immune 1 Flashcards
how does the immune system protect the body
by recognizing and removing foreign substances called ANTIGENS
what substances make up antigens
proteins and carbohydrates
what do we call immune cells
cell mediated immunity
what is the role of cell mediated immunity
immune cells directed at elimination or destruction of pathogen cells
what substances make up humoral immunity
comprised of different antibodies and proteins such as “COMPLEMENT”
how does humoral immunity work
what is the purpose of humoral immunity
the antibodies and proteins called COMPLEMENTS directly or in concert with cellular immunity cause cell injury and destruction
provide Host defense mechanisms
what process also uses protein mediators called cytokines and chemokine are released initially by inflammatory responses
humor immunity
once cytokines and chemokine get release to the site of injury what is the response at the injury
brings other immune cells to the injury/ infection site causing further inflammatory responses, fever, and increase capillary permeability
what is the role of fever, increased capillary permeability, and the inflammatory response in the body
to allow other immune cells to migrate and translocate to the site of injury
what does the inflammatory response cause (4)
hemostatic activation
produces pain
erythema
local edema
when the inflammatory response is activated producing pain, erythema, edema - are these effects only seen at that one area?
no depending on the injury it can be a systemic response
how broad is the inflammatory effect of cytokines
they have an extensive spectrum of inflammatory effect
studied extensively in sepsis
when is the onset of immune response
variable- from immediate (ANAPHYLAXIS) to days
tell me about the “memory” of the immune response
it can remember antigens for many years, especially following IMMUNIZATION
what are antigens
molecules stimulating an immune response (antibody production or lymphocyte stimulation)
describe most commonly used drugs compounds-
simple organic compounds of low molecular weight
what are complete antigens
polypeptides (protamine) and other large macromolecules (dextrans) are complete antigens
what do we call small molecular weight substances such as drugs or drug metabolites that bind to host proteins or cell membranes to sensitize patient
HAPTENS
by themselves are haptens antigenic
NO
for a small molecule to become immunogenic, it must form a stable bond with circulating proteins or tissue to result in an antigen - what is this called
hapten-macromolecular complex
molecular antigen structures in bacteria or fungi can they be immediately recognized as foreign
YES
what is believe (although not proven) to happen to the active metabolite of PCN -penicilloyl-
(hapten) it is believe its binds with macromolecules to become antigens
how are the t cell receptors activated
their receptor binds with foreign antigens and secrete mediators that regulate the immune response
what are the two types of regulatory T-cells
helper (OKT4)
suppressor (OKT8)
what does the suppressor cell do
inhibit the immune function
what do the helpers cells do
stimulate cell responses
what does the thymus of the fetus do to immature lymphocytes
differentiates immature lymphocytes into thymus derived cells called T- cells
infection of helper T- cells with a retrovirus (HIV) - causes an increase in what
the number of suppressor cells
what do cytotoxic T cells do
destroy mycobacteria, fungi and viruses
do natural killer cells need antigen stimulation to set up their role?
no
name the two cells that take part in defense against tumor cells and in transplant rejection
cytotoxic t- cells and natural killer cells
what is the role of t cells that produce mediators
they influence the response of other cell types involved in the recognition and destruction of foreign substances
B- cells represent a specific lymphocyte cell line that can differentiate into specific plasma cells - what do they synthesize
antibodies
the process of b cells and their ability to differentiate into specific plasma cells that synthesize antibodies- how is this controlled?
by helper and suppressor t cells
what else are B cells called
bursa- derived cells
why are b cells called bursa derived cells
BECAUSE IN BIRDS, THE BURSA OF FABRICIUS IS IMPORTANT IN PRODUCING CELLS RESPONSIBLE FOR ANTIBODY SYNTHESIS
name the 5 MAJOR CLASSES OF ANTIBODIES
IgG, IgA, IgM, IgD, AND IgE
HAS AT LEAST 2 HEAVY CHAINS AND 2 LIGHT CHAINS THAT ARE BOUND TOGETHER BY DISULFIDE BONDS
each antibody
what are antibodies
specific proteins called immunoglobuins
what is the antibody function
recognize and bind to specific antigen
DEPOSITION OF ANTIBODY OR COMPLEMENT FRAGMENTS ON THE SURFACE OF FOREIGN CELLS TO PROMOTE KILLING FOREIGN CELLS BY EFFECTOR CELLS. this process is known as
OPSONIZATION:
what is the role of macrophages
regulate immune responses by processing and presenting antigens to effect inflammatory, tumoricidal, and microbicidal functions
where do macrophages come from
circulating monocytes
where are macrophages confined to
specific organs- such as the lung
_____ ingest antigens before they interact with receptors on the lymphocyte surface to regulate their action
MACROPHAGES
macrophages synthesize mediators to facilitate what two responses
b lymphocyte and t lyphocyte responses
what is the first cell to appear in acute inflammatory reaction
neutrophils
once neutrophils are activated what do they produce
hydroxyl radicals
superoxide
hydrogen peroxide
once neutrophils produce hydroxyl radicals, superoxide, hydrogen peroxide what happens next
microbial killing
what do neutrophils contain
acid hydrolases
neutral proteases
lysosomes
what is the function of eosinophils
unclear
where are eosinophils formed
exclusively in the bone marrow
how long do eospinphils travel to reach their final destination
8-12 hours
inflammatory cells recruit eosinophils to collect at what 3 sites
parasitic infections
tumors
allergic reactions
esoniphils are seen in allergic diseases, name 3
asthma
auto immune disease
hay fever
name the acute/chronic allergic diseases basophils are seen in
anaphylaxis, asthma, dermatitis
basophils comprise what percent of circulating granulocytes in the blood.
how common are they?
0.5-1%
least common
basophils contribute to resistance to what two things
internal parasites and ectoparasites (such as ticks)
basophils IgE RECEPTORS ARE ON THE SURFACE WHICH FUNCTION SIMILARLY TO THOSE ON …
MAST CELLS.
what are mast cells important for
immediate hypersensitivity responses
mast cells are tissue fixed and located where
perivascular spaces of skin lung and intestine
what lies on the surface on mast cells and bind to specific antigens
ige receptors
once mast and Kinin cells are activated what do they release
physiologically active mediators important to immediate hypersensitivity responses
where are kinins synthesized
in mast cells and basophils
kinins produce what physiologic response
vasodilation
increased capillary permeability
bronchoconstriction
kinins stimulate vascular endothelium to release what
vasoactive factors, including prostacyclin and endothelial-derived relaxing factors such as NO
TYPE I REACTION:
what type
what is released and what does it bind to?
anaphylactic or immediate type hypersensitivity reaction.
PHYSIOLOGICALLY ACTIVE MEDIATORS ARE RELEASED FROM MAST CELLS AND BASOPHILS AFTER ANTIGEN BINDING TO IgE ANTIBODIES ON THE MEMBRANES OF THESE CELLS. THIS INCLUDES ANAPHYLAXIS, EXTRINSIC ASTHMA, ALLERGIC RHINITIS
TYPE II REACTION:
Mediated by what antibodies?
ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXIC HYPERSENSITIVITY OR CYTOTOXIC REACTIONS.
MEDIATED BY EITHER IgG OR IgM ANTIBODIES DIRECTED AGAINST ANTIGENS ON THE SURFACE OF FOREIGN CELLS
what are the antigens in type 2 reactions
THESE ANTIGENS MAY BE EITHER INTEGRAL CELL MEMBRANE COMPONENTS OR HAPTENS
allergy type 2 reaction integral cell membrane components
A OR B BLOOD GROUP ANTIGENS IN ABO INCOMPATIBILITY REACTIONS
what is the role of haptens in type 2 reaction
absorb to the surface of a cell, stimulating the production of antihapten antibodies (autoimmune hemolytic anemia)
cell damage examples type 2 reaction
drug induced immune hemolytic anemia
heparin induced thrombocytopenia
incompatibility transfusion reactions
type 2 cell damage produced by
direct cell lysis after complete complement cascade activation
increased phagocytosis by macrophages
killer t cell lymphocytes producing antibody dependent cell mediated cytotoxic effects
type 3 allergy reaction results from
circulating soluble antigens and antibodies that bind to form insoluble complexes that deposit in the microvasculature
type 3 reaction role of neutrophils
localized to the site of complement deposition to produce tissue damage
what is “activated” in type three allergy reaction
complement
type 3 allergy reactions examples
serum sickness after snake antisera
antithymocyte globulin
immune complex vascular injury
occur through mechanisms of protamine mediated pulmonary vasoconstriction
how fast is type IV reaction
manifest within?
peak?
disappear?
delayed hypersensitivity reaction
manifest in 18-24hrs
peak 40-80 hours
disappear 72-96hrs
what does a type IV reaction result form
the interactions of sensitized lymphocytes with specific antigens
type 4 allergy cytotoxic t cells are produced to do what
kill target cells that bear antigens identical with those that triggered the reaction
type IV reaction 4 examples
tissue rejection
graft vs host reactions
contact dermatitis-poison ivy
tuberculin immunity
intraoperative allergic reaction risk of periop anaphylaxis is reported how often
1:3,500 AND 1:20,000
intraoperative allergic reaction mortality %?
surviving % with severe brain damage
4%
2% surviving with brain damage
> 90% of the allergic reactions evoked by IV drugs occurs with in how many minutes of administration
5 minutes
what is the most common life threatening manifestation of an allergic reaction
circulatory collapse
circulating collapse is reflecting what hemodynamics
vasodilation with resulting decrease venous return
how is anaphylaxis initiated
an antigen binding to IgE antibodies
how is sensitization produced
prior exposure to the antigen is needed
can a patient have an allergic history and not know it
yes
Arachidonic acid metabolites: name the 4 that are released. why are they released
Arachidonic acid metabolites: (leukotrienes and prostaglandins), kinins, and cytokines are subsequently synthesized and released in response to cellular activation in anaphylactic reaction
On re-exposure, binding of the antigen to bridge two immuno-specific IgE found on the surfaces of mast cells and basophils release
Histamine
Tryptase
Chemotactic factors
arachidonic acid metabolites (leukotrienes and prostaglandins)
kinins
cytokinins
The released mediators (from arachidonic acid metabolites) and histamine, tryptase, and chemotactic factors, kinins and cytokinins produce a symptom complex of:
Bronchospasm Upper airway edema in respiratory system Vasodilation Increased capillary permeability in the CV system Urticaria
when activated what do mast cells and basophils produce
different mediators
when activated releases endothelium derived relaxing factor (nitric oxide) from vascular endothelium, increases capillary permeability, and contracts airway and vascular smooth muscles
H1:
Activation causes gastric secretion, inhibits mast cell activation and contributes to vasodilation. When injected into the skin, histamine produces the classic wheal and flare…(Wheal: increased capillary permeability producing tissue edema: Flare: cutaneous vasodilation)
H2:
how does histamine undergo rapid metabolism
by histamine N methyltransferase and diamine oxidase which is found in the endothelial cells
drug of choice for anaphylactic reaction
EPI
Hypotension EPI dose
5-10mcg bolus titrate to effect
dose of epi for CV collapse full IV cardiopulmonary resuscitative
0.1-1mg of EPI should be given until hemodynamically stable
patents with laryngeal edema without hypotension should receive EPI what route
sub Q because IV should not be given in normotensive patients
what do we know about anesthetized patients and their sympathoadrenergic responses to acute anaphylactic shock/ spinal or epidural
may need larger doses of catecholamines
what are the epi effects we need to treat anaphylactic reaction
vasoconstriction to reverse hypotension. beta 2 receptor stimulation bronchodilator and inhibits mediator release by camp in mast cells ad basophils
what do we do to anesthetic volatiles in an anaphylactic reaction
turn off anesthetic drugs (not the bronchodilator you want especially if hypotension is involved)
they also interfere with the body compensatory response to CV collapse
what is the risk of halothane to the myocardium during an anaphylatic response
halothane sensitizes the myocardium to EPI
why do we give fluids during an anaphylactic response-
40% loss of intravascular fluid into the interstitial space causing rapid hypovolemia
how much fluid do we give initially
2-4liters of LR or NS or colloid
how much additional fluid do they need after the 2-4l bolus
25-50ml/kg given if hypotension persists.
COLLOID NOT PROVEN MORE EFFECTIVE IN ANAPHYLATIC SHOCK
what do we do for refractory hypotension
may require TEE for rapid assessment of intraventricular volume and ventricular function assessment
if we think the patient will have an allergic reaction what do we give
Pretreatment of antihistamines before giving drugs known to release histamine does not inhibit histamine release, but rather compete with histamine at the receptor and may attenuate decreases in SVR.
what do we know about the things given in the or causing a release of
histamine release in a dose dependent non immunologic fashion
why is the or is there non immunlogic histamine release
mechanism is not clear
non immunologic release of histamine is known to represent a select mast cell and not ____ activation
basophil
what is the only cell population that releases histamine in response to both drugs and endogenous stimuli
human cutaneous mast cells
what receptors is histamine release not dependent on? why is that?
mu receptors/c fentanyl and sufentanil do not release histamine in human skin
antibodies of IgG class- if directed against antigenic determinants or granulocyte surfaces can also produce {what}
leukocyte aggregation
antibodies of IgG class are called
leukoagglutinins
investigators have associated complement activation and PMN aggregation in producing the clinical expression of what 4 things
transfusion reactions
pulmonary vasoconstriction after protamine reactions
ARDS
septic shock
Interacts with specific high affinity receptors on polymorphonuclear leukocytes (PMNs) and platelets causing leukocyte chemotaxis, aggregation, and activation.
C5a: non IgE mediated reaction
Aggregated leukocytes embolized to various organs, producing microvascular occlusion and liberation of inflammatory products such as arachidonic acid metabolites, oxygen free radicals and lysosomal enzymes.
C5a: non IgE mediated reaction
They release histamine from mast cells and basophils, contract smooth muscles, increase capillary permeability, and cause interleukin synthesis.
C3a and C5a are the anaphylatoxins.
Immunologic and non-immunologic mechanisms release many of the same mediators without IgE involvement and can present an identical clinical syndrome of
anaphylaxis
Compliment activation follows both:
immunologic:
non-immunologic
Immunologic: antibody mediated or “the classic pathway”
Non-immunologic: alternative to the classic pathway
These include a series of multimolecular, self-assembling, proteins that release biologically active complement fragments of ____
c3 c5
Peptide Mediators of Anaphylaxis
Factors are released from mast cells and basophils that cause granulocyte migration (chemotaxis) and collect at the site of the inflammatory stimulus
Eosinophil (eosinophilic chemotactic factor) in acute allergic response is unclear
Eosinophils release enzymes that can inactivate histamine and leukotrienes
Neutrophilic chemotactic factor is release as well and may be responsible for the recurrent manifestations of anaphylaxis
Arachidonic Acid Metabolites
Arachidonic Acid Metabolites
Leukotrienes and prostaglandins are both synthesized after mast cell activation from arachidonic acid metabolism of phospholipid cell membranes through either lipoxygenase or cyclooxygenase pathways
Classic slow reacting substances of anaphylaxis is a combination of leukotrienes C4, D4, E4.
Leukotrienes: produces bronchoconstriction, increased capillary permeability, vasodilation, coronary vasoconstriction, any myocardial depression
Prostaglandins : potent mast cell mediators. Produces vasodilation, bronchospasm, pulmonary hypertension, and increased capillary permeability
Prostaglandin D2: major metabolite of plasma levels of thromboxane B2 which is a metabolite of thromboxane A2
recognition of anaphylaxis
what is onset?
what are the reactions expected?
Onset and severity of reaction r/t the mediator’s specific end-organ effect
An antigenic challenge in a sensitized patient usually produces immediate clinical manifestation of anaphylaxis BUT the onset may be delayed 2-20 minutes.
Reactions may range from minor clinical changes to full blown syndrome leading to death
