PBL Measles Flashcards
measles DNA and structure (Diebel classification)
ssRNA(-) (Group V) Nonsegmented Helical Nucleocapsid Enveloped Paramyxovirus Morbillivirus
Route of entry
upper respiratory endothelium (maybe conjunctiva)
tropisms
lymphocytes
where does measles virus replicate
conjunctiva, respiratory tract, urinary tract, lymphatic system, blood vessels, central nervous system
measles incubation
10-12 days (10-14?)
replication cycle measles
-ssRNA –> +ssRNA = mRNA
this can be translated into capsomere proteins, and or used to replicate more -ssRNA (DNA of measles), then assembled inot virions which are released
proteins on measles that help it infect cells
hemogluttinin and fusion proteins (also what we make Ab to)
H mediates receptor attachment (to CD46, SLAM, or nectin-4) and fusion helps cause membrane fusion
what TLR recognizes measles
endosomal TLR7/7 (ssRNA)
what is measles transported through (ie air, fluids, blood)
respiratory droplets
measles AKA
rubeola
when is measles contagious
5th day of incubation to 2-3 days of rash
diagnostic features of measles
rash, Koplic spots, conjunctivitis, dry cough, serology
treatment measles
symptomatic
? Vitamin A? (third world countries)
treat secondary infections d/t immunosuppression
vaccination for measles
live, attenuated
human cell receptors that mediate measles infection of cells
CD46 - on all nucleated cells (cofactor in proteolytic inactivation of C3b and C4b)
SLAM - thymocytes, activated lymphocytes, mature dendritic cells, macrophages, and platelets. Absent from monocytes, NK cells, granulocytes (explains tropism).
Human nectin-4 - placenta cells, trachea cells (lesser degree)
Prodrome
10-14 days after exposure, lasts 2-4 days
Fever, cough, fatigue, decreased appetite, red watery eyes, runny nose (vomiting, diarrhea, sore throat, swollen glands/spleen), Koplik spots
Lasts 2-3 days, ends with onset of rash
Rash in measles
Around 14 days after exposure, after 2-4 days of prodrome
Starts on face, spreads to neck, trunk, arms and legs
Feel better about 2 days into rash, fades within 3-4 days
May be some fine peeling
Primary site of infection
respiratory epithelium of nasopharynx
When does primary viremia occur
2-3 days after invasion and replication in respiratory epithelium and regional lymph nodes
After primary viremia, what becomes infected
reticuloendothelial system (mononuclear phagocyte system (MPS) is a part of the immune system that consists of the phagocytic cells located in reticular connective tissue)
Second viremia when
5-7 days after initial infection
what becomes infected with second viremia
respiratory tract and other organs
beneficence and measles vaccination
Do what is good for the patient (is protecting a child from a future measles infection doing good? Or is allowing them to not get the vaccine, preventing any adverse events, doing good?)
non-maleficence and measles
Do no harm
Is vaccination harm (a shot, adverse event, etc.)? Is NOT vaccinating doing them harm (act of omission)?
autonomy and measles vaccination
patient or guardian are only people who can make decision to vaccinate
Must have informed consent (Dr. provide accurate and complete information, no coercion)
justice and measles vaccine
fairness of distribution (vaccinations accessible to all school-age children), also should people who ride on herd immunity be allowed to not vaccinate?
warthin finkeldey cells
giant cells with inclusion bodies - present in measles, may be the infected cells that set off inflammatory measures leading to symptoms like conjunctivitis and cough (body trying to get rid of these cells?)
pathogenesis conjunctivitis
after second viremia, infect cells of conjunctiva. CD8+ T cells attack these cells –> inflammation. Also macrophages release inflammatory cytokines.
Mast cells degranulate –> histamine, PGE2, LTD4
inflammatory cytokines (released by macrophages)
TNF-a and IL-1 - induce local inflammation
what does histamine do
increase vascular permeability
PGE2 does
vasodilation and increased vascular permeability
LTD4 does
increased vascular permeability
pathogenesis fever
Macrophages encounter viral antigen –> release IL-1, TNF-a –> go to increase COX activity –> increased PGE2 in preoptic area –> shivering and increased metabolic rate –> body temp rises = set point of hypothalamus is raised
pathogenesis rash
2 ways:
Type III HS (immune complex) - IgG binds antigen, complex binds FcgR on mast cells and PMNs causing degranulation
Type IV HS (cell-mediated) - T cells attack infected epithelial cells, release inflammatory cytokines (CD8+ kill infected stratum granulosum)–> rash
also C5a opsonization to mast cell degranulation
CD8+ ways of killing infected cells
release perforin
Granzymes,
FasL
TNF production
Pathogenesis loss of appetite and nausea
Infected enterochromaffin cells in GI tract –> release of serotonin –> vagal to solitary nucleus –> nausea and loss of appetite
Pathogenesis vomiting
Infected enterochromaffin cells in GI tract –> release of serotonin –> vagal to solitary nucleus –> nausea and loss of appetite –> vagal motor efferent –> emesis
Diarrhea
Possibly due to immunosuppression (from decreased IL-12), get secondary infection –> diarrhea
Or infected enterochromaffin cells –> release serotonin –> gastroenteritis, diarrhea
OR cell mediated toxicity of infected GI cells –> destroy villi –> diarrhea
MHC Class I and Cell mediated toxicity
Virally infected cells present antigen via MHC Class I to CD8 T cells
CD8+ response to infected cells
Note: Activated by Th1 Sense intracellular pathogen on MHC class I, with CD8+ coreceptor. CD80/86 (B7) on infected cell = costimulatory signal. Binding through ICAM/LFA-3. Cell killing through perforins, granzymes, Fas-L, and TNF.
Role of CD4 Th1 cells in combating measles
Recognize antigen on APC MHC class II –> costimulatory signals. IL-12 to polarize and proliferate into Th1 –> Th1 secretes IFN-g and TNF-a –> angry M1 macrophages, also license APC to show on MHC class I for CD8
Role of CD4+ Th2 cells in combating measles
Activated closer to end of response (stimulated by IL-4)
Stimulate M2 healing macrophages (release IL-4, IL-5, IL-13), limit other immune responses
CD8+ role in combating measles
Kill virally infected cells - activated following interaction iwth CD4+ and cross presentation of Ag to DC cells (licensed). Perforins, granzymes, Fas-L
role of humoral immunity in measles
CD8+ cell mediated toxicity is more important in recovery from initial measles infection (hypogammaglobulinemia can still be vaccinated, live from measles)
Ab memory more important in re-exposure, to quickly shut down new infection (memory T cells take more time to proliferate)
4 immunological functions of antibodies
complement fixation
agglutination
opsinization
toxin neutralization
IgM and IgG roles in measles infection
IgM increase around day 10, first ig to help with initial infection, then clonal switching to IgG which there is way more of (peak around 25 days) and is the humoral memory
Herd Immunity
More people who get vaccinated in a population, more protected those who cannot be (IC, young, old) will be d/t cannot contract and spread disease.
Measles epidemiology
One of leading causes of death worldwide, despite safe and cheap vaccine
115000 deaths globally in 2014, mostly kids under 5
85% vaccination globally in 2014 (1 dose), want over 95%
