Hypersensitivity and autoimmunity Flashcards
Autoimmune disease
Failure or breakdown of immune system that maintains tolerance to self tissues- body thinks own cells organs are foreign and starts attacking them
What is loss of tolerance probably due to?
Abnormal positive/negative selection or lack of control of self-reactive lymphocytes (B and T-cells)
Hypersensitivity responses can be defined as?
damaging responses produced during normal immune responses ie allergies, autoimmunity
What Types of hyper responses are there?
I II III and IV
Which Types are antibody mediated? (humoral)
Type I, II and III
Which type is cell- mediated? (WBC’s rather than antibodies)
IV
What ‘Type’ do autoimmune diseases usually fall into?
Type II, III and IV depending on the type of damage associated with the disease
Type I hypersensitivity
rely on (IgE) antibody- can also be called IgE- mediated sensitivities reaction within minutes- most allergic reactions are type I sensitivity reactions body recognises an environmental antigen as a pathogen and releases IgE and triggers mast cell responses- turns into allergen apc (antigen presenting cell) presents allergen to T helper cell. Causes B cells to differentiate to produce IgE against the antigen- makes IgE antibodies think it's foreign
cytokines released- allergic response occurs- itching/inflammation, tissue damage
What are antigens that cause allergic reactions called?
Allergens
Two steps of an allergic reaction?
Step 1: first exposure- sensitisation
Step 2: subsequent exposure- more serious
Why do some people have allergies?
these people have certain genes that cause their T- helper cells to be more hypersensitive to certain antigens
Allergies: genetic link?
Production of T-helper cells is genetically linked, allergies tend to run in families
Where do you tend to find IgE and where don’t you?
Tend not to find free IgE in the bloodstream but find IgE bound to cells ( particularly mast cells, basophils, eosinophils). Have a v. high affinity for Fc (antibody receptors that antigens bind to) receptors on these cells.
Type II
All about specificity, antiobody-mediated
IgG, bind to specific antigens on its own cell surface
antibodies are produced in response to the antigens on the cell surfaces- trigger the complement system causing cell lysis
blood disorders:- types of anemia
Type III
immune complex-mediated:-
IgG clump together
immune complexes are clumps of antibodies that have stuck together
low conc of antibody + high conc. antigen makes small complexes form (localised)
these then become deposited in tissue (systemic)- recruitment of inflammatory cells- tissue damage
could result in Lupus- attacks healthy tissue by mistake - Rheumatoid arthritis.
Define atopy
Atopy refers to the genetic tendency to develop allergic diseases
Type IV
cell-mediated- The body’s CD4 helper T cells (Th1 and Th2) and CD8 Tcells recognise the foreign antigen. Then CD8 cells start to produce cytokines which leads to apoptosis and furthermore, an inflammatory response
e.g Type 1 diabetes, MS
Early phase response
- occurs within minutes
- pre-formed mast cell mediators (histamine, heparin, chemotactic factors)
Late phase response
newly synthesised mediators
Th2 cytokines
eosinophil mediators
immune complex formation in localised Type III hypersensitivity
causes localised inflammation and can be cleared away by macrophages
Immune complex formation in systemic Type III hypersensitivity
Complexes are deposited in tissues and organs such as the skin, joints, kidneys and blood vessels
Aetiologies (causes) of autoimmune disease
- Genetic Factors- allergies can be hereditary due to T cells
- Immune Regulatory Factors- defective tolerance induction
- Hormonal Factors - particularly female hormones
- Environmental Factors- infectious agents, sunlight, drugs, chemicals etc
- other factors- trauma, malignant disease
what are the pathogenic mechanisms involved in autoimmune disease
cell-mediated- T cell activity
antibody-mediated B cell activity
antibody + complement (auto) antibody activation of complement-mediated inflammation
immune complex-mediated Type III hypersensitivity
recruitment of innate compounds- phagocytes, cytokine, NK cells
Organ specific autoimmune disease:- Thyroid
Graves’ disease
hyperthyroidism
excess of thyroid hormone in the body
over activity of thyroid gland
Organ specific autoimmune disease:- Stomach
pernicious Anaemia- causes your immune system to attack the cells in your stomach that produce the intrinsic factor, which means your body is unable to absorb vitamin B12.
Organ specific autoimmune disease:- Adrenal
Addison’s disease- insufficient amount of certain hormones produced by adrenal glands- causes postural hypotension in back (arched forward), weight loss, weakness
Non-organ specific autoimmune disease:- Muscles
dermatomyositis- distinctive skin rash, muscle weakness, inflamed muscles
Non-organ specific autoimmune disease:- Skin
scleroderma- rare but results in hard, thickened areas of skin
Non-organ specific autoimmune disease:- Joints
Rheumatoid arthritis- pain, swelling and stiffness in the joints
Systemic autoimmune disease example?
Lupus which attacks your own tissues and organs. Inflammation caused by lupus can affect many different body systems- including your joints, skin, kidneys, blood cells, brain, heart and lungs
What is an Fc receptor?
antibody receptor involved in antigen recognition which is located at the membrane of certain immune cells including B lymphocytes, natural killer cells, macrophages, neutrophils, and mast cells
what is a mediator?
mediators are released from the mast cell through de-granulation following the activation of cell surface receptors on mast cells. They can be performed (e.g histamine, heparin, tryptase, chymase) or newly synthesised (e.g prostaglandins, leukotrienes)
Cytokines
a broad category of proteins that are important in cell signalling. They are released during late-phase reactions
Mast cells
a type of WBC
In type 1 hypersensitivity, mast cells remain inactive until an allergen binds to IgE already attached to the mast cell. This leads to de-granulation of the mast cell.
Complement
The complement system is part of the immune system that enhances (complement) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from the organism, and also to attack the pathogen’s plasma membrane.
Which cell types can mediate ADCC (antibody-dependent cell-mediated cytotoxicity?
typically Natural killer cells but macrophages, neutrophils and eisonophils can too
Central tolerance?
Deletion of auto reactive (attacking itself) T and B cells during cell maturation
Peripheral tolerance?
Inhibiting the activity of auto-reactive cells which escape the central tolerance process.
organ specific means
when the specific auto-antigens are present only in a specific organ or tissue, and therefore affects a single organ or tissue
immune tolerance meaning
prevention of an immune response against a particular antigen
e.g usually tolerant to self antigens
