Rheum Exam 1 Flashcards
What are the main inflammatory cytokines?
IL-1, IL-6, TNFa
What is not an immune response to food?
-IgA and TGFB
-IFNy and IgG
-IL-4, Il-5, IL-13, IgE
-IFNy and IgA
IFNy and IgA
Which gender is more likely to suffer with a viral infection; M, F, both, neither?
M
A 56 yo F was infected with SAR-CoV2 at her work. She goes home and wants to sleep. Which cytokine mediates this effect?
IL-1
Your pt was exposed to SARS-CoV2 for the first time on a plane three days ago. Which cells do you expect to be activated now, at 72 hours?
NK cells, macrophages, T cells
Which of the following cell types is already in the tissue when a pathogen invades?
-Neutrophils
-Macrophages
-B cells
-T cells
Macrophages
How do you start your production of inflammatory cytokines?
An inflammatory triggers ikappaB to let go of NFkappaB and NFkappaB translates to the nucleus
Which proteins are involved in resolving infection?
Protectins, maresins, resolvins
Which cytokine is associated with hostile and aggressive behavior?
TNFa
Which T cell is associated with candida infection?
Th17
A microbe binds to a TLR on a macrophage. If this is going to trigger an autoimmune response, what must be present on the macrophage to activate an autoreactive T cell?
CD86
Which cytokines are made in response to Th2?
IL-4, IL-5,IL-13
In a Th1 response, IFN gamma triggers B cells specific to the antigen to produce which type of immunoglobulin?
IgG
You have a pt with mononucleosis, which is caused by Epstein Barr Virus, and causes B cells to overgrow. Which protein would you expect to find elevated in the blood?
Antibodies
SARS-CoV2 virus is able to infect multiple tissues, why?
ACE2 receptors that the virus uses for entry are in multiple tissues
What response type occurs with bacteria + virus? What cytokines are present?
Th1
IFN gamma
What response type occurs with worms? What cytokines are present?
Th2
IL-4, IL-5, IL-13
What response type occurs with food? What cytokines are present?
Th3/Treg
TGFbeta
What response type occurs with asthma? What cytokines are present?
Th2
IL-4, IL-5, IL-13
What response type occurs with mold? What cytokines are present?
Th17
IL-17
What cells and cytokines changes occur with chronic inflammation?
↑ IL-1, IL-6, TNFa
What cells and cytokines changes occur with cancer?
↓ Th1 (↑ TGFB,Treg)
What cells and cytokines changes occur with autoimmunity?
↑ Th1 and Th17
What cells and cytokines changes occur with infections?
↑ Th1 (↓Th2)
What cells and cytokines changes occur with allergies?
↑ Th2 (↓TH1)
What vitamin is important in the production of defensins/antimicrobial peptides (AMP)?
Vit D > IL-22 > defensins
Difference between M1 and M2 macrophages
M1 > IL-12 > Th1
M2 > IL-4 > Th2
Common causes of chronic inflammation
Stress: cortisol
Food: hypersensitivity, obesity, inflammatory foods [sugar, omega 3/6]
Describe the antibody order
My Dog Goes Everywhere Always
What is the main function of T reg cells/TGFB?
STOP SIGN:
> Th1 stop making IFNg
> Th2 stop making IL-4, IL-5, IL-13
> regulates Th1 and Th2
> shut down Th17 and inflammatory cytokines
What are the 5 different forms of IL-17? Which are pro-inflammatory and which are anti-inflammatory?
Pro-Inflammatory:
IL-17A, IL-17B
Anti-inflammatory:
IL-E, IL-F
IL-C, IL-D
How can you drive a Th1 response?
Hydrotherapy: alternation of temps stimulates heat shock proteins
Astragalus, berberine, goldenseal, oregon grape, mints (holy basil, oregano, lemon balm)
How can you drive a Th2 response?
Worms (3-6 worms prevented from dividing given; worm infection is hundreds to thousands); AI, severe allergies
Immune system is focused on worm instead of pollen, etc
How can you drive a Treg response?
Avoid sugar, high fructose corn syrup, no artificial sweeteners, no AGEPs, no charred foods; high fiber, psyllium husks*, 12hr+fasting (7pm-7am)
Prebiotics, probiotics, vit D, vit A, vit C, mushrooms; mold
What cytokines are associated with Th9 cells?
IL-8
What cytokines are associated with macrophages/DC?
IL-1, IL-6, TNF
What causes the class switch for IgG?
IFNgamma
What causes the class switch for IgE?
IL-5
What causes the class switch for secretory IgA?
TGFbeta
What causes the class switch for IgM?
IL-2
What is the age of onset for b cell disease?
6 months
What is the age of onset for T cell disease?
< 5 mon
What is the age of onset for combined T and B cell disease?
At birth
Which immunodeficiency presents with gingivitis and skin abscesses?
Phagocytic defects
Which immunodeficiency presents with URI/sinopulmonary infections?
B cells
Which immunodeficiency presents with meningitis?
Complement defect
Which vaccines do those with immunodeficiencies need to avoid?
Live attenuated vaccines
MMR, TB, chickenpox, and polo
Which organisms infect those with T cell defects?
Viral, fungal, mycobacterial, or opportunistic
Which organisms infect those with B cell defects?
Invasive encapsulated bacteria
Which organisms infect those with neutrophil abnormality?
Bacteria of low virulence
Which organisms infect those with terminal complement defects?
Nisseria
What is a granuloma?
Chronic inflammation/infection causes the body to wall off the area
An organism that the macrophages can’t get rid of they recruit more macrophages to the area and fuse which forms a giant cell in the center then T cells are attracted to the area and create a wall around the macrophages
Disease due to ___ abnormalities are termed primary immunodeficiencies. A secondary immunodeficiency is ____, rather than genetic
Genetic; acquired
Match the neutrophil disorder to its pathophysiology
Body unable to produce neutrophils
Neutrophils can not travel to site of infection due to lack of integrin production
Neutrophil is unable to fuse phagosome with lysosome or degranuate, leaving them unable to kill microbe
Neutrophil is unable to produce superoxide and can not kill catalase positive microbes
Severe congenital neutropenia
Leukocyte adhesion defect
Chediak-Higashi syndrome
Chronic granulomatous disease
Match the immunodeficient component to the type of infection
Staph aureus skin infections
Viral infections
Neisseria caused meningitis
Enterovirus
Phagocytes
T cells
Complement
B cells
A deficiency in the complement protein is associated with an increased risk of
Lupus
Type 2 diabetes
Cardiac defects
Neisseria infection
Lupus
What is the pathophysiology to lupus in relation to complement?
Self cells are apoptosed and can’t get cleared from the body so B cells make antibodies against components of self cells
Lack of complement makes it harder to clear cells
A deficiency in complement proteins 5-9 are associated with
Neisseria infections
Autoimmune disease
Vasculitis
Infections with staph and strep
Neisseria infections
A deficiency of complement C1 inhibitor can lead to an overstimulation of the complement cascade creating excess and unregulated C3a. This C3a binds to macrophages, which in turn release histamine leading to life threatening
Hereditary angioedema
Neisseria infections
Respiratory paralysis
Fungal infections
Hereditary angioedema
Primary immunodeficiencies
Are frequent in low income countries
Affect only the adaptive immune system
Can be cause by infections with HIV
Are the result of a single gene defects in immune function
Are the result of a single gene defects in immune function
Common opportunistic infections in patients with reduced antibody responses are due to
Influenza
Intestinal helminths
Encapsulated bacteria
Atypical mycobacteria
Encapsulated bacteria
X-linked agammaglobulinemia results from a mutation in
IFNg receptor
The CIITA promoter protein
An HLA gene
A tyrosine kinase gene
A tyrosine kinase gene
what types of organisms are pts with wiscott aldrich susceptible to
encapsulated bacteria s/a neisseria meningitidis, haemophilus influenzae, strep pneumoniae
viruses: molluscum contagiosum, varicella zoster
fungus: pneumocystitis jiroveci, candida albicans
what types of organisms are pts with SCID susceptible to
Fungal, viral, opportunistic or mycobacteria pathogens
what types of organisms are pts with b cell disorders susceptible to
Encapsulated bacteria
Enteroviruses
Sinopulmonary
what types of organisms are pts with CGD susceptible to
catalase pos bacteria and fungi
Staph aureus, B cepacia, aspergillus, other organisms
what types of organisms are pts with leukocyte adhesion def susceptible to
pyogenic bacterial infection
what types of organisms are pts with chediak higashi susceptible to
bacteria
name the B cell/humoral immunodeficiencies
agammaglobulinemia
selectiva IgA def
hyper IgM syndrome
CVID
name the T cell (cellular)/combined immunodeficiencies
SCID
digeorge
wiscott aldrich
name the complement immunodeficiencies
hereditary angioedema (HAE)
terminal complement defect
name the neutrophil/phagocytic immunodeficiencies
CGD
chediak-higashi
leukocyte adhesion deficiency
what types of organisms are pts with complement immunodeficincies susceptible to
neisseria meningitis
Which one of the following is true concerning common variable immune deficiency disorders?
Patients always present before the age of 10 years
Is due to a single gene defect on the x chromosome
Patients are treated by replacement immunoglobulin, intravenously or subcutaneously
Most patients die from complication of malignancy
Patients are treated by replacement immunoglobulin, intravenously or subcutaneously
For which of the following immunodeficiency disorders is the conjugate vaccine for H. influenzae type B contraindicated?
B cell
T cell
Complement
None of these
None of these
Pt w/ primary immunodeficiencies are at higher risk of developing
Infections
Autoimmune disease
Cancer
ALL
Which of the following is not a condition associated with secondary immunodeficiency?
HIV
Measles
Cancer
Type 2 diabetes
Malnutrition
Genetic mutation
Genetic mutation
This pathogen typically causes immune deficiency and increases the risk of secondary infections
Measles
Toxoplasma
Candida albicans
Rabies virus
Measles
X linked hyper IgM syndromes is primarily due to
Lack of B cell help from NK cells
A low B cell count due to inadequate development in the bone marrow due to inadequate development in the bone marrow
A lack of T cell help via CD40 ligands
A lack of follicular dendritic cells needed for b cell maturation in the germinal center
A lack of T cell help via CD40 ligands
Deletions in the T-cell CD40L gene produce
hyper-IgM syndrome
Congenital x-linked agammaglobulinemia
IgA deficiency
Wiskott-aldrich syndrome
Deficiency in cytotoxic t-cell activity
hyper-IgM syndrome
Which one of the following is true concerning transient hypogammaglobulinemia of infancy:
Occurs at 3 months of age
Is due to placental absorption of IgG
Is linked with autoimmune disease in later life
Involves only the IgA immunoglobulin class
Is due to waning maternal antibodies in infant circulation
Is due to waning maternal antibodies in infant circulation
Which one of the following statements concerning XLA is correct?
XLA present immediately after birth
It is a disease found in equal numbers of boys and girls
Patients with XLA present with recurrent severe bacterial and fungal infections
Patients usually have panhypogammaglobulinemia i.e. very low serum levels of IgG, IgA, and IgM all of which are < 10% of normal for age
Patient have normal numbers of plasma cells in the gut
Patients usually have panhypogammaglobulinemia i.e. very low serum levels of IgG, IgA, and IgM all of which are < 10% of normal for age
Which one of the following is true concerning the replacement therapy for hypogammaglobulinemia
Consist mainly of IgM
Consist mainly of IgG
Consist mainly of IgD
Consist mainly of IgE
Consist mainly of IgA
Consist mainly of IgG
Which of the following is not associated with a state of B cell immunodeficiency?
IgA deficiency
Leukocyte adhesion deficiency
Transient hypogammaglobulinemia
Common variable immunodeficiency
Leukocyte adhesion deficiency
Which one of the following is true concerning individuals with selective IgA deficiency?
All individuals can be considered to be normal w/o risk of infections
They are more likely to develop heart disease than those with normal IgA
Will always have a high risk of HIV infection
They have a high risk of recurrent serious bacterial infection
They have higher risk of developing an organ specific autoimmune disease than the general populations
They have higher risk of developing an organ specific autoimmune disease than the general populations
Which of the following organisms is someone with a T cell immunodeficiency more prone to infection?
Haemophilus influenzae
Candida albicans
Neisseria
Staph aureus
Candida albicans
Di George syndrome results from a defect in
Purine nucleoside phosphorylase
WASP
Thymic development
DNA repair
Thymic development
Which one of the following findings is the most common indicator in an infant with severe combined immune deficiency?
Lymphopenia
Severe asthma
Dry skin
Pneumonia
Staphylococcal abscess
Lymphopenia
Which combined immunodeficiency is most likely to be fatal under the age of two if left untreated?
SCID
Wiskott-aldrich syndrome
DiGeorge syndrome
Hyper IgM syndrome
SCID
SCID primarily affects
Macrophages, mast cells, t cells
T cells only
T cells and dendritic cells
T cell, B cells, and in some cases NK cells
T cell, B cells, and in some cases NK cells
Which one of the following statements about Wiskott-aldrich syndrome is true?
Platelet size is large
It is a combined primary immune deficiency due to abnormal cell motility
It is always a severe disease
It is common in girls
Staphylococcal abscesses
It is a combined primary immune deficiency due to abnormal cell motility
Which of the following would you suspect the presence of a primary immunodeficiency disease consisting of a problem with neutrophil function?
Recurrent ear, sinus, and lung infection
Recurrent thrush
Recurrent skin abscesses or poor wound healing
Recurrent warts
Recurrent skin abscesses or poor wound healing
Which one of the following is the primary defect in chronic granulomatous disease?
Neutrophil production in the bone marrow
Neutrophil chemotaxis
Neutrophil intracellular killing of organism
Opsonization
Cytotoxic T cell activity
Neutrophil intracellular killing of organism
Defects in neutrophil NADPH oxidase system produce
Chronic granulomatous disease
chediak-Higashi disease
Leukocyte adhesion deficiency
Hashimoto’s disease
Streptococcal infection
Chronic granulomatous disease
The most frequently diagnosed form of specific primary immunodeficiency is
Severe combined immunodeficiency
X-linked agammaglobulinemia
Chronic granulomatous disease
SelectiveIgA deficiency
DiGeorge anomaly
SelectiveIgA deficiency
Poor skin tests to a range of microbial antigens such as tuberculin and mumps indicate a deficiency of
NK cell
B cells
T cell
Complement
Phagocytes
T cell
Primary immunodeficiency producing susceptibility to infection by viruses and fungi is due to
B cell deficiency
T cell deficiency
Complement deficiency
Eosinophil deficiency
Phagocyte deficiency
T cell deficiency
Primary immunodeficiencies are due to
Genetic mutations
Viruses
Medications
Chemical exposures
Genetic mutations
T or F.
Patients with selective IgA deficiency are at increased risk for developing many autoimmune diseases as well as atopy. The safest and most effective approach to treatment is early administration of IgA antibodies to correct the deficiency
False
What cytokines and immunoglobulin are made in a Th2 response?
IL-4, IL-5, IL-13; IgE
IL-1, IL-6, TNF-alpha; IgG
IL-12, IL-6, IL-1; IgG
IL-4, IL-5, IL-1; IgE
IL-4, IL-5, IL-13; IgE
What does peroxidase cause?
- Cause histamine release
- Breaks down collagen
- Increased local blood flow
- Breaks down tissue
Causes histamine release
What does histamine cause?
* Increased local blood flow
* Increases vessel permeability
* Causes edema
* All of the above
All of the above
What do mast cell granules contain?
* Histamine
* Chymase
* Tryptase
* Serine esterase
* TNF-alpha
* All of the above
All of the above
What does serine esterase?
* Activates metalloproteinases
* Break down tissue
* Neurotoxin
* Breaks down collagen
Activates metalloproteinases
Which of the following is NOT an encapsulated bacteria?
* neisseria meningitidis
* haemophilus influenzae
* strep pneumoniae
* mycobacteria
mycobacteria
Which of the following is a test that can be done for allergic asthma?
- Fractional excretion of nitric oxide
- Total serum IgE and specific IgE
- Complete blood cell count with an elevated absolute eosinophil count
- All of these are true
All of these are true
Which cytokine in the gut helps people develop and remain tolerant to food?
- TGF beta
- IFN gamma
- IL-2
- IL-7
TGFb
Your pt gets diarrhea when he eats eggplant. You run a food hypersensitivity test. Which ab do you expect to show up positive?
IgA
IgE
IgG
IgM
IgG
Exposure to secondhand smoke in kids under 4 is highly associated with respiratory allergies in older adults. From this, what ab would you suspect is higher in kids of smoking adults?
IgE
Your pt got a new gold plated fit-bit. She notices she’s developing a rash on the back of her wrist. Which type of hypersensitivity is likely?
Type IV
One of the therapies for COVID19 is convalescent plasma. This is similar to giving immunoglobulin to people with immunodeficiency. What is the danger?
Type I hypersensitivity
Type II hypersensitivity
Type III hypersensitivity
Type IV hypersensitivity
Type III
Your patient discovers that local honey makes her allergies better. Which of the following explains why?
Honey has sugar crystals that stabilizes mast cells so they dont degranulate
Honey can coat pollen and prevent TLR binding
Honey can trigger a class switch from IGE specific for pollen to IgA
All of these are true
Honey can trigger a class switch from IGE specific for pollen to IgA
Why does a Type II Penicillin hypersensitivity result in hemolytic anemia?
Penicillin creates antigen-antibody complexes in the blood vessels
Penicillin interferes with the clotting cascade in sensitive individuals
Antigen (penicillin) sticks to the RBCs and is cleared by macrophage and NKs
Penicillin changes the shape of RBCs and the spleen eats it
Antigen (penicillin) sticks to the RBCs and is cleared by macrophage and NKs
What cell types does IgE activate?
Eosinophils
Mast cells
What are the granules in eosinophils?
Peroxidase
Collagenase
Major basic protein
Cationic protein
What does peroxidase do?
Breaks down H2O2 > H2O
Causes histamine release
What does major basic protein do?
Toxic, causes histamine release
Brain fog
What does cationic protein do?
Neurotoxin
Brain fog
What does histamine do?
Inc local blood flow (red nose)
Inc vessel permeability
Causes edema
What do chymase and tryptase do?
Break down tissue
What does serine esterase do?
Activates metalloproteinases
What does TNFa do when released from mast cells?
Brings more lymphocytes, macrophages, eosinophils
Breaks down tissue
Why is a second allergy response faster and more intense?
Once you have memory B cells for pollen, B cell started as IgM now already class switched to IgE so at second exposure no need for T cell rxn or macrophage carrying pollen
IgE can already be bound to mast cells and eosinophils > so they can degranulate more quickly (almost immediately after exposure to antigen)
What is the basis of oral allergy syndrome?
Antigens that cross react because proteins share similar sequences (molecular mimicry)
Ex: 50-75% ppl allergic to birch tree pollen can develop itchy throat or mouth when eating apple or celery
What types of responses occur with a type I hypersensitivity rxn?
Allergy
IgE
Th2
What types of responses occur with a type II hypersensitivity rxn?
IgG to surface antigen
Penicillin hypersensitivity
What types of responses occur with a type III hypersensitivity rxn?
IgG to soluble antigen
Immune response to inhaled mold
Streptokinase (rx for MI)
Lymphoglobulin (ab for immunodeficiency)
What types of responses occur with a type IV hypersensitivity rxn?
Delayed type; DTH response
TB test
Allergic dermatitis
Food hypersensitivity
Explain the mechanism of Type I hypersensitivity rxn
Pollen contacts macrophage > mo eat pollen through TLR > carries to nearest lymph node > presents pollen ag on iMHC molecule and mo produces IL-4
> pollen specific CD4 T cells binds to MHC molecule on mo
CD86 binds CD28 and activates CD4 T cell
IL-4 binds to IL-4 receptor and tells T cell to become a Th2 T cell
All within about 24 hours..
Once CD4 T cell is producing IL-4, IL-5, and IL-13 > triggers B cells to make IgE to pollen > IgE binds to pollen to try to “sop up” pollen
B cell secretes IgE which binds to FcE receptor on eosinophil > when we cross link FcE receptors with two IgE molecules bound to same antigen on both eosinophils and mast cells > causes degranulation
Explain the mechanism of Type II hypersensitivity rxn
Immune system mistakes own cells with pathogens and activates the complement
IgG and IgM bind to target cells and causing complement activation
B&T cells create auto-antibodies against self antigens which damages cells and tissues
Autoantibodies target body own cells and disrupt normal function
Explain the mechanism of Type III hypersensitivity rxn
Antigen-antibody complexes deposit activating the complement system → neutrophils → degranulate causing damage to area
Explain the mechanism of Type IV hypersensitivity rxn
Antigen presented on MHC II of dendritic cell → CD4 T cell binds via T cell receptor and CD4 receptor → it will express CD28 which will bind to B7 on surface of dendritic cell → dendritic cell releases IL-12 → T cell differentiates into Th1 → release IL-2 and IFN-gamma → ↑ T cell differentiation and macrophage activation → IL-1, IL-6, TNF, lysosomal enzymes, complement, ROS species → inflammation
CD8 target antigens presented on MHC 1 and bind → perforin forms pores and granzymes induce apoptosis
Allergies are characterized by what type of response? What do the cells produce?
Th2
T cells > IL-4, IL-5, IL-13 (mucus)
B cells > IgE (bc of IL-4 production)
Mast and eosinophil degranulation (IL-4, IL-5)
What is the suspected cause of atopic allergies?
Cytokine imbalance, too many IL, IgE, eosinophils, etc
Hygiene hypothesis
What are random allergies attributed to?
MHC related; run in families
Normal cytokine and eosinophil levels
What is the most common EDS?
Hypermobile
Vascular
Classic
Classical-like
Hypermobile
What are common sx for hEDS?
Joint pain
Fatigue
Easy bruising or poor skin healing
All of the above
All of the above
What is the name of the criteria for generalized joint hypermobility?
Beighton score
Alvarado score
Amsel score
Centor score
Beighton score
How is hEDS diagnosed?
Clinical
Labs
Imaging
Genetic testing
Clinical
What are common complications of hEDS?
Aortic root dilation
Aortic dissection
Mitral valve prolapse
All of the above
All of the above
What area doesn’t cause pain in patients with hEDS?
Joint pain
Muscle pain
Nerve pain
GI pain
Headaches
Eye pain
Eye pain
What is the possible connection between MCAS and EDS?
Disordered connective tissue/collagen influences mast cell behavior
There is no connection
They are caused by the same thing
EDS causes MCAS
Disordered connective tissue/collagen influences mast cell behavior
What foods contain histamine?
Tofu
Cheese
Yeast products
Smoked fish
Processed meats
Nuts or seeds
Foods with vinegar
Sweetened beverages
Over ripe fruit
Sauerkraut
Fermented drinks
Chocolate
Mushrooms
Leftovers in the fridge
What is the significance of tryptase levels in MCAS and mastocytosis?
Tryptase levels are normal in MCAS but high in mastocytosis
Run in pts with suspected MCAS still to rule out mastocytosis
What are the names of the two criteria for dx MCAS and what is the major difference?
Valent (requires lab findings; created by those who think MCAS is rare)
Molderings (clinical dx; created by those who think MCAS is common)
What is the approach for treatment of MCAS?
Stepwise; add 1 supplement of med at a time and wait 2-4 weeks before adjustments or additions
What are common comorbidities with MCAS?
SIBO
Crohn’s
GERD
All of the above
A + C
A + C
What are some botanicals for MCAS?
Nettle
Curcumin
Butterbur
CBD
What types of medications are indicated in MCAS tx?
H1 and H2 receptor blockers
Dx criteria of POTS in adults says an increase or at least ___ bpm from supine to standing within 10 mins OR HR exceeding ____ bpm within 10 minutes.
Children: HR increases at least ____ bpm from supine to standing within 10 minutes.
30
120
Children: 40
What are the two types of POTS? Which is more common?
Neuropathic (most common)
Hyperadrenergic
