Anaphylaxis Flashcards
1
Q
immune system categories
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- innate (natural) –> born with
- adaptive (acquired) –> vaccines
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Q
2 type of immune system response
A
- cell-mediated immunity
- humoral immunity
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Q
cell-mediated immunity
A
- immune cells directed at eliminating or destroying pathogens or cells
- T cells, phagocytes, cytokines
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Q
Humoral immunity
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- different antibodies and proteins (exp. complement)
- can work directly or in combo with cellular immunity to create cell injury and destruction
- B cells
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Q
specific (acquired) immunity has
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B cells & T cells
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Q
Non-specific (innate) immunity has
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- Barriers (skin & stomach acid)
- Inflammatory response (vasodilation & phagocytes)
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Q
complete antigen
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capable of inducing a full immune response
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Q
antigen
A
is any toxin or foreign substance that causes an immune response in the body
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Q
incomplete antigen
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- needs something else (like a carrier protein) to cause a response
10
Q
Haptens
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small molecules, incomplete antigens
11
Q
complete antigen 2 examples
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protamine & dextran
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Q
Dextran
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- large macromolecules
- colloid volume expanders
- sometimes used in vascular surgery
13
Q
Protamine
A
- positively charged
- binds with neg charged heparin to neutralize
- Can act as an antigen and bind to IgE antibodies –> cellular degranulation and histamine release
- some insulin preparations have protamine: may be more susceptible to protamine response if taking it
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Q
2 types of immune response
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- antibody-mediated
- cell-mediated
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Q
antibody mediated
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humoral = fluids of the body
B-lymphocytes
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Q
cell-mediated
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phagocytes
T-cells
cytokines
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Q
antibodies also called
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immunoglobulins
they are protein molecules
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Q
5 major classes of antibodies
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IgA
IgD
IgG
IgE
IgM
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Q
structure of antibody
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- 2 heavy chains and 2 light chains: heavy chain determines the structure and function of each molecule
- Fab fragment (antigen binding sites)
- Fc fragment
20
Q
B-cells and T-cells
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specialized immune system lymphocytes
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Q
where are T-cells derived?
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thymus
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how are T-cells activated?
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receptors are activated by binding foreign antigens
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Q
T-cells secrete __ that regulate the immune response
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mediators
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Q
Types of T-cells
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- helper (regulatory)
- Suppressor (regulatory)(inhibit immune functions)
- cytotoxic
- killer (not directly, release cytokines, an things to destroy membrane and have more thinks come in to destroy)
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function of T-helper
- support cells, assist other cells in the immune process
- help B-cells mature into plasma cells and memory cells
- activate cytotoxic t-cells and macrophages
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function of suppressor t-cells
main function = shut down T-cell immunity
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function of cytotoxic t-cells
kill virus-infected cells and tumor cells
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T-cell "army"
cell-mediated immune response directed at a specific pathogen
T-cells main job = release mediators that tell other cells what to do
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killer cells
- dont directly attack a pathogen
- kills things without a reason (antigen)
- transplant rejection
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B-cells are part of __ the immune response system
antibody
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where are B-cells made?
bone marrow
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two type of B-cells
memory & effector
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effector cells
actually do something (opsonization)
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memory cells
body remembers what you were exposed to
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B-cells have receptors (antibodies) on the surface that allow them to attach to a
specific antigen
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each B-cell has a different
antibody
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how do B-cells do their job?
B-cells exposed to antigen
- become activated
- start replicating
Turn into different cells
- memory cells
- effector cells
Effector cells produce antibodies
- antibodies attach to virus and "tag" them
- opsonization
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B-cells make antibodies how
1. binding to antigen
2. chemical signal (helper t-cell) comes
3. becomes plasma cell
4. releases antibodies
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how do T-cells do their job?
- T-cells are mobilized when they encounter a cell such as a dendritic cell or B-cell that has digested an antigen and is displaying antigen fragments bound to its MHC molecules
- cytokines help the T-cell mature
- the MHC-antigen complex activates the T-cell receptor and the T-cell secretes cytokines
- some cytokines spur the growth of more T-cells
- some t-cells become helper cells and secrete cytokines that attract fresh macrophages, neutrophils, other lymphocytes, and other cytokines to direct the recruits once they arrive on the scene
- some t-cells become cytotoxic cells and track down cells infected with viruses
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innate immunity
epithelial barriers
mast cells
phagocytes
dendritic cells
complement
NK cells and ILCs
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adaptive immunity
B lymphocytes --> plasma cells --> antibodies
T lymphocytes --> effector T cells
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hypersensitivity responses
- normally, the immune system works as a protective system, but it may react inappropriately and produce a hypersensitive (or allergic) response
- require a pre-sensitized state of the host
- four types of hypersensitivity responses
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Hypersensitivity reactions names
Type 1: anaphylaxis
Type 2: cytotoxic reactions
Type 3: immune complex reactions
Type 4: delayed hypersensitivity reaction
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Type I reactions
- extrinsic asthma
- allergic rhinitis
- anaphylaxis
antigen binds to preformed antibodies on mast cells and basophils. leads to --> release of histamine, leukotrienes, platelet-activating factor
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Type I involves what antibodies?
IgE antibodies
cross-linking of 2 IgE antibodies is the key, starts degranulation and release of mediators
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Type I reaction also called
immediate-type hypersensitivity (happens in minutes)
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what happens when the mast cell explodes?
- histamine is released
- platelet-activating factor is released
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when histamine is released..
attaches to H1 receptor
- lungs: broncho-constriction --> difficulty breathing
- vascular system: vasodilation and increased permeability --> edema and hives
H2 increased gastric secretion and further exhibits vasofilation
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when platelet-activating factor is released...
- coronary artery constriction --> ischemia
- decreased coronary perfusion --> ischemia
- decreased contractility --> cardiovascular collapse
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anaphylactoid (non-immunogenic)
- No IgE involvement
- less severe
- mast cell activation only
- happens when a drug directly releases histamine or starts complement system
- no previous exposure to antigen required
- think IV contrast reaction
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anaphylactic (immunogenic)
- IgE mediated
- severe reactions
- mast cells & basophils
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non-immunologic release of histamine, have histamine release with no
anaphylaxis
still release histamine but hopefully Benadryl can compete to knock it off
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arachidonic acid metabolites
leukotrienes & prostaglandins: bronchoconstriction and vasodilation
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Histmaine
H1 receptor:
- vasodilation
- increased vascular permeability
- smooth muscle contraction (not vascular)
H2 receptor:
- cardiac stimulation (tachy)
- gastric acid secretion
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another name for type II reactions
cytotoxic reactions
aka antibody-dependent cell-mediated or cytotoxic hypersensitivity
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type II reaction is mediated by what antibodies?
IgG or IgM
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think of what when you see type II reaction.
transfusion reactions
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example of type II reactions
- ABO incompatible transfusion reactions
- drug-induced hemolytic reactions
- Heparin-induced thrombocytopenia (HIT)
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type II reactions
cell damage (cytotoxic)
- direct cell lysis
- increased phagocytosis
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complement activation
- helps the immune system to do its job
- part of the immune system that enhances (or complements) the ability of antibodies or phagocytic cells to:
- recognize bacteria
- "tag" bacteria
- break bacteria apart
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complement activation has how many different proteins?
20
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complement activation starts how
with IgG or IGM and release vasoactive mediators (C3a, C4a, C5a)
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example of complement system gone bad?
acute pulmonary vasoconstriction after protamine
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Type III reactions name
immune complex reactions
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Type III reactions, think of
snake bite, SLE
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Type III reaction
antibodies and antigen bind and make insoluble complexes that lead to vasculitis
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Type III reactions involve what antibodies?
IgG or IgM
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T/F complement is activated in type III reactions
True
neutrophils produce tissue damage
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Type IV reaction AKA
delayed hypersensitivity reaction
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what should you think of with Type IV reactions
think TB test, poison ivy
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type IV reactions
sensitized lymphocytes + antigens
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type IV reactions manifest in
18-24 hrs
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Type IV reactions disappear in
72-96 hrs
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type of reactions with Type IV
- tissue rejection
- graft-host
- contact dermiatits
- TB skin test
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drugs capable of non-immunogenic histamine release
- abx: Vance, pentamidine
- hyperosmotic agents: contrast media, mannitol
- neuromuscular blockers: atracurium, mivacurium
- opioids: morphine, meperidine, codeine
- dextrans
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drugs capable of producing complement activation
- cardiopulmonary bypass
- dextrans
- protamine
- radiocontrast agents
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extra bad things than happen with anaphylaxis
- Mast cells can continue to spill out their content even if the antigen is no longer present as a triggering agent.. will continue to potentiate ongoing symptoms
- ongoing mediators of inflammation can lead to a return rebound of symptoms 6 to 8 hours following the initial allergic response.. this is the reason that patients should be kept and monitored closely following control of initial symptoms
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which histamine receptors are involved in anaphylaxis?
H1 & H2
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where is histamine stored?
mast cells and basophils
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H1 does what?
vasodilation, increased vascular permeability, smooth muscle contraction ( but not blood vessels)
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H2 does what?
cardiac stimulation and gastric acid secretion
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H2 does what
presynaptic terminal is the NS
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H4 does what
in vasculature in lungs, spleen, gut --> inflammation
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what other things can cause anaphylaxis symptoms?
- peptides
- kinins
- Arachidonic acid
- platelet-activating form
not just histamine
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Arachidonic acid
leukotrienes:
- bronchoconstriction (more intense than histamine)
- increased capillary permeability
- coronary vasoconstriction
- myocardial depression
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peptides
Eosinophilic chemotactic factor (ECFA) --> thought to release enzymes that inactivate histamine
77
kinins
released from mast cells and basophils
- vasodilation
- increased capillary permeability
- bronchoconstriction
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platelet-activating facor
- released from mast cells
- aggregates and activates platelets to release inflammatory products
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greater than 90% of perioperative anaphylaxis are evoked by
IV drugs and occur within 5 mins
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risk of perioperative anaphylaxis is
1: 3,500-- 1: 20,000
mortality rate = 4%
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most common clinical features of anaphylaxis during A
- cardiovascular symptoms (73.6%)
- cutaneous symptoms (69.6%)
- bronchospasm (44.2%)
sometimes your only symptom is refractory hypotension (dilute epi and give it)
82
causative agents of anaphylaxis perioperativley
- muscle relaxants (succ, roc, atr)
- latex (gloves, foley, tourniquets)
- abx (pnc & other beta lactams)
- hypnotics (prop, thiopental)
- colloids (dextran, gelatin)
- opioids (morphine, meperidine)
- other substances (protamine, bupivacaine)
83
what percent of NMB drugs cause anaphylaxis reactions? and what's the most common
why?
62-81%
succinylcholine
- structure contains flexible molecules that can cross-link two mast cells IgE receptors, more common w/ benzylisoquinoline compounds than with amino-steroid complexes
- cross-sensitivity between NMBA in most ppl
- may cause direct mast cell degranulation
84
latex comes from what?
milky white sap of Hevea brasiliensis
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latex reaction is __ mediated
IgE
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people at risk for latex reaction
- healthcare workers
- children with spina bifidia
- food allergies: bananas, kiwis, avocado
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crodd sensitivtiy to latex
bananas, kiwis, apple, avocado, chestnut, carrot/celery, papaya, potato, tomato, melons
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prevention of latex
- avoid latex
- antihistamines -- not proven to work
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one of the top three causative agents of anaphylaxis under A and #1 agent in children
latex
89
what things still have latex in them that you have to be careful about in the medical environment
- rubber stoppers from medicine vials,
90
latex free substances
polyvinyl
neoprene
silicone
91
usual presenting reaction of abx allergic reaction
cutaneous
91
prophylactic treatment for latex allergies
H1 & H2 blockers
steroids
prophylaxis has not shown to decrease the occurrence of an anaphylactic response
92
the most general cause of anaphylaxis in general population and may account for __ of all anaphylactic deaths in the US
75%
93
most common abx that ppl are allergic too
penicillin
incidence of anaphylaxis is very low with vanco
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vancomycin is a potent __ releaser
histamine
rare anaphylaxis
severe hypotension with rapid IV administration
102
LA allergic reactions are
uncommon
103
LA ester agents
para-aminobenzoic (PABA) metabolite
104
Sugammadex
delayed approval several time for concern of hypersensitivity reachtions
105
sugammadex reactions
- most are mild
- most occur within 5 mins
- the risk of anaphylaxis but the mechanism is unclear: does not seem to increase with repeated exposure, risk of hypersensitivity seems to increase with higher doses
106
what hypnotic is most likely to have an allergic reaction to?
thipental
107
T/F methohexital causes anaphylaxis reactions
False
108
prop allergic reaction usually involve __ __
egg white
made with egg lectin (yolk) current evidence says okay with egg allergies
108
T/F allergic reactions with etomidate, ketamin, and benzos are often
false
super rare
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Aprotinin incidence of allergic reactions are __ to __ %
0.5; 2.8
110
heparin involve what antibody in the allergic reaction?
IgE reaction very rare
HIT more common
111
protamine 0.4-0.8% can form allergic reaction, __ if previously exposed
higher
fish allergy or men with vasectomies
112
protamine made from
salmon sperm
113
how does heparin work
binds with heparin and neutralizes it
114
patient can have 3 types of "protamine reactions"
- caused by histamine release
- caused by protamine-heparin complex
- anaphylaxis at higher risk with hx of: vasectomy, salmon allergy, insulin use (NPH)
115
atopic patients
may easily develop antibody-mediated allergic responses to foods, environmental factors, and drugs
116
expressed signs and symptoms in atopic patients
allergic rhinitis
asthma
