Exam 3: Immune Dysfunction Flashcards
The Immune system functions to…
Protect the host against micro-organisms
(two types: innate and adaptive/acquired immiunity)
S2
What aspect of the immune system requires no prior exposure to pathogens?
Innate Immunity
S3
What aspect of our immune system is rapid, non-specific, and does not provide long-lasting protection?
Innate Immunity
has no memory, but the response is always identical
S3
What are the 3 non-cellular components of innate immunity?
- Epithelial and mucous membranes
- Complement system proteins
- Acute phase proteins
S4
What are the 4 cellular components of the innate immunity system?
- Neutrophils
- Macrophages
- Monocytes
- NK cells (Natural Killer Cells)
S4
What cell (of the innate immunity response) responds the fastest to infection?
Neutrophils
S4
What cell (of the innate immunity response) provides a slower but more prolonged response to infection?
Macrophages
S4
What is the Complement System?
Over 30 plasma and cell surface proteins that complements both innate and adaptive immunologic systems.
S5
What does the Complement system do to enhance the adaptive and innate immunologic systems?
- Augments phagocytes and antibodies
- Marks pathogens for permanent destruction
S5
Where are the proteins for the Complement system produced?
Most are produced in the Liver
S5
What activates the complement system?
Infection of course.
C1 and C3 (Complement proteins 1 & 3).
S5
What is the most numerous WBC?
Neutrophils
S6
Part of Innate immunity
They are Neumorous
What are the characteristics and actions of neutrophils?
- Migrate rapidly to bacterial infections
- Release cytokines to phagocytize
- ½ life is 6 hours
- Sensitive to acidic infection environments
- Become purulent exudate
S6
What type of immune cell is the largest blood cell and what is their role?
- Monocytes (largest blood cell)
- Circulates to specific tissue areas to differentiate into macrophages
not mentioned in lecture - but the chart also shows them turning into dendritic cells - and we know how tricky they like to be
S7
What are the names of monocytes that have circulated to following areas:
- Epidermis
- Liver
- Lungs
- CNS
- Epidermis → Langerhans
- Liver → Kupffer
- Lung → Alveolar cells
- CNS → Microglia
S7
What are the pertinent characteristics of monocytes/macrophages?
- Mobilize just after neutrophils
- Phagocytic destruction via NO & cytokines
- Persist at site in chronic infections (fight infection long term)
S7
So then what are all the cells a parent Granulocyte-monocyte progenitor can turn into?
S4
What is the least common blood granulocyte? (circulating)
Basophils
S8
What cells reside in connective tissue close to blood vessels?
Mast Cells
S8
What are the characteristics/actions of basophils/mast cells?
- Express high affinity for IgE
- Initiate hypersensitivity reactions
- Stimulate smooth muscle contraction i.e. bronchoconstriction
S8
How do Basophils and Mast Cells initiate hypersensitivity reactions?
- produce histamine
- leukotrienes
- Prostaglandin release
- cytokines
His Large Prostate Crys
S8
What cells play a major role in allergies, asthma, and eczema?
Basophils and Mast cells
S8
Characteristics of Eosinophils
- Heavily concentrated in GI mucosa
- Protects against parasites
- Degrade mast cell inflammation
S9
What characteristics does Adaptive Immunity possess?
- Present only in Vertebrates
- Delayed onset of action
- Capable of memory and specific antigen response
Vaccinations are also a form of adaptive memory
S10
What type of cells do adaptive immunity cells originate from?
Hematopoietic stem cell on the lymphoid side (lymphoid progenitor on the chart)
S10
What is the humoral component of the Adaptive Immunity system?
What does this component do?
B cells → produce antibodies which bind to foreign proteins of bacteria, viruses and tumors
Dr. Google says they produce IgM, IgD, IgG, IgA, and IgE antibodies, not sure if Mordacai actually said all of these - please verify
Nothing was said during lecture for this slide, I think we can delete.
S11
What are the cellular components of the adaptive immunity system?
Helper T-cells
Cytotoxic T-cells
S11
Where do T-cells originate? Where do they mature?
T-cells originate in the bone marrow and mature in the Thymus.
S11
What are the general characteristics of T-cells?
- Produce interferon and interleukin
- Activate IgE
- Role in chronic inflammation
- Respond to infection
S11
What is the primary example of passive immunity?
Maternal IgA antibodies from breast milk
Dr. M also added: IVIG intravenous immunoglobins - given to immunocompromised pts (from pooled plasma) - effective but pricy
S12
How long does passive immunity last?
When a pt receives antibodies from someone else, the protection can last from weeks-months
S12
What is the primary example of active immunity?
Vaccines (they trigger antibodies to be formed)
live, inactive, or recombinant
S12
Describe active immunity
- Pathogen deliberately administered
- repeat exposure for a quick response to pathogens the next time
S12
Is neutropenia an example of excessive or inadequate immune response?
Inadequate
S13
Is Asthma an example of excessive or inadequate immune response?
Excessive
S13
Are autoimmune disorders an example of excessive or inadequate immune response?
Trick Question!
They are a misdirection of the immune response
S13
What is required for hypersensitivity development?
Prior sensitization (grass, latex, nuts, meds etc)
S14
What is hypersensitivity?
Foreign antigen reaction which causes altered T-cell and antibody response
Response varies from uncomfortable rash to fatal anaphylaxis
S14
What is the most common source of hypersensitivity?
Drugs (NMBD, ABX, PPIs, NSAIDS etc.)
Roc is #1 cause of anaphylaxis under anesthesia
S14
What occurs during a Type I Allergic Response?
- 1st exposure: T-Cells stimulate B cells to produce IgE immediately
- 2ⁿᵈ exposure: Antigen releases Ca⁺⁺ → histamine, inflammatory mediators, heparin are released.
(Histamine triggers: bronchostriction, Vascular permeability, vasodilation, gastric acid)
S15
What are examples of a Type I allergic response (aka immediate hypersensitivity)?
Anaphylaxis, Asthma, Angioedema, Conjuctivitis, Dermatitis
S15
What are common drugs used to prevent the histamine effects of Type I allergic responses?
- Antihistamines
- Cromolyn Na⁺
- Bronchodilators
- COX Inhibitors
- Diagnostic allergen tests
- small doses of allergen to desensitize
S16
What is another name for Type II Allergic Responses?
What mediates these types of responses?
What is the reaction severity and time?
- Cytotoxic Hypersensitivity
- Mediated by IgG, IgM, and Complement system → activate B-cells → produce antibodies.
- Severity will vary - reaction time in minutes or hours
mediated by GMC
S17
What are examples of Type II Allergic Responses?
- Hemolytic Anemia
- Myasthenia Gravis
- Transfusion Reactions
S17
What is the treatment for Type II Allergic Responses?
- Anti-inflammatories
- Immunosuppressants
- IVIG up and coming
S17
What is another name for Type III Allergic Response?
Immune Complex Hypersensitivity
S18
What occurs with Type III Allergic Response?
Failure of immune system to eliminate antibody-antigen complex.
S18
Where are the antibody-antigen complexes deposited in immune complex hypersensitivity?
Joints, kidneys, skin, eyes
causes chronic ongoing inflammation of these places
S18
What antibodies mediate Type III Allergic Responses?
IgG and IgM
takes hours-weeks to develop
S18
What are examples of Type III Allergic Responses?
Systemic Lupus Erythematosus and Rheumatoid arthritis
S18
Treatment for type III allergic response?
- Anti-inflammatories
- might need immunisuppressives
S18
What is a Type IV Allergic Response?
T-lymphocyte and monocyte/macrophage mediated response that does not involve antibodies.
S19
What are examples of Type IV Allergic Responses?
- Contact Dermatitis
- Tuberculosis
- Stevens-Johnson Syndrome
S19
What are the most common symptoms with Type IV Allergic Responses?
Cutaneous symptoms
S19
Treatment for type IV allergic reaction?
- anti-inflammatories
- immunosuppressives
S19
Anaphylaxis
- life threatening condition (oh really?)
- about 1:5000 to 1:20,000 anesthetics
- usually occur within 5-10 min of exposure
S21
Symptoms of Anaphylaxis and what rhythm occurs with untreated anaphylaxis?
- Systemic vasodilation
- Hypotension
- Extravasation of protein and fluid (bc increased vessel permeability)
- Bronchospasm
- PEA
S21
What causes the loss in BP noted with anaphylaxis?
Vasodilation from NO release
This is from Andy - but its not anywhere on Mordacai’s slides…
What is the pathophysiology of anaphylaxis?
- Previous exposure had made IgE antibodies
- Mast cells and basophils degranulate: release histamine, leukotrienes, prostaglandins, eosinophil/neutrophil chemotactic factor, and platelet-activating factor
- Anaphylaxis: up to 50% of intravascular fluid extravasates
S22
lifetime prevalence 5%
What is Biphasic anaphylaxis?
- Occurs following an asymptomatic period without second exposure
- Secondary anaphylactic episode occurring 8 - 72 hours later.
occurs is 4-5% of the pts that experience anaphylaxis
S23
What are risk factors for a secondary anaphylactic episode?
- Severe initial response
- Initial response required multiple epi doses
S23
What are risk factors for perioperative anaphylaxis?
- Asthma (or any baseline hypersensativivity)
- Female (not in teen years)
- Long Anesthetic
- Multiple past surgeries
- Presence of other allergic conditions
FLAAM
S24
A quick anaphylaxis diagnosis can be compromised by…
- communication issues (you are trying to troubleshoot high airway pressures first etc..)
- pt is covered by drapes
S25
What labs can verify mast cell activation and release?
- Plasma Tryptase concentration: takes 1-2 hours, and verifies mast cell activation and release
- Plasma Histamine concentration
- Skin testing: 6 weeks after reacion wheel and flare response
S25
Plasma histamine concentration should be at baseline within ____ minutes of treatment.
60 minutes
S25
What is the treatment for anaphylaxis?
- first Call for help
- Stop blood, drugs, colloids
- 100% O₂
- Epi
- Fluids
S26
What is the epinephrine dose for adult anaphylaxis?
10 mcg - 1000mcg IVP q 1-2 min
S26
What is the epinephrine dose for child anaphylaxis?
1-10 mcg/kg IVP q 1-2 min
S26
If a patient experiencing anaphylaxis is resistant to epi, what should be given?
Vasopressin or Methylene blue
These will inhibit NO production and thus counteract vasodilation.
S26
What is the crystalloid dosage for anaphylaxis?
NS: 10 - 25 mL/kg over 20 min
repeat PRN
S26
What is the colloid dosage for anaphylaxis?
10 mL/kg over 20 min
repeat PRN
S26
Why is epinephrine the drug of choice for anaphylaxis?
- ↓ degranulation of mast cells & basophils → reduced vasodilation
- α1 = Increased blood pressure
- β1 = positive Inotropy & chronotropy
- β2 = Bronchodilation
S27
What drug classes are secondary treatments for anaphylaxis?
- Bronchodilators
- Antihistamines
- Corticosteroids
S28
What are the antihistamines (and dosages) used as secondary treatments for anaphylaxis?
- H1 → Diphenhydramine 0.5 - 1 mg/kg IV
- H2 → Ranitidine 50 mg IV
S28
What are the corticosteroids (and dosages) used as secondary treatments for adult anaphylaxis?
- Hydrocortisone 250 mg IV
- Methylprednisolone 80 mg IV
S28
What are the corticosteroids (and dosages) used as secondary treatments for pediatric anaphylaxis?
- Hydrocortisone 50-100 mg IV
- Methylprednisolone 2 mg/kg IV
S28
Type A blood will have what Antibodies, what antigens, and is compatible with what?
Type A blood will have
- Anti-B antibodies
- A-antigen
- compatible with A and O
S29
Type B blood will have what Antibodies, what antigens, and is compatible with what?
Type B will have
- Anti-A antibody
- B antigen
- compatible with B and O
S29
Type AB blood will have what Antibodies, what antigens, and is compatible with what?
Type AB will have
- no antibodies
- A and B antigens
- Universal recipient
S29
Type O blood will have what Antibodies, what antigens, and is compatible with what?
Type O will have
- Anti-A and Anti-B antibodies
- No antigens
- Compatable with O (although it is the universal donor bc of lacking antigens)
S29
Specific immune reactions: How does a transfusion reaction happen?
- This is a response to surface antigen on the donor RBC
- responds to A, B and Rh factors
S30
Specific Immune reactions: how does transplant rejection happen?
- Response to antigens on the donor organ
- this is due to preexisting antibodies
- can be acute or chronic
S30
Specific immune reactions: Graves disease
Autoantibodies to TSH receptor
most common cause of hyperthyroidism
S30
Specific immune responses: Multiple sclerosis
- immune mediated inflammation
- destroys myelin and underlying nerve fibers
S31
Specific immune responses: Rheumatoid arthritis
- abnormal production of proinflammatory factors
- infection is thought to play a role
S31
Specific immune reactions: SLE
- Autoimmune and inflammatory
- Antibodies against: RBCs, WBCs, nucleic acids, platelets, coagulation proteins
- affects multiple organ systems
S31
What is/are the cause(s) of hereditary angioedema?
C1 Esterase inhibitor deficiency/dysfunction (decreased C1) → leads to excessive bradykinin.
S33
What factors can cause C1 esterase problems?
- Menses
- Trauma
- Infection
- Stress
- Oral contraceptives
MOIST
S33
Could you of chosen another word? Perhaps Omits
What typically limits the production of excessive bradykinin?
C1
C1 limits kallikrein and Factor XIIa.
S33
What occurs anatomically with excessive bradykinin?
- Laryngeal swelling
- Vasodilation
S33
What dose of antihistamine should be used for hereditary angioedema?
Trick question. Hereditary Angioedema = excessive bradykinin and is unaffected by antihistamines.
S33
What body parts are typically effected by hereditary angioedema?
Legs, hands, face, upper resp tract
S33
What is the typical cause of acquired angioedema?
- ACE Inhibitors
S34
What symptoms are conspicuously absent with acquired angioedema?
No Urticaria or Pruritus
S34
What is responsible for the breakdown of bradykinin?
ACE
Thus ACE inhibitors = ↑ bradykinin = angioedema.
S34
What are the treatments for Angioedema?
- Airway maintenance (usually fiberoptic intubation or tracheostomy)
- FFP (reestablish volume)
- C1 Inhibitor concentrate
- Epinephrine
- Antihistamines
- Glucocorticoids? (not first line but give later)
GA- FACE
S35
How does the HIV infect the host?
- The virus (HIV) thru reverse transcription makes a double helix DNA with all viral genetic material
- Can change amino acid sequence; new version of the amino acids not recognized
S36
What cells are destroyed by the HIV virus?
Monocytes/Macrophages and T-cells
S36
How long does seroconversion take after inoculation with the HIV virus?
2-3 weeks
host experiences flu-like symptoms during the seroconversion
S37
What are the initial signs and symptoms of HIV conversion to AIDS?
Weight loss and failure to thrive
S38
How is HIV/AIDS diagnosed?
- ELISA: 4-8 weeks after infection
- Viral Load
- CD4/Helper T lymphocytes < 200k
- HAART agent sensitivity
S38
Big ass list of comorbidities associated with aids, but in general….
In general, if our pt is immunocompromised, they are more susceptable to more diseases (duh)
S39
Anesthesia assessment for immunocompromised: cardiac function
- Abnormal EKG
- LV dilation
- Pulmonary hypertension
- MI
- Pericardial effusions (25%)
S40
Anesthesia assessment for immunocompromised: Neuro function
- Dementia
- Increased ICP
- Autonomic nervous dysfunction
- Peripheral neuropathy (35%)
S40
Anesthesia assessment: pulm
- Respiratory failure
- Pneumothorax
- COPD
S41
Anesthesia assessment: Endocrine/hematologic
- Adrenal insufficiency
- Glucose intolerance
- Anemia
- Bone marrow suppression
- Thrombocytopenia
S41
Anesthesia assessment: Renal
- ATN
- ESRD
S41
Inhibition of the liver’s ____ has huge implications for anesthetic delivery in HIV/AIDS patients.
CYP 450’s
Affects: Hormone synthesis
Cholesterol synthesis
Vit D metabolism
Drug metabolism (prolonged)
Bilirubin metabolism (hyperbilirubinemia)
Drugs will also take much longer to clear
S42
What s/s characterize scleroderma? (AKA: systemic sclerosis)
- Inflammation
- Vascular Sclerosis
- Fibrosis of skin/viscera
IVF
S44
At what age does scleroderma typically occur?
What gender is typically affected? Cure?
- 20-40
- Females
- No cure
S44
Where are the mobility issues and pain of scleroderma?
- decreasing mobility of fingers
- facial pain d/t vascular sclerosis affecting the facial nerve
- Reynaud’s is common
S45
What GI symptoms of scleroderma are particularly pertinent to anesthesia?
- GI Tract Hypomotility
- ↓ LES tone (increased risk of aspiration)
S45
What cardiac issues is associated with scleroderma?
- dysthythmias and conduction abnormalities
S45
____ fibrosis and ____ artery stenosis are prominent considerations for anesthesia in scleroderma patients.
Pulmonary fibrosis and renal artery stenosis
S45
What are the overall anesthesia implications of scleroderma?
- Could have multiple organs dysfunctional
- Arterial catheter issues i.e. may have trouble placing an Aline
- Contracted intravascular volume
- Aspiration risk
- Limited neck mobility
- ↓ pulmonary compliance
S47
What do inhalation agents do the immune system?
- Suppress NK cells
- Induce apoptosis of T-cells
- Impair phagocytes
Unclear effects on tumor cells - sevo stimulates renal cell carcinoma, but inhibts small cell carcinoma.
we are the knights who say “NII”
S48
This benzodiazepine, ____, decreases the migration of neutrophils.
Midazolam
S48
This induction agent, ____, will depress natural killer cell activity.
Ketamine
S48
K for Killer
This induction agent, ____, decreases cytokines but promotes NK cells.
Propofol
S48
What drug class will suppress NK cells?
Opioids
Particularly morphine and fentanyl.
S48
What cell type plays the greatest role in chronic inflammation?
T-Cells
Andy
What cell type activates IgE and produces interleukins and interferons?
T-Cells
Andy
What drug class will inhibit prostaglandin synthesis?
NSAIDS
S48
