Immunopathology Flashcards
Name and describe the different classes of hypersensitivity reactions
Class 1 - immediate/atopic. IgE mediated.
Class 2 - Cytotoxic/antibody dependant. IgM or IgG (usual cause) bound to cell. Common cause of autoimmue
Class 3 - Immune complex mediated. IgG/IgM bound to soluble Ag.
Class 4 - Cell mediated. (T cells)
Describe features of class 1 hypersensitivity reactions
Responds immediately and tends to increase in severity with repeated challenge. Responsible for most allergies such as asthma, eczema and hayfever.
Describe the process of an allergy
- Sensitiation.
- Mast cells primed with IgE.
- Re exposure to antigen,
- Antigen binds to IgE associated with mast cells.
- Mast cells degranulate releasing toxins (histamine), tryptase, pro-inflammatory cytokines, prostaglandins and leukotrienes.
- Pro-inflammatory process stimulates and amplifies future responses.
What are the tissue effects of allergies?
Early - Smooth muscle contraction and increased vascular permeability which occurs largely due to release of histamine and prostaglandins.
Late - mediated via recruitment of T cells and other immune cells causing sustained smooth muscle contraction/hypertrophy and tissue remodelling.
Name and describe an example of type 1 hypersensitivity reactions.
Anaphylaxis.
- There is widespread mast cell degranulation caused by systemic exposure to an antigen. Vascular permeability causes soft tissue swelling which threatens the airway and it causes loss of circulatory volume causing shock.
Describe the process of type 2 hypersensitivity
- Sensitisation.
- Opsonisation of cells (antibodies bind to cells).
- Cytotoxicity resulting in complement activation, inflammation and tissue destruction.
Explain in more detail, type 3 sensitivity
- Immune complexes bind to soluble antigen. These often aggregate in small blood vessels which can cause direct occlusion, complement activation or perivascular inflammation.
- It is a cause of autoimmune diseases or drug allergies.
Describe in more detail type 4 hypersensitivity reactions
- Delayed response which presents several days after exposure,
- Occurs due to lymphocytes infiltrating the area.
Name some different autoimmune conditions
Single organ - Type 1 DM, Myasthenia Gravis.
Systemic - Rheumatoid arthritis, SLE, IBD, connective tissue disease and systemic vasculitis.
Describe features of type 1 DM
Autoimmune destruction of pancreatic beta cells (mis of type 2 and 4 hypersensitivity reactions) resulting in insulin deficiency and death if not treated
Describe feature of myasthenia gravis
It is a syndrome of fatigable muscle weakness which can affect limbs, respiratory system and head and neck.
It is caused by IgG binding to acetylcholine receptors preventing signal transduction require in muscle contraction.
What does rheumatoid arthritis cause?
- Joint arthritis,
- Pulmonary nodules and fibrosis,
- Pericarditis and vascular inflammation,
- Small vessel vasculitis (can lead to kidney damage)
- Small tissue nodules,
- Skin inflammation,
- Weight loss and anaemia.
Explain the pathophysiology of rheumatoid arthritis
- Formation of rheumatic factors which occurs when IgM and IgA are directed against the IgG Fc region. These complexes are found in high concentration in synovial fluid. However this is not specific for rheumatoid arthritis
- Inflammation leads to release of inflammatory enzymes (PAD) which alters proteins by converting alanine to citrulline. In RA anti-citrullinated antibodies are common.
- Cells release TNF alpha and IL-1 which leads to attraction of inflammatory cells, osteoclast activation
Explain the treatment of RA
- Older treatments target immunosuppression via steroids, inhibitors of metabolism (methotrexate) and inhibitors of T-cell function
- New treatment uses biologic therapy such as infliximab or etanrcept which targets TNF alpha
What are the pros and cons of biologic therapy
Pros - Reduces joint swelling and pain, decreases systemic inflammation and delays and prevents appearance of erosions and bone deformity.
Cons - Expensive and increased risk of infections. Especially TB so prior to treatment, patients should be screened for latent TB
