Viral Immunology and Vaccines

Question 1

What is the first defense agsint viruses

Answer 1

Physical barriers

These include intact skin, a mucous barrier in the respiratory and gastrointestinal tract, cilia, tears, saliva, and the low pH of the stomach and vaginal tract.

Question 2

Do antimicrobial products help protect againsty viruses?

Answer 2

Yes, especially on mucosal surfaces

Question 3

What is Type I Interferon

Answer 3

one of the primary innate system defenses against viruses

Are triggered by PAMPs and can be tailored to specific virus

Question 4

What are the mechanism of action for Type I IFN

Answer 4

Type I interferons can act in both an autocrine and paracrine fashion

It interferes with the replication cycle of viruses:

There are many antiviral proteins turned on by type I interferon. The two most commonly talked about are protein kinase RNA (PKR) and 2’, 5’ oligo A synthetase (OAS). PKR will be activated in a viral infection, phosphorylate EIF2-α, and turn off protein synthesis. OAS will activate RNase L, which will degrade mRNA in the cell. This will result in turning off viral replication and, most of the time, lead to cell death.

Question 5

An immune cell that produces IFN without being infected:

Answer 5

pDC

Question 6

When are NK cells activated and what role do they play

Answer 6

These cells are activated by the second day of infection and can kill infected cells in a nonspecific innate manner or help clear cells in the adaptive response.

Question 7

How does MHC 1 impact the behavior of NK cells

Answer 7

Because of the role that CD8+ cytotoxic killer cells (CTL’s) play in killing infected cells and CTL’s requirement for peptide/MHC I engagement, many viruses have devised ways to downregulate MHC I expression on the surface of the infected cell. While this might help the infected cell escape CTL killing, the absence of MHC I triggers infected cell killing from NK cells

Question 8

What is antibody-dependent cell-mediated cytotoxicity (ADCC)

Answer 8

Later in infection when the antibody response is activated, NK cells can kill infected cells that are coated by antibodies. These antibodies recognizing viral antigens expressed on the surface of the cell and bind the FcγRIII receptor on the NK cell. Only helpful if viral antigens are presented on surface of cells

Question 9

Function of macrophages

Answer 9

• Phagocytose virus and dying/infected cells
• They are stimulated by pattern recognition receptors to produce nitric oxide, TNFα, and interferons as nonspecific antiviral responses
• Alveolar macrophages in the lung are also a significant producer of type I IFN in influenza-infected lungs
• very importantin the resolution of infection by clearing the body of infected cells

Question 10

What are antibody responses to viral antigens dependent on?

Answer 10

T cells

CD4 helped T cells must interact with B cells that present the same antigen

Question 11

Isotype switching:

Antigens encountered in the mucosal surface produce primarily dimeric ______ which happens in the mucosal associated lymphoid tissue (MALT). Antigens present in the blood class switch primarily to ______.

Answer 11

Antigens encountered in the mucosal surface produce primarily dimeric IgA which happens in the mucosal associated lymphoid tissue (MALT). Antigens present in the blood class switch primarily to IgG.

Question 12

What are neutralizing antibodies

Answer 12

They block the virus from infecting a cell, making them the essential antibody during an infection

Question 13

From where do viral antibodies presented on the surface of cells come from?

Answer 13

infected cells express antigens on the surface of the cell that are found on the surface of the virion

This means that for viruses containing a lipid bilayer (enveloped viruses), only proteins expressed in the surface bilayer would be useful for a neutralizing antibody response; these proteins are usually viral envelope glycoproteins. For viruses that do not contain lipid bilayers (naked viruses), the proteins that comprise the capsid are the most important for a neutralizing antibody response

Question 14

Role of CTL (CD8 cytotoxic T cells) in viral infection

Answer 14

Cytotoxic T lymphocytes or CD8 CTL’s kill virally infected cells by recognizing viral peptides presented in MHC class I

CTL’s can recognize any viral antigen expressed and presented in MHC I, not just the antigens expressed on the surface of the virion. This is important because many viruses change their surface proteins to escape neutralizing antibodies. However, there are more conserved proteins in a virus that change very little from strain to strain. These conserved proteins can elicit a CTL response

Question 15

What are the main killer cells in a viral infection

Answer 15

1. NK cells - innate
2. CD8 T cells - adaptive

Question 16

What happens if you become reinfected with the same strain of virus?

Answer 16

If you encounter the same strain of the virus, in general, you are protected from reinfection due to the long-lived plasma cells and secreted antibodies - they work as neutralizing antibodies. (IgA may not last as long –> RSV reinfection)

You also activate the memory CTL response, which can help clear an infection faster if cells are infected

Question 17

Possible outcomes of being infected with a different strain of the same virus?

Answer 17

1. No cross-protection, you start from scratch
2. Partial immunity (partial cross protection), you have some protection and may be protected from getting sick at all or as sick as you would from an initial infection
3. Cross-protection, the new strain of the virus is similar enough to a previously encountered strain that the immune system stops the infection and you do not get sick

Question 18

How do viruses subvert the immune system? (5 ways)

Answer 18

1. Antigenic drift - mutations in virus
2. Latency - live in cells without replicating
3. Infect immune-privileged sites - clearing takes longer
4. Generalized immune suppression
5. Specific immune suppression

Question 19

Serum sickness-like syndrome

Answer 19

Type III hypersensitivity

his occurs when antigen/antibody complexes form and are deposited in the blood vessel walls; there complement is fixed, leading to inflammation and leukocyte recruitment. Clinical symptoms are fever, skin rash, and polyarthritis.

Question 20

High levels of cytokines are produced leading to adverse conditions

Answer 20

Hypercytokinemia

Question 21

The most efficacious vaccines are to pathogens that

Answer 21

1. Produce lifelong immunity from natural infections.
2. Only have a few (1 to 4) strains.

Question 22

It is difficult to vaccinate against viruses that:

Answer 22

1. Have a large number of strains.
2. Change rapidly from season to season
3. Natural infection does not lead to lifelong immunity
4. The immune system fails to clear the virus, and chronic infection is established (HSV, HIV)

Question 23

What is sterilizing immunity

Answer 23

The most important correlate to an effective vaccine is the ability of the vaccine to elicit neutralizing antibodies. Effective neutralizing antibodies will prevent infection

Question 24

What are attenuated virus vaccines

Answer 24

Vaccines that allow a viral infection + viral replication, but at a much lower rate. The virus is very weak and can be cleared easily

Question 25

What are subunit vaccines

Answer 25

Subunit vaccines contain just the protein(s) from the virus that can elicit a neutralizing antibody response (usually becuase virus is difficult to grow in culture).

Has to have an adjuvant added - something that activates the immune system

Question 26

Why must some time after birth pass before certain vaccines can be given?

Answer 26

Attenuated vaccines need to replicate a little bit to be effective. If maternal antibodies to the vaccine are present, then they will bind to the attenuated virus and prevent infection of cells.

Question 27

Theory behind Herd Immunity (Community Immunity)

Answer 27

If enough people get vaccinated, then they will help slow or stop the spread of a virus., helping those who cannot be vaccinated. The entire community is protected.

Question 28

How is passive immunity achieved

Answer 28

Transfer of immununoglobulin, usually only after of exposure.

Breast milk confers passive immunity (mostly IgA)

Question 29

Pooled non-specific immune globulin (IG)

Answer 29

This is total IG pooled from plasma obtained from normal blood donors

Question 30

Specific immunoglobulin-Hyperimmune globulin (XIG)

Answer 30

This is IG from donors who are known to have high titer antibodies to specific agent. There are specific preparation techniques if the antibody is to be given IM vs. IV