Part 11 Flashcards
Lymphatic drainage left side vs right
Left side is handled by thoracic duct emptying into subclavian vein and is all of lower limb, all of left side up to head, right side is handled by right lymphatic duct emptying into right subclavian vein and is only right side of upper limb to head
Example of active natural acquired immunity
Infection
Example of active artificial acquired immunity
Immunization
Example of passive natural acquired immunity
Maternal antibodies
Example of passive artificial acquired immunity
Exogenous antibody infusion
2 types of B cells
Plasma cells
memory cells
What cell type recognizes MHC Class II?
T helper cells
A CD4 count below ___ indicates ___
200, AIDS
CD4 T Cell function, what type of MHC does it interact with? What mediated immunity is it?
T helper cells activate B cells and release cytokines, interact with MHC class II, and promote cell mediated immunity
CD8 T cell function, what type of MHC does it interact with? What mediated immunity is it?
Cytotoxic T lymphocytes kill cancerous/infected/diseased cells, interact with MHC class I, and promote cell mediated immunity
NK cell function, what mediated immunity is it?
Kill virus related cells independant of MHC, innate immunity
Defining characteristics of the neutrophil, eosinophil, basophil, and monocyte
Neutrophil - small suicidal cells that form pus
eosinophil - present in parasitic reactions and allergic reactions
Basophils - allergic reactions
Monocytes - circulate in blood and travel to tissues where they become macrophages
IgE characteristics (2 key things)
Present in allergies by stimulating histamine release, attracts eosinophils
What is the only antibody type to cross the placenta?
I
IgG
IgG characteristics (3 key things)
Crosses placenta, indicative of 2ndary immune response, activates complement
IgM characterists (2 key tings)
Primary immune response, activates compliment
List the 3 types of phagocytes
1) Neutrophils
2) Macrophages
3) Dendritic cells
Type 1,2, and 3 sensitivities are ___ dependent, while type 4 is not
Antibody
Type 1 hypersensitivity
Anaphylactic reaction from degranulation of mast cells and release of inflammatory mediators, often IgE antibody is the source and it is immediate
Type 2 hypersensitivity
Host cellular destruction after small antigens bind covalently to cell surface structures causing it to appear foreign to the immune system and face the humoral response
Type 3 hypersensitivity
Immunocomplex formed when protein antigens bind to IgG made against them, then become deposited in different parts of the body that activates compliment system to initiate inflammation and physical damage
Type 4 hypersensitivity
Delayed onset, Effector T cell cause that results in cell death, such as from contact dermatitis
Best practice on preventing pediatric allergies
-Breastfeed, delay intro of solid foods until 6 months, introduce highly allergic foods before first year of life
Type I hypersensitivity uses what kind of Ig molecule? When is this molecule created?
IgE, made the first time they are exposed to the antigen (called sensitization, could have occurred due to exposure to a cross reactive compound)
Timeframe of type I hypersensitivity
IV response is within seconds to minutes, oral allergens take 5-60 min depending on stomach contents
Food intolerance vs type I hypersensitivity
No IgE or immune system activation is involved in food intolerance, it is amount dependent (unlike allergies) but it manifests as a difficulty digesting a food resulting often in diarrhea or associated symptoms but not systemic or as severe effects
Does type I sensitivity result in fever?
NO! That’s part of how you can differentiate it from infection
If a patient has an anaphylactic allergy to penicillin, what drug class should also be avoided? vs if they just have a rash reaction to PCN then this is acceptable
Cephalosporins
Anaphylactic episodes can not be predicted on ___ or ___ of progression
severity, rate
Use of trendelenberg in immediate management of type I hypersensitivity
Encourage venous return limiting drastic drops in BP
How do antibodies work? (3 things
Neutralize pathogens, fixate complement to the surface of cells to allow for lysis, allow for binding various cell types such as phagocytes, lymphocytes, platelets, mast cells, and basophils (opsonization)
H2 blockers function in type 1 hypersnsitivity and example
Used in type I hypersensitivity to relieve GI symptoms of anaphylaxis, ranitidine (zantac)
Complement and its 4 actions
A group of globulin proteins that act as enzymes to facilitate the immunologic and inflammatory response by increasing vascular permeability, chemotaxis, phagocytosis, and opsonizing the antigen for binding
Type II and III hypersensitivity uses what two types of Ig molecule?
IgM, IgG
Type II hypersensitivity rxn mech
-IgM and IgG bind to antigens covalently bound to the cell surface resulting in complement activation, increased vascular permeability results in antibodies and WBC’s to enter the area of inflammation and lyse/phagocytose cells
Type III hypersensitivity rxn mech
-Antibodies bound to antigens in circulation form immune complexes that deposit in tissue causing damage and inflammation
Type IV hypersensitivity rxn mech
-Contact of antigen with pre sensitized T lymphocytes results in macrophage activation and inflammatory reaciton of tissue most often manifested as contact dermatitis
Key diff between type II and type III hypersensitivities
If the antigen binds to a cell surface or is free floating
Type II hypersensitivity examples (7)
- transfusion reactions
- autoimmune hemolytic anemia
- goodpasture’s(lung and kidney)
- graves disease (hyperthyroidsism)
- myasthenia gravis (neuromuscular weakness)
- rheumatic fever (post strep infection)
- erythroblastosis fetalis
Direct and indirect coomb’s test and what they measure
Direct detects antibodies on RBC cell surface (bound immunoglobins) and a positive is indicative of a hemolytic reaction, indicrect detects antibodies floating freely in circulation (unbound immunoglobins) and a positive indicates that blood is incompatible with another type
Erythroblastosis fetalis can be witnessed within even the ___ pregnancy. Also, anytime ___ occurs this does not exclude the possibility of future pregnancies suffering the same disease. What do we treat it with preventativly for the mother?
first, conception (even if abortion or ectopic or whatever), rhogam Rh immune globin is given at 28 weeks and within 72 hrs of delivery
Type III hypersensitivity examples
- Serum sickness
- Arthus reaction (localized painful reaction at vaccine antigen injection site)
- Farmer’s lung
- systemic lupus erythematosus
- Post streptococcal glomerulonephritis (untreated strep)
3 things almost always seen in a type III hypersensitivity
1) skin eruptions such as systemic urticaria
2) fever
3) joint symptoms
type IV hypersensitivity example
contact dermatitis
Type IV hypersensitivity reaction mech
-Langerhan’s cells on skin process antigen from epidermis and drain to lymph nodes where it is processed by T cells, which then cause the entire skin to become hypersensitive to the contact allergen
Mycobacterium avium complex (MAC) opportunistic infection
Bacterial infection causing recurring fevers and malaise in immunocompromised host
Significant molecule in the production of neutrophils and macrophages
Colony stimulating factor (G-CSF)
Congenital neutropenia (what type is it, what should you know about it)
Production disorder, rare, caused by an ELANE gene mutation
Cyclic neutropenia (what type is it, what should you know about it)
Production disorder, monthly rise and fall in wbc being produced, might see patient getting sick during those times but rarely impacts life significanly
Chediak Higashi syndrome(what type is it, what should you know about it)
Production disorder, autosomal recessive disorder resulting in partial albinisim, impaired phagolysosome production resulting in large granules, frequent bacterial infections, and peripheral neuropathy later in life
Felty syndrome and the triad for diagnosis
Mostly assymptomatic, some develop serious and life threatening infections secondary to granulocytopenia
Rheumatoid arthritis, splenomegaly, neutropenia
Glucocorticosteroids (oral or like a knee injection for example) positive and negative effects on the neutrophil
Positive - enhance production and mobilize marginated (peripheral pool ) into circulation
Negative - reduce adherence capacity and chemotactic properties
X linked agammaglobulinemia (bruton syndrome) notes (4)
- tyrosine kinase enzyme is deficient preventing the progression of B cells in development
- No mature B cells reach periopheral circulation
- Lymphoid structures are hypoplastic
- Found only in boys
Common variable acquired immune deficiency notes (4)
- most common of treatable immunoglobulin deficit states
- B cells do not respond to T cell signaling
- Absence of helper T cells
- Most common onset ages are between 6-8 and 15-35
Most common of all immunodeficiencies and what group does it affect the most?
IgA, caucasians
DiGeorge syndrome key points (4)
- Deficit of T cells
- Defect of chromosome 22 in 50% of cases
- Results in poor or no development of several body systems
- Has triad of absent thymus, absent parathyroid (hypocalcemia), tetralogy of Fallot
- Facial congenital abnormalities
Severe combined immunodeficiency (SCID) clinical presentation and labs and treatment
Medical emergency, often see pneumocystis jiroveci infection
Low lymphocyte count (by definition complete lack of B and T cells, normal IgG, high IgE and A, low IgM
isolation bubble, Iv Ig, stem cell transplant
Water and electrolyte effects of Glucocorticoids/corticosteroids
Glucocorticoids to varying degrees act like aldosterone to act on kidney promoting retention of sodium and water resulting in hypernatremia, edema, and hypokalemia
Glucocorticoids/corticosteroids release mech and feedback loop
- stress acts on hypothalamus
- hypothalamus releases CRF
- Ant pit receives CRF and releases ACTH
- The adrenal cortex receives ACTH and causes release of glucocorticoids that has neg feedback on hypothalamus and ant pituitary
NSAIDS act on ___ enzyme to prevent ___ formation
cyclooxygenase, prostacyclins
Glucocorticoids/corticosteroids act on ___ enzyme to prevent ___ formation, and are thus ___ than NSAIDS
arachodonic acid formation (delta 6 desaturator), leukotrienes and prostacyclins downstream, stronger
DOC for life threatening allergic reactions is…
Why isn’t it glucocorticoids?
Epi, because the response is delayed they cannot serve acute allergic rxns
2 main applications of immunosuppressants
1) prevent organ rejection
2) tretment of autoimmune disorders
2 big toxicities of immunosuppressants
Increased risk of infection, increased risk of neoplasm development
Cyclosporine/tacrolimus/pimecrolimus mech of action
Inhibit calcineurin, blocking IL2 for T cell proliferation
DOC for preventing organ rejection after allogenic transplant
Cyclosporine
Cyclosporine differs from other immunosuppressants in that…
Prevent rejection of allogenic organ without suppressing bone marrow
Methotrexate summary, what class of drugs does it belong to?
Anticancer drug also used for immunosuppression
Cytotoxic
Efffects of H1 receptor stimulation
- Vasodilation
- increased capillary permeability
- bronchoconstriction
- increased itching or pain
effects of H2 stimulation (1)
Secretion of gastric acid
2 classes of H1 antagonist
1st gen - diphenhydramine and chlorpheniramine
2nd gen - cetirizine, levocetirizine, fexofenadine, loratidine, desloratidine
Diff between 1st and 2nd gen H1 antagonists
- 1st gen are highly sedating, 2nd not very much
- 1st gen have anticholinergic effects leading to dry mouth, difficulty in micturition, tachycardia, constipation, virtually absent in 2nd generation
H1 antagonist mech of action
Competes with antihistamine for H1 receptors, does not inhibit histamine already attached to receptors so therefore should be taken 2 to 5 hours before allergen exposure (prophylactically)
ADR’s of H1 (primarily 1st gen but some 2nd gen) antagonist (4)
- sedation (1st gen)
- psychomoor performance
- GI disturbances
- anticholinergic effects (primarily 1st gen)
Name the 5 big 2nd gen H1 blockers (brand name and generic)
Fexofenadine (allegra) Cetirizine (zyrtec) Loratadine (claritin and alavert) Desloratadine (clarinex) Levocetirizine (xyzal)
Pseudoephedrine is a ___ often included in 2nd gen H1 blockers under the suffix ___
decongestant, -D
Mast cell stabilizers mech of action
Inhibit release of histamine and other mediators of inflammation from sensitized mast cells as preventative measure
Intranasal cromolyn (Nasalcrom) drug class, who is it primarily recommended for?
Nasal mast cell stabilizer, young children, pregnant, and elderly because it is very safe but only moderately effective
Rhinitis medicamentosa
Rebound congestions resulting from down regulation of a adrenergic receptors when prolonged repeated use of intranasal decongestants occurs, requiring limitation of 3-5 days of use of intranasal decongestants, occurs orally as well requiring slow withdrawal to prevent sharp increase in congestion
Sympathomimetics ADRs (3)
- rebound congestion
- CNS stimulation
- cardiovascular effects raising blood pressure and heart rate slightly
Sympathomimetics mech of action
Decongestants through stimulating a1 adrenergicc receptors on nasal blood vessels resulting in vasoconstriction and shrinkage of swollen membranes followed by nasal drainage breaking up mucus
Ipratropium bromide (atrovent nasal spray) mech of action
Anticholinergic agent that decreases mucus secretions
Omalizumab(Xolair) mech of action
Composed of injected monoclonal antibodies directed against IgE preventing release of inflammatory mediators from mast cells and basophils
4 common routes of allergens to enter the body
- Skin contact
- Injection
- Ingestion
- Inhalation
Drug allergies are ___. Most reactions are actually ___ and not a true allergy
Rare, negative side effects
Is there a correlation between consumption of food in utero or in breast milk and development of allergies?
No relationshipo has been evidenced
Skin prick test definition
Use of a small drop of the possible allergen placed on skin and pricked, if allergic develops redness, swelling, and itching within 20-40 min
Patch testing definition
Placing a patch on arm or back or 48 hours, avoiding shower or sweat, then removed when returned to Dr’s office, irritated skin at site may indicate allergy, can detect delayed allergic rxns and typically done for contact dermatitis
Alternating nares is characteristic of ____ in an individual without anatomic defect
True allergic rhinitis
Allergic crease definition
Transverse crease across bridge of nose from rubbing and bending the cartilage repeatedly
Lymphoid hyperplasia/cobblestoning of mucosa
Visible characteristic patterning of bumps on physical exam indicative of allergic rhinitis
Immediate evaluation of a patient with urticaria should include these 2 things…
…airway and hemodynamic status
H2 blockers are only used effectively as an ___ to H1 blockers
Adjunct
The big 8 food allergies
Peanuts Treenuts Fish Shellfish Eggs Milk Soy Wheat
Food allergy definition
An adverse rxn to a food that is mediated by an immunologic mechanism, occurs consistently after consumption of that food
Common non-allergic food hypersensitivities example (1)
-Lactose intolerance
Galactosemia definition
Intolerance of galactose, more severe than lactose intolerance because can cause failure to thrive or mental retardation
Proven symptoms and signs of food allergy (4)
- GI reaction
- Cutaneous reaction
- Systemic reaction
- Respiratory reaction
Generally, as individuals age, they ___. However, if they have a late phase response, that means that their repsonse is likely to be ____
outgrow their allergies, chronic/lifelong
Hirschsprung’s disease definition
-Lack of nervous supply to colon resulting in a lack of peristalsis and constipation
PKU definition
rare inherited disorder causing phenylalanine amino acid buildup in body due to change in gene that creates enzyme to break it down, screened for in US at birth as often if undiagnosed develop symptoms by a few months old including musty odor, neurologic dysfunction, delayed development, microcephaly, have to follow strict dietary restrictions low in protein entire life
Most common type of WBC in blood stream
Neutrophil
Eosinophils target ___ cells and play a role in ___. They do not respond to ____
large cells too big for ingestion, allergies, viral infection
Baophils do not ____ foreign cells, play a role in ___, and do not respond to ____
ingest, allergies, viral infection
Classical pathway of complement activation
Antibody binds to and exposes complement binding sites on the foreign cell invader, complement proteins then for the membrane attack complex to tear cell apart
Alternative pathway of complement activation
Directly binds to the polysaccharides of microbial cell walls and forms the membrane attack complex to tear cell apart
What is the common protein between the classical and alternative pathway of complement activtation? Why is this one extra important to measure?
C3, it allows assessment of both classical and alternate pathways
Interferons definition
A type of cytokine that interferes with the reproduction of viruses
Pancytopenia definition
Decrease in all blood cell lines (WBC and RBC)
B cells don’t only produce antibodies and memory cells, but are also…
….APC’s
IgG 3 key facts
- constitutes the majority of circulating antibodies
- crosses the placenta
- fixes complement
Anergy panels and what antigens are commonly used to test them?
a test for T cell immune function to show a patient who previously demonstrated cell mediated immunity to an antigen no longer demonstrates the response, often found in HIV patients, lymphomas, etc. Common antigens used to test are candida and mumps
Live attenuated vaccine
Disease producing virus or bacterium weakened in lab, can still replicate but generally does not cause illness
Inactivated whole vaccine
The entire body of a dead virus or bacteria, cannot cause illness response
Inacivated fractional vaccine
A component of the virus or bacteria that the immune system recognizes to mount an antigenic response to, cannot cause illness, such as toxoids, subunits, or polysaccharide
Toxoid
Modified bacterial toxins that retain immunogenic properties but lack toxicity
List the 8 live vaccines
Measles mumps rubella varicella zoster rotavirus intranasal influenza typhoid
Inactivated vaccines are ___ compared to live vaccines, and therefore typically require a ___
Not as effective, booster
Can live vaccines be administered together?
Yep except cholera and yellow fever, no decrease in antibody response or adverse reactions
Can live vaccines be given one a day after the other?
No, require 4 week interval between two live injected
Should vaccine series be restarted if time has gone past the recommneded interval?
No, just start where you left off
4 day grace period
Refers to requirement that vaccine doses be administered no more than 4 days before the minimal interval or age in order to be counted as valid, otherwise must repeat the vaccine!
Can patient’s with mild illness be vaccinated?
Yes, no contraindication to withold vaccination from patients on antibiotics or with mild acute illness
VAERS
Vaccine adverse events reporting system, used to report a bad response to a vaccine regardless of if it is believed to be caused by the vaccine itself or not
3 contraindications for live vaccines
Pregnancy, moderate or severe acute illness, recent receipt of antibody containing blood product
Hep B vaccine: Type, schedule
- Inactivated fractional vaccine
- birth, 1-2 months, 6-18 months, 3 dose schedule for adolescents and adults otherwise
DTaP vaccine: type, schedule
- Inactivated fractional vaccine
- used for children younger than 7 and has a larger pertussis conc for initial exposure in children to gain immunity at 2/4/6/15-18 months, and 4-6 yrs
Tdap vaccine: type, schedule
- Inactivated fractional vaccine
- Used on anyone older than 7 ever 10 years as a booster to the DTaP
Polio vaccine: type, schedule
- Inactivated whole
- 2/4/6-18 months, 4-6 years
Almost always a vaccine should be administered with the bevel facing….
….upward
