Immune System Part 3 Flashcards
Infectious Process
Infectious diseases can be bacteria, viruses, fungi, and animal or insect-borne parasites that enter the body by penetrating natural bariers
_____ are the single most common cause of infectious diseases
The transmission of infection or disease requires an _____ chain of events to enable one host to infect another
Transmission can be via (3) with body fluids
Viruses
unbroken chain of events
Airborne, Droplet, Direct contact (in order of most to least contagious)
Chain of Transmission
- ______ = organism exists in large numbers
- Portal of _____
- ____ of Transmission = a way to get into host (blood/bodily fluids)
- Portal of _____ = any epithelial border
- ______ Victim: pt characteristics that increase likelihood of infection (poor nutrition, immunocompromised)
- Reservoir
- Portal of Exit
- Mode of Transmission
- Portal of Entry
- Susceptible Victim
Infectious Process
Control of disease acquisition depends on ____ the chain of transmission in one or more places
- # 1 way to prevent spread of infection is?
- Optimal nutrition: especially in low income countries with bad sanitation
Breaking the chain
hand washing
Host Characteristics Influencing Infection
The ability and speed with which a host can clear an infection depends on many factors
- Exposure
- En_____
- Hy____
- Social B____
- T______
- Host Health
- N______ Status
- A_____ Exposure
- Exposure
- Environmental
- Hygiene
- Social Behaviors
- Travel
- Host Health
- Nutritional Status
- Antibiotic Exposure
Climate Change
has effected the spread of many vector-borne diseases
Environmental factors influence the likelihood of exposure and infection by microorganisms. S_____, a__ quality, living con_____, and cli___ are important factors
Rising _____ and longer warm _____ increase the pro_____ and terr____ of disease vectors such as mosq____ and t_____
As a result, there has been a world-wide rise in diseases such as Malaria, Dengue fever, west nile virus, lyme disease, ____ virus, and others
Sanitation, air quality, living conditions, climate
temperatures, longer seasons, proliferation and territories, mosquitos, ticks
Zika virus
5 Mechanisms of Antimicrobial Resistance
(1): Bacteria can produce ____ that inactivate drugs (e.g B-_____ can inactivate penicillins)
(1): Bacteria can create a modified _____ that is no longer susceptible to the antibiotic
(1): A reduction in _____ of the bacteria to the drug prevents entry through the bacterial wall
(1): Bacteria can employ an export mechanism that uses an (1) (H+) to actively ____ ____ the drug
(1): amplifying the target of the antibiotic (by ____ by 1000 so drug dosage is ineffective)
Antibiotic inactivation: enzymes, B-lactamase
Target modification: modifies target
Decreased influx: permeability
Efflux pumps: ion gradients (H+), pump out
Target Amplification: multiplying
All the above mechanisms result from the expression of resistant genes
Bacteria Resistance Genes
Acquired through 2 mechanisms
Gene _____
Gene _____ - conjugation
Gene Mutation
Gene Transfer-Conjugation
ex) we have a bunch of cells susceptible to penicillin with just few that aren’t susceptible bc they produce penicillinase -> penicillin then wipes out al the cells w/o penicillinase leaving a diff gene pool -> penicillanse cells start to multiply rapidly and can transfer penicillinase producing genes to othe rbacteria that don’t have it (two bacteria connect through cytoplasmic bridge and share genes) -> comingling diff varietes of bacteria can actually increase likelihood that resistant gene switches to other cells
What does this picture show?
Historical progression of Staphylococcus aureus resistance to antibiotics
Overall, it is shortly after we introduce abx that we start to see resistance
RESISTANCE IS INEVITABLE
What does this picture show?
The developing world will suffer more from antibiotic resistance bc of sanitation, infrastructure is not there
Hazard Levels of different Antibiotic Resistant Pathogens
Urgent
Serious
Concerning
What problem does this picture show?
Problem with Agricultural use of antibiotics
- actually about 1/4 of abx is on humans
- and about 3/4 is used on livestock!
Examples of Abx use in Animals
After _____
___-Cow therapy
Before T_____
Potential Out____
S_____ conditions
It is not uncommon for ______ to give abx to animals that are not currently ill with a particular disease, but are at high risk of acquiring an infection.
After Surgery
Dry-Cow Therapy (to produce more milk)
Before Transportation
Potential Outbreaks
Stressful Conditions
veternarians
No one pays attention to agricultural policy but it has everything to do with human health….-pesticides, cost of food, etc.
Historical Perspective: Immunizations
- The rise of civilization with the domestication of plants and animals permitted people to live in denser communities with each other and their animals. Such proximity provided ideal breeding ground for infectious pathogens, and their spread resulted in _____ throughout the world.
- As people began to question the underlying causes of disease and the apparent protection to reinfection afforded to some survivors of a disease, ideas of _____ and disease p_____ were born, apparently as early as the 5th century.
- The concept of immunity goes back at least to the 17th century when e_____ K’ang of China documented his practice of v_____, or in______ of his troops and his own children with s_____ to confer protection from the disease
- Variolation involved taking liquid froma smallpox p____ of an infected patient, cutting the skin of an uninfected person, and then introducing the inoculum.
- Approximately 2-3% of ppl would die from varioloation compared to 20-30% who died from natural infection with small pox.
- Epidemics
- immunity, disease prevention
- Emperor, variolation, inoculation, smallpox
- pustule
Immunzations: Historical Perspective
- In 1796, Edward Jenner, who coined the term ______ from vacca, Latin for “cow”, helped to advance vaccine _____.
- He tested the hypothesis that smallpox protection could be achieved by using cowpox, a nonfatal, self-limited disease in humans caused by a virus of the Poxviridae family that includes monkeypox and smallpox and that can spread from cows to humans.
- Jenner infected a boy with _____ pus from an infected milkmaid; the boy mildly got ill from cowpox, recovered, and when challenged with smallpox collected from scabs of a smallpox pt, was unaffected, showed no symptoms, and was fully proteted against the disease.
- With continued progress over time in our ability to understand the infectious process, develop safer and more effective vaccines, and provide them to peopl around the globe smallpox was “eliminated” in 1979.
vaccination, safety
cowpox
FIRST ACTUAL VACCINATION
Immunzations: historical Perspective
In 1955, Jonas Salk released a vaccine against the ____virus. The Salk vaccine, an _____ virus preparation administered by injection, was followed in 1961 by the Sabin oral vaccine, which employs an att_____ poliovirus that provides immunity to all three types of poliovirus
As a result of the polio vaccines, the annual # of cases in the US fell to 161 in 1961 from 35,000 in 1955.
Polio, inactivated, oral vaccine, attenuated
- Polio can cause paralysis and was incredibly common*
- Jonas Salk released an inactive virus vaccination and then later an oral vaccine*
Polio
Red areas =
Yellow areas =
Polio is not gone, we still have some countries where it is an epidemic
Indigenous
Imported from ppl who traveled to those red countries
How Vaccines Work
Most modern vaccinations involve the introduction of an ______ Antigen into tissue. Frequently the antigens are attached to ________.
The antigen is then taken up by ______ (macrophages and/or dendritis cells) which then “present” the antigen to ____ cells
Activated CD4 cells then trigger proliferation of __ and ___ cells, creating ______.
attenuated, ADJUVANTS
phagocytes, CD4
B and CD8 cells, immunity
most vaccines = attenuated antigen
very few vaccinations = attenuated live virus - a live virus that is weakened so cannot replicate
Adjuvants
Enhance production of immunity
(3) mechanisms
Example: What is Aluminum Hydoxide gel (Alum)?
- Creates a reservoir/depot to slow absorption at injection site so more likely macrophage and dendritic cells will arrive and phagocytize
- Enhance antigen presenation
- Enhance CD4 activation and proliferation
Widely used Adjuvant in human vaccines- it creates depots for slower absorption and enhances the activation of Th2 cells (also misinformation example -> ppl think aluminum causes alzhemiers, neurotoxicity -> but not the same form, good safety profile)
Vaccine Preventable Diseases
-
About __ preventable diseases and we tend to vaccinate at different points in life
- Frequency and booster depends on the disease
17
CDC Recommended Vaccine Schedule from Birth - 18 years
Range of times + catch up times
- Starts at birth like Hep C
- Ppl will be like omg 6 vaccines for a 2 mth old that’s too much but in reality?
In reality a baby will expose itself to more things in a day by putting things it its mouth- simply our immune system will not be overwhelmed by 6 targeted vaccines, child may have fever but not bc their sick but evidence that their immune system is working
Also is all in 1 needle with all 6 vaccines inside (not multiple sticks)
CDC Recommended Vaccine Schedule for Adults
Tdap protects us from (1), we actually have outbreaks every year and recommendation is if you are an adult with a young child you should get it more _____ than every __ years
HZV - herpes zoster virus is the same as the chicken pox virus, sometimes reemerges later in life and causes _____
whooping cough, more often than 10 years if adult withh child
shingles
Vaccine Type and Disease Prevented
Hep B: vaccine only includes the ____ antigen
Rotavirus: vaccine is a ____ virus- for infants that drink the liquid what should you tell the parents?
DTap: not the bacteria itself just the bacterial ______ (toxoid)
surface
live - anyone immune suppressed should avoid diaper changes bc the baby will shed the rotavirus in the next two BM’s
protein
Vaccine Health Stats
- Hep B: In those who get infected around the time of ____, 90% develop chronic hepatitis B while less than 10% of those infected after the age of five do. Mortality of chronic disease ~25%
- Rotovirus: Most common cause of _____ diseases world-wide. Rotavirus caused 37% of deaths of children from diarrhea and 215,000 deaths worldwide.
- Dtap: Diptheria complications include myo____, neph___, thrombocytopenia, temporary ____ and is fatal in 5-10% of cases. Tetanus causes muscle spasm disease (___ jaw) - complications include bone fr______ and 10% fatality. Pertussis causes (1) aka 100 day cough - complications include apnea and death in children.
- HiB (Haemophilus influenza B): A major life-threatening childhood bacterial disease, including buccal, preseptal, and orbital cell____, epiglottitis, bacteremia with sepsis, and men_____.
- birth
- diarrheal
- myocarditis, nephropathy, paralysis, lock jaw, bone fractures, whooping cough
- cellulitis, meningitis
Imp to vaccinate for Hep B ASAP bc childbirth high risk for transmission to the infant through lots of exposure to maternal blood at birht
Pertussis particular deadly in children
Vaccine Health Stats
- Pneumococcal: The gram-positive encapsulated S.**pneumoniae causes invasive diseases in infants and young children, including men____, bacteremia, and s____, and pneumonia. Complications include _____ damage, _____ loss, and death.
- Inactivated Polio Virus (IPV): Poliomyelitis or infantile ______ - causes muscle paralysis leading to temp or permanent paralysis and/or loss of r_____ muscle control
- Influenza (IIV, LAIV): Complications of influenza include p_____, sepsis, and death
- MMR: Complications of Measles range from diarrhea to pneumonia, and also include b____ inflammation, physical scars, corneal _____, and death.
- meningitis, sepsis, brain damage, hearing loss
- paralysis, respiratory
- pneumonia
- brain inflammation, corneal ulcerations
Influenza that turns into pna is one of the top 10 causes of death in adults in the US
Vaccine Health Stats
- Varicella (VAR): Complications include pneumonia, brain inflammation, bacterial sk___ infections, and death
- Hepatitis A (HepA): Acute ____ failure is rare but can occur
- HPV2, HPV4 Human papillomavirus: Causes genital ____ and pre_____ lesions, implicate din 70% of all ______ cancers
- Meningococcal (Hib-MenCy): Invasive bacterial diseases like m_____ and sepsis - can be fatal.
- skin
- liver
- genital warts, precancerous lesions, cervical cancers
- meningitis
We’re discovering that there’s a whole host of cancers of the rectum and anus in men also caused by HPV - so important for both young women and men to get vaccinated
Experiments on POC
- A lack of ____ in: Pharmaceutical manufacturers, government agencies (FDA, CDC), and the medical establishment
- Tuskegee syphilis study: 1932-1972 the purpose was to observe the natural progression of untreated syphilis on rural ____ _____ males. By US Public Health Service- the Men were told they they were getting free ____ for participating in the study but never were.
- There’s a long history of the US conducting experiments on People of _____, the m____/chronically ill, and men and women in _____.
- 1942: Federally funded study injected experimental ___ vaccine in male pts at a state asylum in Ypsilanti, Michigan and exposed men to the flu several months later, work was co-authored by (1) - v sad
- 1957: Federal researchers _____ Asian flu virus in the noses of 23 inmates at a prison in Jessup MD to compare to a group of 32 inmates who were exposed to both the flu and experimental vaccine.
- 1946-1948: Guatemala syphilis study - US researchers infected sol_____, pro_____, and as_____ pts with _____ without their knowledge or consent
- Lack of trust
- syphillis on African American males, free treatment but no
- POC, mentally ill, prisoners
- expiremental flu vacc, Jonas Salk (polio)
- sprayed asian flud virus to inmates
- infected soldiers, prostitutes, asylum pts with syphilis
On Immunity, An Inoculation by Eula Biss
The difference between children who are __-vaccinated and those who are _____ vaccinated.
- Un-vaccinated children’s parents ->
- Under vaccinated children’s parents ->
- Conclusion: Vaccination is a _____ issue rather than just a health care issue
un-vaccinated vs. under vaccinated
- more often higher SES, more education, higher salaries, greater access to health care
- can’t make it to adequate # of well visits, difficulty in access to health care (barriers ie not having insurance, no days off work, etc) -> these children are highly vulnerable
- MORAL ISSUE - that the most privileged among us in society are choosing not to vaccinate and putting at risk the most vulnerable in society
1985: Rock Hudson
=
First highly public case of AIDS
Ryan White and the HIV/AIDS hysteria of the late 1980’s-early 1990s
Ryan White was a teenager from Konomo, Indiana who was diagnosed HIV positive in 1984 at age 13. Ryan was a hemophiliac and contracted HIV from contaminated blood products.
When the news of his diagnosis surfaced, parents in the County rallied the school board and managed to get Ryan?
The battle between the White family and the school board drew national attention to both Ryan and the _____ surrounding the ____ of HIV/AIDS.
Ryan raised _____ about HIV transmission
barred from school
ignorance, transmission
raised awareness about HIV transmission
The Human Immunodeficiency Virus
HIV belongs to the viral family of human _____viruses with two types (2)
Retroviruses have ___ genomes and use (1) to form ___ upon infection of a host cell just before replicating.
HIV- __ is the more common cause of HIV disease world-wide and in the USA.
(1): protein on outer surface is how virus binds to cells its going to infect
retroviruses, HIV1, HIV2
RNA based and uses reverse transcriptase to form DNA
HIV1
GP120
Replication Cycle of HIV
- HIV binds to the host cell via its _____ (it binds directly to the ___ molecule but can also bind to (3) types of cells which carry the virus to the CD4 T cell.
- HIV then fuses with with the plasma membrane and the viral capsid uncoates to allow the viral ____ to enter the cell
- Using ____ _____, the viral RNA is used to produce viral ____
- Viral DNA then enters the ____ and integrates into the host cell’s _____
- Using host cell enzymes and organelles, viral DNA is transcribed into many ____ of genomic and mRNA
- New HIV is assembled using the newly formed _____ and ____
- Budding and ____ of HIV from host cell
- gp120, CD4 (prefers), monocytes/macrophages, dendritic, Langerhan cells
- RNA
- Reverse Transcriptase -> DNA
- nucleus, genome
- copies
- genomic and mRNA
- released from host cell
Basically this cell will stop production of proteins that keep it alive and only produce virus (turns into virus making factory) its housekeeping functions stop and will do this until it dies -> then the new HIV will go and find other cells to infect
Typical Course of an Untreated HIV infected individual
Overall, if left untreated from initial exposure to time of death ave about __ yrs
Purple line =
Green line =
(3) phases
10 yrs
CD4 count
Viral count
Latency Period
Acute Phase
Chronic Phase
Latency Period
At first where virus is ______ / will test _____ bc this is the time the virus is trying to?
If caught early enough _____ can prevent HIV ____ exposure (like at work)
undetectable, will test negative, find host cells
PrEP can prevent HIV post exposure
Acute Phase
Peak in green line = _______ = from viral count rising dramatically, acute phase of HIV infection, precipitous ____ in ____ count that coincides with this viremia
- Will ppl report having symptoms?
- This is the time that a person is most likely to?
VIREMIA, precipitous drop in CD4 count
Most will report having no symptoms or not remembering having sx, many ppl also report similar to catching the flud (pretty much unaware they have HIV)
Most likely to transmit the disease (when viral counts are super high)
Chronic Phase
(1)
_____ in viral count starting from __ yr post exposure
highly predicts progression?
- Ironically, ppl with a more _____ immune response tend to have _____ viral set counts, HIV seems to feed off of all the activity that’s typical of immune activation
- Eventually towards tail end of chronic phase CD4 cell drops and viral count starts to rise -> when CD4 count reaches < 200 cells/micrometer = _______
- or CD4 count > 200 + ______ infection
Viral Set Count
Plateau, 1 yr post
Higher viral set count = quicker disease will progress and more likely to transmit
- more robust immune system -> higher viral set counts
- CD4 200 = AIDS
- or CD4 >200 + opportunistic infection = AIDS
What the Virus does Inside the Body
- (1): first group of immune cells that virus tends to target, a system of lymphoid organs in the GI tract and significant branch of lymph tissue bc GI tract is a major _____ point for pathogens (virus is attracted bc has a lot of CD4 cells)
- (1): HIV tends to attack these type of CD4 cells, so by the time acute phase is concluded 90% of them are wiped out (huge hit)
GALT
CD4 Memory Cells
Acute HIV Syndrome
The acute burst of viremia and wide dissemination of virus in primary HIV infection may be associated with the _____ phase HIV syndrome, which occurs to varying degrees in ~50% of individuals with primary infection.
This syndrome is usually associated with high lvls of viremia measured in millions of copies of HIV RNA per ml of plasma that last for several weeks. Acute ____nucleosis- like symptoms are well correlated with the presence of viremia.
Virtually all pts develop some degree of viremia during primary infection, which contributes to virus dissemination throughout the lymphoid tissue, even though they may remain _____ or not recalling experiencing symptoms.
acute
mono
asymptomatic
Establishment of Chronic and Persistent Infection
HIV infection is unique among human viral infections. Despite the robust cellular and humoral immune responses that are mounted following primary infection (see “Immune Response to HIV” below) once infection has been established the virus succeeds in _____ complete immune-mediated clearance, paradoxically seems to thrive on _____ activation, and is never completely eliminated from the body.
Inherent to the establishment of chronicity of HIV infection is the ability of the virus to _____ adequate control and elimination by both the cellular and humoral limbs of the immune system. There are a number of _______ whereby the virus accomplishes this evasion.
Paramount among these is the establishment of a sustained level of replication associated with the generation of viral ______ via m____ and re______.
The lvl of _____-state viremia, called the viral set point at ~1 year following acquisition of HIV infection has important prognostic implications for the _____ of HIV disease in an untreated patient.
It has been demonstrated that as a group untreated HIV-infected individuals who have a ___ set point at 6m to 1 yr following infection progresses to AIDS much more slowly than individuals whose set point is very high at that time.
escaping clearance, thrives on immune activation
evade, mechanisms
diversity via mutation and recombination
steady state, progression
low set point = progression to AIDS is more slow
Blue line highest viral set point -> slope of that line is very steep - rate of progression v high
Stage of HIV Infection Defined by age-dependent CD4 counts
Overall takeaway?
The younger the person, the stages progress even though cell counts are higher bc immune system is less mature in babies/kids
Opportunistic Diseases
- Can happen in someone without HIV but when it happens in HIV pts will?
- Some almost always only happen in HIV pts such as (1)
- progresses much more rapidly
- Kaposi Sarcoma
cART
(4)
- Entry Inhibitors: impairs ability for GP120 to bind to receptors on cells and prevent entry
- Reverse Transcriptase Inhibitors: blocks reverse transcriptase to prevent virus’s ability to convernt RNA to DNA
- Integrase Inhibitors: blocks ability of viral DNA to incorporate/integrate into host genome
- Protease Inhibitors: block formation of virus specific proteins (prevents assembly of new virus that leaves and infects another cell)
Combo allows smaller doses of each to help control SE/AE, less drug resistance
