Lecture 32 - Hypersensitivity and autoimmunity Flashcards
Type 1 reaction
Type 1 - igE mediated (alelrgic or anaphylactic)
Most people - have a low igG, however if you have more igE and have more sensitivity reactions
igE antibodies have high affinity receptors to mast cells and basophils
- mast cells are typically found in mucosal surfaces in your skin
- if you meet the allergen, this binds to igE and cross links them, and this signals the cell to be granulated
- these granules do a number of things, some attract nuetrophils to areas, some result as vasodilators, compelemnt activation ect.
- So if you have more igE, then will get more binding to allergens and then lead to more mast cell actiaiton
Common causes of allergies
-house mights, duts, pollens, insect stings,
food allergins - peanuts
drugs - penicillin
Treatment for allergies
- avoidance (not always easy)
- antihistamin (histamine is one of the mediators, and are common to treat symptoms)
- corticosteroids e.g ashtma
life threatening - give epinephrine
Desenstisation - gradually inreases doses of allergen to induce high affinity igG antibodies , these compete for igE allergen (injections)
Type 2 Hypersensitivity reactions
- Autoimmune responses
- Antibodies made against our own cell surface antigens
- these bind to tissue antigen and can lead to
1. antibody dependent cellular cytotoxicity
2. Complement activation, leading to MAC to kill cell
3. C3b activation of complement which attracts neutrophils for phagocytosis - also lead to complement
- this can lead to tissue damage where antibodies are bound and also activate c3b which will be an attachment for neutrophils
- neutrophils will phagocytose this
Example of type 2 hypersensitivity
-haemolytic disease of newborn
Anti D negative mother, w anti D positive baby. Mother makes anti D igG antibodies
-and these will go onto complement mediated red cell lysis
TO stop this - immediately after birth of first baby, you inject mother with anti RHD antibodies to remove these antibodies.
Type 3 hypersensitivity
These antibodies form soluble immune complexes
- when have a chronic infection, then have antibody relating for longer
- lots of antibodies are made against this antigen
- when there is an equal concentration of antibody and antigen, the complexes that form will be large lattice like structures
- and these will 1. get sitcky, lodge in small vessles
2. have alot of complement activation, and nuetrophil attachment - can lead to removal of antigens, but also patholoigcal consequences for the host
- may lead to platelet aggregation and thrombus formation, leads to neutrophils being recruited and complement activated, to damage blood vessel walls due to late complement cascade componenets (MAC) which damage the blood vessel walls
Type 4 hypersensitivity
Involves CD4 T cells
Can use this hypersensitivty to see if someone has a CD4 memory against particular antigen associated infectious agents such as TB, ect.
Mantoux test - take a small amount of antigen, and see weather person has a number of circulating memory cells
- wait 24 hours to see what happens
- if have a lot of these antigens, then they start to release their cytokines which will recruit other cells into the site and change vessel permeability and get sweling and lump developing - delayed reaction (delayed type reaction) - measure of memory t cells against antigen
Contact sensitivity
someone develops a rash, e.g something with nikle or metal irons on it
Process - if repeatedly exposed to something on skin, then antigen presenting cells in that area, will take up that material, process it and then end up activating cd4 T cells to produce circulating th1 cells.
-then have lymphocytes and monocytes activated
Earing - getting sensitivity
Eg. have an earing, and nikle expsoure
- In skin have an antigen presenting cell (dendritic cell) on skin
- then have some nikle molecuels getting into skin, and modifying some of our own normal proteins to become potentially antigenic
- call these haptens - when they are big enough to beable to stimulate the immune response
- we then get these transported to lymph node, and get T cell stimulation
- We then get the memory th1 cells returning to provoke inflammation
Autoimmune
get mainly type 2 and type 3 reactions
there is autoimmunity directed at certain tissues - organ specific immunity (type 2 mediated repsonse)
there is autoimmunity directed at some soluble molecuels , get immune complex formned - and this is type 3 responses
Autoantibodies
- we have natural igM low affinity autoantibodies - however normally not much response
- but as we get older, more likely to develop responses against our own antigens
- autoimmune disease is rare, but autoantibodies are common
Mechanisms of tolerance
1.Clonal deletion - central - bone marrow and thymus (deletes self reacting t or b cells)
ALso have peripheral tollerance
- can get signal to self antigen, however no response of danger signals so no response = anergy
- have t regulator cells that control self-reactive cells
- some parts of our body that we make antigen, and immune system doesnt get to see it. e.g privileged sites e.g testes and ovaries
- sequestrated antigens
- if damage these areas, and teh antigens become accesible then could get immune mediated damage
How might autoimmunity happen?
Self peptides look like other antigenic peptides, presented on same HLA
- so response to bacteria will make anitbodies that also respond to self tissue
- post infective development
- doesnt happen in everyone, depends on HLA phenotype
insulin depenedent diabetes
cytotoxic cells and antibodies against pancreas B cells, compromising insulin production
-leading to low insulin problems
Pernicious anaemia
- Antibodies developing in cells in stomach against IF
- B12 uptake decreased, and lead to pernicious anaemia
