Hypersensitivity & Immunodeficiency Flashcards
Type 1 hypersensitivity is [time frame], [Ig]-mediated, and can lead to anaphylaxis
Type 1 hypersensitivity is immediate, IgE-mediated, and can lead to anaphylaxis
Type 1 hypersensitivities always begin with [stage]
Type 1 hypersensitivities always begin with sensitization
Asthma and allergic rhinitis are examples of [Type] hypersensitivity
Asthma and allergic rhinitis are examples of Type 1 hypersensitivity
In a type 1 hypersensitivity reaction, mast cells are activated by _
In a type 1 hypersensitivity reaction, mast cells are activated by cross-linking of bound IgE
The immediate response in a T1 hypersensitivity reaction involves activation of mast cells followed by release of _
The immediate response in a T1 hypersensitivity reaction involves activation of mast cells followed by release of pre-formed granules (histamine, proteases)
* This immediate phase is what can cause anaphylactic shock
Histamine effects include:
* Smooth muscle _
* Vascular permeability _
* Vascular smooth muscle tone _
* Mucus secretion _
* Pruritus
Histamine effects include:
* Smooth muscle contraction (wheezing)
* Vascular permeability increases (swelling, hives)
* Vascular smooth muscle tone decreases (hypotension)
* Mucus secretion increases
* Pruritus
Also part of the immediate response, _ and _ are synthesized and act as potent bronchial constrictors and increase vascular permeability
Also part of the immediate response, prostaglandins and leukotrienes are synthesized and act as potent bronchial constrictors and increase vascular permeability
* Neutrophils and macrophages also get recruited to the site
The release of [cytokine] from Th2 cells stimulates eosinophils
The release of IL-5 from Th2 cells stimulates eosinophils
The late phase of a T1 hypersensitivity reaction is focused on synthesizing _ to further amplify the immune response
The late phase of a T1 hypersensitivity reaction is focused on synthesizing cytokines to further amplify the immune response
Mast cells make [cytokines] in the late phase
Mast cells make IL-4, IL-5, IL-13, TGF-b in the late phase
* IL-5 recruits eosinophils which further tissue damage
(True/False) Chronic urticaria is Ig-E mediated
False; if the patient has hives daily/ continuously it cannot be IgE-mediated
* IgE mediated means immediate response –> degranulation of mast cells
* It then takes time to make granules again
In order to diagnose anaphylaxis, there must be signs of _
In order to diagnose anaphylaxis, there must be signs of 2 systems involved
1. Cutaneous
2. Respiratory
3. GI
4. Cardiovascular
(True/False) Only use Epi when a patient has respiratory involvement
False; it is anaphylaxis once two systems are involved- don’t wait to use Epi
Epinephrine treats anaphylaxis via its affect as an _
Epinephrine treats anaphylaxis via its affect as an alpha and beta agonist
* In addition to treating hypotension and bronchoconstriction it mitigates some mast cell degranulation directly via unknown mechanism
Why are anti-histamines and steroids not indicated for treatment of anaphylaxis?
Why are anti-histamines and steroids not indicated for treatment of anaphylaxis?
* Anti-histamines only help the pruritus symptoms and steroids do not work acutely
Steroids are more helpful in the late phase of T1 hypersensitivity; explain
Steroids affect transcription in the nucleus which takes time, only helps in the late phase to reduce cytokine synthesis
_ is a monoclonal antibody that binds free IgE to prevent its binding to mast cells and basophils; it can be given to patients with allergies to improve reaction threshold
Omalizumab is a monoclonal antibody that binds free IgE to prevent its binding to mast cells and basophils; it can be given to patients with allergies to improve reaction threshold
The first line treatment for allergic rhinitis is _
The first line treatment for allergic rhinitis is intranasal steroid (fluticasone, budesonide, triamcinolone)
* Most effective if taken over time, does not work immediately
Azelastine and olopatadine are [drug category] which are second-line options for allergic rhinitis
Azelastine and olopatadine are intranasal antihistamines which are second-line options for allergic rhinitis
* Work immediately but only 50% as effective as intranasal steroids
Cetirizine, fexofenadine, and loratadine are [drug category] which are third-line options for allergic rhinitis
Cetirizine, fexofenadine, and loratadine are 2nd gen antihistamines which are third-line options for allergic rhinitis
* Minimal effect on congestion
[Drug class] should not be used for more than 3 days in a row due to risk of rebound vasodilation, “rhinitis medicamentosa”
Intranasal alpha-agonists (Oxymetazoline) should not be used for more than 3 days in a row due to risk of rebound vasodilation, “rhinitis medicamentosa”
* Generally avoid
Albuterol is a drug that improves asthma via _
Albuterol is a drug that improves asthma via beta-agonism
Allergic contact dermatitis is primarily mediated by [cells]
Allergic contact dermatitis is primarily mediated by CD4+ T cells
* Poison ivy reaction is another example
Type 4 hypersensitivity is a [time frame], _ mediated reaction
Type 4 hypersensitivity is a delayed, T cell mediated reaction
* Time course 24-72 hours
When CD8+ cells recognize foreign cells they release _ and _ to perforate the cell membrane and induce apoptosis
When CD8+ cells recognize foreign cells they release perforin and granzymes to perforate the cell membrane and induce apoptosis
Dendritic cells present antigen that is recognized by CD4+ cells which secrete _ and _ to activate CD8+ cells and macrophages in a type 4 hypersensitivity reaction
Dendritic cells present antigen that is recognized by CD4+ cells which secrete IL-2 and IFN-gamma to activate CD8+ cells and macrophages in a type 4 hypersensitivity reaction
_ is the test used for evaluation of contact dermatitis
Patch testing is the test used for evaluation of contact dermatitis
SJS/TEN is a severe cutaneous adverse reaction in which skin sloughs off, DRESS stands for _ ; both are Type 4 reactions involving T cells
SJS/TEN is a severe cutaneous adverse reaction in which skin sloughs off, DRESS stands for drug rash with eosinophilia and systemic symptoms ; both are Type 4 reactions involving T cells
* SJS: 1-4 weeks
* DRESS: 2-6 weeks
Transfusion reactions are an example of [Type] hypersensitivity
Transfusion reactions are an example of Type 2 hypersensitivity
Glomerulonephritis, RA, and SLE are examples of [Type] hypersensitivity reactions
Glomerulonephritis, RA, and SLE are examples of Type 3 hypersensitivity reactions
B lymphocytes, aka “humoral immunity” is most important in fighting _ infections
B lymphocytes, aka “humoral immunity” is most important in fighting bacterial infections
* Without humoral immunity expect chronic sinusitis and pneumonia
T lymphocytes or cell-mediated immunity is most important in fighting _ infections
T lymphocytes or cell-mediated immunity is most important in fighting fungal and viral infections
* Particularly important for intracellular pathogens
* Also helps in bacterial infections
When it comes to fighting off skin and surface infections, [immune cells] are most important
When it comes to fighting off skin and surface infections, granulocytes (eosinophil, basophil, neutrophil) are most important
Recurrent _ or _ infections do not indicate immune deficiency; however other recurrent infections might
Recurrent UTIs or strep throat infections do not indicate immune deficiency; however other recurrent infections might
Warning signs of primary immunodeficiency include:
* More than _ ear infections in a year
* More than _ sinus infections in a year
* More than _ pneumonias in a year
Warning signs of primary immunodeficiency include:
* More than 4 ear infections in a year
* More than 2 sinus infections in a year
* More than 2 pneumonias in a year
Really you should have concern if you see infections equal to or greater than these numbers
Lack of antibodies will lead to recurrent bacterial infections, especially with _ type bacteria
Lack of antibodies will lead to recurrent bacterial infections, especially with encapsulated bacteria
* SHiN: Strep pneumo, H flu, Neisseria meningitidus
The most common B-cell deficiency is _
The most common B-cell deficiency is IgA deficiency
* Recall that IgA is in the mucosa
* Many cases asymptomatic or presents with sinopulmonary infections or anaphylaxis to blood
* Associated with celiac, GI disorders
The most common symptomatic immune deficiency is _
The most common symptomatic immune deficiency is common variable immune deficiency (CVID)
Symtoms of CVID most commonly present at age _
Symtoms of CVID most commonly present at age 20-40
* Presents with recurrent sinopulmonary infection
* Bronchiectasis affects 30-50% of patients
CVID is caused by _
CVID is caused by faulty B cell differentiation into plasma cells
How do you work up a possible B-cell deficiency?
DiGeorge is caused by chromosome deletion at _ ; it is [inheritance pattern]
DiGeorge is caused by chromosome deletion at 22q11 ; it is autosomal dominant
DiGeorge syndrome is ultimately caused by a failure of _ development
DiGeorge syndrome is ultimately caused by a failure of pharyngeal pouch development, pouches 3, 4
* Pouch 3 –> thymus + inferior parathyroid
* Pouch 4 –> superior parathyroid
The downstream effect of absent thymus is _
The downstream effect of absent thymus is improper T cell differentiation
* Recall that the T cells go from bone marrow –> thymus to mature
* These patients get recurrent viral infections and CMV, EBV, JC virus, VZV + fungal infections, Candida, PJP, Crypto
The mneumonic to remember DiGeorge symptoms is _
The mneumonic to remember DiGeorge symptoms is CATCH22
* Cardiac
* Abnormal facies
* Thymic hypoplasia
* Cleft palate
* Hypoparathyroidism
* Chromosome 22q11
SCID is often caught in newborns but at least seen by _
SCID is often caught in newborns but at least seen by year 2 of life
* Recall that newborns get maternal antibodies for the first 6 months
Signs of SCID
SCID presents with:
* Recurrent, severe infections (T cell, B cell, NK cell dysfunction)
* Chronic diarrhea, failure to thrive
* Absence of lympoid tissue (tonsils, adenoids, axilla)
The most common cause of SCID is a _ defect which is [inheritance pattern]
The most common cause of SCID is a IL-2 receptor gamma chain defect which is X-linked recessive
The less common, autosomal recessive form of SCID is caused by _
The less common, autosomal recessive form of SCID is caused by ADA deficiency
* Build up of metabolic toxins that destroy T and B cells
MMR is a [type] vaccine
MMR is a live attenuated vaccine
Varicella is a [type] vaccine
Varicella is a live attenuated vaccine
Live attenuated vaccines induce [immune response]
Live attenuated vaccines induce humoral IgG and cellular
* MHCI presents pathogen to CD4+
* CD4+ activates B cell and allows class switching –> IgG
* Dendritic cell can be infected and also present via MHCII –> cellular response
Whole inactivated vaccines will induce [immune] response
Whole inactivated vaccines will induce humoral IgG response
* Cannot infect the dendritic cells to trigger cellular response (CD8+)
* However, can be presented via MHC-I, activate CD4+, class switch
Subunit protein inactivated vaccines induce [immune] response
Subunit protein inactivated vaccines induce humoral IgG response
* Cannot infect the dendritic cells to trigger cellular response (CD8+)
* However, can be presented via MHC-I, activate CD4+, class switch
Subunit polysaccharide inactivated will induce [immune response]
Subunit polysaccharide inactivated will induce humoral IgM only
* Its an inactivated vaccine, so it cannot infect dendritic cell = no MHC-II and no cellular response
* MHC I can only present protein so it cannot present it either; no class switching, IgM only
Subunit polysaccharide + conjugate inactivated vaccines will induce [immune response]
Subunit polysaccharide + conjugate inactivated vaccines will induce humoral IgG
* Because the polysaccharide has been conjugated to a protein we can get class switching
The MMR and varicella vaccine can be given to HIV+ patients if CD4+ cell count is at least _
The MMR and varicella vaccine can be given to HIV+ patients if CD4+ cell count is at least 200
* Live vaccines are contraindicated in pregnancy and patients with immunodeficiency because they can revert to a virulent form
[Coombs test] detects antibodies attached to the RBC surface
Direct coombs test detects antibodies directly attached to the RBC surface
[Coombs test] detects presence of unbound antibodies in the serum
Indirect coombs test detects presence of unbound antibodies in the serum
Rheumatoid arthritis is an example of a [hypersensitivity reaction]
Rheumatoid arthritis is an example of a type III hypersensitivity
[Transfusion rxn] involves urticaria, pruritis, wheezing, hypotension, respiratory arrest within minutes to 3 hours of receiving blood products
Allergic/anaphylactic reaction involves urticaria, pruritis, wheezing, hypotension, respiratory arrest within minutes to 3 hours of receiving blood products
Fever, hypotension, tachypnea, tachycardia, flank pain, hemoglobinuria, and jaundice within 24 hours of blood transfusion may be [transfusion reaction]
Fever, hypotension, tachypnea, tachycardia, flank pain, hemoglobinuria, and jaundice within 24 hours of blood transfusion may be acute hemolytic transfusion reaction
Acute hemolytic transfusion reaction is a [type HS reaction]
Acute hemolytic transfusion reaction is a type II hypersensitivity
* Which typically causes intravascular hemolysis- hemoglobinuria
Acute hemolytic transfusion reactions typically occur secondary to _
Acute hemolytic transfusion reactions typically occur secondary to ABO blood group incompatability
[Transfusion reaction] occurs when cytokines created by donor WBCs accumulate during storage of blood products
Febrile nonhemolytic transfusion reaction occurs when cytokines created by donor WBCs accumulate during storage of blood products
Febrile nonhemolytic transfusion reactions will present as _
Febrile nonhemolytic transfusion reactions will present as fever, headachem chills, fushing within 1-6 hours
* From preformed cytokines
Respiratory distress and noncardiogenic pulmonary edema following a transfusion is likely _
Respiratory distress and noncardiogenic pulmonary edema following a transfusion is likely Transfusion related acute lung injury (TRALI)
Transfusion related acute lung injury (TRALI) occurs due to _
Transfusion related acute lung injury (TRALI) occurs due to neutrophil activation by a product in the blood –> inflammation –> pulmonary edema
* Neutrophils sequestered in pulmonary vasculature get released
[Transfusion rxn] is a response to a foreign antigen on donor RBCs that was previously encountered by recipient and presents within 1-2 weeks
Delayed hemolytic transfusion reaction is a response to a foreign antigen on donor RBCs that was previously encountered by recipient and presents within 1-2 weeks
Thrombosis of graft vessels is most indicative of [transplant rejection]
Thrombosis of graft vessels is most indicative of hyperacute transplant rejection
* Pre-existing recipient antibodies
Vasculitis of graft vessels is most indicative of [transplant rejection]
Vasculitis of graft vessels is most indicative of acute transplant rejection
* Cellular or humoral response
[Transplant rejection] is dominated by arteriosclerosis
Chronic transplant rejection is dominated by arteriosclerosis
Graft-vs-host disease is caused by _
Graft-vs-host disease is caused by grafted immunocompetent T cells proliferating in the host and targeting host
Name (3) B cell disorders and what patients most often present with
- Bruton agammaglobulinemia: defect in BTK results in no B-cell maturation –> recurrent bacterial and enteroviral infection after 6 months of age
- Selective IgA deficiency mostly asymptomatic; GI infections, atopy/anaphylaxis/autoimmune
- Common variable immunodeficiency defect in B-cell differentiation –> sinopulmonary infections, increased risk of autoimmune
_ is a deficiency of Th17 cells due to STAT3 mutation which impairs the recruitment of neutrophils to sites of infection
Autosommal dominant hyper-IgE syndrome is a deficiency of Th17 cells due to STAT3 mutation which impairs the recruitment of neutrophils to sites of infection
* Also called Job syndrome
Failure to thrive, chronic diarrhea, thrush, and recurrent infections (all kinds) is a common presentation of _
Failure to thrive, chronic diarrhea, thrush, and recurrent infections (all kinds) is a common presentation of SCID
* Also decreased TRECs, absent thymic shadow and germinal centers
Hyper IgM syndrome is most commonly due to defective _
Hyper IgM syndrome is most commonly due to defective CD40L on Th cells
* Will present with severe pyogenic infections early in life
