Hypersensitivity and Autoimmunity Flashcards
Type I
- Allergy
- Inappropriate genesis of IgE
- IgE is directed against environmental antigens which may be airborne, ingested, injected or encountered through skin contact
- You need symptoms otherwise it’s atopy
Reasons we get these allergic reactions
Combination of:
- interacting genetic factors
- environmental influences
- hormonal
- neurological influences
Pathogenesis of type I
- Allergen exposure
- Mast cell + allergen specific IgE
- Release of inflammatory mediators (mucosal oedema, capillary leakage, secretions, smooth muscle contraction, vasodilatation)
Type II
- Mediated by IgG or IgM antibodies which are directed against antigens found on the surface of cells or fixed within certain tissues
- Antigens can be exogenous or derived from self
Mechanisms of type II damage
- Complement-dependent lysis (complement activation)
- Fc receptor-mediated damage: Fc binding of immunoglobulin and stimulation of phagcytes
- Antibody-dependent cellular cytotoxicity (ADCC): actively lysing target cell
- Effect on target cell function: inhibition and stimulation
Type III
- Abnormal deposition of formed antigen (Ag)/antibody (Ab) complexes (immune complex formation) in tissues
- Can be exogenous or self
Type III - Immune complex formation
- Normal physiological process
- Complex formed to gain access to the blood stream and are kept soluble in the blood and transported to liver and spleen where the complexes are destroyed
What are the two ways that immune complexes can be formed?
- Physiological: normal, no symptoms or disease association
- Pathological: antigen factors, host response factors. 2 forms, serum sickness where immune complexes are deposited everywhere and arthus reaction where complexes form locally in tissues
Pathogenesis of type III
- Excessive or abnormal immune complex formation -> complement activation + recruitment of inflammatory cells -> tissue damage
Type IV
- Mediated by Th1 cells and the cytokine products (mostly interleukin-2 and gamma-interferon)
- Inappropriate response to inert environmental substances
- Reaction to infection with certain micro-organisms
- Usually delayed onset of about 48-72 hours
Why is there a type IV reaction from inert environmental substances?
- Too low a molecular weight to produce a substantial immune response
- Agent = HAPTEN and host protein is a CARRIER
- Carrier is necessary to produce antigenic bulk but the immune response is physically directed against the HAPTEN
Why is there a type IV reaction from micro-organisms?
- Happens when body finds it hard to destroy these environmental agents
- Micro-organisms such as mycobacteria don’t do any harm but the immune response causes tissue damage.
- It evades, confounds or counteracts the immune response
Pathogenesis of type IV reactions
- Hapten + endogenous protein or microorganism
- > antigen uptake & presentation (HLA class II) -> Th1 antigen recognition/cytokine production -> inflammation
Mechanisms of immunological tolerance
- Central tolerance
- Peripheral tolerance
Central tolerance
- Arises through deletion of autoreactive T&B cells during cell maturation
- AKA positive and negative selection
Peripheral tolerance
- Inhibiting the activity of autoreactive cells which escape the central tolerance process
Why is recognition of self not always damaging?
- T cells recognise antigen which is complexed with self molecules
- Antibodies can recognise and bind portions of other antibodies which regulates their production and activity
What is autoimmune disease?
- Clinical disorders characterised by tissue or organ damage mediated through aberrant cellular and/or humoral immunological mechanisms
- Directed against autoantigens: can be throughout many tissues, or localised in specific organs or tissues
Factors involved in autoimmune disease
- Genetic factors
- Immune regulatory factors (defective tolerance induction, defective peripheral tolerance mechanisms)
- Hormonal factors (esp. female hormones)
- Environmental factors (infectious agents, sunlight, drugs, chemicals, nutritional factors)
- Misc (age, trauma, malignant disease)
What pathogenic mechanisms are involved in autoimmune disease?
Same as normal immune response:
- Cellular or antibody activity
- (auto)antibody activation of the complement-mediated inflammation
- Immune complex formation (Type III hypersensitivity)
- Recruitment of innate immune components (phagocytes/cytokines/NK cells)
Pathogenesis of autoimmune disease
Initiating event (environment) -> genetic factors e.g. particular HLA alleles -> breakdown of self tolerance -> autoreactivity -> humoral =/- cellular -> tissue damage
Organ-specific vs non-organ specific
- Organ specific: Hashimoto’s thyroiditis
- Non-organ: Rheumatoid arthritis
