Immunity to Viral Infections (Exam 1) Flashcards

1
Q

What are the anatomic, physiologic, and cellular components of innate immunity?

A

Anatomic: skin, mucosa, ciliary apparatus
Physiologic: lysozymes in tears, gastric acid, bile, digestive enzymes
Dendritic cells, macrophages, NK cells
Interferons and cytokines
Complement
Presence/absence of cellular receptors, enzymes, etc. needed to support virus replication

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2
Q

What are general characteristics of innate immunity?

A

First line of defense
No antigen specificity
No memory
No MHC class restriction
No antibody dependence

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3
Q

How does the innate system recognize microbes and not self?

A

TLRs
Pattern Recognition Receptors

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4
Q

Describe the discovery of interferons

A

1957: Issacs & Lindenman
Chicken cells exposed to non-infectious influenza virus produce substance that “interfered” with infection of other cells

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5
Q

Define: Interferons

A

Produced by virus-infected cells and uninfected sentinel cells in response to products released from cells (e.g. viral nucleic acid)

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6
Q

Source and Activity of Type I Interferons

A

IFN alpha
Source: Leukocytes
Activity: Antiviral
IFN beta
Source: Fibroblasts, Epithelium
Activity: Antiviral

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7
Q

Source and Activity of Type II Interferons

A

IFN gamma
Source: T cells, NK cells
Activity: Immunoregulatory

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8
Q

What does the IFN system cause systemically?

A

IFN induces the expression of many deleterious gene products
Have dramatic physiologic consequences: fever, chills, nausea, malaise
Every viral infection results in IFN production, one reason why “flu-like” symptoms are so common

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9
Q

Characteristics of Interferons

A

No viral specificity
Species specific
Produced early in the course of infection
Protect neighboring cells
Inhibit early spread of virus
Production/treatment correlates with recovery
Inhibition of product leads to severe disease

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10
Q

Define: Sentinel Cells (+ Examples)

A

Patrol all tissues looking for signs of change
Dendritic cells, macrophages, NK cells

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11
Q

Define: Dendritic Cells

A

Travel to lymph node with viral peptides

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12
Q

Define: NK Cells

A

Recognize non-self

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13
Q

Define: Complement

A

Serum and membrane proteins
Activation results in amplification of products that form pores in membranes, mediate inflammation, act as opsonins, solubilize immune complexes

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14
Q

What complement molecules form holes in membranes?

A

C6, C7, C8, C9 (Membrane Attack Complex)

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15
Q

What complement molecules mediate inflammation?

A

C3a, C4a, C5a

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16
Q

What complement molecules act as opsonins?

A

C3b

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17
Q

What are characteristics of the inflammatory response?

A

Infected cells produce cytokines and chemokines
Redness, pain, heat, swelling
Loss of function
Increased blood flow, increased capillary permeability, influx of phagocytic cells, tissue damage

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18
Q

What are the 2 effects cytokines have?

A

Pro-inflammatory
Anti-inflammatory

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19
Q

Characteristics of Acquired Immunity

A

Inducible protection against infection, disease, or death
Requires time to develop
Specific for antigen
Responds to many antigens
Memory
Humoral vs cell-mediated components

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20
Q

Define: Leukocyte

A

General term for white blood cell
Lymphocytes, neutrophils, eosinophils, macrophages

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21
Q

Define: Lymphocyte

A

Subset of leukocytes
T, B, NK cells
Have variable antigen-detecting cell surface receptors

22
Q

What does lymphocyte activation trigger?

A

Massive cell proliferation

23
Q

Characteristics of Neutralizing Antibodies

A

Essential defense against many virus infections
Neutralize virus particles in the blood, prevent virus spread
IgA at mucosal surfaces (secretory antibody) blocks entry
Some neutralizing antibodies are important for recovery from infection

24
Q

What are the anti-viral actions of antibodies?

A

Neutralization (prevents virus from binding to receptor and uncoating)
Opsonization
Antibody-dependent cell-mediated cytotoxicity (macrophages, neutrophils, NK cells)
Complement activation

25
Q

What are practical considerations of viral antibody levels in serum?

A

Determining the presence of antibodies and their relative concentration in serum
1. Is evidence of prior infection or vaccination
2. Can be used as an estimate of protection (increased titer = decreased risk)

26
Q

What are practical considerations of viral maternal antibody levels?

A

Passive transfer of maternal antibodies to young animals
1. Provides protection against severe disease
2. Interferes with immunization by neutralizing vaccine viruses
3. Successful transfer depends on maternal immunity, health & behavior, environmental, and management factors

27
Q

What is the purpose of cell mediated immunity?

A

Essential for clearing most viral infections
CTL and target cells form an immunological synapse
Lysis of target cell
Countermeasures

28
Q

What are the different types of T cells?

A

T helper cells (CD4+)
-Th1 (inflammatory)
-Th2 (helper)
T Cytotoxic (CD8+)
T Suppressor (CD4+)
T Delayed Type Hypersensitivity (CD4+/CD8+)

29
Q

MHC I recognition and AA derived by

A

Recognized By: CTLs
AA Derived By: Endogenous

30
Q

MHC II recognition and AA derived by

A

Recognized By: T helper, T Suppressor
AA Derived By: Exogenous

31
Q

What is the endogenous virus pathway for exportation?

A

Proteins made in the cytosol are digested by proteosomes into peptides
TAP transports the peptides to the ER
MHC I molecules associate with the peptides
MHC I + peptide complex is exported to the cell’s surface

32
Q

What are the 2 mechanisms in which a target cell is lysed?

A

Release of cytoplasmic content
Apoptosis

33
Q

What is the exogenous viral pathway for exportation?

A

Endocytosis of extracellular proteins
Endosomal/lysosomal enzyme digestion produces peptides
MHC II molecules are transported to the endosomes and pick up the peptides
MHC II + peptide complex is exported to the cell’s surface

34
Q

What triggers T helper activation?

A

T helper activation is triggered by viral antigen bound to MHC II molecules

35
Q

What cell types determine the correct antibody response?

A

T helper cells

36
Q

Why do T helper cells determine the correct antibody response?

A

Th cells contact in the lymph nodes with sentinel DCs and macrophages
Information exchanged causes differentiation into Th1 or Th2

37
Q

What is the practical consideration of antibodies and vaccination?

A

Viral infections or modified live vaccines stimulate both B cell (antibodies) and CTL activity
Inactivated (killed) and subunit viral vaccines stimulate B cell and T helper cell activity (cytokine)

38
Q

What is the practical consideration of virus and serum?

A

Parenteral inoculation with viral vaccines stimulates systemic immunity which we measure by serologic testing (Abs) in serum

39
Q

Why are serum antibodies important?

A

Serum antibodies are important in protecting animals against severe disease due to viruses with a viremic or systemic phase

40
Q

What are practical considerations of mucosal immunity?

A

Mucosal immunity is stimulated by viral vaccines delivered to the mucosal surface
Parenteral administration of vaccines does not effectively stimulate mucosal antibodies
Mucosal antibodies are not routinely measured

41
Q

Type I Hypersensitivity Reaction Classification

A

Anaphylaxis

42
Q

Type II Hypersensitivity Reaction Classification

A

Cytotoxic

43
Q

Type III Hypersensitivity Reaction Classification

A

Immune Complex
Arthus Reaction

44
Q

Type IV Hypersensitivity Reaction Classification

A

Cell-Mediated
Delayed Hpersensitivity

45
Q

Characteristics of Type I Hypersensitivity Reactions

A

Anaphylaxis
IgE and viral antigen release of granules from mast cells containing histamine, heparin, serotonin, and plasma kinins
May account for erythema, congestion, swelling in upper respiratory tract post-RSV infections
Important in anaphylaxis due to proteins present in vaccines

46
Q

Characteristics of Type II Hypersensitivity Reactions

A

Cytotoxic
IgM/IgG and viral antigen on the cell surface results in cell destruction
May account for hemolysis during acute infection with EIAV leading to anemia
May account for liver necrosis in hepatitis B, yellow fever, or Theiler’s disease

47
Q

Characteristics of Type III Hypersensitivity Reactions

A

Immune Complex
IgG and viral antigen leads to immune complex formation
Lattice formation dependent on relative amounts of IgG and antigen
Dependent on Ig affinity, presence of complement, ability of the RE system to remove complexes by phagocytosis
Activation of complement and neutrophils

48
Q

Examples of Type III Hypersensitivity Reactions

A

Immune Complex
Aleutian disease of mink
Parvovirus
Persistent infection
Immune complex formation
Deposition in renal glomeruli, skin, synovium, choroid plexus

49
Q

Characteristics of Type IV Hypersensitivity Reactions

A

Cell-Mediated
Virus-specific T lymphocytes and viral antigens presented in the context of MHC
Inflammation in an unfortunate location
Ex: CTLs and encephalitis in LCMV infection in adult mice or Borna disease virus in rats

50
Q

Define: Autoimmunity

A

An immune response directed against normal host components which results in tissue injury
Can be primarily a humoral immune response
Can be primarily a cell-mediated immune response
Vaccine-induced suspect cases

51
Q

What are the different types of autoimmunity?

A

Broad and directed against many organs and tissue antigens

52
Q

What are the 3 proposed mechanisms for virus-induced autoimmune disease?

A
  1. Exposure of hidden (intracellular) antigens following cell injury
  2. Molecular mimicry; similarity between viral and cellular antigens
  3. Failure of regulatory control of the immune response