Third Exam - Week 6 Flashcards
Impetigo
- how deep is it
- what’s it look like
- how does it feel
- superficial
- golden crusty “stuck on” appearance, not a lot of redness or inflammation
- not itchy, not painful
Folliculitis
- how deep is it
- what’s it look like
- how does it feel
- hair follicle disease
- pustule with purulent discharge
- itchy
Furuncle
- how deep is it
- what’s it look like
- how does it feel
- deeper folliculitis
- firm tender nodule, sometimes draining, (inside of nose), red and purulent
- painful, tender
Carbuncle
- how deep is it
- what’s it look like
- how does it feel
- extensive furuncle into subcutaenous fat
- punched out lesion, lower extremities, not very purulent, has heaped border, inflammation
- painful
Erysipelas
- how deep is it
- what’s it look like
- how does it feel
- superficial lymphatic involvement
- face and lower extremities, red, swelling, fairly well demarcated, clear border, can get bacteremia and fever in diabetics
- pain, red, hot
Cellulitis
- how deep is it
- what’s it look like
- how does it feel
- spreading infection including sub-cutaneous tissues - deeper
- streaking, lymphanditis, warm, red, tender, ulcer (not escar), warm, acute fever, chills
Necrotizing fasciitis
- how deep is it
- what’s it look like
- how does it feel
- subcutaneous fat and deep fascia (includes muscle)
- forms bullae (blue), rapidly progressing skin infection, cutaneous necrosis (sloughing), not well demarcated, dark edema
- PAIN OUT OF PROPORTION to clinical findings, crepitus, eventual loss of pain due to compression of nerves
Clostridial myonecrosis (gas gangrene)
- how deep is it
- what’s it look like
- how does it feel
- deep - musculoskeletal
- see subcutaneous air on xray or CT, sepsis, renal failure, fever - rapid progression, DOESN’T BLEED when cut - pale.
- painful, smelly
Medullary osteomyelitis
- how deep is it
- what’s it look like
- how does it feel
- in the bone
- non-specific tenderness, back pain, see degradation of vertebrae on xray and CT
- back pain for months, sometimes neurological deficits or throat issues (Depending on direction of spread) +/ fever
Superficial Osteomyelitis
- how deep is it
- what’s it look like
- how does it feel
- CONTIGUOUS FOCUS - wound from outside in to bone
- chronic ulcer (months) sometimes can actually see bone
- painful (diabetics might not feel it) sometimes with fever and malaise
- vascular SUFFICIENT - bedsores, pressure sores, screws/metal implant infections - see on CT
- vascular INSUFFICIENT - diabetic foot ulcers -
Infectious arthritis
- how deep is it
- what’s it look like
- how does it feel
- joint infection in synovial fluid
- usually in knee, fever, palpable joint effusion, limited motion (dont want to extend), warm, swollen, tender, CLOWDY ASPIRATE with high white count
- painful, tender, don’t want to move
Septic bursitis
- how deep is it
- what’s it look like
- how does it feel
- in the bursae (elbow and knee)
- focal bursal inflammation with lesion - point of entry
- tender, inflammed, don’t want to flex - want to stay straight
Impetigo
- what’s it caused by
- who does it affect
- caused by group A strep (pyogenes) or staph aureas, in hot or humid weather
- any age, classic in children, highly communicable
Folliculitis
- what’s it caused by
- who does it affect
- hot tub folliculitis, tight work-out clothes, dirty razor, staph aureus
- diabetics, athletes, people with hair
Furuncle
- what’s it caused by
- who does it affect
- friction and hair follicles, perspiration, staph aureus
- develop from folliculitis
Carbuncle
- what’s it caused by
- who does it affect
- either strep or secondary to lesion, pseudomonas in cancer patients
- extremes of age - children and old people
Erysipelas
- what’s it caused by
- who does it affect
- strep pyogenes
- ppl with predisposing lymph issues, ppl with lesion or abrasion, infants and elderly, alcoholic, diabetic
Cellulitis
- what’s it caused by
- who does it affect
- tx
- staph and strep, maybe MRSA (hx could point to others - pasteurela, aeromonas (fresh water), eikenella (human bite), vibrio (warm water))
- MOST COMMON, depends on exposure - burn, injury etc.
- treat empirically for staph and strep
Necrotizing fasciitis
- what’s it caused by
- who does it affect
- tx
- 2 types of microorganisms (1- polymicrobial mixed anaerobes, or 2- group A strep) secondary to lesion
- anyone, diabetics
- might need fasciotomy for compartment syndrome, PROMPT surgical intervention and antibiotics
Clostridial myonecrosis (gas gangrene)
- what’s it caused by
- who does it affect
- tx
- gram pos sporulating anaerobic rod (clost perfring), stool or soil contamination (war wounds)
- those with preexisting wounds, toxins are everywhere in environment, post surg, war, stool infection
- surgery and antibiotics
Medullary osteomyelitis
- what’s it caused by
- who does it affect
- tx
- caused by staph aureus - hematogenous spread, sometimes pseudomonas for IV drug users
- IV drug users
- IV tx (might be hard for drug users)
Superficial Osteomyelitis
- what’s it caused by
- who does it affect
- tx
- vascular SUFFICIENT - bedsores, pressure sores, stool bacteria from diapers, bone fracture not properly debrieded, screws/metal implant infectons
- vascular INSUFFICIENT - diabetic foot ulcers - new shoes, toenail clipping, shows mixed anaerobic gram neg culture
- tx is limited unless you’re able to remove original insult - diabetes, bedrest etc.
Infectious arthritis
- what’s it caused by
- who does it affect
- tx
- synovial fluid is vascular and no BM - so hematogenous spread is easy, adults/adolescent cause is usually STD - gonorrhea, or staph aureus, babies is usually group B strep or staph aureus
- people who are IV users, have prosthetic joints, have other inflammatory arthritis, systemic infections, or post surgery or trauma
- tx take fluid out (helps feel better) take culture, and treat with appropriate antibiotic
Septic bursitis
- what’s it caused by
- who does it affect
- tx
- caused by puncture- acute infection
- antibiotic tx
Scabies
- mode of transmission
- site of infection
- route of infection
- likely host
- person to person, including STI and fomites
- hands and feet, waistline and genitals
- female bug burrows in skin and lays eggs (sperpinginous burrows)
Scabies
- clinical signs
- diagnosis
- intense itching 3-4 WEEKS AFTER BITE (or sooner for reinfection. also rash, redness, papules, vesicles, red tracks, allergic reaction to the burrowing and eggs
- dx by history and clinical presentation, or scrape onto microscope slide. also do BURROW INK TEST to see tract
Scabies variants (2)
- Crusted/Norweigan scabies - immunocompromised patients (HIV, HTLV1, Hep C, Alcohol) presents with uncontrolled replication - millions, highly transmissible
- Nodular scabies - intense inflammatory response that causes bumb
Scabies
- treatment
- tx with topical cream or single dose of antiparisitic agent. RETREAT 1 WEEK LATER (drugs only kill adults)
- treat sexual contacts
- if kid infected treat all members of house
- wash fomites with HOT water
Lice variants (3)
1) Pediculus humanis capitis (head lice)
2) Pediculus humanis corpus (body lice) - VECTOR for epidemic typhus and relapsing fever
3) Pediculus humanis pubis (pubic lice)
Head lice
- mode of transmission
- site of infection
- route of infection
- likely host
- person to person (kids)
- scalp (sometimes beard and eyelashes)
- adult lice lay nits on hair shaft, feed on blood from scalp
- children, non-industrialized countries, fomites
Body lice
- mode of transmission
- site of infection
- route of infection
- likely host
- person-to- person, or fomite to person, adult lice live on clothing
- chest and back, body hair
- adult lice live in clothes, come onto body to feed
- homeless, economically poor, adult, (body louse is vector for epidemic typhus and relapsing fever)
Pubic lice
- mode of transmission
- site of infection
- route of infection
- likely host
- sexual contact
- pubic hair
- sexual transmission - lice from person to person, same as other lice
- sexually active adults
Lice
- clinical signs
- diagnosis
- itchiness - TYPE 1 hypersensitivity rxn to saliva
- see nits (eggs) (nits hatch no nymphs, which become adults in 1-2 weeks, which live for 1-3 months NEED BLOOD daily)
- can have secondary bacterial infection due to itching
- visualize lice or nits with Wood’s lamp - can fluoresce LIVE nits
Lice
- treatment
topical pediculocides, gels that stay for a while, retreat later, get rid of fomites (treat sexual parters for pubic lice)
Bed bugs
- mode of transmission
- site/route of infection
- clinical signs
- tx
- bed bugs live in furniture/fomites
- anywhere on body, but tend to have clustered bites “breakfast lunch and dinner”
- nocturnal, will feast at night, attracted to heat and CO2
- corticosteroids, topical for sympoms. have to kill bugs by heat - hard to get rid of.
Tungiasis
- AKA
- mode of transmission
- site/route of infection
- clinical signs
- tx
- AKA “jigger” “chingo”
- female will penetrate skin of lower extremeties/feet/nailbed and burrown to lay eggs
- seen in travellers to Africa, Carribean, Central/South America
- have reaction to flea. can see the rear part stiking out and expelling eggs
- tx - extract and treat symptoms
Myasis
- AKA
- mode of transmission
- site/route of infection
- clinical signs
- tx
- AKA maggots - TUMBU fly in Africa, BOTFLY in South/Central America
- mode for Tumbu fly, fly lands on damp clothing, lays eggs, maggots hatch and burrow into skin
- mode for Botfly, fly captures mosquito, lyas eggs, and eggs get transferred during mosquito bite
- clinical - 3 types of infections (furuncular (most common looks like cellulitis), wound, cavitary)
tx - suffocate with vaseline etc. iron clothes and prevent mosquito bites
Amphotericin B
- molecular mechanism
- binds egosterol forming artificial pores (bad for fungus, good for us)
Amphotericin B
- use
- mode of administration
- broadest spectrum for systemic fungal infections
- pregnancy category B - preferred over axoles and capsofungin
- NOT through BBB
- give IV - no oral absorption
Amphotericin B
- toxicity
- long term use associated with neprhotoxicity (later generations have hepatotoxicity instead)
Nystatin
- mechanism
- use
- same as amphotericin
- parental administration
- can be used topically for thrush
Azoles
- mechanism
- egosterol synthesis inhibitor - binds to and inhibits cytochrome p450 in fungi
Flucanozole
- use
- toxicity
- best CSF penetration (use for cryptococcal meningitis) and prophylaxis for HIV or cancer
- widest range of use therapeuticaly
- toxicity: CYP2C9 inhibiton (warfarin and phenytoin), stephen johnson syndrome, alopecia with longer treatment, teratogenic for pregnancy
Itraconazole
- use
- toxicity
- poor CNs penetration
- good for dimorphic fungi
- toxicity, congestive heart disease, CYP3A4 inhibition (many drug-drug)
Voriconazole
- use
- toxicity
- broadest spectrum of all azoles
- use for invasive asperigillosis (less tocity than amphotericin B)
- toxicity: produces visual disturbances, inhibits many P450 enzymes (many drug-drug)
Capsofungin/Echinocandin
- mechanism
- mode of administration
- use
- toxicity
- mech: inhibition of B(1-3) glucan cell wall - disrupts cell wall synthesis
- IV - water soluble
- use for candida and asperigillus. can be used for people not responding to voriconazole
- toxicity: flushing, GI discomfort, hepatotoxicity (esp when used with cyclosporine), embryotoxic
Griseofulvin
- mechanism
- use
- toxicity
- microtubule diruption
- inhibits mitosis - interferes with microtubule assembly
- used for onychomycosis (drug is depositied in newly growing keratin)
- have to be on the drug for 6-9 months. P450 INDUCTION (also rifampin) increases metabolism of drugs - warfarin etc.
Terbinafine
- AKA
- mechanism
- use
- administration mode
- toxicity
- aka Lamisil
- inhibits squalene epoxidase fungal enzyme (increasing squalene levels and decreasing egosterol levels)
- used for onychomycosis - keratophilic and fungicidal
- orally administered
- well tolerated- no P450 interaction, shorter time of use (3mo)
Flucytosine
- mechanism
- use
- toxicity
- gets into cell, gets converted to 5-fluoroacil, which gets incorporated into DNA and RNA - disrupting synthesis and is cytotoxic
- only works for fungal cells
- narrow spectrum of action - has to be used in combination with other drugs
- toxicity: hematotoxicity (anemia, leukopenia)
Type 1 hypersensitivity
- immune mediator
- antigen (soluble? surface?)
- effector mechanism
- example of reaction
- IgE
- soluble antigen
- mast-cell activation
- allergic rhinitis, asthma, systemic anaphylaxis, atopic dermatitis
Type 2 hypersensitivity (2)
- immune mediator
- antigen (soluble? surface?)
- effector mechanism
- example of reaction
- IgG
- platelet/tissue/RBC- associated antigen or cell-surface receptor
- complement, FcR+ cells (phagocytes, NK), signal altering (receptor-mediated)
- penicillin allergy, rheumatic fever, HIT, chronic urticaria (receptor)
Type 3 hypersensitivity
- immune mediator
- antigen (soluble? surface?)
- effector mechanism
- example of reaction
- IgG
- soluble antigen (immune complex)
- complement - phagocytes
- serum sickness, arthrus reaction, syphilis treponema
Type 4 hypersensitivity (3)
- immune mediator
- antigen (soluble? surface?)
- effector mechanism
- example of reaction
1) Th1
- soluble antigen
- macrophage activation
- contact dermatitis, PPD
2) Th2
- soluble antigen
- IgE production, eosinophil activation, mastocytosis
- chronic asthma, chronic allergic rhinitis, granulomas in TB
3) CTL
- Cell-associated antigen
- cytotoxicity
- contact dermatitis
example of genetic succeptability for hypersenstivity reactions
atopic dermatitis - Th2 response, IgE, type 1 hypersensitivty
Steps for sensitization in Type 1 hypersensitivity rxn (6)
- protease (der p1) penetrates barrier tissue and enters dermal space
- interacts with resident antigen presenting cells
- get immune response, takes antigen to LN, primes T cells
- Some T cells become Th2, which help B cells produce IgE
- IgE from plasma cells bind to mast cells via FceR1
- next time you see antigen you get degranulationu
Steps for effector phase for Type 1 hypersensitivity rxn (4)
- IgE bound to FceR1 (with ITAM) on mast cells/basophils (from sensitization) is CROSS-LINKED by re-exposure to allergen (protease)
- mast cells and basophils are activated to secrete pre-formed granule contents (symptoms w/i 1-5 minutes) and synthesized lipid mediators (5-30 min) and cytokines/chemokines (hours)
- chemokines recruit eosinophils to secrete toxins
- inflammation and tissue damage occurs
PPD skin test is an example of what type of hypersensitivity reaction
type 4
what do mast cell toxic mediators cause (3) (and what’s an example) (1)
vascular leak broncho constriction interstinal hypermotility (histamine)
what do mast cell lipid mediators cause (5) (and what are some examples) (5)
- vascular leak
- broncho constriction
- intestinal hypermotility
- mucus secretion
- inflammation (chemotaxis of eosinophils, basophils and Th2 cells)
(prostaglandins D2, E2
leukotrienes C4, D4, E4)
what do mast cell cytokines cause (3) (and what are the cytokines) (4)
- amplify Th2 cell response (Il-4, IL-13
- promote eosinophil production and activation (IL-5)
- promote inflammation (TNFalpha)
what do mast cell enzymes do (1) (and what’s an example) (1)
tissue damage/ remodel CT matrix (tryptase)
what do eosinophil granule proteins cause (1) (and what’s an example) (2)
killing of parasites and host cells (major basic protein, eosinophil cationic protein)
what do eosinophil granule enzymes do (1) (and what’s an example) (1)
tissue remodeling (eosinophil peroxidase)
chronic allergen exposure results in what (4 things)
Chronic Th2 mediated inflammation: - increased mucus production - remodeling of tissue collagen - less elasticity increased airway hyperresponsiveness to allergen
HIT is an example of what kind of hypersensitivity reaction (how does it work)
Type 2:
Ab directed at heparin-platelet factor 4 complexes binds to Fc receptors on adjacent platelets, causing aggregation and thromboembolism
Coomb’s test is an example of what kind of hypersensitivity reaction (how does it work)
Type 2:
antibodies on RBCs will agglutinate in response to presence of anti-antibody antibody (test for autoimmune hemolytic anemia)
What type of hypersensitivity response is the Arthus reaction? and what are the steps? (4)
Type 3 (slower than type 1):
- previous immune sensitization (pre-existing IgG)
- when injected with antigen, immune complexes form and activate complement
- complement recruits additional cells (through C5a)
- mast cells also have receptors for C5a. C5a binds, causing mast cell to produce proinflammatory cytokines and tissue swelling through FcgammaR3 activation
2 examples of arthus reaction
1) vaccine-mediated local dermal necrosis - repetitive vaccines to tetanus
2) hypersensitivity pneumonitis (farmer’s lung) - response to fungal molds in damp hay (also involves Type 4 reaction)
serum sickness is what kind of hypersensitivity reaction?
Type 3:
- patients are treated with immunogenic proteins (polyclonal antibodies, antivenom)
- after 10 days, they will make antibodies and if there is still antigen (wrong dosing on the doctor’s part), will mount a response and have immune complex deposition in tissues
3 types of type 4 hypersensitivity reactions (and examples)
1) delayed-type (mycobacteria, insect venom)
2) contact hypersensitivity (haptens: poison ivy, small metal ions: nickel)
3) gluten-sensitive enteropathy (celiac)
Poison Ivy (mechanism of reaction, Th mediated, end result)
- not a peptide, but modifies proteins in skin, makes chemical reaction and complexes (haptenated proteins), which are presented to T cells by Langerhans and macrophages in the draining LN
- upon reexposure, T cells migrates to site
- Th1 cells are activated, which secrete IFN gamma, TNF alpha and chemokines, which recruit macrophages which secrete mediators of inflammation
Celiac disease (mechanism, reaction)
- peptide gets deaminated, deaminated protein gets presented by HLA-DQ2 and DQ8
- naive T cell responds to deaminated peptide
- inflammatory effector T cell causes villous atrophy
- the more you’re exposed to gluten, the more symptoms you have
Granuloma formation (mechanism, Th mediated, reaction)
- Th1 effector cell activation, IFN gamma stimulates macrophage
- TB evades macrophages causing chronic immune activation
- get central accumulation of epithelioid macrophages (decreased mobility and phagocytosis) with outer T lymphocyte ring
- T lymphocytes produce IFN gamma and other cytokines - positive feedback for chronic inflammation
2 categories of granulomas
1) (infectious) caseous necrosis - TB, Ghon complex (granuloma in tissue AND lymph node)
2) non-necrotizing - sarcoid, inorganic, fungi - no central region of necrosis
what molecules mediate signaling for effector function of granuloma
CD40 on macrophage, CD40L on T cell
Th17 is related to what disease
psoriasis
first generation histamine antagonists
- diphenhydramine
- doxylamine
- chlorpheniramine
second generation histamine antagonists
- loratadine (claritin)
- cetirizine (zyrtec)
- fexofenadine (allegra)
endogenous histamine synthesis and metabolism
- decarboxylation of L-histidine by histidine decarboxylation
- histamine is rapidly broken down to inactive metabolite methylimidazole acetic acid by monoamine oxidase and excreted into urine
what is an autacoid
compound that is released and locally in periphery (histamine, serotonin, prostaglandins, leukotrienes, kinins, etc)
what’s an auto- iso- allo- and xenograft?
auto - self
iso - identical twin
allo - other of same species
xeno - different species
if you’re blood type O, what kind of blood types can you receive? What antibodies do you have?
get blood from type O - have antibodies to A and B
if you’re blood type A, what kind of blood types can you receive? What antibodies do you have?
get O or A
have antibodies to B
if you’re blood type B, what kind of blood types can you receive? What antibodies do you have?
get O or B
have antibodies to A
if you’re blood type AB, what kind of blood types can you receive? What antibodies do you have?
get blood from any type - have no antibodies against A or B
where do you find blood cell antigens? (anti- A/B etc.)
circulating - they’re shed, on RBCs, and on endothelial cells
describe the mouse study for histocompatibility (skin transplants)
- Gave skin transplants from mice with the same MHCa - no rejection
- Gave MHCa to MHCb - rejection
- repeated this discordant transplant and rejection was even faster (T cell mediated - memory)
why do we have T cells that recognize non-self MHC?
What is the clinical significance of this in terms of transplants?
we have a huge polymorphism in repertoire of T cells. in order to be positively selected in thymus, have to recognize self MHC, but some will also recognize non-self MHC, but won’t be negatively selected because they were never presented with non-self MHC during development
This is important because we need to match MHC 1/2 for graft and transplants (not important for RBC transfusions because RBCs don’t have MHC expression)
classic allograft rejection - timing and cause (think - why do people reject cadaveric transplants more?)
- happens within 2 weeks and intiates memory (second set rejection will be accelerated)
- require damage to occur first and initiate innate immune cell activation and inflammation which will then lead to lymphocyte (T cell) activation to non-self
Direct allorecognition (what is it, and what MHC/CD is involved)
donor antigen presenting cell from transplanted organ migrants to LN, and its MHC (with endogenous donor peptide - MHC1) is recognized by T cells and activates recipient effector function. effector cells migrate to organ and destroy it (CD8 - mediated)
Indirect allorecognition (what is it, and what MHC/CD is involved)
self antigen presenting cell will phagocytose endothelium (for example) from donor organ, which contains donor MHC. self MHC will present donor MHC peptides and mount immune response and rejection (exogenous peptide - self MHC class 2 to CD4 cells)
Hyperacute rejection (how long does it take, what causes it, what’s activated in response, what kind of hypersensitivty reaction is it, how can you avoid)
happens within minutes or hours.
caused by PRE-FORMED antibodies to donor antigens - causes rapid interaction with antigen on organ endothelial cells, activates COMPLEMENT, causing inflammatory response and tissue destruction. this is an example of TYPE 2 HYPERSENSITIVITY (IgG)- tissue antigen response.
avoid by mixing recipient serum with donor tissue to see if anythign binds or reacts.
what are some reasons people have pre-formed anti HLA antibody?
- pregnancy - giving birth exposes you to paternal HLA
- previous transplant rejection
- multiple transfusions
Acute rejection (how long does it take, what causes it, what’s recruited)
- classic rejection
- happens over days to weeks
- T cell dependent - causes damage to transplanted organ
- recruitment of lots of lymphocytes (T cells)
Chronic rejection (how long does it take, what causes it, what happens)
- takes months to years
- analagous to chronic inflammation - promotes deposition of collagen and fibrotic tissue
- causes changes in vasculature - more fibrotic, tissue remodeling, IMMUNE COMPLEX DEPOSITION, recruitment of T and B cells
- recruitment of nuclear cells like macrophages that cause tissue damage
- causes occlusion of BVs
Graft vs. Host (mechanism, timing, avoidance)
- during bone marrow transplantation, donor immune cells migrate to lymphoid tissue, and alloreact with host dendritic cells and proliferate, causing effector function in inflammed tissues - works through the same mechanism as acute graft rejection, but the opposite way (host vs. donor immune response).
- can be acute or chronic
- want better HLA match, however, some graft vs host disease is protective against relapse of leukemia
List 3 categories of lab tests used for identifying HLA type and predicting rejection
- serologic testing (cross-match)
- molecular (DNA PCR)
- cellular (mixed lymphocyte culture)
Cross-match test
add donor lymphocytes to recipient serum. if you add complement and the cells lyse, then you have a problem (for example, person who expresses B27, their leukocytes will lyse in the presence of anti-B27 antibodies and complement – not a match), OR if you add fluorescent anti-Ig, they will fluoresce. — question! is it donor lymphocyte and recipient antibody or vis versa?
Mixed Lymphocyte Reaction
- mix immune cell lymphocytes (T cells, antigen presenting cells etc.) from donors and recipients to see if they react to each other.
- If T cells respond to non-self MHC on donor cells, you get activation and proliferation as well as effector function (problematic)
Immunosuppressive therapies to avoid rejection (6)
- corticosteroids (reduce inflammatory response)
- antibodies that block cytokines/cytokine receptors
- co-stimulation blockade (CTLA4-Ig)
- calcineurin inhibitors - block NFAT transcription factor (cyclosporine and tacrolimus)
- antimetabolites - inhibits guanine nucleotide synthesis in lymphocytes (azathioprine, mycophenolate mofetil)
- TOR inhibitiors - blocks lymphocyte proliferation (rapamycin)
genes that are associated with autoimmunity (5)
- AIRE (APECED)
- CTLA4 (Graves)
- FOXP4 (IPEX)
- FAS (autoimmune lymphoproliferative syndrome)
- C1q (SLE)
molecular mimicry (mechanism and example)
antigen receptor has CROSS-REACTIVITY between microbial peptide and self-peptide (example: antibodies to S. pyogenes cross-react with epitopes on muscle, kidney and joints causing rheumatic fever)
bystander activation (mechanism and example)
- because of inflammatory microenvironment, you activate self-reactive T-cells - indirect consequence of inflammation.
- thyroid cells don’t normally express HLA class 2 molecules, but IFN gamma produced during infection/inflammation induces HLA class2 expression on thyroid cells.
- Activated CD4 T cells recognize thyroid peptides and induce autoimmune thyroid disease
Epitope spreading (mechanism and spreading)
- tissue damage and immune response to self-antigen promotes spreading of immune response to additional self epitopes
- tissue damage/stress (smoking) changes regulation of post-translational modifications – enzyme PAD converts arginine to citrulline residues, making it susceptible to degradation - residues are presented by HLA class 2 to CD4 T cells - associated with RHEUMATOID ARTHRITIS
MHC/HLA regulation, susceptibility of autoimmune disease (mechanism and associated disorder)
MHC haplotype influences both peptide presentation in periphery AND T cell receptor repertoire through pos/neg selection – genetic.
- changes in MHC (charges/molecules in binding grooves etc) can alter the selectivity of binding and what is presented
- Celiac - HLA DQ2/DQ8 mutations
pemphigus vulgaris is what type of hypersensitivity reaction
Type 2 - direct interaction with cell (desmoglein) causing blistering of skin
subacute bacterial endocarditis is what type of hypersensitivity reaction
type 3 - immune complexes cause deposition in vascualture. Neutrophils involved with immune complexes
autoimmune hemolytic anemia is what type of hypersensitivity reaction
type 2 - Fc mediated phagocytosis because of Rh blood group antigens
insulin-dependent diabetes mellitus is what type of hypersensitivity reaction
type 4- pancreatic beta cell antigen - tissue damage mediated by T cells
MS is what type of hypersensitivity reaction
type 4 - T cell destruction of myelin
graves disease is what type of hypersensitivity reaction?
type 2 - antibody binds to receptor on thyroid epithelial cells, stimulating production of thyroid hormone, not subject to normal regulation - causes hyperthyroidism
rheumatoid arthritis is what type of hypersensitivity reaction
type 4 - autoantibodies and T cells that cause destruction in various tissues
myasthenia gravis is what type of hypersensitivity reaction
type 2 -
specific antibody reacting to Ach receptors - antibody binds to receptor and interferes with stimulation - get muscle weakness and paralysis
psoriasis is what type of hypersensitivity reaction
type 4 - autoreactive T cell response against skin-associated antigens causing aberrant regulation of skin proliferation
genetic pathway therapeutic targets for autoimmune diseases (6)
- co-stimulatory molecules
- Treg
- antigen clearance
- antigen presentation/ autoantibody secretion
- cytokine polarization
- inflammatory mediators
Give example of co stimulatory target for therapy against autoimmune disorders
If you block CD28-B7 interaction with CTLA4 (which binds to B7), it blocks T cell activation and promotes tolerance
example of cytokine target for therapy against autimmune disorders (4)
- IL-5 - interfere with eosinophil production
- IgE - decrease type 1 hypersensitivity reactions
- IL-6 and IL-17 decreasing Th17
- IL-12 (proinflammatory)
example of inflammatory mediator for target of therapy against autoimmune disorders
interfere with TNF alpha
- either make antibody to bind to TNF, or make chimeric molecule that adds receptor to TNF binding site and prevents binding to receptors on cells
- effective anti-inflammatory agent for rheumatoid arthritis that decrease acute phase protein production
histamine has 3 roles, what are they
1) immune response (allergic IgE type 1 hypersensitivity via cross-linking and complement activation inflammation)
2) gastric acid secretion
3) neurotransmitter
what does cromolyn do to histamine
cromolyn blocks release of histamine
Histamine receptor H1 -what type of receptor is it, where is it located, what is the post-receptor response
- G protein coupled receptor (Gq)
- endothelium, CNS
- increases NO, increases cGMP, increases IP3
Histamine receptor H2 -what type of receptor is it, where is it located, what is the post-receptor response
- G protein coupled receptor (Gs)
- vascular smooth muscle
- increases cAMP
what effect does histamine cause on vascular smooth musche
causes vasodilation/edema
- decreases blood pressure, increases reflex tachycardia and heart rate
- via endothelial H1 receptors and NO production
- via smooth muscle H1 causing calcium increase and contraction
what effect does histamine have on non-vascular smooth muscle (resp. system)
bronchocontsriction via H1 receptors (increases in asthma)
what effect does histamine have on the peripheral nervous system
- acts as autocoid
- stimulates primary afferent nerve endings (itch, pain)
- H1 receptor
what effect does histamine have on cns
- acts as neurotransmitter
- regulate wakefulness, appetite and body temp
- via post-synaptic H1
what effect does histamine have on GI
- acts as secretagogue
- stimulates gastric acid release (H2) and increased motility (H1, H2, H4)
histamine toxicity
- found in spoiled tuna, causing nausea vomiting but can be suppressed by H1 receptor blockers
is anaphylaxis caused by histamine
no.
what local allergic reactions do histamine cause
urticaria (hives) allergic rhinitis (hay fever)
pharmacotherapy for sub-acute and preventative allergies
inhaled steroids (flonase)
mast cell stabilizers (pharmacotherapy)
cromolyn sodium - directly inhibit mast cell degranulation by blocking ion channels
first generation antihistamines list and notable characteristics
- diphenhydramine (very sedative, very anti Ach, anti-motion sickness)
- doxylamine (longer lasting, very sedative)
- chlorpeniramine (less able to cross BBB, somewhat sedative)
first generation antihistamines mechanism of action
- inverse agonists
- all lipid soluble
- crosses BBB, placenta and breast milk
- metabolized in liver, cleared in renal
first generation antihistamines adverse reactions
- cardiac (sinus/reflex tach - dose related)
- contraindicated for glaucoma or prostatic hypertrophy
- respiratory depression
- CNS
first generation antihistamines vulnerable patients
- renal/liver issues
- elderly
- pregnancy
- nenonates/infants (CNS stimulation)
second generation antihistamines list and notable features
- fexofenadine (Excreted unchanged, transported by OATP1A2, don’t drink orange, grapefruit, apple juice)
- loratidine (24hr duration)
- cetirizine (24hr duration, metabolite of hydroxyzine)
second generation antihistamines characteristics and uses
- not a neurotransmitter
- all lipid soluble
- wide distribution
- NO BBB
- metabolized in liver (except fexo)
- cleared in renal (excpet fexo)
- use for allergic rhinitis, allergic conjuctivitis and urticaria
- NOT useful against anaphylaxis, for common cold, sleep aid or anti-motion sickness
second generation antihistamine adverse effects
- less than first gen - no CNS penetration - no sedation
promethazine uses
motion sickness and morning sickness (first gen)
incidence vs prevalence
incidence = new diagnoses over time prevalence = people who have it right now
quarantine vs isolation
isolation = isolate for however long they're contagious quarantine = exposed but not yet showing illness (for incubation period)
epidemic triad
host, environment, agent
steps for outbreak investiagion (9)
- confirm outbreak
- confirm diagnosis
- create case definition
- count and identify additional cases
- perform epidemiological analysis
- develop and test hypotheses for risk factors or causal agents
- implement control measures to prevent further infections and morbidity
- communicate findings
- monitor surveillance data
if you have a neutrophil defect, which fungi will cause issues? (3)
candida
aspergillus
mucor infections
if you have T cell defect, which fungi will cause issues? (5)
cryptococcus neoformans pneumocystic jirovecii blastomyces dermatitidis coccidiodes immitis histoplasma capsulatum
superficial mycoses - characteristics, types (4) and causative fungus
-limited to outermost layers of hair/skin
- mild infections with little/no inflammation
include:
- black piedra - gritty brown/black concretions on scalp (piedraia hortae)
- white piedra - white cranules on hair shaft genital and beards (trichosporon beigelii)
- tinea nigra - black/brown macules on palms/soles (exophiala werneckii)
- pityriasis versicolor - hyper/hypo pigmented scaly macules on torso (malassezia furfur) culture on sabouraud’s agar with 1% olive oil
superficial mycoses diagnosis and treatment
dx: clinical, wet mount with potassium hydroxide
tx:
- remove hair for black/white piedra
- topical azole or keratolytic agent for tinea nigra
- selenium sulfide for pityariasis versicolor
cutaneous mycoses - characteristics and types (6)
- infect the keratinized tissues and elicit immune response “ring worm”
- dermatophytes belong to 3 genera (microsporum, trichophyton, epidermophyton)
include: - tinea capitis (head)
- tinea corporis (body)
- tinea pedis (feet)
- tinea barbae (beard)
- tinea cruris (perineum)
- tinea unguium (nails)
cutaneous mycoses - diagnosis and treatment
dx: clinical - redness around infection, skin sample, drop of potassium hydroxide.
tx: systemic agent for tinea capitis, topical agent for other tineas
subcutaneous mycoses - characteristics and types (3)
below skin - dermis and subcutaneous tissue - need trauma or portan of entry. some have high enough burden of disease to need surgery. types: - lymphocutaneous sporotrichosis - chromoblastomycosis - eumycetoma mycetoma
lymphocutaneous sporotrichosis - caused by, clinical, dx
caused by dimorphous fungus (sporothrix schenckii)
- requires trauma through skin
- nodule forms, spreads centrally along lymph tracts
- dx: look for fungus, culture with sab agar at roomp temp and 37 deg
chromoblastomycosis- caused by, clinical, dx
- caused by fonsecaea or cladosporium
- happens in the tropics
- looks warty
- biopsy for culture - use h&e or black ink, see spherical fungi with copper color - MEDLAR BODIES
- looks like cauliflower in late stages - NOT purulent
eumycetoma mycetoma - caused by, clinical, dx
- caused by pseudallescheria boydii and madurella grisea
- true mycetoma (not bacteria)
- PURULENT as opposed to chromoblast
- has sinus tract similar to nocaridia and actinomyces
- have to culture to determine if bacteria or fungus
deep tissue fungal infections - characteristics and types of infections (4)
- acquired from either endogenous or environment
- invasive
- dimorphic, primary pathogens in immunocompetent
types: - blastomyces dermatitidis
- coccidioides immitis
- histoplasma capsulatum
- paracoccidiodes brasiliensis
blastomyces dermatitidis - geographic distribution, clinical, dx, tx
- eastern US - E of mississippi
- spores enter lung - primary infection in lungs, in immune compromised can be dissemminated
- if left untreated can infect any part of skin, form ulcers, disseminate to prostate and skin, looks like blizzard on CXR
- on culture with KOH, yeast is much larger thanother cells
- tx: itraconazole, amphotericin B for disseminated
coccidioides immitis- geographic distribution, clinical, dx, tx
- SW US and NW Mexico (dry parts of SW)
- get through inhalation
- LAB TECHS CAN INHALE TOO
- if left untreated looks like TB, and in immunecompromised can diseminate to CNS, bone and skin - see abnormal spinal x-ray, skin ulceration, sinus tract in knee
- on culture, see ENDOSPORES - spherule with endospores within - small
- can do antibody test for recurrent or disseminated infection
tx: flucanosole, amphotericin B for disseminated
histoplasma capsulatum- geographic distribution, clinical, dx, tx
- Ohio river valley (not coastal)
- found in soil contaminated by BAT and BIRD poop
- spores inhaled - lungs are first site
- old lung lesions can calcify when healing
- chronic lung infections can cause CAVITATION
- seen in macrophages and monocytes (seen on Giemsa)
- dimorphic (cold mold heat yeast)
- causes ulcerations around gums
- can be acquired by LAB TECHS
- can see antigen after dissemination and complement fixation
tx - itraconazole, amphotericin B
paracoccidioides brasiliensis - geographic distribution, clinical, dx, tx
- south american distribution
- spores inhaled - lungs first site
- likes mucous membrane of entire GI tract
- see MARINER’S WHEEL on wet mount
- causes mucosal lesions and ulcerations in GI tract
- tx - itraconazole, amphotericin B for disseminated
Opportunistic infections- characteristics and list (5)
- associated with neutrophil defects and T cell defects list: - candida - aspergillus - zygomycosis (mucor, rhizopus, absidia) - cryptococcus neoformans - pneumocystis jirovecci
opportunistic infections that affect hosts with neutrophil defects
- aspergillus
- candida
- zygomyces (mucor, rhizopus, absidia)
opportunistic infections that affect hosts with T cell defects
- cryptococcus neoformans
- pneumocystic jirovecii
candidiasis - immune cell defect, what does it cause (2), clinical, dx, tx
- endogenous flora
- chemotherapy or defect reducing neutrophils allows for invasive disease
- causes:
1) superfiical disease - mucosal thrush in esophagus, vandida in vagina, skin and nail involvement
2) chronic mucocutaneous candidiasis in T cell immunocompromised - skin nails and oropharynx - spreads hematogenously
dx: culture, germ tube test - C. ALBICANS will form PSEUDOHYPHAE at 37deg
- cottony white spots on oropharynx, chronic coating in mouth, tongue and nails
- liver and spleen abcesses on CT
tx: fluconazole, ampho for disseminated
Aspergillus- immune cell defect, what does it cause (3), clinical, dx, tx
- ubiquitous
- affect neutorphil deficient hosts
- spore forming
- inhaled
3 disease manifestations:
1) allergic bronchopulmonary aspergillosis (pts w/ asthma, immediate IgE response to antigen)
2) aspergilloma (aspergillus makes fungus ball in preexisting lung cavity - can hemorrhage)
3) invasive aspergillosis (causes invasion into sinuses, lungs, and systemic - causes infarctions in eyes CNS, skin and bone and air crescent in lungs) - clinically, CXR aspergilloma that shifts with positioning
- on culture, aspergillus fumigatus looks like aspergil - sprinkling with holy water. SEPTATED HYPHAE with ACUTE ANGLE BRANCHING
tx- have to restore neutrophil function. then treat with amphotericin B
Zygomycosis - types (3), patient population affected and clinical presentation, dx, tx
3 types:
1) mucor
2) rhizopus (bread mold)
3) absidia
patient population and presentation:
- poorly controlled diabetes (rhinocerebral infection)
- burn patients (skin infections)
- neutropenia (pneumonia)
- chelating therapy (pneumonia)
on culture, see broad, NON-SEPTATED HYPHAE with RIGHT ANGLE BRANCHING - also causes infarctions due to attraction to BVs
tx - also depends on treatment of underlying cause (acidosis or neutropenia), give amphotericin B
Cryptococcus - serotypes (4), clinical presentation,dx, tx
4 serotypes
- A and D (neoformans) from pigeon excreta
- B and C (gattii) from debris under red gum tree
- predispotion of AIDS, steroid, lymphoma or nothing (50%)
- presents with pneumonia and lung cavity, meningitis and dissemination to skin eye bone and prostate
- UMBILICATED papules
- dx: india ink staining, see sugar capsule virulence factor (capsule glistens and can be stained with mucicarmine), antigen for dx too
- tx - amphotericin B +/- 5-fluorocytosine, need to chronically suppress in HIV+ patients with fluconazole/amph B
pneumocystic jirovecii - characteristics, clinical, dx, tx
- related to fungi but no egosterol in membrane (won’t respond to ampho b)
- all people are carrier s- dormant, but comes out of dormancy if T cell immunocompromised
- get pneumocystic pneumonia in HIV (PCP) also with bone marrow transplantation
- dx with lavage to be stained with Giemsa or monoglocal antiboy stain
- tx with trimethoprim-sulfamethoxazole. give prophylaxis with AIDS diagnosis (primary = risk but no infection, secondary = prevent recurrence)
papule
less than 1 cm, raised, erythematous
plaque
more than 1 cm with scale
maccule
discoloration, flat, less than 1 cm
patch
discoloration, flat, more than 1 cm
nodule
greater than 1 cm, more elevated than wide
vessicle
less than 1 cm, clear fluid
bulla
more than 1 cm, clear fluid
