Virology - Host Resistances

What ancient Greek philosopher came up with the world immunis to describe people who had gotten sick once but were immune from subsequent infection?

Thucydides

All immune cells derive from what precursor cell?

Hematopoietic cells

Where do hematopoietic cells come from?

Bone marrow

Lymphoid progenitor cells give rise to what?

B cells, T cells, and NK cells

Granulocyte precursors give rise to what?

Neutrophils, basophils, and eosinophils

Monocytes give rise to what?

Macrophages and dendritic cells

What leukocytes are part of innate immunity?

Neutrophils, basophils, eosinophils, NK cells, monocytes, and macrophages

What leukocytes make up adaptive immunity?

B and T lymphocytes

What cell bridges the gap between innate and adaptive immunity?

Dendritic cells

T cells can differentiate into what 3 types of cells?

Helper T cells, Regulatory T cells, and Cytotoxic T cells

What are the receptors for helper and cytotoxic T cells?

CD4+ Helper T cell and CD8 cytotoxic T cell

B cells can differentiate into what?

Plasma cells, long-lived plasma cells, and memory B cells

What are the 4 polymorphonuclear leukocytes?

Monocytes, neutrophils, macrophages, and NK cells

(T/F) Neutrophils make up the highest proportion of leukocytes in the blood at any given point but are short lived and are considered the first on scene “shocktroopers” of infection.

True

What 3 leukocytes are primarily responsible for phagocytosis?

Macrophages, neutrophils, and dendritic cells

(T/F) Dendritic cells serve as antigen presenting cells (APCs) and have high expression of MHC I and MHC II (major histocompatibility complex).

True.

PRR is…?

Pattern recognition receptors

PRRs recognize…?

PAMPs (pathogen associated molecular patterns)

(T/F) TLRs (toll like receptors) were originally found in fruit flies.

True

What 2 TLRs are found on the cell surface and recognize viral proteins?

TLR2 and TLR4

What TLR is located in the cytoplasm and recognizes both dsRNA and ssRNA?

RIG-1

What TLRs are found in endosomes and recognize viral nucleic acids?

TLR3, TLR7, TLR8, TLR9

What does TLR3 recognize?

viral dsRNA

What do TLR7 and TLR8 recognize?

ssRNA

What does TLR9 recognize?

CpG motif of viral dsDNA

Recognition by TLR causes activation of what transcription factor?

NF-kB

What cytokines are commonly activated from NF-kB?

IL-1a, IL-1b, TNFa, and IL6

What interferons (IFN) are commonly stimulated by TLR activation?

IFNa and IFNb

In cellular altruism, IFN release activates what 2 pathways in neighboring cells?

Oas1B and PKR

What does Oas1B induce?

Ribonuclease L that degrades all mRNA

What does PKR induce?

eIF-2 that inhibits all translation

What do cytokines IL-1B and TNF-a do?

Permeabilize blood vessels to allow effector cells and soluble molecules to reach site of infection

What does IL-6 do?

Activates metabolism in muscle and fat cells to make heat and increase temperature in infected tissue

What does CXCL8 do?

A chemokine that recruits and guides neutrophils to the site of infection

What does IL-12 do?

Activates and recruits NK cells

MHC I is used to express what?

Internally digested foreign antigens

MHC II is used to express what?

Externally degraded viral antigens

NK cells recognize what to detect viral infection?

Reduced MHC I expression

Once activated, what do NK cells release?

Perforins, granzymes, and chemokines

CD8 Cytotoxic T cells bind to what MHC?

MHC I

CD4 Helper T cells bind to what MHC?

MHC II

(T/F) Dendritic cells act as scouts that engulf and digest pathogens and then display the antigen fragments on MHC II to CD4 helper T cells; also expressed on MHC I to CD8 cytotoxic T cells

True

What are the 2 categories for specific immunity?

Antibody (humoral) and cell mediated

(T/F) Cells present extracellular antigens on MHC II which is recognized by CD4 T cells which then stimulates them to become effector helper T cells → The effector CD4 T cells can then stimulate B cells to clonally differentiate to plasma cells and release antibodies.

True

(T/F) B cells and antibodies recognize whole protein antigens whereas T cells recognize fragments on MHC complexes.

True

Lymphocytes congregate where?

Lymph nodes

Where do B lymphocytes mature?

Bone marrow

Where do T lymphocytes mature?

thymus gland

(T/F) Dendritic cells present antigen on MHC II to CD4 Helper T cell → CD4 T cell becomes activated to effector → activates B cell to clonally differentiate to plasma cells and memory cells.

True

What are the 3 antibodies/immunoglobulins associated with fighting viruses?

IgG, IgA, IgM

What monomer count are IgG, IgA, and IgM respectively?

IgG = Monomer | IgA = dimer | IgM = pentamer

(T/F) IgM is the first antibody to be secreted (signals early infection stage) and is short lived.

True

(T/F) IgG comes later in infection and also has a much longer half-life in the blood (up to a month?). It also accumulates much faster upon subsequent infection. It is also the only immunoglobulin of the 3 to be able to cross the placenta.

True

(T/F) IgA is secreted in much higher concentrations than the other 2.

True

What are some ways viruses evade the immune system?

Mutation to avoid antibodies, latency, overexpress antigens to bind to all antibodies, inactivate cytokines, inactivate immune cells, block cellular pathways such as apoptosis complement and IFN

(T/F) Ebola has a high fatality rate because it suppresses the immune system, promotes vascular leakage and causes a cytokine storm.

True

What is the evidence that Ebola suppresses the immune system?

Absence of neutrophils and dendritic cells as well as lack of specific antibodies

What are 2 proteins Ebola uses to suppress the immune system?

sGP and VP35

What does sGP do?

Protease that inhibits activation of neutrophils

What does VP35 do?

Impairs activation of type I IFN by imparing IRF-3 phosphorylation

What is serum therapy?

Injecting inactivated pathogen into mice → collect antibodies in serum → inject serum into other mice to immunize them

(T/F) Vaccination causes immunization, but immunization can also come from a patient naturally fighting off an infection on their own.

True

How are traditional vaccines made?

Live or attenuated viruses

What are some risks of traditional vaccines?

Inadequate attenuation, reversal, straight up not working,

What are some new generation style vaccines?

Recombinant subunits, recombinant live vectors, VLP (Virus like particles), mRNA

Define recombinant subunit vaccines.

Gene of viral surface protein taken and transformed into yeast cell → grow yeast → lyse and extract pure viral surface protein

Define recombinant live vector vaccines.

Take gene for viral surface protein and transform it into harmless virus then let harmless virus infect cell and express protein

Define VLP (virus like particle) vaccines.

Take genes for capsid and transform into yeast → let yeast grow and then extract empty viral capsid and inject

Define mRNA vaccine

Designed mRNA strand that codes for viral surface protein → usually delivered in lipid vesicle to allow entry into cells (endocytosis)

mRNA vaccines can be made without the need for cells and are mass producible

The lipid vesicles usually contain cholesterol for support and PEG (polyethylene glycol) to reduce opsonization by serum proteins