disorders of the immune system

Question 1

what is hypersensitivity

Answer 1

is an exaggerated or inappropriate immune response that results in tissue damage.
there are 4 types

Question 2

what is type 1 hypersensitivity

Answer 2

immediate hypersensitivity. is an allergic reaction provoked by reexposure to an allergen

Question 3

what are the two stages of a type 1 hypersensitivity reaction

Answer 3

a sensitisation phase and an effector phase.

Question 4

how does the body become sensitised to allergens

Answer 4

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

Question 5

type 1 hypersensitivity reaction to an allergen

Answer 5

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

Question 6

examples of type 2 hypersensitivity

Answer 6

Myasthenia gravis
Haemolytic disease of the new-born
Grave’s disease

Question 7

what happens in myasthenia gravis

Answer 7

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

Question 8

what is haemolytic disease of the newborn

Answer 8

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

Question 9

what is graves disease

Answer 9

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

Question 10

what is type 3 hypersensitivity

Answer 10

accumulation of antigen-antibody complexes that have not been adequately cleared by innate immune cells .’. inflammatory response and attraction of leukocytes.

Question 11

what happens in systemic lupus erythematosus (SLE) (type 3 hypersensitivity)

Answer 11

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

Question 12

abnormalities of immune cells in SLE

Answer 12

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

Question 13

what is type 4 hypersensitivity

Answer 13

delayed type hypersensitivity. Is Tcell mediated but dendritic cells, macrophages and cytokines also contribute to the disease process.

Question 14

examples of type 4 hypersensitivity

Answer 14

Manoux test
type 1 diabetes
coeliac disease
crohns disease

Question 15

what is the manoux test

Answer 15

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

Question 16

type 1 diabetes as a type 4 hypersensitivity response

Answer 16

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

Question 17

what is autoimmunity

Answer 17

an acquired immune reactivity to self-antigens and autoimmune disease occurs when this autoimmunity leads to tissue damage.

Question 18

factors that may predispose/contribute to development of autoimmune disease

Answer 18

age and gender, genetics, infections, drugs, immunodeficiency

Question 19

link between genetics and autoimmunity

Answer 19

Infection may result in autoimmune disease, there is a link between EBV and SLE for example

Question 20

link between drugs and autoimmunity

Answer 20

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

Question 21

link between immunodeficiency and autoimmunity

Answer 21

infections/inflammation persist that consequently results in autoimmunity due to it being so prolonged

Question 22

what is primary immunodeficiency

Answer 22

congenital or inherited immunodeficiency

Question 23

potential causes of primary deficiency

Answer 23

problems with: complement, phagocytes, bcell deficiency, tcell deficiency

Question 24

example of complement problem that leads to primary immunodeficiency

Answer 24

C1q inhibitor deficiency= hereditary antioedema. continuous complement activation .’. C3 deficiency .’. complement cascade cannot really occur .’. recurrent infections

Question 25

example of tcell problem that leads to primary immunodeficiency

Answer 25

lack of thymus or hyplastic thymus .’. cannot produce tcells

eg in digeorge sydrome

Question 26

example of bcell problem that leads to primary immunodeficiency

Answer 26

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

Question 27

example of phagocyte problem that leads to primary immunodeficiency

Answer 27

Chediak-Higashi syndrome. phagocytes unable to form phagolysosomes and degranualte lysosomes. Thus phagocytosed bacteria cannot be destroyed.

Question 28

what may cause secondary immunodeficiency

Answer 28

HIV infection -> CD4+ count drops leading to AIDS
Malnutrition
Tumours -> Cancerous cells can release immunosuppressive factors
Therapy using cytotoxic drugs and irradiation