Hypersensitivity & Autoimmunity

Question 1

<p>What is an autoimmune disease?</p>

Answer 1

<p>A failure or breakdown of immune system that maintains tolerance to self tissues</p>

Question 2

<p>What is loss of tolerence most likely due to?</p>

Answer 2

<p>Abnormal selection of self-reactive B and T cells</p>

Question 3

<p>What may autoimmune disease may arise due to?</p>

Answer 3

<p>Genetics</p>

<p>Environment</p>

Question 4

<p>What does the treatment of autoimmune diseases deal with?</p>

Answer 4

<p>Symptoms rather than curing the disease</p>

Question 5

<p>How many people suffer from an autoimmune disease?</p>

Answer 5

<p>1 in 20 worldwide</p>

Question 6

<p>What is a hypersensitive response?</p>

Answer 6

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

Question 7

<p>What are the 4 categories of hypersensitive responses?</p>

Answer 7

<p>Type I</p>

<p>Type II(also type V)</p>

<p>Type III</p>

<p>Type IV</p>

Question 8

<p>Which of the hypersensitive responses are antibody mediated?</p>

Answer 8

<p>Type I, II and III</p>

Question 9

<p>Which hypersensitive response is T cell mediated?</p>

Answer 9

<p>Type IV</p>

Question 10

<p>What are the exposures during a hypersensitive response?</p>

Answer 10

<p>First exposure (sensitisation)</p>

<p>Second exposure</p>

Question 11

<p>What is the produce of type I hypersensitivity?</p>

Answer 11

<p>1) First exposure to antigen</p>

<p>2) Activation of T_FHcells and stimulation of IgE class switching in B cells</p>

<p>3) Production of IgE</p>

<p>4) Binding of IgE to mast cells</p>

<p>5) Repeated exposure to antigen</p>

<p>6) Mast cells form cross links with allergen and are activated</p>

<p>7) Release mediators such as cytokines, amines and lipid mediators</p>

<p>a) Histamine/lipid mediators cause immediate reaction which is vascular and smooth muscle</p>

<p>b) Cytokines cause late phase reaction which is inflammatory</p>

<p>8) During the late phase, cytokines activates eosinophils, neutrophils and T cell infiltrates which travel to the site</p>

Question 12

<p>What do amines cause during a type I hypersensitive response?</p>

Answer 12

<p>Vasodilation and increased permeability</p>

Question 13

<p>What do lipid mediators cause in a type I hypersensitive response?</p>

Answer 13

<p>Broncho-constriction and intestinal hypermotility</p>

Question 14

<p>What do cytokines cause during a type I hypersensitive response?</p>

Answer 14

<p>Inflammation</p>

Question 15

<p>What do enzymes (proteases) cause during a type I hypersensitive response?</p>

Answer 15

<p>Tissue damage</p>

Question 16

<p>How do mast cells bind to allergens?</p>

Answer 16

<p>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</p>

Question 17

<p>What is atopy?</p>

Answer 17

<p>Genetic tendency to develop allergic diseases</p>

Question 18

<p>What are levels of immunoglobulin E like in atopic patients?</p>

Answer 18

<p>Raised</p>

Question 19

<p>What is the process of type II hypersensitivity?</p>

Answer 19

<p>1) Self reactive T cells pass through central tolerance and escape</p>

<p>2) Escaped B cells produce IgM and IgG antibodies which attach to antigens on host cells, creating an antigen-antibody complex</p>

<p>3) There are then 4 process of killing the cell:<br></br>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</p>

<p>b) Compliment proteins from this system attract neutrophils which degranulate and kill the cell</p>

<p>c) C3b compliment protein binds to antibody-antigen complex which optimises the cell which encounters phagocytes which bind and engulf the cell by phagocytosis</p>

<p>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</p>

Question 20

<p>What are the ways cells are killed in type II and III hypersensitive responses?</p>

Answer 20

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

<p>Compliment proteins from this system attract neutrophils which degranulate and kill the cell</p>

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

<p>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</p>

Question 21

<p>What is type V hypersensitive response?</p>

Answer 21

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

Question 22

<p>What is the process during type V that differs from type II?</p>

Answer 22

<p>1) Antibodies bind to antigen on the cell</p>

<p>2) Blocks binding of other things and effects the function of the cell, or may activate the receptors</p>

Question 23

<p>What are the two types of antigens involved in hypersensitive responses?</p>

Answer 23

<p>Intrinsic (normally made by the host)</p>

<p>Extrinsic (antigen from infection)</p>

Question 24

<p>What are key differences between type II and III?</p>

Answer 24

<p>During type III antigens bind to soluble antigens and not cells</p>

<p>During type III compliment system is used in large amounts not small</p>

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

Question 25

<p>What is the process of a type III hypersensitive response?</p>

Answer 25

<p>1) Self reactive cells escape</p>

<p>2) B cells switch from making IgM to IgG antibodies</p>

<p>3) Antibodies bind to soluble antigens (different from type II not cell surfaces)</p>

<p>4) Creates a small complex which is less immunogenetic (macrophages are not as attracted and not removed from the blood as quickly)</p>

<p>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</p>

<p>6) Compliment system is activated (different from type II as used in large amounts instead of small)</p>

<p>7) Causes the same effects as type II such as neutrophils being recruited</p>

<p>8) Degranulation causes inflammation and tissue necrosis</p>

Question 26

<p>What is the process of type IV hypersensitivity?</p>

Answer 26

<p>1) Dendritic cell presents antigen at lymph node using MHC II receptor</p>

<p>2) T helper cell binds using MHC II receptor</p>

<p>3) Dendritic cell releases cytokines, causing the helper T cell to mature into a T_H1 cell</p>

<p>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</p>

<p>5) Activated macrophages produce proinflammatory cytokines causing leaky epithelial barriers allowing more immune cells into the area</p>

<p>6) Leading to local swelling, redness and systematic symptoms like fever</p>

<p>7) Macrophages release enzymes which damages tissue</p>

<p>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</p>

Question 27

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

Answer 27

<p>1) MHC I receptors are present on all nucleated cells which presents antigens from inside the cell</p>

<p>2) T cell receptor (TCR) binds to MHC I receptor on the cell</p>

<p>3) Releases granzymes which form pores that allow the granzymes to enter the cell, inducing apoptosis</p>

Question 28

<p>Which of the hypersensitive responses is a delayed type of reaction?</p>

Answer 28

<p>Type IV</p>

Question 29

<p>What are common type IV immunological diseases?</p>

Answer 29

<p>Type 1 diabetes</p>

<p>Rheumatoid arthiritis</p>

<p>Multiple sclerosis</p>

Question 30

<p>What do autoimmune diseases seem to be due to a combination of?</p>

Answer 30

<p>Genetic background and the environment</p>

Question 31

<p>What have twin coordinance studies suggested?</p>

Answer 31

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

Question 32

<p>What is the most likely environmental factor?</p>

Answer 32

<p>Previous infection</p>

Question 33

<p>What are other environmental factors other than previous infection?</p>

Answer 33

<p>Drugs</p>

<p>Trauma</p>

<p>Food</p>

Question 34

<p>What is immunological tolerance?</p>

Answer 34

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

Question 35

<p>What does understanding immunological tolerance allow?</p>

Answer 35

<p>To understand why autoimmune diseases develop</p>

<p>Intervene with novel therapeutics based on immune tolerance mechanisms to treat or cure many diseases</p>

<p>Replacement of long term immunosuppresion with short term therapeutic strategies with less toxicity</p>

Question 36

<p>What is systematic autoimmune disease?</p>

Answer 36

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

Question 37

<p>What is an example of a systematic autoimmune disease?</p>

Answer 37

<p>Lupus</p>

Question 38

<p>What is an organ specific autoimmune disease?</p>

Answer 38

<p>Autoimmune process directed againt one organ (examples are type 1 diabetes and thyroiditis)</p>

Question 39

<p>What is loss of tolerance probably due to?</p>

Answer 39

<p>Abnormal selection of self-reactive lymphocytes</p>

Question 40

<p>What are hypersensitive responses?</p>

Answer 40

<p>Damaging responses produced during normal immune responses</p>

Question 41

<p>What is autoimmune disease?</p>

Answer 41

<p>A failure or breakdown of immune system that maintains tolerance to self tissues</p>