Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

SPM > PBL Cases 18-23 > Flashcards

PBL Cases 18-23 Flashcards

1
Q

What tests is used for community acquired penumonia and how does it work?

A
  • Community Acquired Pneumonia Diagnostic Tests: Urinary antigen test
    • Detecting the C-polysaccharide antigen of Streptococcus pneumoniae (leading cause of CAP)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q
  • Define blood glucose levels and the hemoglobin A1C test and what they measure.
  • Define the normal and diabetic levels of A1c.
  • What can cause a false normal A1C level in a diabetic patient?
A
  • Blood glucose: instantaneous measure of glucose in the blood
  • The hemoglobin A1c test measures the percentage of red blood cells with a sugar coating over a three month period (~life cycle of a RBC)
    • Normal: 4-5%
    • Diabetes: >9%
  • However, in reality this is a false statement in this case due to his hemolytic anemia. As a result, it can how normal HgA1c levels if there is a high rate of RBC hemolysis
    • Alternative: Fructosamine Test - measures glycosylated albumin over a 3 week period
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Define the causes, physical exam findings, labs, and treatment for DKA.

A
  • Causes: stress, infections, insulin noncompliance anything that increases glucose, epinephrine, cortisol, or adrenaline
  • Physical Exam: Delirium/psychosis, Kussmaul respirations (rapid/deep breathing), abdominal pain, nausea, vomiting, diarrhea, dehydration, fruity breath odor (due to acetone)
  • Labs: hyperglycemia, rise in H+, decrease in HCO3, increase in free fatty acids, increase in ketones, large anion gap, high blood glucose
  • Treatment: IV fluids, IV insulin, and potassium to replete intracellular stores, glucose as needed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q
  • What are the signs/sx of uncontrolled diabetes type I?
  • How is managed (what are the two types of insulin)?
  • How is it monitored?
A
  • Signs and Symptoms of poorly controlled Diabetes Type I: neuropathy, nephropathy, retinopathy, edema of lower extremities
  • Management
    • Glargine: long acting insulin
      • Same amount of base insulin throughout
    • Lispro: short-acting insulin
  • Monitoring: monitor blood glucose, pump insulin as needed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q
  • What allows for the crossover of diabetes and Celiac Disease?
A

HLA Types of Diabetes and Celiac Disease: HLA-DQ2 & HLA-DQ8 (MHC II types)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q
  • What do the HLA Types of Diabetes and Celiac Disease: HLA-DQ2 & HLA-DQ8 present?
A

o Present the gliadin or transglutaminase (TTG) peptide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What group is most at risk for Celiac? Name three diagnostic tests for Celiac and which is the most definitive?

A
  • People with HLA-DQ2 and HLA-DQ8 are more likely to have Celiac Disease, but they are not guaranteed the disease
  • Diagnostic tests:
    • Transglutaminase Antibody
    • Gliadin Antibody
    • Duodenum biopsy (definitive)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the step-by-step process of how Celiac is presented and how the immune system responds? Also, where does dermatitis herpetiformis fit into this process?

A
  1. Gluten is digested → broken down into gliadin
  2. Gliadin is picked up by IgA in lumen → crosses mucosal epithelial layer
  3. Gliadin is released and deaminated by transglutaminase
  4. APCs pick up modified gliadin and present these antigens via MHC IIs
  5. CD4+ cells recognize these antigens as foreign and release interferon gamma and TNF-alpha
  6. Release of cytokines → causes damage to epithelial layers and recruits B-cells
  7. B-cells make more antibodies against gliadin and transglutaminase → circulated throughout the body including epidermis layer→ dermatitis herpetiformis
  8. CD8+ (recruited by cytokines) cells cause further damage to epithelial layer
  9. Damages causes → villous atrophy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What vitamin deficiencies may Celiac patients have and why does this occur? What effect do these deficiencies have?

A
  • The atrophy of villi in the duodenum (small intestine) makes it harder for celiac patients to absorb both fat-soluble and water-soluble vitamins
  • Fat soluble: vitamin D deficiency → osteoporosis
  • Water soluble: B12 deficiency → macroblastic anemia
  • Minerals: deficiency in iron → anemia. Zinc → required for immune system.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q
  • What does dapsone treat and what is the normal pathway?
  • What can be a side effect of dapsone in prolonged use? Describe that pathway.
  • What drug can counteract this effect while maintaining therapeutic effect?
A
  • Normal pathway to treat dermatitis herpetiformis: sulfonic antibiotic/potent inflammatory → treats dermatitis herpetiformis
  • Side effect: Dapsone → N-hydroxy dapsone (ROS) via CYP450
    • Oxidizes hemoglobin(Fe2+) → methemoglobin (Fe3+)
    • NADPH correction (G6PD) pathway: reduces methemoglobin → hemoglobin
      • Overwhelming of G6PD pathway causes a buildup of ROS → oxidative stress → cell lysis
  • Cimetidine acts on CYP450s to inhibit Dapsone → N-hydroxy dapsone
    • Dapsone still has therapeutic effects for dermatitis herpetiformis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Compare and contrast the following anemias (including their blood stain appearances):

  • Folate deficiency
  • Iron deficiency
  • Hemolytic anemia

How can all of these occur at the same time?

A
  • Folate deficiency - B12:
    • Macrocytic, pernicious (neuro) anemia
    • Impaired DNA synthesis → buildup of macromolecules inside cell → inability to divide → macrocytic anemia
  • Hemolytic anemia - ROS:
    • Overwhelming of G6PD pathway → decrease in NADPH levels → increase in ROS → lysis of RBC → hemolytic anemia
    • Release of hemoglobin into blood stream → bilirubin → secondary jaundice
  • Iron deficiency:
    • Deficiency in iron → heme is unable to bind iron → decreased binding of O2 → anemia
    • Secondary tiredness due to lack of O2 to tissues
  • All three at the same time: Celiac patients have folate and iron deficiencies, and if taking dapsone, they will also be prone to hemolytic anemia
    • Blood stain: Macrocytic (folate), Heinz bodies and bite marks (hemolytic anemia), and microcytic, hypochromic (iron deficiency)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the general epidemiology of TB?

A
  • Epidemiology of TB worldwide
    • Prevalence of latent infection: ⅓ of global population (2 billion)
    • Incidence of disease: 10 million new cases per year (out of the 2 billion) and 1.5 million of the 10 million die
  • Epidemiology of TB in United States
    • Prevalence of latent infection: ~11 million latently infected people
    • Incidence of disease: ~10,000 cases per year
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How is TB transmitted and how can it be prevented?

A
  • Person-to-person transmission through the air via droplet nuclei
    • Singing, talking, coughing from infected individuals
    • This is special because it can spread much farther than typical infections (i.e. influenza)
    • Particles are suspended in the air for a long period of time
  • Preventing transmission
    • Negative air pressure rooms, allowing air to flow into the room but not out of the room
    • N95 mask and PAPR mask
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are three phases of TB?

A
  • Exposure
  • Infection
  • Disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Define TB exposure.

A
  • Exposed: sharing air space with infected individual
    • A small percentage of individuals exposed become infected
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Define primary TB infection and what occurs in an infetion. Discuss the following possibilities post-infection: latency and primary TB pneumonia.

A
  • Primary Infection: this small percentage that inhale bacteria which reach peripheral part of airways, multiply, and drain to the hilar lymph nodes (towards center of lungs)
    • This collective peripheral multiplication of the bacteria and the draining lymph nodes are called the primary or Gohn complex
    • Types:
      • Latent: Macrophages are recruited as primary immune response, and form a granuloma and contains infection.
        • At this point the patient is infected but not ill or contagious
        • Can persist for years until immune system can no longer control infection
      • Primary TB pneumonia: symptomatic TB immediately following exposure
        • Most likely cause of miliary TB (dissemination of bacteria in blood throughout body)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Define secondary TB disease and what can cause it? How can one become contagious again?

A
  • Secondary Disease: reactivation of bacteria after the bacteria escapes the granuloma (also called a tubercles) and can reactivate
    • Due to anything that causes immunosuppression (i.e. HIV, smoking, diabetes)
    • Upon reactivation, it leads to caseating necrosis making the patient symptomatic and infectious (only if the necrosis is in the lung)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the four principal sx of TB?

A
  • Weight loss
  • Night sweats
  • Cough
  • Hemoptysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the three diagnostic tests for TB? Define what is done in each test

A
  • PPD Skin Test
    • Take a purified protein derivative (PPD), injected intradermal
    • If they have a delayed type IV hypersensitivity reaction, they are considered to have a positive test
    • Detects that your body has created memory T cells in response to M. tb infection
  • IGRA (IFN-gamma release assay)
    • Measures how much IFN-gamma T cells releases in response to exposure of three cloned proteins that only exist in M. tb
  • Acid Fast Stain
    • Sputum culture staining
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the treatment for latent infection and the treatment for active TB? Provide drug name(s).

A
  • Treatment for latent infection (9 months)
    • Isoniazid (INH): inhibits synthesis of mycolic acid allowing immune system to attack cell wall
  • Treatment for active TB
    • Cocktail of 4 drugs: Rifampin (always combine), Isoniazid, Pyrazinamide, and Ethambutol (RIPE)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What type of vaccine is the BCG vaccine, what is its effect on the PPD skin test and why is not given in the USA?

A
  • BCG vaccine
    • Attenuated version of Mycobacterium bovus
    • Vaccination wanes over time and does not affect PPD skin test
    • Not given in the United States because PPD test is method of testing
    • Countries with high prevalence
      • 90% of newborns will be given vaccine across the globe
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What mosquito transmits malaria?

A

· Anapholes mosquitoes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the 5 species of plasmodium and describe key charactersistics of each type (including most severe, fever patterns, possibility of relapse, and types of malaria associated if any)?

A
  • P. falciparum (most common)
    • Most severe and much more likely to kill you
    • During the life cycle, it makes adhesion molecule that clogs of blood vessels
    • Variable fever pattern, cannot relapse
    • Cerebral malaria
  • P. malariae
    • Very unlikely to be fatal
    • 72 hr fever pattern
  • P. ovale (stay dormant in liver because they form hypnozoites)
    • Very unlikely to be fatal, can relapse
    • 48 hr fever pattern
  • P. vivax (stay dormant in liver because they form hypnozoites)
    • Very unlikely to be fatal, can relapse
    • 48 hr fever pattern
  • P. knowlesi
    • Very unlikely to be fatal
    • 24 hr fever pattern

*Cyclical fever is due to synchronized lysis of blood cells, suggesting malaria. If fever happens every 48, hours, individual has tertian fever, is due to P. ovale, P. vivax and P. falciparum. Quartan fever, every 72 hours is due to P. malariae.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the detailed life cycle of malaria? Include the two stages.

A

Life Cycle

  1. Infected female anopheles mosquito bites a human. Mosquitoes infect human with sporozoites.

Hepatic Stage, steps 2-3 (P. vivax and P. ovale can hide in the liver as hypnozoites for weeks to years; individual can relapse)

  1. Sporozoites travel to liver and infect liver cells. Parasites divide many-1000-fold (1st stage of multiplication).
  2. Infected hepatocytes rupture and release merozoites into blood stream.

Erythrocytic Cycle, steps 4-6

  1. Merozoites invade RBCs and multiply approximately 30-fold(2nd stage of multiplication)
  2. RBCs rupture and release more merozoites.
  3. Released merozoites invade other RBCs.
  4. Some merozoites are able to form gametocytes.
  5. Mosquito bites individuals and gametocytes are ingested by mosquito. The gametocytes sexually reproduce in midgut producing sporozoites. (cycle back to step 1 with a different individual)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is the basic epidemiology of malaria? Where is it most prevalent?

A
  • 5th leading cause of death in the world
    • 98% of deaths from malaria occur in Africa
    • 2nd leading cause of death in Africa after HIV
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is the innate and adaptive response to malaria?

A
  1. Innate:
    • When TLRs are engaged, macrophages and dendritic cells produce Th1 cytokines such TNF-alpha and IL-1 and IL-12
    • IL-12 stimulates T cells and NK cells to produce interferon (IFN)-gamma, which stimulates macrophages to phagocytize infected RBCs in the liver and spleen
    • Activates all 3 complement pathwa
  2. Adaptive:
    • IL-4 from CD4→ Th2 activation → Phagocytosis of Merozoites
    • CD8+ T cell response directed against infected hepatocytes
    • Short-lasting adaptive response. Still at risk when revisiting a malaria-infected region
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are the sx of malaria?

A
  • Fever, chills, anemia
  • Hypotension
  • More severe: jaundice, seizures, coma, death
28
Q

What is the gold standard diagnostic modality of malaria?

A

Blood smear is the gold standard

  • Thick blood smear shows parasitemia.
  • Thin blood smear shows the presence of specific ring formation.
    • The parasite can be identified through examining a patient’s blood smear, specimen is stained by giemsa stain, giving the parasites a distinctive “headphone” appearance. Below shows P. falciparum.
29
Q

What mosquito avoidants are available and what chemoprophylaxis (4 drugs) are available?

A

Mosquito Avoidance - while traveling

  • Bug repellant
  • Bed nets

Chemoprophylaxis - begin before travel, and for a duration after traveling. The time frames differ between drug types.

  • Chloroquine (unless travelling to a geographic region with Chloroquine resistance)
  • Atovaquone plus Proguanil (Malarone)
  • Doxycycline
  • Mefloquine
30
Q

What are 4 drugs used in treatment of malaria?

A
  • Clindamycin
    • Bind to 50S subunit and inhibits protein synthesis
    • Used with quinidine (IV) for P. falciparum infections
  • Quinidine
    • G6PD - contraindications
  • Chloroquine
    • Variable sensitivity. Use quinidine
  • Primaquine targets hypnozoites (P. vivax/P. ovale)
31
Q

What two diseases provide immunity against malaria and describe how this takes place?

A
  1. Sickle Cell patients have a differently structured RBC that lack a receptor for the “duffy” antigen presented from the parasite. The lack of the receptor protects the RBC from being infected.
  2. G6PD deficiency make parasite-infected Erythrocytes more susceptible to dying from oxidative stress
    • Plasmodium oxidizes RBC NADPH from the Pentose Phosphate pathway for its metabolism

*These diseases ward off malaria infection and confers a natural selection advantage in “Malaria Heavy” regions

32
Q
  • What is the general strucutre of the influenza virus?
  • What type of nucleic acid does it have?
  • Does it have an envelope? If so, what are the glycoproteins and their functions?
A

Structure:

  • They have segmented negative sense ssRNA
    • There are 8 pieces in influenza A and B
      • Each of the 8 codes for a different protein
    • Influenza C has 7
  • It has an envelope that contains 2 glycoproteins hemagglutinin (HA) and neuraminidase (NA).
    • NA helps with virus release
    • HA binds to sialic acid (sugars) residues on upper respiratory epithelial cell surface glycoproteins.
33
Q

What is the DETAILED process of replication of the flu virus?

A
  • Replication:
    • Influenza binds to the membrane of the host cell via HA.
      • HA binds to sialic acid (sugars) residues on upper respiratory epithelial cell surface glycoproteins.
    • The virus is then endocytosed
    • The acidic environment of the endosome causes a conformational change in the virus → fusion of envelope with endosome membrane
    • Nucleocapsid is released into the host cytoplasm.
    • The nucleoplasm travels to the nucleus
      • THIS IS UNUSUAL FOR AN RNA VIRUS (most undergo replication in the cytoplasm)
    • The negative RNA strand is transcribed into the positive RNA strand via transcriptase
    • The positive strand is translated into protein
    • M1, M2, HA, and NA are transported to the cell membrane of the host and stick to it. The virion uses the cell membrane to form its envelope.
      • HA keeps the virus in the cell
      • NA clips the host sialic acids on the host membrane to let the virion out
34
Q

Distinguish between antigenic drift and antigenic shift.

A

Antigenic Drift:

  • Causes new strains (i.e. H1N1 #12)
  • A gradual change in antigenicity that results from continually occurring point mutations in the NA or HA genes of type A or B

Antigenic Shift:

  • Causes new subtypes (i.e. H1N1 to H7N9)
  • When more than 1 influenza A virus (especially if one is from an animal) infect the same cell, reassortment of the segmented genome can result in new subtypes, causing a rare but dramatic antigenic shift in 1 of the surface glycoproteins and leading to pandemics due to lack of immunity in the population.
35
Q

What is the epidemiology of influenza, including seasons, pandemics, and animal strains?

A
  • Birds are natural hosts of influenza A.
  • Pigs are considered a mixing vesicle. Pigs have receptors for both avian flu and human flu.
  • Between 1 in 20 and 1 in 5 people worldwide will get influenza yearly.
    • 3-5 million of those will be severe leading to about 500,000 deaths worldwide.
    • US: 200,000 are hospitalized per year.
    • Death usually due to other infections.
      • Grouped with pneumonia deaths
    • Timing: more prevalent in the winter
      • People spend more time indoors and are exposed to a higher concentration of the virus
      • Nasal passages are dry as well
      • Southern Hemisphere: has opposite seasons (prevalent May to Sep)
36
Q

How is influenza transmitted and what is the incubation period?

A
  • Transmitted when an infected person coughs or sneezes within 6 feet.
  • Sxs begin within 1-4 days (after incubation) and they are the most infectious at the beginning of sx onset (roughly the end of 4 days).
  • A person can be infectious up to 5-7 days after sx onset
37
Q

What is the immunopathogenesis?

A

Immunopathogenesis

  • Flu: establishes in upper respiratory ciliated epithelial cells
  • When the flu escapes these cells they are destroyed
    • Causes a lot of sxs
  • When you inhale bacteria it cannot be expelled from these cells because they are damaged
  • This cells release interferons and cytokines which triggers the immune system
  • Escape: virus leaves the apical surface and escapes back into the airway. This is how it promotes spread and transmission to other people
  • APCs have MHCII and MHCI which activates Th and CTL response, respectively
    • Th lead to antibody production.
    • Abs are important for future protection
      • Specific for NA and HA
38
Q

What are the symptoms of influenza and when do they appear (see image)?

A

Non-productive cough, myalgias, fever, chills, sweats

39
Q

How is influenza diagnosed and treated (what drugs)?

A
  • Nasopharyngeal swab (halfway through the head) until first patient in community is found → PCR assay → flu diagnosis
    • Once patient zero is in community, diagnosis made based on symptoms.
  • Treatment
    • Amantadine and rimantadine act on Influenza A
    • Oseltamivir and zanamivir (Neuraminidase inhibitors) can make a healthy person get better 1 day faster if started in the first 48 hours, and can reduce deaths of hospitalized patients.
40
Q

What is the importance of vaccines? What types of vaccines are available?

A
  • Though anti-flu drugs can prevent the flu, vaccination is the major way to save lives. Vaccination is safe but is needed every year to account for antigenic drift and because immunity from flu vaccines only lasts several months. Tetravalent vaccine.
  • Types
    • Inactivated - injected IM
    • Attenuated - mist in nose
41
Q

What is the HIV retrovirus life cycle?

A
  1. Binding: gp120 fuses with the surface of the T-cell, macrophage, and dendritic cells via a CD4 receptor and
    1. In early stages, binds a CCR5 coreceptor/chemokine receptor on macrophages or dendritic cells
    2. In late stages, binds CXCR4 on CD4+ T-cells
  2. Fusion: The virus’s core (capsid, genome, proteins, enzymes) then enters the cell.
  3. Reverse Transcription (cytoplasm): The shell of the capsid disintegrates and the HIV protein called reverse transcriptase transcribes the viral ss, + sense, linear RNA into one copy of ds linear DNA.
  4. The viral DNA + integrase is transported across the nucleus.
  5. Integration: HIV protein integrase inserts the HIV DNA into the host’s DNA.
    1. At this point, individuals have HIV permanently integrated into genome - you have infection
  6. Transcription of viral genome using host machinery (nucleus)
    1. Makes ss + sense RNA, which can act as mRNA or for packaging of new viruses
  7. Translation (cytoplasm): mRNA gets translated into polypeptides
  8. Packaging (cytoplasm): the new viral RNA and HIV proteins move to the surface of the cell, where a new, immature HIV virion form.
  9. Budding: the immature non-infectious virus is released from the cell (has long polyprotein chain with all proteins/enzymes)
  10. Release: the HIV protein called protease cleaves newly synthesized polyproteins to create a mature infectious virus.
42
Q
  • What is the structure of HIV?
  • What type of nucleic acid, containing what genes?
  • What enzymes does it have/require?
  • What surface glycoproteins does it have?
A
  • 2 + single stranded RNA molecules, containing gag, pol and env.
    • Gag - capsid protein p24 (structural proteins)
    • Pol- reverse transcriptase, integrase and protease. (all enzymes)
  • Env- gp120 (attachment to the host, surface gp) and gp41 (diffusion and entry into the cell, transmembrane gp)
43
Q

In detail, describe the immunopathogenesis of HIV?

A
  • With initial infection, dendritic cells present HIV antigens to CD4 cells in lymph nodes, causing immune activation. Widespread dissemination of virus occurs to lymphoid organs, as well as bone marrow and the brain, with progressive CD4 cell depletion, particularly in gut-associated lymph tissue. Depletion of CD4 lymphocytes (T-helper cells) is key because these cells are the “conductor of the immune orchestra.”
  • The immune response to HIV is substantial, but inadequate. The high levels of antibodies against HIV are typically non-neutralizing. High levels of virus replication and thus mutation lead to constant evolution of different species with altered antigens and reduced recognition by antibodies that have been made up to that point.
  • Additionally, mature memory T cells, which appear normal to immune effector cells, serve as a reservoir of virus even after decades of complete pharmacologic control of viral replication.
44
Q
  • What groups are most likely to get HIV?
  • What are risk factors?
  • What are modes of transmission and rank the most likely to transmit?
A
  • Prominent in Homosexual males → African Americans → latinos
    • Respectively
  • Risk Factors for HIV
    • Sexually Active, Homosexuals, heroin (needle-stick) users
  • Modes of Transmission
    • Unprotected sex (mostly anal, but also vaginal & oral)
    • Contaminated blood transfusions or hypodermic needles
    • Mother-to-child – pregnancy, delivery, or breastfeeding
    • Probability:
      • Blood transfusion > non-medicated perinatal transmission > receptive anal > insertive anal > vaginal fluid exposure
45
Q

Differntiate between the three phases of HIV and what occurs in each phase?

A
  • Acute infection: people have a flu-like syndrome, during which HIV viremia is transiently very high
    • Virus shifts from a CCR5-tropic non-syncytia-forming → CXCR4-tropic syncytia-forming predominance, the viral load significantly rises, and rate of CD4 decline becomes more rapid.
  • Latent: Patients are then asymptomatic, but still make 10 billion new virions every day
    • CD4 count gradually declines.
    • Persistent generalized lymphadenopathy (PGL).
  • When the CD4 <200 cells/uL = AIDS
    • Risk for opportunistic infections
46
Q

What are diagnostic tests for HIV?

A
  • Antigen tests (for p24 capsid)
  • Antibody tests (EIA with confirmatory western blots) are specific and sensitive.
  • Patients are monitored by CD4 T-helper cell counts, and PCR for plasma viral load.
47
Q

What are the classes of HIV drugs (5 big classes) and what are the mechanisms of actions and toxicities associated with each one?

A
  • Protease inhibitors - Prevent virally encoded proteins from cleaving proproteins into mature proteins to complete maturation of the virion
    • Toxicities: lipodystrophy
  • Nucleoside reverse transcriptase inhibitors -Prevent the transcription of ssRNA into dsDNA for integration into the genome by using by acting as nucleoside analogs, must be phosphorylated to be incorporated and active (chain terminators)
    • Toxicities: lactic acidosis, fatty stool, Type IV hypersensitivity reaction
  • Non-nucleoside reverse transcriptase inhibitors - Direct inhibition of RT with a different binding site and do not require phosphorylation to be active
  • Fusion inhibitors - Interfere with binding, fusion, and entry of an HIV virion into CD4 cells
    • Enfuvirtide: blocks gp41 conformational change
    • Maraviroc: acts as CCR5 antagonist
  • Integrase inhibitors - Block the integrase-mediated insertion of viral DNA into the host genome
48
Q

Name the antibodies.

A
49
Q

What are primary immunodeficiencies?

A
  • Primary
    • Hereditary/genetically determined
    • Deficiencies in: Humoral immunity, cell-mediated immunity, innate immunity, and complement proteins
    • Example: hyper-IgM Syndrome
      • Not an immediate concern following birth because children have their mom’s IgG antibodies transferred through placenta with half-life of one month
50
Q

What are secondary immunodeficiences?

A
  • Secondary
    • Acquired, often from external sources
    • Possibly from: Diabetes, HIV infection, immunosuppressive treatments, prolonged illness, hospital stay.
51
Q

Describe the epidemiology of X-linked hyper-IgM syndrome and autosomal recessive hyper-IgM syndrome.

A
  • X-linked hyper-IgM Syndrome
    • All forms of hyper-IgM syndrome are rare.
    • Loss of CD40L on T-cell, required for activating class-switching
  • Autosomal Recessive hyper-IgM Syndrome
    • Mutations in AID
52
Q

Explain the underlying genetic, molecular (e.g. CD40L), and cellular defects that are responsible for hyper-IgM syndrome and the consequence of these defects on the immune system of an individual who is afflicted with hyper-IgM syndrome.

A
  • Loss of CD40 ligand on T-helper follicular cells → Decreased naive B-cell to T-helper follicular cell binding → Decreased class switching → Decreased IgG, IgA, IgE antibodies
    • Naive B-cells natively express IgM
    • IgM has a short half-life compared to other immunoglobulin subtypes
53
Q

Describe the molecular basis of heavy chain isotype (class) switching and the role that CD40-CD40 ligand (CD40L) interactions play in this process.

A

CD40L to CD40 receptor binding releases AID → ds breaks in V(D)J area (MD Gea) → class switching (changes of constant regions of the heavy chain) → formation of immunoglobulin subtypes

54
Q

Predict the immunological-based tests that are used in the diagnosis of hyper-IgM syndrome.

A
  • CD40 Ligand Flow Cytometry
    • Functional test that determines whether CD40 ligand protein is expressed on the surface of activated T cells
  • Quantitative Ig Test
    • Detects the number of each Ig subtype
    • Decrease in IgA, IgG, IgE with a normal or slightly elevated IgM indicate possible hyper-IgM syndrome
  • Antigen-specific Antibody Titers
    • Used to determine presence of antibodies against certain antigens.
55
Q

Explain the relationships that exist among hyper-IgM syndrome, susceptibility to infectious pathogens, and the generation of protective immunity via vaccination.

A
  • IgG is especially useful for attacking encapsulating bacteria and viral and infections. He lacks IgG, so he will be vulnerable to those infections.
  • Antibodies against T-cell–dependent antigens, such as antibodies to tetanus-toxoid, diphtheria-toxoid, and protein-conjugated H influenzae type b antigens, are absent.
  • Avoidance of live, attenuated vaccinations is recommended because he cannot make long-lasting antibodies against them.
  • Patients with hyper-IgM are able to take killed/inactivated vaccines, but it is important to take a series of these vaccinations to maintain immunity.
56
Q

Identify the indications for kidney transplantation including the common diseases that lead to end-stage renal disease.

A
  • ESRD damage is irreversible; need dialysis or will have blood toxicity
    • Eligible for transplant if GFR < 15
    • Only cure is kidney transplant
  • Risk factors for ESRD: Focal segmental glomerulosclerosis (scarring of kidney), Hypertension, diabetes (both types)
57
Q

Describe the different types and sources of organ transplants.

A
  • Allograft - between two non-identical individuals
  • Isograft - from an identical individual
  • Autograft - from self, one part of the body to another
  • Xenograft - foreign species (animal)
58
Q

What are the immune-based tests that are used to determine transplant compatibility and how genetics contributes to this compatibility.

A
  • PRA: Test patient’s serum against lymphocytes of all donors that represent the potential HLA makeup
    • PRA - % of population that wouldn’t be able to donate to you. 1-19% PRA - low probability of rejection
    • High # = high chance or rejection; Low # = low chance or rejection
  • Cross reactive testing
    • Testing to see if a specific individual can be a donor.
    • Positive = not compatible. Negative = compatible
    • Mixing recipient and donor’s serum to see if there’s a reaction
59
Q

What are the HLA types?

A
  1. MHC Class I - Chromosome 6
    1. HLA-A
    2. HLA-B
    3. HLA-C
  2. Main MHC Class II HLA Types (each has an alpha and beta chain) - Chromosome 6
    1. HLA-DP
    2. HLA-DQ
    3. HLA-DR (This has one alpha chain, and four beta chains)
60
Q

Percentage match between siblings?

A

Each person has two sets of HLA haplotype clusters. One haplotype cluster (i.e. A, B, C) is inherited from each parent. Therefore, with any sibling, there is a 25% chance of a exact HLA match.

61
Q

Compare and contrast hyperacute, acute, and chronic graft rejection.

A
  • Host vs. Graft (Recipient attacks donor)
    • Hyperacute rejection - humoral response
      • Immediate response usually during surgery - thrombosis and occlusion
      • Occurs due to wrong blood type or cross-contamination of blood type
      • Can have pre-made HLA antibodies
    • Acute rejection - cell-mediated and humoral response
      • Response in weeks to months
      • Antibodies made after transplantation
    • Chronic rejection
      • Response in months to years
      • Slow degradation of organ over time from T-cell mediated responses
62
Q

Graft vs. Host

A
  • Graft vs. Host (Donor transplant attacks recipient tissue)
    • Donor T-Cells in the graft proliferate and attack the recipient’s tissue. Common in bone marrow transplants.
63
Q

Transplant: Desensitization therapy?

A
  1. Desensitization therapy
    1. Rituximab
  2. Fab domain of rituximab binds to the CD20 antigen (NFAT) on B-lymphocytes, and the Fc domain recruits immune effector functions (NK cells) to mediate B-cell lysis
  3. Can’t make antibodies (No humoral response)
64
Q

Calcineurin Inhibitors

A
  1. Calcineurin Inhibitors -
    1. Stop Calcineurin from dephosphorylating (activating) NFAT which is a transcription factor that activates the expression of genes involved in T expansion → prevents IL-2 transcription
    2. Side effects: nephrotoxicity, neurotoxicity, HTN, and DM
    3. Types
      1. Tacrolimus - Binds FKBP12, creating a complex that inhibits calcineurin

Cyclosporine - Binds to cyclophilin, inhibiting calcineurin

65
Q

Block lymphocyte proliferation drugs?

A
  1. Azathioprine - metabolized to 6-mercaptopurine in the body blocks de novo purine synthesis (which lymphocytes depend heavily on) and prevents lymphocyte proliferation
    1. Nonspecific to the immune system
    2. Side effects – leukopenia, anemia, thrombocytopenia

Mycophenolate mofetil - prevents guanine nucleotide synthesis in lymphocytes, inhibiting de novo purine synthesis and preventing lymphocyte proliferation → Specific to immune system,

66
Q

Inhibits B & T cell responses to IL-2 drugs?

A
  1. Rapamycin (Sirolimus) - inhibits mTOR (important for translation), a kinase which is required for T cell responses to IL-2, a cytokine growth factor involved in T cell activation
    1. Side effects – NOT nephrotoxic, causes anemia, thrombocytopenia, leukopenia, insulin resistance, HLD
      1. Has lower toxicity to kidneys than calcineurin inhibitors
67
Q

Predict the side effects associated with treatments that are used to prevent allograft rejection.

A
  1. Increased risk of infection (neutropenia)
  2. Increase risk of cancer from oncoviruses.
  3. Nonspecific immunosuppression

SPM (17 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions