PBL Case 1

Question 1

How can you prevent/treat measles?

Answer 1

• MMR given within 72 hours as post-exposure prophylaxis for non-immune individuals
• IvIg between 3-6 days

Question 2

If MMR is not given within 72 hours of measles exposure, when can it be given?

Answer 2

After 5 months, otherwise, antibodies would just bind vaccine and it would not be effective

Question 3

How does measles spread?

Answer 3

• Respiratory droplets

- Replicates in lymph nodes around the respiratory system

Question 4

What is the measles incubation period?

Answer 4

• It is longer than other viral infections (10-14 days)

- Virus is contagious before appearance of a rash

Question 5

When is measles infectious?

Answer 5

-/+ 4 days from rash

Question 6

What is the staged process of immunity?

Answer 6

-Starts cell-mediated & later humoral gives you lifelong immunity

Question 7

What causes the rash?

Answer 7

When APCs bind to B and T cells in lymphatic organs, the adaptive immune system kicks in and this causes the rash!
(T cell response to viral infected endocapillary cells)

Question 8

How does measles get into the cell?

Answer 8

-Binds to CD46 and CD150 (SLAM)

Question 9

What does CD46 do?

Answer 9

• Downregulates complement

- On almost every cell in the body –> measles can infect any cell (systemic)

Question 10

What does CD150 (SLAM) do?

Answer 10

-Costimulatory molecule, important in replicating T cells in lymph nodes

Question 11

What happens with the cell detects measles virus?

Answer 11

1. PAMP (ssRNA) binds TLR 7/8
2. NF-kB pathway is activated
3. IFN-beta released first - trying to induce cells to express MHC-1 –> want to reveal you are harboring an infection
4. IFN-alpha and TNF-alpha (drives E selectin), IL-6, IL-12, IL-1 (causes fever) released

Question 12

In seeking to protect the public health. . .

Answer 12

. . .mandate advocates rely on the values of beneficience, utilitarianism, justice and nonmaleficence.

Question 13

Beneficence

Answer 13

The moral imperative to act for the benefit of others
-Beneficence subsumes an obligation to avoid harm, but nonmaleficience carries an independent duty that applies regardless of attempts to create benefits

Question 14

Nonmaleficence

Answer 14

The directive against inflicting harm on others.
-The principle of nonmaleficence would conflict with a vaccine mandate, if the vaccine carries medical risks, as many do; some recipients would suffer harm to their health that would have been avoided but for the mandate

Question 15

Autonomy

Answer 15

Recognizes the right of individuals to govern their own behavior.
-To exercise this right, it is necessary to be free from outside influences and limitations and to have the ability to comprehend the action to be taken, the alternatives and the consequences, which are the components of agency.

Question 16

Justice

Answer 16

Calls for the fair, equitable, and appropriate distribution of scarce goods.

• It requires a reasoned system of allocating resources based on an underlying principle such as egalitarianism, fair opportunity, or underlying need
• Health care is a scarce resource, so justice demands such a system for determining access
• A program to encourage widespread use of a heath care resource, such as a vaccine, whether through a mandate or otherwise, cannot be just if only those with financial means could comply; justice requires equitable means of access

Question 17

Utilitarianism

Answer 17

Best societal outcome, even at the expense of others

Question 18

What causes the rash?

Answer 18

1. Measles virus enters epithelial cells
2. Cytotoxic CD8+ cells kill infected cells
3. Epithelial irritation
4. RASH!

Question 19

What causes the conjunctivitis?

Answer 19

1. Measles virus enters endothelial cells
2. Cytotoxic CD8+ cells kill infected cells
3. Endothelial irritation and vasodilation

Question 20

What causes the fever?

Answer 20

1. Secretion of IL-1 by M1 angry macrophages
2. Upregulates production of PGE2 in pre optic anterior hypothalamus
3. Decreased firing rate of neurons
4. Heat response
5. FEVER
   - -Acetaminophen blocks production of PGE2 via the COX pathways!

Question 21

Explain the relationship between MHC Class I expression and Cell Mediated toxicity:

Answer 21

• MHC Class 1 is expressed on all nucleated cells. Cytotoxic T cells and NK’s are constantly surveying cells and looking for foreign pathogen presentations
• When cells become infected and start to produce the necessary components for viral replication, MHC 1 is able to express these components on the cell surface as non-self
• Cytotoxic T cells and NKs are able to recognize the MHC 1 complex, and if non-self is displayed in the variable region, they will induce apoptosis and also release granzymes and perforin to destroy the infected cell

Question 22

What is the role of Th1 in combatting measles infection?

Answer 22

• Early in infection CD4+ T cells are producing IFN-gamma & IL-2
• In general, CD4+ T cells remain active for a longer time than CD8+ T cells

Question 23

What is the role of Th2 in combatting measles infection?

Answer 23

• When measles envelope glycoprotein hemagglutinin binds to the SLAM receptor (on lymphocytes), it causes release of IL-4, along with other cytokines. IL-4 causes differentiation to Th2 cells, which helps with down regulating the immune response. So this is a reason why the measles virus can evade the immune system response
• –Recovery response promoted by IL-4, IL-10, IL-13
• –These cytokines dame the M1 macrophage response, and drive humoral response for long-term memory

Question 24

What is CD8 T cells role in combatting measles infection?

Answer 24

• Viremia is cleared primarily thru CD8+ T cells, which interact with MHC I presenting the virus from infected epithelial cells and other infected leukocytes (DCs, macrophages, CD4+ T cells)
• Activation of CD8+ T cells early on in infection is done thru IFN-gamma and IL-2 production by CD4+ T cells!