Disorders of the Immune System

Question 1

What is hypersensitivity?

Answer 1

exaggerated or innapropriate immune response

Question 2

What does hypersensitivity result in?

Answer 2

tissue damage

Question 3

What is hypersensitivity classified into?

Answer 3

type I
type II
type III
type IV

Question 4

What is type I hypersensitivity?

Answer 4

allergic response provoked by re-exposure to antigen

there are 2 stages

Question 5

What are the 2 phases of hypersensitivity I?

Answer 5

1. sensitization phase

2. effector phase

Question 6

What happens in the sensitization phase of type I hypersensitivity (use pollen as allergen)?

Answer 6

1. first exposure to pollen
2. B lymphocytes recognise antigens
3. B lymphocytes bind to antigen and internalize them
4. B cells present antigen to Th2 cells
5. Th2 secretes IL4
6. causes B cells to switch class and become IgE producing cells
7. IgE circulates
8. IgE comes into contact with mast cells

Question 7

On what region of mast cells do the antibodies bind?

Answer 7

antibodies have Fc region
Mast cells have Fc receptors
antibodies bind to this region
now mast cells can recognise the antigen

Question 8

What happens in the effector phase of type I hypersensitivity?

Answer 8

1. 2nd exposure to pollen
2. mast cells recognise antigen and bind to it
3. single pollen binds to 2 IgE antibodies
4. lead to immediate phase reaction
5. this will lead to an latent phase reaction

Question 9

What is immediate phase reaction?

Answer 9

release of vasodilator amines such as histaminefrom the mast cell

Question 10

What is type II hypersensitivity?

Answer 10

when antibodies bind to host cell antigens on cell surface

Question 11

What are examples of type II hypersensitivity?

Answer 11

myasthenia gravis
rhesus isoimmunization
grav’es disease

Question 12

What is myasthenia gravis?

Answer 12

antibodies produced against nicotinic Ach receptors
receptor gets blocked
no muscle contraction

Question 13

What is rhesus isoimmunization?

Answer 13

RhD is antigen carried by RBC

Question 14

If a father is RhD positive and a mother is RhD negative and mother gets pregnant with an RhD positive baby, what does the mother produce?

Answer 14

anti-RhD antibodies (IgM)

Question 15

Why can’t IgM cross the placenta?

Answer 15

IgM is too big

Question 16

If a mother gets pregnant again and the first child was RhD positive, what happens in the second pregnancy?

Answer 16

memory B cells stimulated

anti RhD antibodies (IgG) can cross the placenta and lyse the foetal blood

Question 17

What type of disease is Grave’s Disease?

Answer 17

autoimmune- high levels of thyroid hormone are produced

Question 18

What does the body produce in Grave’s disease?

Answer 18

autoantibodies to TSH receptor

Question 19

What do autoantibodies in Grave’s Disease do?

Answer 19

bind to and stimulate the TSH receptor on the thyroid gland
more thyroid hormone release
hypertrophy of thethyroid gland

Question 20

What do high levels of thyroid hormone do?

Answer 20

turn down TRH and TSH

Question 21

What is type III hypersensitivity?

Answer 21

when antibodies target soluble circulating antigens

Question 22

In Lupus, against what are the autoantibodies made?

Answer 22

self molecules such as DNA and nuclear ribonucleoproteins

Question 23

How do autoantibodies work in Lupus?

Answer 23

bind to self molecules

form immune complexes

Question 24

What can immune complexes in Lupus do?

Answer 24

recruit complements to attack self cells

get deposited in glomerulus of the kidney- lead to glomerulonephritis

Question 25

What things are seen in Lupus patients?

Answer 25

- abnormal B cell activation - B cells become more sensitive to stimulatory cytokines - B cells can polyclonally activate - changes in cytokine levels - T cell function changes - phagocytic cells do not function properly,

Question 26

What happens in Type IV hypersensitivity?

Answer 26

T cell mediated

Question 27

What test is used to screen for Tb?

Answer 27

Mantoux

Question 28

What are examples of Type IV hypersensitivity?

Answer 28

``` Mantoux test for Tb Type I diabetes Coeliac disease Ulcerative colitis and Crohn’s disease Psoriasis ```

Question 29

What happens in the mantoux test?

Answer 29

1. inject patient with mycobacterial antigen extract under the skin 2. macrophages engulf antigen 3. present antigen coupled with MHC II to CD4+ cells 4. specific Th cells will get activated and then release cytokines that activate the macrophage and cause it to release cytokines 5. get firm red swelling of skin

Question 30

How is type I diabetes a Type IV hypersensitivity reaction?

Answer 30

1. beta cells in the islets of Langerhans of the pancreas act as the autoantigen 2. APC engulf these and present the peptides complexed with MHC II 3. stimulates corresponding CD4+ T cells that release cytokines to activate cytotoxic T lymphocyte 4. they damage the beta cells and insulin cannot be produced

Question 31

How is coeliac disease a Type IV hypersensitivity reaction?

Answer 31

- genetically predisposed - HLA gene is somehow important (it codes for MHC proteins) - patients have IgA anti-gliadin, anti-endomysium and anti-reticulin antibodies - gliadin is a component of gluten and reticulin and endomysial proteins are host proteins - these antibodies are believed to be released from the intestine where T-cells are also present - there is inflammation, resulting in damage to intestinal mucosa so we see villous atrophy and malabsorption

Question 32

What is coeliac disease?

Answer 32

When person is intolerant to gluten

Question 33

What happens in Ulcerative colitis and Crohn’s disease

Answer 33

- changes in the proportion of T and B cells - it is seen that there are a large number of B cells producing autoantibodies to the intestinal mucosa - there is also complement deposition in the intestinal mucosa - this could have possibly occurred due to presentation of autoantigens on MHC II by antigen presenting cells to CD4+ T helper cells-this naturally results in increased interleukin levels

Question 34

What is seen in high numbers in psoriasis?

Answer 34

CD4+ cells seen in skin

Question 35

What is good treatment for psoriasis?

Answer 35

immunosuppressive treatments such as UV therapy are effective. suggesting that these cells are involved

Question 36

What is autoimmunity?

Answer 36

acquired immune reaction to self antigens

Question 37

What are causes of autoimmunity?

Answer 37

``` age gender infection genetics- HLA specific autoantigens drugs immunodeficiency ```

Question 38

What is primary immunodeficiency?

Answer 38

this happens due to problems with complements, phagocytes, humoral immunity or cellular immunity

Question 39

What are examples of primary immunodeficiency (problems with complement)?

Answer 39

C1q inhibitor deficiency | C3 deficiency

Question 40

What is C1q inhibitor deficiency?

Answer 40

this results in hereditary angioedema due to continuous complement activation

Question 41

What happens in C3 deficiency?

Answer 41

complement cascade cant occur without C3 | so you get recurrent infections

Question 42

What are problems with phagocytes (in primary immunodeficiency)?

Answer 42

chediak higashi syndrome

Question 43

What happens in chediak higashi syndrome?

Answer 43

phagocytes cant form phagolysosomes | so phagocytosed bacteria cant be destroyed

Question 44

What are problems with B cells (in primary immunodeficiency)?

Answer 44

severe combined immunodeficiency syndrome hyper IgM syndrome common variable immunodeficiency

Question 45

What are problems with T cells (in primary immunodeficiency)?

Answer 45

lack of thymus or hypoplastic thymus-this is seen in DiGeorge syndrome (22q11 deletion)

Question 46

What happens in secondary immunodeficiency?

Answer 46

this is due to a result of external forces e.g. HIV-CD4+ count drops leading to AIDS -malnutrition -tumors-some cancer cells can release immunosuppressive factorsthis is treated using cytotoxic drugs and radiation