Hypersensitivity disorders II Flashcards
which of the following symptoms of anaphylaxis is the most life threatening?
vascular permeability (drops blood pressure, and organs don’t receive oxygenated blood)
Hygiene hypothesis
explains why western nations have such a high rate of hypersensitivity
- too clean
- reduces exposure to pathogens (from animals and such)
- vaccination
- overreliance on antibiotics (reduced the educaiton of the immune system)
outcome:
- development of the immune system is held bacl
- develops an immune system that is incapable of fighting off “real world infections”.
basophils
- key cell initiating Th2 response
- make IL4 and IL13 , at the start of the immune response
- can drive isotype switching to IgE and IgG4 through interaction with B cells through their CD40L
They can kind of act like a T cell in this way
lipid mediators
prostaglandins and leukotrienes
These are targeted in treatment of allergies and inflammation
Type II Allergic Rxn
Antibody induced
- cell or matrix associated antigen
- complement, FcR+ cells (phagocytes, NK cells)
- Some drug allergies (ex: penicillin)
IgG driven
Type III
Antibody induced
IgG driven
- soluble antigen
- complement phagocytes
- serum sickness, Arthus reaction
Type IV hypersensitivity
Th1 driven, T cell induced
- soluble antigen
- macrophage activation
- contact dermatitis, tuberculin reaction
Type II mechanism
existing structures, generating an anitbody response
Type III mechanism
serum coming from another individual, forms immune complexes.
Type IV mechanism
- T cell expansion and Th1 response with macrophages and T cells. Causes rash or swelling around the nickel containing jewelery
Type II
Small molecules that bind to cell surface molecules, changing their structure. Perceived by the immune system as foreign.
- antibody response develops, IgG
- Upon Ab binding altered molecules on cells, leads to their destruction by complement and phagocytosis
- Penicillin is one molecule that can induce this activity
Penicllin structure
Has a reactive bond, that is able to focus on a bacterial transpeptidase or localize on an erythrocyte.
- Binds to bacterial transpeptidase and inactivates it OR
- Penicillin modifies proteins on human erythrocytes to create foreign epitopes.
Penicillin - Protein conjugates
stimulate the production of anti-penicillin antibodies
- complement coated penicillin modifed erythrocytes are phagocytosed by macrophages
- Macrophages present peptides from penicillin-protein conjugate and activate specific CD4 T cells to become Th2 cells.
- B cells are activated by antigen and by help from activated Th2 cells
- plasma cells secrete penicillin specific IgE which arms mast cells. IgG is also produced
- Penicillin modified erythrocytes activate armed mast cells causing anaphylaxis.
Blood group antigens and transfusions
- Transfusion can give rise to a life threatening Type II hypersensititvity response
- the major immunogenetic barrier to transfusion is the structural polymorphisms of the carbohydrates decorating the erythrocyte surface
- The antigenic difference in these molecules are reffered to as the ABO system of blood group antigens.
A antigen
has a GalNAc on its terminal residue
B antigen has
terminal residue of Gal (galactose)
O antigen
absence of terminal residue
why do we produce antibodies against other people’s blood group antigens?
because blood group antigens are very similar to those expressed by many bacteria and we only develop tolerance to those our RBCs express
which blood type is the universal donor?
Blood group O
which blood type is the universal donor?
Blood group O
what blood group can recieve blood from any group?
AB
AB blood can only be transfused safely into another
AB patient
Type III hypersensitivity
Initiated by immune complexes (antigen-antibody complexes) depositing on the walls of small blood vessels or alveoli
- immune complexes activate complement
- inflammation and tissue damage follow complement deposition
- can be a side effect of therapeutic treatment with Ab or other proteins from non-human animal species
- Arthus reaction or serum sickness
Mediated tissue injury - immune complex
site of immune complexes -> complement and Fc receptor - mediated recruitment and activation of inflammatory cells
leads to recruitment of neutrophils and lysosomal enzymes and ROS
all leads to
Vasculitis (inflammation of vasculature)
- shows up as hemmorrhage in the skin and uricarial rash (both result from serum sickness)
vasculitis
blood vessel walls
nephritis
renal glomeruli
arthitis
joint spaces
Arthus reaction
perivascular area
Farmer’s lung
Alveolar/capillary interface
immune complexes
- can be small or large
- their size, depends on the concentration of antigen and antibodies
small complex
little antibody, excess antigens
Early response
large immune complexes
equal amount of antigens and antibodies
potenitally very damaging
Middle of immune response
medium sized immune complex
excess antibody, little antigen
late in immune response
type IV hypersensitivity
caused by the products of antigen specific T cells
- CD4+ Th1 mediate the majority of these responses, reactions to insect bites, tuberculin skin test
- reffered to as delay type hypersensitivity (DTH) because it takes several days for symptoms to develop
DTH
proteins and local skin swelling
proteins
- insect venom
- mycobacterial proteins (tuberculin, lepromin)
skin swelling
- erythema
- induration
- cellular infiltrate
- dermatitis
contact hypersensitvity (type IV)
Haptens:
- Pentadecacatechol (poison ivy)
- DNFB
Small metal ions
- Nickel
- Chromate
Local epidermal reaction
- Erythema
- cellular infiltrate
- Vesicles
- intraepidermal abscesses
Gluten sensitive enteropathy (celiac disease)
Antigen - Gliadin
Villous atrophy in small bowel - malabsorption
Gluten sensitive enteropathy (celiac disease)
Antigen - Gliadin
Villous atrophy in small bowel - malabsorption
DTH reactions on the cellular level
Mediated by antigen-specific effector T cells
Manifested as local irritation that occurs 24-72 hours after exposure
- Antigen is injected into subcutaneous tissue and processed by local antigen presenting cells
- Th1 effector cell recognizes antigen and releases cytokines which act on vascular endothelium
- Recruitment of phagocytes and plasma to site of antigen injection causes visible lesion
granulomas
chronic DTH response
Occurs in lungs and lymph nodes of those infected with mycobacterium. Provides a mechansm for walling off the infection from the rest of the bosy. Sometimes have a caseous or necrotic center.
activated macrophages and T cells. walled off by fibroblasts - contains the infection. kept in a latent state until there is some sort of stress or activation.
Th1 is the driving factor of a Type IV rxn
produces IFNy
- activates macrophages, increasing release of inflammatory mediators
the pathogenesis of celiac disease
inflammation of the small intestine is caused by CD4+T cells, responding to peptides derived from gluten.
- gluten degraded in the gut lumen to give resistant fragment
- gluten fragment enters gut tissue and is deaminated by transglutaminase
- Naive CD4 T cell responds to deaminated peptides presented by HLA-DQ
- Inflammatory effector T cells cause villous atrophy
