Hypersensitivity +Immunity Flashcards
what is hypersensitivity?
group of disorders where the normally beneficial components of the immune response, act in an EXAGGERATED or inappropriate fashion to environmental antigens which do not normally cause tissue damage
what is responsible for the tissue damage in a hypersensitivity response?
the exaggerated response directed at the antigen (rather than the antigen itself)
What is Type 1 hypersensitivity?
ALLERGY:
- most common
- caused by inappropriate production of IgE which is directed at allergens
how do allergens cause an allergic reaction? (4)
- inhaled (airborne)
- ingested
- injected
- skincontact
Mere synthesis of IgE is not enough on its own to produce a clinical allergy, but allergic problems arise through a combination of different factors- what are they?
- genetic factors
- environmental influences
- hormonal factors
- neurological influences
- immune regulatory factors
Describe mechanism of T Helper cells in type 1 hypersensitivity (3)
- allergen is shown to T helper cells by an APC (antigen presenting cell)
- T helper stimulates B cells to differentiates and stimulate IgE against the foreign antigen
- from then, any exposure to the antigen will cause the release of cytokines from mast cells resulting in an allergic response
what is an allergy?
a clinical expression/disorder of the atopic tendency (15-20% of population)
what is an atopy?
- A genetic tendency to produce IgE to normally innocuous, common environmental allergens
- state of sub-clinical immune sensitisation
- most people will have increased IgE towards something but it doesn’t make it an allergy as there aren’t any symptoms
what are the 2 types of mast cell mediators?
- preformed
2. newly synthesised
what are examples of preformed mast cell mediators?
- histamine
- heparin
- tryptase
- chymase
- eosinophil/neutrophil chemotactic factors
what are examples of newly synthesised mast cell mediators?
- prostaglandins
- leukotrienes
what do mast cell mediators cause in the body?
- mucosal oedema
- capillary leakage
- secretions
- smooth muscle contraction
- vasodilation
what is an early phase response to type 1 hypersensitivity?
- happens within minutes
- preformed mast cell mediators
what is late phase response to type 1 hypersensitivity?
- happen within hours
- newly synthesised mediators
- TH2 cytokines (produced by T helpers)
- eosinophil mediators
therefore, what two factors produce the allergy response?
- mast cells (produce mediators)
- IgE (antibodies)
what is Type 2 hypersensitivity?
- IgG/IgM mediated
- body’s antibodies bind to the antigen on the cell surface
- the target antigens are:
1. self or exogenous/foreign
2. cell surface or fixed in tissues - can be seen as an autoimmune response
- antigen can be self or exogenous
what do IgG and IgM antibodies trigger?
- The complement system causing cell lysis
what are the steps for tissue damage in type 2 hypersensitivity? (4)
- complement- dependent lysis
- Fc receptor mediated damage (antibody binds to Fc receptor on cells and stimulates phagocytes)
- antibody- dependent cellular cytotoxicity
- effects on cellular function can be either inhibitory or stimulatory
What is Type 3 hypersensitivity?
- mediated via action of antibodies
- abnormal formation and deposition of antigen/antibody complexes (immune complexes)
- low conc. of antibody coupled large conc. antigens causes small complexes to form
what can cause a Type 3 hypersensitivity reaction to arise in terms of antigens?
antibody reaction occurring against an exogenous or self-antigen
Is immune complex formation a normal physiological process?
Yes, but can also be pathological
Describe reasons for having normal/physiological immune complexes (which occur in us all the time in healthy humans)
Protective mechanism for:
- opsonisation
- transportation
- destruction
Describe pathological immune complexes
- antigen factors
- host response factors (skin, joints, kidneys, blood vessels)
Describe normal physiological process of immune complexes
- complexes formed
- complexes gain access to bloodstream and kept soluble in blood
- complexes are transported (usually attached to RBCs) to the liver and spleen
- There, fixed phagocytes such as Kupferr cells take up and destroy complexes
Describe the pathogenic process of immune complexes
- complexes precipitate out into tissues
2. inflammation occurs
Inflammation as a result of type 3 hypersensitivity arises in what 2 forms?
- SERUM SICKNESS:
- systemic illness
- immune complexes deposited throughout many tissues - ARTHUS REACTION:
- complexes form in local tissues (localised disorder)
What is Type 4 sensitivity?
- antibodies play no role in type 4 hypersensitivity
- body’s CD4 Helper T cells recognise foreign antigen and produce cytokines which leads to an inflammatory response
- takes place when immune system finds it difficult to destroy environmental agents
- mediated by T cells of Th1 subclass and cytokine products
what are the main 2 types of cytokines in type 4 hypersensitivity?
- interleukin-2
- gamma- interferon
why does Type 4 hypersensitivity occur specifically?
because of…
- structure of the agent
- infections agents (e.g. mycobacteria)can evade, confound or counteract the immune response (trick immune system)
what type of response is a type 4 hypersensitivity?
Delayed response (48-72 hours between antigen exposure and clinical effect)
what antigens are associated with type 4 hypersensitivity
non-infectious environmental agents of low molecular weight
To initiate an immune response, what do these agents of low molecular weight (in type 4 hypersensitivity) need to do?
they need to bind to host proteins to produce an antigenic stimulus of sufficient size
what is the low molecular agent termed as in type 4?
Hapten
what is the host protein termed as in type 4?
carrier
what is the immune response in type 4 directed at?
Directed against hapten but the carrier is necessary to produce sufficient antigenic bulk
describe the pathogenesis steps for type 4 hypersensitivity
- endogenous protein carrier combines with the microorganism
- carrier uptakes microorganism antigens and presents them (HLA class 2)
- T cells (TH1 subclass) recognise antigen
- T cells produce cytokines (overactivity/ dysregulation)
- inflammation occurs
what is an autoimmune disease?
large group of clinical disorders which are characterised by tissue or organ damage mediated through aberrant immunological mechanisms which are directed against autoantigens (SELF-ANTIGENS)
what is tolerance?
process whereby the immune system avoids producing damaging reactions against self antigens
what are 2 types of tolerance?
- CENTRAL:
- deletion of autoreactive (acting on self) T and B cells during cell maturation
- positive/negative selection - PERIPHERAL:
- inhibiting the activity of autoreactive (acting on self) cells which escape the central tolerance process
- antibody idiotype regulation
Describe factors involved in aetiology of autoimmune disease (multifactorial)
- genetic factors
- familial predesposition
- inheritance of particular HLA types - immune regulatory factors
- defective tolerance induction
- defective peripheral tolerance mechanisms - hormonal factors
- particularly female hormones - environmental factors
- infectious agents
- sunlight
- drugs
- chemicals
- nutritional factors - “other” factors
- age, trauma, malignant disease
describe pathogenic mechanisms involved in autoimmune disease
- cell mediated
- antibody-mediated
- antibody + complement
- immune complex-mediated
- recruitment of innate components
what are 2 most important contributants to autoimmunity
- environmental factors (e.g. viruses, infections)
2. inheritance of particular HLA alleles
what can autoreactivity be?
- humoral; B cells
2. cellular (cell-mediated); T cells
what is organ specific autoimmune disease?
damage and inflammation is localised to one part of the body
what are 3 examples of organ specific autoimmune disease?
- Thyroid; Hashimoto’s Thyroditis, Primary Myxoedema and Thyrotoxicosis
- Stomach; pernicious anaemia
- adrenal: Addison’s disease
what is non-organ specific autoimmune disease?
Connective tissue disorders (often around the body)
what are 4 examples of non-organ specific autoimmune disease?
- Muscles; dermatomyositis
- Skin; scleroderma
- Kidneys; SLE
- Joints: Rheumatoid arthritis
