Hypersensitivity Flashcards
humoral AB response process
T cell priming
1) Antigen bound to and internalised by APC phagocytosis
2) antigen processed and peptide displayed on APC cell surface with MHC II
3) TCR of niave T cell (CD4) binds to Ag/MHC II complex
4) Niave T cell become activated and turn into primed Th2 cell
T and B cell cooperation and antibody production
1) B cells also internalise and present the same antigen with MHC class II – to the primed Th2 cells
2) Th2 cells secrete cytokines (IL4/5/10/13)
3) These cause B cells to divide (clonal expansion) and differentiate into plasma cells (AFC = antibody forming cells) and memory B cells (Bm)
4) plasma cells secrete Ab with high specificity to the antigen
humoral immune reposnce features
occurs quickly
systemic and widespread
(ab are souble proteins, can reach most parts of the body quickly via blood, tissue fluids and body secretions)
cell mediated immune response process
1) APC engulfs the antigen and presents it
2) binds to a niave T cell
3) Niave T cell turns into a CD8+ cytotoxic cell (Tc)
4) when the same antigen encountered Tc kills the antigen displaying cell via perforin and granulysin or apoptosis
5) can secret chemokines to recruit more cells
6) secretes IFNy which activates macrophages to enhance their activity
what is cellular repsonce mainly targeted against
Directed mainly against cellular targets
- Tumour cells
- Virally transformed cells
- Foreign cells
cellular immune responses tend to be
- localised
- slow to develop
- slow to resolve
failure of immune response two types
1) fail to produce an adequate immune response
- immunodeficiency
2) produce an overactive, damaging response
- hypersensitivity – allergy
hypersensitivity
When the immune system responds in an exaggerated or inappropriate way resulting in harm
- usually occurs on second exposure to the antigen
- characteristic of the individual (genetic susceptibility)
types of hypersensitivity
1) type 1
- immediate/anaphylaxis
2) typ 2
- cytotoxic
3) type 3
- immune complex
4) type 4
- delayed
- cell mediated
which types are part of the humeral antibody mediated repsponce
1-3
type 1
immediate hypersensivity
- acute hypersensitivity (anaphylaxis)
- rapid onset
- IgE mediated
People with predisposition to Type 1 have abnormally high IgE levels
- overproduction when antigen encountered
what are most allergens
small proteins (10-40kDa)
what is an allergen
antigen that drives type 1 reaction
what do many cells and basophils contain and have on their surfaces
histamine granules
IgE receptors on surface (FcE receptors)
1st and secondary exposure steps to an allergen (type 1 reposnce)
- With the first reaction, lots of IgE binds to the surface of mast cells (specific for the allergen)
Second exposure - allergen comes along
- antibodies specific to the antigen are on the surface of the mast cells
- these bind to the antigen/allergen (to the IgE), antigen corss links the FcE receptors
- this triggers intracellular signalling
- drives IL5 release which recruit eosinophils
- causes degranulation, secreting large amounts of histamine
Tryptase and chymase also released
histamine release causes
1) vascular dialtion
2) increased vascular permabilty i.e. oedema (plasma to the tissues from circualtion)
3) bronchospasm
4) urticarial rash – nettle rash
5) increase nasal and lacrimal secretions
wheel and flare skin test
Skin response is fast
1) wheel
- caused by extravasion of serum into skin due to histamine – angio-odema
2) flare
- (erythematous red patch) caused by axon reflex
management of type 1 hypersensitive
1) adrenaline (epinephrine)
2) anti-histamines
3) corticosteroids
- reduce immune repsonce
- however can lead to candida infections
4) avoidance of allergen
type II sensivity
Antibody mediated hypersensititvy - antibdodies target cell surface self antigens (auto antibodies) - usually IgG or IgM These antibodies induce - cell damage - inflammation
steps for type II sensitivity
1) antibodies target self antigen (auto antibodies)
- thinks it’s a foreign protein
2) Autoantibodies activate immune response
can recruit immune cells (T cell, neutrophil, macrophage), antibody binds to Fc receptor causing ADCC (antibody dependant cell cytotoxicity)
- WBC will kill the cell, thinking it’s a forgin invading cells
Also secretion of cyto/chemokines
- recrtuit other cells to site of infection, leading to inflammation
Complement can also be activated
- produced by liver into circulation
- can drive inflammation C5a and C3a
- forms MAC therefore leading to cell death
what are type II responses important in
1) acute transplant rejection/blood transfusion
2) haemolytic diseases of new born
3) autoimmune diseases
- pemphigus
- pemphigoid
pemphigus
Auto antibodies destroy desmogelin 1 and 3
(desmoglein binds cells together)
- Ab prevents formation of junctions between epithelial cells (upper epithelium cannot attatch to the lower epithelium)
- epithelial shedding – mainly mucosal
pemphigoid
Hemidesmosomes – attach to basement membrane
- Auto antibodies against hemidesmosomes
- Ab prevents binding of epithelium with dermis at basement membrane (loose epithelium)
- epithelial shedding – skin and mucosal
type III hypersensitive
Antibody mediated
Immune complex- mediated hypersensitivity
Immune complexes form in the serum between: - antibodies - antigen form precipitates/complexes - generally taken away by RBC
induces They induce - complement activation - leukocyte binding - inflammation Therefore damaging the blood vessels
steps of type III hypersensitive
2) In inflammation, immune complexes bind to blood vessels where they act on platelets and basophils (contain granules)
3) there are activated, release vasoactive peptides (eg histamine)
4) histamine increases vascular permeability
5) allows more immune complexes to be deposited
6) more platlet aggregation and complement activation (C5a and C3a – leukocyte chemotaxis)
7) neutrophils are attracted to the site but cannot phagocytose complexes (foreign body is too large therefore they degranulate instead)
8) Neutrophils secrete lysosomal enzymes causing further tissue damage (contain ROS)
type IV hypersensivity and what its important in
Cell mediated immunity/delayed type hypersensivity
- mediated by T cells
As the response is cellular, it is usually
- slow to develop (12-48 hr)
- slow to resolve
- localised
Important in
- delayed type hypersensitity responses
- contact hypersensitivity eg dermatitis
- lichenoid reactions to amalgam fillings and other materials
small molecules (another name for antigen)
haptens
- usually involved in type 4 reactions
steps of Type IV sensitive
1) Hapten gains entry through the epithelium and interacts with langerhams cells
2) langerhams cells internalise antigen/hapten and move from epidermis to lymph nodes through the blood stream
3) they release Ag to memory CD4+ T cells in lymph nodes
4) These are activated, travel to dermis (the specific part) and secrete INFy
5) This increases expression of ICAM-1 and MHCII on keratinocytes
6) and cause secretion of pro inflammatory cytokines
7) more leukocytes are attracted to site
8) neutrophils arrive after 4h, monocytes and T cells after 12 hours and secrete tissue damaging cytokines
summary of the types
Type 1
eg pollon
- IgErepsonce
Type 2 - autoantibodies - recognsise self antigen Type III - into blood vessels Type IV - T cell mediated - slow to happen and resolve
