disorders of the immune system Flashcards
what is hypersensitivity
is an exaggerated or inappropriate immune response that results in tissue damage.
there are 4 types
what is type 1 hypersensitivity
immediate hypersensitivity. is an allergic reaction provoked by reexposure to an allergen
what are the two stages of a type 1 hypersensitivity reaction
a sensitisation phase and an effector phase.
how does the body become sensitised to allergens
1st exposure - bclles recognise allergen, bind and internalise them. present the antigen to Th2 cells .'. get secretion of IL4 .'. bcells switch class and become IgE producing cells antigen specific IgE circulates body and Fc region binds to Fcr on Mast cells .'. mast cell can recognise allergen itself and become sensitised
type 1 hypersensitivity reaction to an allergen
2nd exposure - mast cells recognise the allergen and bind it. mast cell degranulate and release histamine . immediate phase reaction = release of vasodilator amines. late phase reaction = other cytokines produced and encourage Th cells to produce cytokines. allergic reaction prolonged and see muscle spasm, oedema, inflammation, leukocyte recruitment
examples of type 2 hypersensitivity
Myasthenia gravis
Haemolytic disease of the new-born
Grave’s disease
what happens in myasthenia gravis
body produces autoantibodies against nAch .’. bind and block nAch at NMJ .’. when motor neurone stimulated Ach cannot bind .’. muscle fibre cannot contract .’. weak muscle contraction
what is haemolytic disease of the newborn
father is RhD pos, mother is RhD neg
-> mother gets preg with RhDpos. during birth some of fetal blood can enter mother circulation .’. mother will recognise foreign blood and produce RhD antibodies.
If mother preg again with RhDpos some of the Ig can cross placenta and cause lysis of fetal blood
what is graves disease
is an autoimmune thyroid disease .
body produced antibodies to TSH receptor .’. bind and stimulate receptor .’. inc release of TH and hypertrophy of thyroid gland
high levels of thyroid hormone turn down TSH and TRH but still have high TH
what is type 3 hypersensitivity
accumulation of antigen-antibody complexes that have not been adequately cleared by innate immune cells .’. inflammatory response and attraction of leukocytes.
what happens in systemic lupus erythematosus (SLE) (type 3 hypersensitivity)
make autoantibodies against several self-molecules eg DNA & nuclear ribonucleoproteins
can bind DNA etc in plasma forming immune complex which can:
fix complement .’. tissue injury and inflammation
deposited primarily in glomerulus of kidney-> glomerulonephritis as complement gets recruited
abnormalities of immune cells in SLE
bcell activation
bcells in SLE = more sensitive to cytokines
polyclonally active bcells
changes in tcell function esp decline in th1 response
phagocytic cells don’t clear immune complexes circulating or being deposited efficiently
what is type 4 hypersensitivity
delayed type hypersensitivity. Is Tcell mediated but dendritic cells, macrophages and cytokines also contribute to the disease process.
examples of type 4 hypersensitivity
Manoux test
type 1 diabetes
coeliac disease
crohns disease
what is the manoux test
is a screening test for TB. patient is injected with extract of m. TB antigen under the skin. Macrophages engulf antigen and (with MHC2) present it to CD4+. Th cells activated and release cytokines resulting in inflammatory response
type 1 diabetes as a type 4 hypersensitivity response
APC engulf b-cells of islets of langerhans of the pancreas. present its peptides complexed with MHC2 to CD4+ .’. release of cytokines and activate CTL that damage b-cells and insulin cannot be produced
what is autoimmunity
an acquired immune reactivity to self-antigens and autoimmune disease occurs when this autoimmunity leads to tissue damage.
factors that may predispose/contribute to development of autoimmune disease
age and gender, genetics, infections, drugs, immunodeficiency
link between genetics and autoimmunity
Infection may result in autoimmune disease, there is a link between EBV and SLE for example
link between drugs and autoimmunity
drugs can initiate autoimmune reactions, exactly how is unknown. eg patients on treatment for ventricular arrhythmia seem to develop SLE. Stopping the treatment then resolves the problem
link between immunodeficiency and autoimmunity
infections/inflammation persist that consequently results in autoimmunity due to it being so prolonged
what is primary immunodeficiency
congenital or inherited immunodeficiency
potential causes of primary deficiency
problems with: complement, phagocytes, bcell deficiency, tcell deficiency
example of complement problem that leads to primary immunodeficiency
C1q inhibitor deficiency= hereditary antioedema. continuous complement activation .’. C3 deficiency .’. complement cascade cannot really occur .’. recurrent infections
example of tcell problem that leads to primary immunodeficiency
lack of thymus or hyplastic thymus .’. cannot produce tcells
eg in digeorge sydrome
example of bcell problem that leads to primary immunodeficiency
Severe combined immunodeficiency syndrome= lack of development of bone marrow stem cells into B and T cells
Hyper IgM syndrome is where B cells produce lots of IgM but little or no IgG
example of phagocyte problem that leads to primary immunodeficiency
Chediak-Higashi syndrome. phagocytes unable to form phagolysosomes and degranualte lysosomes. Thus phagocytosed bacteria cannot be destroyed.
what may cause secondary immunodeficiency
HIV infection -> CD4+ count drops leading to AIDS
Malnutrition
Tumours -> Cancerous cells can release immunosuppressive factors
Therapy using cytotoxic drugs and irradiation
