PATH 201 - LECTURE 18

What is hypersensitivity

• an exaggerated immune response against an antigen or allergen

what is hypersensitivity a conseqeunce of

• reactions against self antigen

• innapropriate reactions against microbes

• reactions against environmental antigens

what are the types of hypersensitivity

types I-IV

what is type I, II, III mediated by

• antibody mediated

what is type IV mediated by

cell

does hypersensitivity occur on the primary exposure

no

only on the second and subsequent exposures

which antibody mediates type I hypersensitivity

IgE

which antibody mediates type II and III hypersensitivity

IgG

what is an allergen

• substance that causes an allergic reaction

what are some examples of allergens

• small soluble proteins or glycoporteins (often proteases)

• dust mites

• food

• insect saliva

• plant excretions

• chemicals

• drugs

how long does type I hypersensitivity take to develop

• immediate

• develops in 30 mins

what does the central area of type I response look like

blister

what does the peripheral area of type I response look like

red flare

what is the palpation of type I response

soft

what is the main cell involved in type I response

mast cell

what is local anaphylaxis

• mast cell activation in local areas

• eg nose>allegric rhinitis - sneezing

• airways>asthma

• skin>urticaria

what is systemic anaphylaxis

when the mediator release affects the body broadly

• often presented as widespread vasodilation and vascular leakage which lowers blood pressure dramaticaly

• bronchoconstriction and airway swelling impair breathing

• life threatening

what is type I hypersensitivity initated by

Th2 cells

what cytokines do Th2 cells produce in type I

Il-4, il-5, il-13

what is the functon of IL-4 when produced in response tp type I hypersensitivity

• drive production of IgE

What is the common function of Il-4 IL-5 and IL-13

• they all amplify the Th2 response, along with other thigns

what does IL 5 do (when released by Th2 in response to type I)

• recruit eosinophlils

what does IgE do (when recruited by Th2 in response to type I)

• binds to FceR on mast cells

what is the conclusion of the primary exposure to allergen with type I hypersensitivty

• mast cells coated in IgE via FceR

what is the immediate response of type I hypersensitivity

anaphylaxis

vasodilation

increased vascular permeability

what is the later response of type I hypersensitivity

• recruitment of effector cells

what effector cells are recruited in late response of type I hypersensitivity

• Th2 lymphocytes

• eosinophils

• neutrophils

describe the morphology of eosinophils

• large cells with multi lobed nucleus and large orange granules

how long do eosinophils circulate for

8-12 hours

describe the nromal function of eosinophils

• defend against parasites

• phagocytic

describe the function of eosinophils in allergy

release catonic granule proteins which contribute to skin itching and bronchial irritibality

• induce mast cells to degranulate

what happens on secondary exposure to allerge with type I hypersensitvity

• mast cells are coated in IgE from primary exposure (adaptive immunity has been built)

• antibody recognises antigen and crosslinks receptors which causes mast cell to degranulate

what does initial activation of mast cells on re-exposure in type I hypersensitivity do

• release of vasoactive amine and lipid mediators which leads to vasodilation and vascular leakage etc

what does later activation of mast cells on re-exposure in type I hypersensitivity do

• release of cytokines Il4, Il5, IL13

• IL4 amplifies Th2 response

• IL5 activates eosinophls IL13 stimulates mucus secretion and amplifies TH2 response

• TNF-a promotes infalmmation

when does the late response of re-exposure of type I hypersensitivity peak

12 hours - cells infiltrating

what is atopy

genetic tendency to develop allergic diseases

• increases susceptibility not a guarantee

what are some factors that individuals with atopy have

• increased IgE and mast cells

• high affinity FC receptors for IgE

is hypersensitivity type I manifested by autoimmune disease

• no it was manifested by allergy

which hypersensitivites are manifested by autoimmune disease

types II-IV

what are some features of autoimmune disease

• breakdown of tolerance

• presence of autoantibodies

• more than one autoimmune condition

• lymphocyte, macrophage infiltration into lesions

• human leukocyte antigen associations

define tolerance

• unresponsiveness to an antigen that is induced by exposure to that antigen

• dont react to something because youve already seen it before

what is central tolerance

• antigen induced death of self reactive B and T cells

what is peripheral tolerance

• anergy

• suppression by regualtory T cells

• activation induced death

what are some local autoimmune disorders

• multiple sclerosis

• hashimoto’s thyroiditis

• type 1 diabetes

• graves

• myasthenia gravis

what are some systemic autoimmune disorders

• SLE

• sjogrens syndrome

• scleroderma

• rheumatoid arthiritis

describe the primary mechanism of type II hyperacivity

• antibodies directed against target antigens on the surface of cells or tissue components

what are the mechanisms of tissue injury of type II hypersensitivity

• opsonisation and phagocytosis

• complement and Fc mediated inflammation

• antibody mediated cellular dysfunction

what is the primary antibody in type II hypersensitivity

• IgG

describe opsonisation ahd phagocytosis as a mechanism of tissue injury in type II hypersnesitivty

• target gets coated, so a phagocyte recognsies and removes it

• IgG and C3b can both act as tags

• target just happens to be our own cells

what is an exmaple of opsonisation and phagocytosis as a mechanism of type II hypersensitivty

• autoimmune hemolytic anemia

• antigen is red cell membrane proteins - get coated

• cell is removed or destroyed

• fewer RBC’s=anemia

describe complement and Fc receptor mediated inflammation as a mechanism of tissue injury in type II hypersensitivity

• target is part of TISSUE - so body cannot phagocytose the structure

• antibodyes attach and activate complement and Fc receptors on recruited immune cells

• neutrophils release enzymes and reactive substrances near the tissue causing damage and inflammation

what is an example of complement and Fc-receptor mediated inflammation as a mechanism of tissue injury in type II hypersensitivty

• sjogrens syndrome

describe sjorgrens syndrome

• destruction of exocrine salivary and tear producing glands

• dry mouth and dry eyes

• infiltration of CD4 t cells and B cells that release cytokines that cause inflammation

• autoantibodies have a role via FcR and induction of apoptosis and inflammation

describe antibody mediated cellular dysfunction as a mechanism of tissue injury in type II hypersensitivity

• antibodies bind antigen and mediate dysfunction by blocking or activating the receptor

what are examples of antibody mediated cellular dysfunction as a mechanism of tissue injury in type II hypertension

graves

myasthenia gravis

describe graves disease

• antibodies developed acting against thryoid receptor on thyroid cell

• binds TSH receptor and stimulates it causing increased thyroid hormone production and therefore hyperthyroidism

describe myasthenia gravis

• antibodies target Ach receptor at the NMJ which reduces the effective nerve to muscle signalling

• this cause fatigable muscle weakness and paralysis