Autoimmunity and Hypersensitivity Flashcards
What is an autoimmune disease
A failure or breakdown of immune system that maintains tolerance to self tissues, loss of tolerance is probably due to abnormal selection or lack of control of self-reactive lymphocytes (B and T-cells)
How may damage in different autoimmune diseases result
from different effector mechanisms
2 risk factors
environmental and genetic (normaly both cause it)
treating autoimmune disease
- blanket immunosuppression (stops immune system)= side effects e.g. infection
- targeted selective approach= target the aberrant immune activation while leaving the rest of the immune system intact
hypersensitivity responses
*Hyper response from the immune system causes autoimmunity
*Harmful immune responses that may produce tissue injury and cause serious disease
*4 categories: Type I, II, III, IV (V)
*Type I, II (V), and III, are antibody mediated while type IV is T cell mediated
*Autoimmune diseases usually fall into Type II, III, and IV categories depending on the type of damage associated with the disease
*Type 1 associated with allergy
type I hypersensitivity
IgE mediated
1. first exposure to allergen
2. activation of TFH cells and stimulation of IgE class switching in B cells
3. production of IgE
4. binding of IgE to FcęRI on mast cells
5. repeated exposure to allergen
6. activation of mast cells: release of mediators- can be immediate or late-phase reaction
Important in allergy but also give rise to autoimmunity
immediate immune response in allergy
*Immediate reaction
*IgE mediated effects
*Vasodilation, oedema and vascular congestion
Is type 1
late-phase immune response in allergy
*Late reaction
*Eosinophil, neutrophil and T cell infiltrates
Type 1 effects
Mast cell:
* Vasodilation
* Vascular leak
* Broncho-constriction
* Intestinal hypermobility
* Inflammation
* Tissue damage
Eosinophil:
* Killing of parasites and host cells
* Tissue damage
atopy
Definition + clinical consequence
Aa predisposition to an immune response against diverse antigens and allergens (allergy)
Clinical consequence= increased propensity to hypersensitivity reactions
type II hypersensitivity
labeled cytotoxic/ cytolytic & involve IgM or IgG interacting with foreign cells to cause their destruction (cell lysis), such as when donor blood is rejected or Rh mother forms antibodies against Rh+ fetus
Injury caused by anti-tissue antibody
type III hypersensitivity
labeled immune complex; antigens combine with antibodies and deposit in tissues & blood vessels, causing inflammation & tissue destruction
Immune complex-mediated tissue injury
type IV hypersensitivity
T cell (cytokine) mediated-> cell killing and tissue injury
T-cell mediated immunologic disease
- type 1 diabetes; [T cell specificity= islet cell antigens (GAD65, insulin)]
- rheumatoid arthritis; [T cell specificity= Joint synovial antigen (Type 2 collagen)]
- multiple sclerosis; [T cell specificity= Myelin basic protein (MOG PLP)]
genetic risk factors
- Genetic background of an individual may pre-dispose them to an autoimmune disease
- Complex, multi-factorial, and by no means the whole story - there are risk factors that are independent of genetic background
environmental risk factors
- most likely by far is prior infection
- Other factors may include drugs, trauma, food
immunological tolerance
State of unresponsiveness to specific antigen:
* Antigens can be self or foreign
* Prevents adaptive responses that are damaging (immune pathology)= B cells and T cells
* Can be exploited by microbes and tumours
* Pregnancy, transplantation, autoimmune disease and cancer
Challenge of immunological tolerance
T cell pool: autoimmunity OR productive immunity (want this but need to control only self-recognising mechanisms)
examples of autoimmune disease
2 types
- systemic
- organ specific
systemic autoimmune disease
- Autoimmune process is diffuse is spread throughout the body
- Affects more than one organ - not necessarily the same ones in different individuals
- Mozaics of disease
organ specific autoimmune disease
- Autoimmune process directed against one organ
- Type 1 Diabetes - pancreas
- Autoimmune Thyroiditis
- Clear certain organ is being targeted
what are hypersensitivity responses
damaging responses produced during normal immune responses
what can chronic activation lead to
autoimmune disease - different effector mechanisms influence the disease phenotype
Autoimmune disease
Failure or breakdown of immune system that maintains tolerance of self tissues
Loss of tolerance is probs due to abnormal selcetion or lack of control of self-reactive lymphocytes (B and T-cells)
relationship between igE and igG and fc receptors
Yeah not sure, but is learning outcome… google? :)
differences between type II and III antibody mediated hypersensitivity
type 2 and type 3 hypersensitivity both result from the same class of antibody, called IgG. The difference between them lies in the form of antigens that generate a response. Additionally, type 2 can also involve IgM antibodies.
type 1 results from which class of antibody
IgE
Define immune tolerance
(brief)
state of unresponsiveness to specific antigens
