Hypersensitivity and Autoimmunity Flashcards
What is a hypersensitivity?
Having a hypersensitivity means that someone’s immune system has reacted to something in a way that ends up damaging them rather than protecting them.
What are the different types of hypersensitivities?
- Type I
- Type II
- Type III
- Type IV
What is Type I hypersensitivity important in?
Allergy
Normal response that give rise to allergy and autoimmune disease in some circumstances
What immunoglobulin is involved in Type I hypersensitivity?
IgE
What immunoglobulin is involved in Type II hypersensitivity?
IgG
What is Type I hypersensitivity known as?
Immediate reaction
What are the effects of an activated mast cell in type I hypersensitivity?
- Vasodilation
- Vascular leak
- Broncho-constriction
- Intestinal hypermotility
- Inflammation
- Tissue damage
What are the effects of an eosinophil in type I hypersensitivity?
- Killing of parasites and host cells
- Tissue damage
Discuss type II hypersensitivity
-IgG
-Cell or matrix antigen
-AIHA or rhematic fever
Discuss type III hypersensitivity
-IgG
-Soluble antigen
-SLE
-Arthritis
Discuss type IV hypersensitivity
- Th1, Th2, CTL
- soluble antigen, cell
- antigen,inf-gamma
Type 1 diabetes
What is an autoimmune disease?
A failure or break down of the immune system which maintains tolerance to self tissues
What are different ways to treat autoimmune diseases?
Blanket immunosuppression(can lead to infection)
Target selective approach target the aberrant immune activation whilst leaving the rest of the immune system intact)
Define immune tolerance
A prevention of an immune response against a particular antigen
Describe central tolerance
The process of eliminating lymphocytes that are self reactive
Describe peripheral tolerance
The process of eliminating T cells which avoided central tolerance
What type of lymphocytes acquire central tolerance?
Immature lymphocytes during their development
How may self reactive lymphocytes escape negative selection?
Due to low affinity to self MHC/antigen and the exclusive expression of some proteins in the periphery
Name some factors which affect auto-immune diseases?
Genetic predispositions
Hormonal/sex
Environmental co-factors
Immunity regulatory factors
Describe systemic autoimunne disease
Systemic
Autoimmune process is spread throughout the body - affects more than one organ. eg systemic lupus erythematosus (SLE)
Describe organ specific autoimmune disease
Autoimmune process directed against one organ. eg type 1 diabetes
Describe organ specific autoimmune disease
Autoimmune process directed against one organ. eg type 1 diabetes
Compare early and late phase responses
Early phase response
-occurs within minutes
-preformed mast cells mediators(histamin, heparin, chemotactic factors)
Late phase response
-New synthesised mediators (prosaglandins,leukotrienes)
-Th2 cytokins
Eosinophil mediators
Define atopy
Predisposition to an immune response against diverse antigens and allergens leading to CD4+ Th2 differentiation and overproduction of immunoglobulin E (IgE).
The clinical consequence is genetic tendency to develop allergic diseases.
What can cause a loss of tolerance?
Abnormal selection
Lack of control of self-reactive lymphocytes (B and T cells)
What types of factors lead to autoimmune disease?
Enviromental
Genetic
What is a hypersensitivity?
Hyper response from the immune system
What can harmful immune responses cause?
Tissue injury and cause serious diseases
What mediates Types 1-3 hypersensitvities?
Antibodies
What mediates type four hypersensitivity?
T cell
What happens in the immediate response in allergy?
IgE mediated effects
Vasodilation, oedema and vascular congestion
What happens in the immediate response in allergy?
Eosinophil
Neutrophil
T cell infiltrates
What hypersensitivity types are mostly involved with autoimmune disease?
Type II
Type III
Define immunological tolerance
State of unresponsiveness to a specific antigen - self or foreign
What does immunological tolerance tolerate?
Prevents adaptive responses that are damaging )immune pathology)
What can exploit immunological tolerance?
Microbes and tumours
What can cause immunological tolerance?
Pregnancy
Transplantation
Autoimmune disease
Cancer
What are systemic autoimmune diseases?
Autoimmune process is spread throughout the body and effects more than one organ - not necessarily the same ones in different people
What is an organ specific autoimmune disease?
Autoimmune process directed against one organ
What is an autoimmune disease of the pancreas?
Type 1 diabetes
What is an example of a systemic auto immune disease?
Systemic lupus erythematosus
Who does systemic lupus erythematosus effect?
Mainly women in 20s-60s
M to F ratio - 1:10
What is a risk factor of systemic lupus erythematosus?
DR2/DR3 HLA
What compliment deficiency is seen in systemic lupus erythematosus?
C2 or C4 - 10% of ptients
What does T1 diabetes result from?
A deficiency or inadequate function of insulin, leading to glucose metabolism abnormality
What does T1 diabetes cause?
Initially ketoacidosis, thirst excess urine
Renal failure, heart disease, blindness
Destruction of the insulin producing Beta cells of the islets of langerhans in the pancreas
What is the main therapy in T1 diabetes?
Insulin replacement
What is islet damage in T1 diabetes mediated by?
CD4+ Th1 T-cells that are reactive with islet autoantigens
What first first exposure of an antigen result in in type I hypersensitivity?
IgE antibodies
What do IgE molecules do?
Bind to their receptors on the surface of mast cells and basophils
Upon re-exposure to the same antigen, the antigen binds to adjacent IgE molecules, bringing their receptors together, triggering a signalling cascade that induces the release of histamine and other inflammatory chemicals - causing allergic reaciton.
What happens in type II hypersensitivity?
IgG/IgM antibodies bind to antigens on the surface of a particular cell type.
Antibody binding marks the cells for destruction, either by the complement system or phagocytosis.
Antibodies might also interfere with normal functions of the cells without killing them.
What is Type II hypersensitivity the basis of?
Many autoimmune diseases where the body produces antibodies to destroy its own cells
What happens in Type III hypersensitivity?
Mediated by IgG/IgM antibodies.
Antibodies bind to free-floating antigens forming antibody-antigen complexes.
Complement system activated and inflammation results causing damage to the affected tissue.
What happens in type IV hypersensitivity?
Delayed reaction mediated by T cells.
Pre-sensitisied T cells are produced during a previous contact with the antigen.
Upon re-exposure to the same antigen, T-helper cells release inflammatory cytokines while T-killers induce cytotoxic reactions.
What type of hypersensitivity is SLE?
Type IV
What type of hypersensitivity is diabetes mellitus?
Type IV
