Hypersensitivity and Autoimmunity

Question 1

What is an autoimmune disease?

Answer 1

A failure or breakdown of immune system that maintains tolerance to self tissues

Question 2

What is loss of tolerence most likely due to?

Answer 2

Abnormal selection of self-reactive B and T cells

Question 3

What may autoimmune disease may arise due to?

Answer 3

Genetics

Environment

Question 4

What does the treatment of autoimmune diseases deal with?

Answer 4

Symptoms rather than curing the disease

Question 5

How many people suffer from an autoimmune disease?

Answer 5

1 in 20 worldwide

Question 6

What is a hypersensitive response?

Answer 6

Hyper response from the immune system, harmful that may produce tissue damage and cause serious disease

Question 7

What are the 4 categories of hypersensitive responses?

Answer 7

Type I

Type II (also type V)

Type III

Type IV

Question 8

Which of the hypersensitive responses are antibody mediated?

Answer 8

Type I, II and III

Question 9

Which hypersensitive response is T cell mediated?

Answer 9

Type IV

Question 10

What are the exposures during a hypersensitive response?

Answer 10

First exposure (sensitisation)

Second exposure

Question 11

What is the produce of type I hypersensitivity?

Answer 11

1) First exposure to antigen
2) Activation of T_FH cells and stimulation of IgE class switching in B cells
3) Production of IgE
4) Binding of IgE to mast cells
5) Repeated exposure to antigen
6) Mast cells form cross links with allergen and are activated
7) Release mediators such as cytokines, amines and lipid mediators
a) Histamine/lipid mediators cause immediate reaction which is vascular and smooth muscle
b) Cytokines cause late phase reaction which is inflammatory
8) During the late phase, cytokines activates eosinophils, neutrophils and T cell infiltrates which travel to the site

Question 12

What do amines cause during a type I hypersensitive response?

Answer 12

Vasodilation and increased permeability

Question 13

What do lipid mediators cause in a type I hypersensitive response?

Answer 13

Broncho-constriction and intestinal hypermotility

Question 14

What do cytokines cause during a type I hypersensitive response?

Answer 14

Inflammation

Question 15

What do enzymes (proteases) cause during a type I hypersensitive response?

Answer 15

Tissue damage

Question 16

How do mast cells bind to allergens?

Answer 16

Fc receptors on mast cells bind to antibodies unique to the allergen, which must bind to two of these to create a cross bridge and release its mediators

Question 17

What is atopy?

Answer 17

Genetic tendency to develop allergic diseases

Question 18

What are levels of immunoglobulin E like in atopic patients?

Answer 18

Raised

Question 19

What is the process of type II hypersensitivity?

Answer 19

1) Self reactive T cells pass through central tolerance and escape
2) Escaped B cells produce IgM and IgG antibodies which attach to antigens on host cells, creating an antigen-antibody complex

3) There are then 4 process of killing the cell:
a) Compliment cascade (MAC, membrane attack complex) bind to this and kill the cell by creating a pore, causing the cell to swell and burst

b) Compliment proteins from this system attract neutrophils which degranulate and kill the cell
c) C3b compliment protein binds to antibody-antigen complex which optimises the cell which encounters phagocytes which bind and engulf the cell by phagocytosis
d) Antibody dependent cell mediated cytotoxicity (ADCC) where natural killer cells bind and release toxic granules which form pores in the cell, enzymes enter and destroy the cell by apoptosis

Question 20

What are the ways cells are killed in type II and III hypersensitive responses?

Answer 20

Compliment cascade (MAC, membrane attack complex) bind to this and kill the cell by creating a pore, causing the cell to swell and burst

Compliment proteins from this system attract neutrophils which degranulate and kill the cell

C3b compliment protein binds to antibody-antigen complex which optimises the cell which encounters phagocytes which bind and engulf the cell by phagocytosis

Antibody dependent cell mediated cytotoxicity (ADCC) where natural killer cells bind and release toxic granules which form pores in the cell, enzymes enter and destroy the cell by apoptosis

Question 21

What is type V hypersensitive response?

Answer 21

The same as type II, except, instead of destroying the cell the function is just lost which is known as antibody mediated dysfunction

Question 22

What is the process during type V that differs from type II?

Answer 22

1) Antibodies bind to antigen on the cell
2) Blocks binding of other things and effects the function of the cell, or may activate the receptors

Question 23

What are the two types of antigens involved in hypersensitive responses?

Answer 23

Intrinsic (normally made by the host)

Extrinsic (antigen from infection)

Question 24

What are key differences between type II and III?

Answer 24

During type III antigens bind to soluble antigens and not cells

During type III compliment system is used in large amounts not small

In type III clinical systems correspond to where the immune system complexes are deposited and not where they are made

Question 25

What is the process of a type III hypersensitive response?

Answer 25

1) Self reactive cells escape 2) B cells switch from making IgM to IgG antibodies 3) Antibodies bind to soluble antigens (different from type II not cell surfaces) 4) Creates a small complex which is less immunogenetic (macrophages are not as attracted and not removed from the blood as quickly) 5) Complex flows around in blood and makes their way into basement membranes of blood vessels, becoming ionically attracted due to being positively charged while the basement membranes are negatively charged 6) Compliment system is activated (different from type II as used in large amounts instead of small) 7) Causes the same effects as type II such as neutrophils being recruited 8) Degranulation causes inflammation and tissue necrosis

Question 26

What is the process of type IV hypersensitivity?

Answer 26

1) Dendritic cell presents antigen at lymph node using MHC II receptor 2) T helper cell binds using MHC II receptor 3) Dendritic cell releases cytokines, causing the helper T cell to mature into a T_H1 cell 4) T_H1 cell releases IL-2 (causes differentiation of more T cells) and IFNgamma (activates phagocytes like macrophages and creates more T_H1 cells 5) Activated macrophages produce proinflammatory cytokines causing leaky epithelial barriers allowing more immune cells into the area 6) Leading to local swelling, redness and systematic symptoms like fever 7) Macrophages release enzymes which damages tissue 8) Original naive T cell could have also differentiated into T_H17 cells due to different cytokines from the dendritic cells which secreates cytokines (IL-17) which recruits lots of neutrophils

Question 27

What is another way that cells are killed during type IV hypersensitivity (T cells)?

Answer 27

1) MHC I receptors are present on all nucleated cells which presents antigens from inside the cell 2) T cell receptor (TCR) binds to MHC I receptor on the cell 3) Releases granzymes which form pores that allow the granzymes to enter the cell, inducing apoptosis

Question 28

Which of the hypersensitive responses is a delayed type of reaction?

Answer 28

Type IV

Question 29

What are common type IV immunological diseases?

Answer 29

Type 1 diabetes Rheumatoid arthiritis Multiple sclerosis

Question 30

What do autoimmune diseases seem to be due to a combination of?

Answer 30

Genetic background and the environment

Question 31

What have twin coordinance studies suggested?

Answer 31

Genetics is important, but not solely responsible with other unknown environment and genetic factors having a role

Question 32

What is the most likely environmental factor?

Answer 32

Previous infection

Question 33

What are other environmental factors other than previous infection?

Answer 33

Drugs Trauma Food

Question 34

What is immunological tolerance?

Answer 34

State of unresponsiveness to specific antigens which may be self or foreign, preventing adaptive responses that are damaging

Question 35

What does understanding immunological tolerance allow?

Answer 35

To understand why autoimmune diseases develop Intervene with novel therapeutics based on immune tolerance mechanisms to treat or cure many diseases Replacement of long term immunosuppresion with short term therapeutic strategies with less toxicity

Question 36

What is systematic autoimmune disease?

Answer 36

Autoimmune process that spreads throughout the body, affecting more than one organ (example being lupus)

Question 37

What is an example of a systematic autoimmune disease?

Answer 37

Lupus

Question 38

What is an organ specific autoimmune disease?

Answer 38

Autoimmune process directed againt one organ (examples are type 1 diabetes and thyroiditis)

Question 39

What is loss of tolerance probably due to?

Answer 39

Abnormal selection of self-reactive lymphocytes

Question 40

What are hypersensitive responses?

Answer 40

Damaging responses produced during normal immune responses

Question 41

What is autoimmune disease?

Answer 41

A failure or breakdown of immune system that maintains tolerance to self tissues