Quiz 1 Flashcards
- Affect who more? 4
- m/c disability in US?
- 66% of those diagnosed with arthritis are?
- More common over age of?
- Affects women more than men
- Leading cause of disability among persons age 65 and older in the US
- 66% of those diagnosed with arthritis are overweight or obese
- More common over age 65 (49.5%)
The most famous transmembrane PRRs are called?
toll-like receptors (TLRs) – they play a huge roll in autoimmune diseases
Common molecules that trigger innate immunity: 2
- Pathogen-associated molecular patterns (PAMPs) – microbial molecules “Intestinal dysbiosis” (turn it on or off)
- Damage-associated molecular patterns (DAMPs) – molecules from damaged or necrotic host cells (Cell destruction)
•Activated complement does the following: 3
- Coats microbes
- Stimulates phagocytosis
- Chemotaxis of leukocytes
- Stimulates inflammation
- Cause direct cell lysis
- Coats microbes and stimulates phagocytosis by the innate immune system
- Promotes chemotaxis of leukocytes and stimulates inflammation
- Forms a complex that can cause direct cell lysis
•C3 and C4 can be measured in the blood: 2
- Increased values: cancer, infection, UC
* Decreased values: liver disease, autoimmune disease (lupus), kidney disease.
B Cell Lymphocytes do what?: 2
- Present
- Recognise antigens
- B-cells present antigens to T-helper cells through MHC peptides
- Antibodies are responsible for recognizing antigens – they can stimulate the complement cascade, activate phagocytes or stimulate activation of T-cells.
T cell Lymphocytes do what?: 3
- stimulate further immune response
- (MHC) bind to T-cells (at TCRs) and stimulate activation.
- MHC in humans = known as (HLAs) - human leukocyte antigens -> highly polymorphic
- Their biggest function is to interact with other cells to stimulate further immune response (phagocytes/B cells) or kill infected cells.
- Major histocompatibility complexes (MHC) on antigen presenting cells will bind to T-cells (at TCRs) most often and stimulate activation.
- MHC proteins in humans are known as human leukocyte antigens (HLAs) – they are highly polymorphic in humans.
Types of T-Cells: 3 (MEN)
- Th1 – produce IFN-gamma – associated with macrophages, autoimmunity and chronic inflammation
- Th2 – produce IL-4, IL-5, IL-13 – associated with eosinophils and allergy
- Th17 – produce IL-17, IL-22 – associated with neutrophils and autoimmunity
MEN- macrophages Th1, eosinophils Th2, neutrophils Th3
Immunogenic Determinants: 7
- Foreignness (“self” vs “non-self”)
- Molecular size (The bigger the protein, the more immunogenic it tends to be)
- Chemical-structural complexity
- Antigenic determinants (epitopes) (Different epitopes can elicit different immune responses)
- Dosage, route and timing of antigen administration
- Genetic constitution of the host (HLA genes)
- Adjuvants – or immune system enhancers
The Development of Autoimmunity: 4 (SIP-R)
•Onset of autoimmune response and development of clinical symptoms are generally separated in time.
- Susceptibility phase
- Initiation phase
- Propagation phase
- Regulation/resolution phase
- Susceptibility phase – several preconditions for disease are satisfied (Environment)
- Initiation phase – autoimmune response present but no clinical disease
- Propagation phase – clinical disease begins
- Regulation/resolution phase – immunoregulatory pathways activated; may result in resolution but this is rare.
Autoimmunity Pathogenesis: 2
Environmental triggers for autoimmunity: 6
- Susceptible genes + environmental triggers are needed to trigger autoimmunity.
- Many autoimmune diseases are linked to HLA (MHC) alleles.
•Environmental triggers for autoimmunity:
- Hormone production (Reproductive & Cortisol)
- Infections
- Microbial flora (skin, GI, vaginal…etc)
- UV radiation
- Toxic exposure (heavy metals, pharmaceuticals…etc)
- Diet and lifestyle (obesity, food allergies…etc)
Laboratory Assessment:
*Common Basic Laboratory Testing: 8
- CBC
- Chem Panel
- CRP/ESR
- Serum Ferritin
- Thyroid Panel
- 25-Hydroxy Vitamin D
- Specific antibody testing
- Serum uric acid
Pharmacologic Treatment:
•NSAIDs- CV event-just helps w/pain
Action & MOA- 3
- Actions: analgesic, anti-inflammatory, antipyretic
- MOA: inhibit cyclooxygenase (COX) activity
- NSAIDs DO NOT stop progression of tissue injury
Pharmacologic Treatment:
NSAIDs Adverse effects: 3
- Increased risk of MI, stroke and death
- Gastrointestinal bleeding, hemorrhage and perforation
- Acute renal failure
Pharmacologic Treatment:
•Glucocorticoids-Tapered/topical injections to jts- 4
- Used to modify disease progression in acute flares
- Actions: reduce activation, proliferation and differentiation of immune cells
- Glucocorticoids are often not used in OA, Scleroderma and Sjögren’s
- Glucocorticoids HAVE to be tapered down
Pharmacologic Treatment:
Glucocorticoids Adverse effects: 3
*Osteoporosis
•Fluid retention, hypertension, arrhythmias, MI
•Impaired wound healing
Pharmacologic Treatment:
•DMARDs- immuno-suppressants- NEEDS to be Tapered
Action & MOA-4
- Actions: anti-inflammatory, immunomodulatory
- MOA: many different actions, usually down-regulating the immune system
- DMARDs should NOT be discontinued after remission without careful consideration – this could lead to more flares in the future
- Patient compliance with DMARDs is generally low due to adverse side effects or cost
Pharmacologic Treatment:
DMARDS Adverse Effects and Toxicities-3
- A CBC needs to be monitored on a regular basis (every 1-3 months) initially for every DMARD.
- Myelosuppression can occur with use of methotrexate, sulfasalazine, azathioprine, cyclophosphamide.
- Liver enzymes need to be monitored on a regular basis for methotrexate, azathioprine, leflunomide.
Pharmacologic Treatment:
Methotrexate (MTX)- M/c DMARD (1st line->usually MonoTherapy)
•Side effects??? (10)
•Nausea, vomiting
•Skin rashes, photosensitivity
•Anemia, leukopenia
•Hepatotoxicity
•Thrombocytopenia
•Folic acid (1mg/day) should be given conjunctively (Folic acid analog inhibits cell division and
growth- lowers immune system)
•Liver Enzymes need to be monitored every 8-12 weeks
•Patients with MTHFR defects will have more severe adverse reactions
•SEVERAL block box warnings for this medication
•Pregnancy Category X (NEVER TO PREGNANT WOMEN)
Pharmacologic Treatment:
Azathioprine (Imuran): 4
- Black box warning for increased risk of lymphomas.
- Liver enzymes need to be monitored every 1-2 months.
- CBC needs to be monitored weekly for the first month,2x a month for months 2-3 then monthly.
- Absolutely contraindicated in pregnancy – Category D
Pharmacologic Treatment:
Leflunomide (Arava): 3
- Absolutely contraindicated in pregnancy – Pregnancy Category X
- Liver Enzymes need to be monitored every 8-12 weeks
- Avoid use of this medication when possible
Pharmacologic Treatment:
Sulfasalazine (Enteropathic arthritis – ulcerative colitis)-3
- Monitor CBC with Diff and LFTs initially, then every other week for the first 3 months, then every month for second 3 months, then once every 3 months or as needed.
- Avoid in those with allergies to sulfa drugs or salicylates
- Pregnancy category B – can be used but with caution; supplement folic acid
Pharmacologic Treatment:
Hydroxychloroquine (Plaquenil)-> Most used for Lupus/alopecia/
4- pregnancy?
- Doses should not exceed 6.5mg/kg in chronic therapy to minimize the risk of retinal toxicity
- Patient is REQUIRED to receive an initial and yearly eye exam while on this medication
- Run CBC initially and then every 3 months for the first year.
- Safe in pregnancy TQ
Pharmacologic Treatment:
Cyclophosphamide (Last ditch efford in case of death-> anti-Cancer med): 3
- Anti-neoplastic alkylating agents that crosslinks DNA which leads to cell death
- CBC and LFT initially and then every other week for 3 months then every month for the next 3 months then every 3 months.
- Urinalysis periodically for hematuria
Pharmacologic Treatment:
Biological DMARDs: 4
*These are only to be used after the failure of non-biologic DMARD therapy
•MOA: inhibit TNF-alpha and IL-1 (key inflammatory cytokines); can also inhibit other cytokines and T-cell activity
•VERY expensive
•Generally only effective in combination with non-biologics (MTX)
Naturopathic Approaches:
2.Correct underlying causes, imbalances and triggers (6)
a) Dysbiosis/microbial triggers
b) Diet/lifestyle triggers
c) Stress (physical/mental/emotional)
d) Nutritional imbalances
e) Hormone imbalances
f) Xenobiotic/heavy metal exposure and accumulation
Naturopathic Approaches:
Bacterial Dysbiosis: 6
- Dietary modifications (low carbohydrates): Specific carbohydrate diet, GAPS diet, low FODMAP diet.
- Herbal antibiotics:
- Berberine: 1,000 – 5,000mg po qd (hydrogen producing bacteria)
- Garlic: 450mg TID (methane producing bacteria).
- Conventional antibiotics
- Rifaximin: 1650mg/day (550mg TID) x 2 weeks – nonabsorbable antibiotic
Naturopathic Approaches: 5
Intestinal Candidiasis:
- Dietary modifications: reduce intake of sugars including carbohydrates, dairy and processed sugars.
- Herbal anti-fungals:
- Caprylic acid (time release): 1,000 – 2,000mg po cc
- Berberine: 1,000mg – 5,000mg per day
- Oregano oil: 150mg TID
Naturopathic Approaches:
Hormone Imbalances:
•Prolactin – high •Prolactin lowering agents: 2
- Vitex astus-cagnus: 40 – 160mg TID of chaste tree extract
* Bromocriptine (dopamine agonist): 2.5mg po qd – main pharmacologic treatment.
Naturopathic Approaches:
Hormone Imbalances:
•Estrogen – high
•Estrogen regulating strategies: 4
- Promote weight loss if patient is overweight or obese.
- Reduce alcohol consumption
- Promote healthy liver function (improves estrogen metabolism)
- Supplementation – Indole-3-carbinol, DIM,
Naturopathic Approaches: Hormone Imbalances: •Prolactin – high/low? •Estrogen – high/low? •Insulin - high/low? •Testosterone - high/low? •Cortisol - high/low? •DHEA-S - high/low? •Thyroid hormone - high/low?
- Prolactin – high
- Estrogen – high
- Insulin - high
- Testosterone - low
- Cortisol - low
- DHEA-S - low
- Thyroid hormone – low or high
Naturopathic Approaches:
Heavy Metal Exposure: 2
- Mercury can induce autoimmunity, immune complex formation and deposition and the formation of ANAs.
- Chelating or otherwise detoxing metals and xenobiotics may stimulate autoimmune responses.
Naturopathic Approaches:
Nutritional Supplementation: 11
- Multivitamin/multimineral supplementation
- Vitamin D:
- Essential fatty acids:
- Probiotics:
- Green Tea Extract:
- Lipoic Acid:
- Niacinamide:
- Glucosamine Sulfate:
- Chondroitin Sulfate:
- SAMe:
- Methylsulfonylmethane (MSM):
Naturopathic Approaches:
Acute Treatment: 3
- Capsaisin
- Bromelain:
- Curcuma:
•Environmental triggers for autoimmunity: 6
- Hormone production (Reproductive & Cortisol)
- Infections
- Microbial flora (skin, GI, vaginal…etc)
- UV radiation
- Toxic exposure (heavy metals, pharmaceuticals…etc)
- Diet and lifestyle (obesity, food allergies…etc)
