Allergies And Immunocompromised Hosts Flashcards
Define hypersensitivity
The antigen-specific immune responses that are either inappropriate or excessive and result in harm to the host
What are the 2 phases of allergic reaction?
Sensitisation phase - first exposure
Effector phase - re-exposure gives clinical manifestation eg. Anaphylaxis
What are the different types of hypersensitivity reactions?
Type 1 - immediate
Type 2 - antibody mediated
Type 3 - immune complex mediated
Type 4 - cell mediated
Describe type 1 hypersensitivity reactions
Allergies
Caused by environmental non-infectious antigens (allergens)
IgE produced
Describe a type II hypersensitivity reaction
Antibody mediated
Against tissue antigens
IgG/IgM
Describe a type III hypersensitivity reaction
Immune complexes mediated
Against soluble antigens
What is atopy?
Genetic predisposition of an individual to produce IgE against different allergens
What is a TH1 phenotype?
Less likely to get allergies
Protects against
Describe the type of person who is most likely to develop a TH1 phenotypes for allergies
Large family Live near overstock Variable GI flora Low antibiotic use High likelihood of getting parasites Poorer sanitation (Exposed to more things)
What is the TH2 phenotype for allergies?
IgE production
More likely to develop allergies
Describe the type of person more likely to develop an allergy
Urban homes Small families GI flora is stable - less diverse High Abx use Less likely to get parasites Good sanitation
Name some common allergens
House dust mites Animals Tree/grass pollens Insect venom - wasp/bee stings Medicines Chemicals Foods
Describe the basis of clinical cross reactivity
If you allergic to one thing then you are more likely to become allergic to others
Where are mast cells located?
Next to vessels and in mucosal tissue
What enzymes are in mast cells?
Tryptase
Chymase
Carboxypeptidase
What are the toxic mediators of mast cells and what do they do?
Histamine Heparin Toxic to parasites Increase vascular permeability Vasodilation
What happens on the first exposure to an allergen?
Antigen specific IgEs start to be made
Coat the mast cells
What happens on the second exposure to allergens?
Allergen binds to specific IgEs on mast cells
Causes mast cell activation
What happens when mast cells are activated in the epidermis?
Urticaria (hives)
Itchy rash with reddish flare
Vasodilation
What happens following deep dermis activation of mast cells?
Angioedema
Non-itchy swelling
Can occur in lips, eyes, tongue and upper resp tract
What effects does the systemic activation of mast cells have?
Hypotension Cardiovascular collapse Generalised urticaria Angioedema Breathing problems
What are the 3 rules for anaphylaxis?
Sudden onset of symptoms
Rapidly progressing
At least 2 organ systems involved
What occurs when mast cells are activated in the lungs?
Bronchoconstriction
What is the treatment of anaphylactic shock?
IM adrenaline
How does adrenaline help with anaphylaxis?
Vasoconstriction and increased force of myocardial contraction to increase BP
Bronchodilation
Inhibits mast cell activation
What do we need to monitor in anaphylaxis?
Pulse
BP
ECG
Oximetry - O2 sats
What percentage of cases will have another anaphylactic response without re-exposure?
20%
How do we diagnosis allergy?
Clinical Hx of atopy, allergens
Blood tests - allergic specific IgE, mast cell enzymes
Skin prick tests - wheel and flare reactions
Challenge tests - for food and drug allergies - risky
How do you manage having an allergy?
Allergen avoidance/elimination Education Medic alert identification Antihistamines, steroids Epipens Allergen desensitisation/immunotherapy
Describe allergen desensitisation/immunotherapy
Administration of increasing doses of allergen extracts over a period of years
Hopefully to become desensitised so no longer allergic to these
Describe a sickle cell crisis
Vaso-occlusive crisis
Painful episodes which can be very severe and can last up to a week
Caused by blocked blood vessels due to the sickle shaped cells
(rigid and sticky)
Approximately how many primary immuno deficiencies are there?
> 300
Why do many PIDs have permanent tissue/organ damage when diagnosed?
Takes a long time to diagnose
Often symptoms aren’t specific
Lots of PIDs
Define immunocompromised
State in which the immune system is unable to respond appropriately and effectively to infectious microorganisms
What are primary immunodeficiencies?
Congenital
Due to intrinsic gene defect
Missing protein/cell or non-functional components
What is a secondary immunodeficiency?
Acquired
Due to an underlying disease/treatment
Decrease production/function of immune components
OR
Increased loss or catabolism of immune components
SPUR infections suggests underlying immune deficiency, what does it stand for?
S = severe P = persistent U = unusual (site/microorganism) R = recurrent
What is a big warning sign for PIDs?
Family history of PID
What are the limitations of the warning signs for PIDs?
Lack of population based evidence
Presentations are all different
Non-infectious manifestations
What 3 things in children would lead you to think of PIDs?
Family Hx
Failure to thrive
Diagnosis of sepsis
What is SCID?
Severe combined immunodeficiency
Combined T and B cell problem
15% of all PIDs
65% of PIDs are …
Antibody deficiencies
Give the most common PIDs
Common variable immunodeficiency (CVID) IgA deficiency IgG deficiency X linked agammaglubulinaemia Neutropenia
If a PID manifested at the age of <6 months, what type would you expect it to be?
T cell or phagocyte defect
If a PID manifested between the ages of 6 months and 5 years, what type would you expect it to be?
B cell/antibody or phagocyte defect
If a PID manifested at the age of >5 years, what type would you expect it to be?
B cell/antibody or complement defect
Or actually a secondary ID
Which pathologies suggest complement deficiencies and of which part?
Pyogenic infections (C3)
Meningitis/sepsis/arthritis (C5-9)
Angioedema (C1 inhibitor)
Phagocytic defects tend to be found in which infections?
Skin/mucous infections
Deep seated infections
Invasive fungal infections
What pathologies may suggest antibody deficiencies?
Sinoresp infections Arthropathies GI infections Malignancies Autoimmunity
What pathologies may suggest T cell defects?
Failure to thrive
Deep skin and tissue abscesses
Opportunistic infections
What does it mean if people have a weak IgG response to vaccines?
Their B cells are affected
What do you never give to people with T cell defects?
Live vaccines
How do you manage PIDs?
Supportive - prophylactic Abx, treat infections promptly, nutritional support, CMV negative blood products only, avoid live vaccines
Specific - regular immunoglobulin therapy, haematopoietic stem cell therapy
Describe immunoglobulin replacement therapy
IgG from many donors Make pt immune to the diseases the donors are immune to Life long treatment Improves quality of life Can be IV or SC
Which conditions have we found that immunoglobulin replacement therapy works against?
CVID (common variable)
Bruton’s disease (XLA)
Hyper IgM syndrome
Give examples of things that can cause decreased production of immune components
Malnutrition Infection Liver diseases Lymphoproliferative diseases Splenectomy
What are the functions of the spleen?
Clears blood-borne pathogens
Produces antibodies (IgM, IgG)
Splenic macrophages remove opsonised microbes and immune complexes
Give some examples of encapsulated bacteria
H influenzae
Strep pneumoniae
Neisseria meningitidis
What is OPSI?
Overwhelming post-splenectomy infection
Sepsis and meningitis
What is the management for people without a spleen?
Penicillin prophylaxis
Immunisation against encapsulated bacteria a
Medic alert bracelet
Why to haematological malignancies increase susceptibility to infections?
Chemo induced neutropenia
Damage to mucosal barriers
Vascular catheters
What can give a pt an increased loss of immune components?
Protein losing conditions - nephropathy, enteropathy (eg. Crohn’s)
Burns
Viral and fungal infections suggest which type of immune cell deficiency?
T cell
Bacteria and fungal infections suggest which immune cell deficiency?
B cell
Or
Granulocyte
