?
severe, systemic type 1 hypersensitivity
- widespread mast cell degranulation. caused by systemic exposure to antigen
- vascular permeability is principle immediate danger:
> soft tissue swelling threatening airway
> loss of circulatory volume causing shock (hypotension)
- can be rapidly fatal
Describe the early and late phase tissue effects of a type I hypersensitivity reaction
Early Phase:
- occurs within minutes of exposure to antigen
- Largely as a result of histamine and prostaglandins
- smooth muscle contraction
- ↑ vascular permeability
Late Phase:
* hours - days after exposure to antigen
* principally mediated through recruitment of T-cells and other immune cells to site
* Results in:
> Sustained smooth muscle contraction/hypertrophy
> Tissue remodelling
Outline the development of Type II Hypersensitivity reaction
- Sensitisation
- Opsonisation of cells
- Cytotoxicity
> complement activation
> Inflammation
> Tissue destruction - In some cases:
> direct biological activation with antigen (ie receptor activation, impaired enzyme action)
Define “autoimmune disease”
harmful inflammatory response directed against ‘self’ tissue by adaptive immune response
- organ specific
- systemic
(usually not single category od hypersensitivity)
(organ specific AD often co-exist in the same patient)
Brief overview of T1DM
selective, autoimmune destruction of pancreatic B-cells (often mix of Type II & Type IV)
- > profound insulin deficiency and death if not treated with insulin replacement
- Symptoms only occur once Islets of Langherans mostly destroyed, after years of inflammation
Brief overview of Myasthenia Gravis
Syndrome of fatiguable muscle weakness
- limbs
- respiratory
- head + neck
- Caused by IgG against ACh receptor
- Antibody blocks receptor and prevents signal transduction
Give some examples of systemic Autoimmune diseases
Rheumatoid Arthritis Systemic lupus erythematosus IBD Connective tissue disease Systemic vasculitis
Brief overview of RA
Multisystem autoimmune disease Chronic auto-inflammatory condition. Symptoms: * Pulmonary nodules + fibrosis * Pericarditis + valvular inflammation * Small vessel vasculitis * Soft tissue nodules * skin inflammation * weight loss, anaemia * (constant flu-like symptoms)
Pathophysiology of RA
Rheumatoid factor less important than previously thought (many people, especially over 50, have Rf. Women with RA usually have).
* IgM and IgA directed against IgG Fc region
* Forms large immune complexes:
> ↑ conc within synovial fluid and found in other tissues
* Inflammation leads to release of PAD from inflammatory cells
* Alters variety of proteins by converting alanine to citrulline (not normally found in uninflammed systems)
* in RA, anti-citrullinated protein/ peptide antibodies are common
- Amplification of inflammatory cascade
- Further chemoattraction of inflammatory cells into synovial:
- macrophages
- neutrophils
- lymphocytes
- Osteoclas activation + joint destruction
- Fibroblast activation + synovial hyperplasia
- Systemic inflammation
Treatment of RA
historically, immunosuppression:
steroids (bluntest - enter nucleus and switch off immune system, nasty Sx after few weeks)
inhibitors of metabolism + T-cell function
+monoclonal antibodies
