Innate

Acquired

Innate immunity

Phagocytosis of bacteria, etc by _______

Destruction of swallowed organisms by _______

Resistance of ____to invasion

Chemical compounds in blood which destroy _____

Name 4 of these chemical compounds

Phagocytosis of bacteria, etc by WBCs & tissue macrophages

Destruction of swallowed organisms by stomach acid & digestive enzymes

Resistance of skin to invasion

Chemical compounds in blood which destroy foreign organisms or toxins

lysosymes

basic polypeptides

complement complex

natural killer lympocytes

(Ron didn't seem to interested in this type of immunity)

*Acquired immunity involves humoral & cell mediated responses.

Humoral=__-cell immunity

Cell mediated=__-cell immunity

Humoral=B-cell immunity

Cell mediated=T-cell immunity

Antigens

Protein or large ___ unique to a specific toxin or organism

Usually of a ____ molecular weight

Antigenicity requires __________ molecular groups (epitopes) on the ______

Protein or large polysaccharide unique to a specific toxin or organism

Usually of a high molecular weight

Antigenicity requires regularly recurring molecular groups (epitopes) on the surface

Acquired immunity requires the presence of ____

These are present in greatest numbers in the _____, but also what 4 other areas?

see slide 4 for pic/lymphocyte dvpt

Acquired immunity requires the presence of lymphocytes

These are present in greatest numbers in the lymph nodes

spleen

submucosal tissue of GI tract

thymus

bone marrow

What is the primary mechanism in organ transplant rejection?

Where does B-cell production take place in mid fetal life? After that?

T cell immunity

liver

then later bone marrow

An antigen reacts with ___ or ___ & activates them.

T/F: T-cells have surface receptor proteins & the whole cell reacts, whereas B-cells have antibodies & only the antibody reacts.

An antigen reacts with T-cells or B-cells & activates them.

True

(B-cells have thousands of antibodies on their surface)

What is initiated by activation of T or B cells by antigen?

What amplifies this process?

Initiates extremely rapid reproduction of that specific T or B cell, resulting in a "clone" of that particular cell.

Macrophages-attack & liberate antigenic matter; secrete interleukin-1, which causes more reproduction of lymphocytes

Helper T cells-secrete lymphokines; very imp in B cell immunity

Plasma Cell Antibody Formation

Dormant _____ + specific antigen→

enlarge to form _____→

some of lymphoblasts differentiate to form _____→

plasmablasts divide to form _______

What do plasma cells produce?

How long does this process continue?

Dormant B cells + specific antigen→

enlarge to form lymphoblasts→

some of lymphoblasts differentiate to form plasmablasts→

plasmablasts divide to form plasma cells

Bcells→lymphoblasts→plasmablasts→plasma cells

Plasma cells produce Gamma Globulin Antibodies

Continues for days to weeks or until plasma cell dies

Following activation of B lymphocytes, some of the lymphoblasts form new _____ rather than plasma cells.

What do memory B-cells do until they are activated?

What does a subsequent exposure to a specific antigen produce?

circulate throughout the body but remain dormant until activated by the same antigen

produces a much more rapid, pronounced, & sustained response

Anitbodies are either what 2 kinds of proteins?

These account for ~20% of _____

Each antibody is _____ for a particular antigen

What are 5 classes of antibodies?

Which class is the largest # of antibodies?

Which class is involved in allergy & is only a small % of all antibodies?

gamma globulins or immunoglobulins (Ig)

These account for ~20% of plasma proteins

Each antibody is specific for a particular antigen

IgA, IgD, IgE, IgG, IgM 

largest #: IgG

allergy: IgE

What are 4 ways in which the invading organism is inactivated (antibody mechanisms)?

Briefly describe each.

1. Agglutination: bound together in a clump

2. Precipitation: antigen-antibody complex becomes too large & precipitates out

3. Neutralization: antibodies cover all the toxic sites of the antigenic substance

4. Lysis: attack cellular membranes & rupture the cells

The complement system consists of _____ present in plasma, many are ______

___ of these are primary importance

Normally ____, but activated mainly by the _____ pathway

The complement system consists of ~20 proteins present in plasma, many are enzyme precursors

11 of these are primary importance

The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime. However, it can be recruited and brought into action by the adaptive immune system.

Normally inactive, but activated mainly by the Classical pathway

Describe the 4 steps of the "Classical Pathway"

What is the result of complement activation?

1. antigen-antibody rxn occurs

2. a reactive site on the antibody becomes "uncovered" & binds w/ protein C1

3. The activated proenzyme C1 sets in motion a cascade of rxns

4. Produces marked amplification

 "attack, disable & destroy invading cells"

What stimulates the "classical" pathway?

"alternative" pathway?

Which pathway is more common?

Classical:

IgG or IgM (transfusion rxns)

plasmin

Alternative:

lipopolysaccharides (endotoxin)

radiographic contrast media*

drugs

membranes

vascular graft material

latex

classical more common

On antigen exposure the specific clone of T-cells ___ & is ____

These T-cells recirculate in the body for ___ to ____

On antigen exposure the specific clone of T-cells proliferates & is released

These T-cells recirculate in the body for months to years

Memory T cells are formed in a process analogous to memory B-cell formation

What do the memory T-cells do until a subsequent exposure to that specific antigen?

What does activation of memory T cells result in?

they remain dormant

results in a more rapid & pronounced effect on subsequent exposure

When do T-cells react to antigens?

Name 3 antigen-presenting cells.

Only when they are bound to specific MHC proteins on the surface of antigen-presenting cells

macrophages

B-lymphocytes

dendritic cells

majory histocompatibility complex

carry antigen proteins degraded in antigen-presenting cells to the cells surface

What cells are the most numerous of the T-cells?

What role do helper T-cells play?

Helper T-cells do this via production & secretion of _______ which act on: (2)?

major regulator of virtually all immune fcn

via production & secretion of lymphokines which act on:

other immune systems

bone marrow

Helper T-cells cause:

Stimulation of growth & proliferation of ___ & ___ 

Stimulation of B-cell ___, ___, ___ & ___ secretion

Accumulation & activation of_____

_____ feedback (_____) of helper T-cells

Stimulation of growth & proliferation of cytotoxic & suppressor T-cells

Stimulation of B-cell growth, proliferation, plasma cell formation, & antibody secretion

Accumulation & activation of macrophages

Positive feedback (stimulation) of helper T-cells

Cytotoxic "killer" T-cells

___ proteins on their surface bind w/specific antigen

___(____) secreted, which puncture the attacked cell

____ substances released into attacked cell

Attacked cell ____&____

Cytotoxic "killer" cell moves away to ____ & later ____ other cells

Receptor proteins on their surface bind w/specific antigen

Perforins (hole forming proteins) secreted, which puncture the attacked cell

Cytotoxic substances released into attacked cell

Attacked cell swells & dissolves

Cytotoxic "killer" cell moves away to circulate & later attack other cells

normal tissue cells w/viral particles entrapped in them

cancer cells

transplanted tissue

regulation "suppression" of the cytotoxic & helper T-cells

limiting the immune system's ability to attack the host

What does tolerance of acquired immunity mean?

What does most tolerance result from?

recognition of "host" tissues as distinct from invading organisms

most tolerance results from "preprocessing"of lymphocytes to destroy the ones that would attack the host

What happens in failure of tolerance?

What happens to this w/age?

What are 4 examples of this?

destruction of body tissues releases "self-antigens" which may activate T-cells or antibodies

increases w/ age

rheumatic fever

some glomerulonephritis

myasthenia gravis

SLE

Name 3 types of immunizations & describe them

Killed: dead organism, but antigenic material remains

Chemically treated: no longer toxic, but antigenic material intact

Live-attenuated: cultured in special media or passed thru animals until mutated enough that it won't cause disease, but still antigenic

What is passive immunity?

How long does this last?

T-cells or antibodies from another person or animal transfused

Confers immunity for hrs to wks

Type I (classic allergic rxn)

IgE mediated

involves mast cells & basophils

Type II

IgG, IgM and complement

Type III

tissue damage via immune complex formation or deposition

Type IV

T-cell mediated delayed hypersensitivity

What type of allergic rxn is anaphylaxis?

What mediates this?

What is tryptase?

Immediate Type I hypersensitivity rxn

IgE mediated release of active substances

(many different vasoactive substances are released; see slide 28 for full list)

Tryptase is a diagnostic marker that distinguishes b/n anaphylaxis & anaphylactoid rx

(released in anaphylaxis)

What are 3 major systems affected by anaphylaxis?

What are s/s of each?

Skin: urticaria

Respiratory system: bronchospasm & upper airway edema

CV system: vasodilation, changes in inotropy, incr capillary permeability

(some pts lose 1/2 their intravascular vol d/t capillary permeability; if you see an unexpected drop in BP, think anaphylaxis)

Anaphylaxis time frame

Typically _____

May be delayed ____

Rarely delayed _____

Timing unpredictable following _____

Severe symptoms may recur ___ later, requiring several hours of ________

Typically immediate

May be delayed 2-15 min

Rarely delayed 2.5 hrs

Timing unpredictable following oral admin

Severe symptoms may recur 6-8 hrs later, requiring several hours of close observation

(1st wave of symptoms-caused by vasodilation & feeling of impending doom, quickly followed by 2nd wave as cascade of mediators amplifies the rxn)

What is the definitive diagnosis of anaphylaxis?

When does it have to be measured?

plasma tryptase concentrations

measure w/in 1-2 hrs of rxn

What is the gold standard for definitive identification of causative antigen?

What are 2 other tests?

Skin testing-use preservative free, diluted antigen; pt can have anaphylaxis rxn during test, so need trtmt nearby

RAST & ELISA

Correct hypotension & hypoxemia

Replace intravascular vol

Inhibit further degranulation & release of vasoactive mediators

What is the #1 treatment for anaphylaxis?

What are 4 other treatments?

#1=Epi

fluid resuscitation

B2 agonists

corticosteroids

antihistamines?

*When should epi be given for anaphylaxis?

How does it help?

Early & as needed

correction of hypotension

relaxation of bronchial smooth muscle

restoration of membrane permeability

-decr release of vasoactive mediators

Why do we use B2 agonists in anaphylaxis?

T/F: Antihistamines are effective following release of vasoactive mediators

reversal of bronchospasm

F: Antihistamines are ineffective following release of vasoactive mediators

but might still give them if anticipate ongoing rxn (ongoing mast cell degranulation)

What are the effects of corticosteroids in anaphylaxis?

When might they be particularly useful?

enhances effect of B-agonist drugs

inhibition of arachidonic acid release & subsequent production of leukotrienes & prostaglandins

may be particularly useful following activation of the complement cascade

T/F: Treatment of anaphylactoid rxn is identical to anaphylaxis rxn

T/F: The s/s of anaphylactoid rxn are clinically distinguishable from anaphylaxis

true

False!!!

clinically indistinguishable

only way to distinguish is with plasma tryptase test

Is anaphylactoid rxn mediated by IgE?

How is anaphylactoid rxn produced?

No

produced by activation of:

blood coagulation & fibrinolytic systems

kinin-generating sequence

complement cascade

What drug is responsible for most fatal anaphlactic rxns in general population?

PCN

What is intolerance?

What is an idosyncratic rxn?

undesirable effect at low drug dose

undesirable effect independent of dose administered

MR

latex

antibiotics

Why is there a high incidence of anaphylaxis rxns w/ MRs?

Why might you see anaphlyaxis on 1st exposure to MR?

How long can a person remain sensitized after developing antibodies?

Antibodies to MR may also cross-react w/ what?

IgE antibodies to quaternary or tertiary ammonium ions

Quaternary & tertiary ammonium ions are contained in many cosmetics & OTC drugs

up to 30 yrs

ammonium ions of neostigmine & morphine

With what class of MRs might you see histamine release from direct mast cell degranulation (non-immune mediated)?

Name 3

Benzylisoquinolinium NDPMRs

mivaurium

atracurium

curare

Is anaphylaxis common w/ barbs?

What about opioids?

rare, more common in atopic individuals

very rare, but morphine may cause direct release of histamine

Anaphylaxis & propofol

have occured following ___ or ___exposures

higher risk in pts ____ to other drugs

high incidence of ______

have occured following  1st or subsequent exposures

higher risk in pts allergic to other drugs

high incidence of bronchospasm

Do ppl have anaphylactic rxns more often w/ amide or ester LAs? Why?

What can be causative in both classes of LAs?

Esters-more common d/t metabolism of PABA

preservatives:

methyparaben & proplyparaben

desflurane

decr metabolism

With protamine, anaphylaxis is more common in which 3 types of pts?

Besides anaphylaxis, what else can protamine cause?

seafood allergy

diabetic using protamine-containing insulin

following vasectomy

may also cause direct histamine release & activate complement cascade

Which ABX most commonly causes anaphylaxis?

Which ABX has a rare incidence of causing anaphylaxis? When can this incidence be incr?

What 3 blood & vol expanders cause anaphylaxis?

What is the #1 cause of anaphylactoid rxn? why?

most common: PCN

rare: cephalosporins; minimally incr w/ PCN allergy

blood, dextran, hespan

Radiocontrast media: iodine containing

Life-threatening periop allergic drug rxns are reported w/ most all anesthetic drugs, except which 2?

BZDs

Ketamine

*What is the primary manifestation of anaphylaxis in an anesthetized pt?

When does it typically occur?

Exception?

CV collapse

typically occurring w/in 5-10 min of drug exposure

exception: latex allergy might take ~ 30 min

Hx of multiple surgical procedures

[congenital urinary tract anomolies & *Myelomeningocele (spina bifida)]

Health care providers

Occupational exposure

Hx of atopy, hay fever, rhinitis, asthma, or excema

Hx food allergy

What is a diagnostic procedure for Type IV latex rxn?

for Type I?

Type IV: patch testing

Type I

serologic testing-RAST, EAST, ELISA

skin prick testing (gold standard)

skin or mucous membranes

 inhalation

ingestion

parenteral injection

wound inoculation

irritant contact dermatitis

Type IV (contact) hypersensitivity

Type I (IgE mediated) hypersensitivity

Type IV latex rxn

aka ____ type hypersensitivity

occurs over ___

___ mediated

limited to _____

aka delayed type hypersensitivity

occurs over ~24hrs

Cell mediated

limited to site of contact

Type I (IgE mediated) latex rxn

T/F: this is a true allergic rxn

Does this type of rxn have localized or systemic effects?

True

Localized and/or systemic effects

When should you schedule surgery for a pt w/ latex allergy?

Is prophylaxis in latex-sensitive pt always successful in prevention?

What is a problem with prophylaxis in these pts?

What 3 drugs would you use for prophylaxis?

see slide 52 for treatment of latex allergy

1st case of the day

not universally successful

may attenuate early immune response, leaving anaphylaxis as the 1st sign

H1 blocker-diphenhydramine

H2 blocker-ranitidine

Glucocorticoid-methylprednisolone

*Dr Anderson says go for it cause it wont hurt anything

Tx of Type IV Latex allergy is ______ & ______.

Tx of Type I reactions depends on what?

avoidance

steroids

whether the reaction is localized or systemic

rhinitis = antihistamines

hives = antihistamines and systemic steroids

anaphylaxis = as discussed before