Hypersensitivity & Autoimmunity Flashcards
<p>What is an autoimmune disease?</p>
<p>A failure or breakdown of immune system that maintains tolerance to self tissues</p>
<p>What is loss of tolerence most likely due to?</p>
<p>Abnormal selection of self-reactive B and T cells</p>
<p>What may autoimmune disease may arise due to?</p>
<p>Genetics</p>
<p>Environment</p>
<p>What does the treatment of autoimmune diseases deal with?</p>
<p>Symptoms rather than curing the disease</p>
<p>How many people suffer from an autoimmune disease?</p>
<p>1 in 20 worldwide</p>
<p>What is a hypersensitive response?</p>
<p>Hyper response from the immune system, harmful that may produce tissue damage and cause serious disease</p>
<p>What are the 4 categories of hypersensitive responses?</p>
<p>Type I</p>
<p>Type II(also type V)</p>
<p>Type III</p>
<p>Type IV</p>
<p>Which of the hypersensitive responses are antibody mediated?</p>
<p>Type I, II and III</p>
<p>Which hypersensitive response is T cell mediated?</p>
<p>Type IV</p>
<p>What are the exposures during a hypersensitive response?</p>
<p>First exposure (sensitisation)</p>
<p>Second exposure</p>
<p>What is the produce of type I hypersensitivity?</p>
<p>1) First exposure to antigen</p>
<p>2) Activation of TFHcells 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>
<p>What do amines cause during a type I hypersensitive response?</p>
<p>Vasodilation and increased permeability</p>
<p>What do lipid mediators cause in a type I hypersensitive response?</p>
<p>Broncho-constriction and intestinal hypermotility</p>
<p>What do cytokines cause during a type I hypersensitive response?</p>
<p>Inflammation</p>
<p>What do enzymes (proteases) cause during a type I hypersensitive response?</p>
<p>Tissue damage</p>
<p>How do mast cells bind to allergens?</p>
<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>
<p>What is atopy?</p>
<p>Genetic tendency to develop allergic diseases</p>
<p>What are levels of immunoglobulin E like in atopic patients?</p>
<p>Raised</p>
<p>What is the process of type II hypersensitivity?</p>
<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>
<p>What are the ways cells are killed in type II and III hypersensitive responses?</p>
<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>
<p>What is type V hypersensitive response?</p>
<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>
<p>What is the process during type V that differs from type II?</p>
<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>
<p>What are the two types of antigens involved in hypersensitive responses?</p>
<p>Intrinsic (normally made by the host)</p>
<p>Extrinsic (antigen from infection)</p>
<p>What are key differences between type II and III?</p>
<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>
What is the process of a type III hypersensitive response?
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
What is the process of type IV hypersensitivity?
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 TH1 cell
4) TH1 cell releases IL-2 (causes differentiation of more T cells) and IFNgamma (activates phagocytes like macrophages and creates more TH1 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 TH17 cells due to different cytokines from the dendritic cells which secreates cytokines (IL-17) which recruits lots of neutrophils
What is another way that cells are killed during type IV hypersensitivity (T cells)?
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
Which of the hypersensitive responses is a delayed type of reaction?
Type IV
What are common type IV immunological diseases?
Type 1 diabetes
Rheumatoid arthiritis
Multiple sclerosis
What do autoimmune diseases seem to be due to a combination of?
Genetic background and the environment
What have twin coordinance studies suggested?
Genetics is important, but not solely responsible with other unknown environment and genetic factors having a role
What is the most likely environmental factor?
Previous infection
What are other environmental factors other than previous infection?
Drugs
Trauma
Food
What is immunological tolerance?
State of unresponsiveness to specific antigens which may be self or foreign, preventing adaptive responses that are damaging
What does understanding immunological tolerance allow?
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
What is systematic autoimmune disease?
Autoimmune process that spreads throughout the body, affecting more than one organ (example being lupus)
What is an example of a systematic autoimmune disease?
Lupus
What is an organ specific autoimmune disease?
Autoimmune process directed againt one organ (examples are type 1 diabetes and thyroiditis)
What is loss of tolerance probably due to?
Abnormal selection of self-reactive lymphocytes
What are hypersensitive responses?
Damaging responses produced during normal immune responses
What is autoimmune disease?
A failure or breakdown of immune system that maintains tolerance to self tissues
