Immuno Exam 1 - Adaptive immunity - Extracellular Pathogens

Question 1

Give a brief summary of how macrophages and neutrophils initiate the immune response to extracellular pathogens

Answer 1

Microbes bind to neutrophils receptors → phagocyte membrane zips up around microbe → microbe ingested in phagosome → fusion of phagosome with lysosome → activation & killing of microbes by lysosomal enzymes in phagolysosomes & of phagocytosed microbes by ROS & NO

Question 2

What kind of immunity does Th1 drive?

Answer 2

Th1 immunity referred to as a driver of cell mediated immunity – kicks off CD8+ T cells, activates macrophages other phagocytes

Question 3

What kind of immunity does Th2 drive?

Answer 3

Th2 immunity drives the humoral antibody response – interacts with B cells, based on cytokine being secreted, what antibody is produced is determined

Question 4

What antibody activates complement?

Answer 4

IgM

Question 5

What antibody does INF-gamma activate?

Answer 5

IgG – Fc receptor-dependent phagocyte responses, complement activation, neonatal immunity

Question 6

What antibody does IL-4 activate?

Answer 6

→ IgE – immunity against helminthes, mast cell degranulation

Question 7

Describe stimulation of isotype switching

Answer 7

Antigen stimulated B cells may differentiate into IgM antibody-secreting cells CD40L and cytokines, or cells that produce different Ig heavy chain classes influence…
IFN-γ induces to IgG
IL-4 induces to IgE
Mucosal tissues, cytokines TGF-β induce to IgA

Question 8

How can B cells be activated to produce antibody?

Answer 8

B cells produce antibodies but must become activated to do so; naïve cannot
Can be activated by binding to microbe
T cell independent antibody production – neutralize free floating pathogen
Complement activation → recognition by B cell → signals from Ig-CR2 complex
Soluble antigen is capable of activating B cells
Involves crosslinking of immunoglobulin receptor
Typically involves antigens with large repeating epitopes but not proteins
Primarily results in production of IgM (no class switching)

Question 9

How long does it take for antibodies to develop after initial interaction

Answer 9

About a week

Question 10

What antibodies are T-cell dependent and what is the consequence?

Answer 10

IgG is usually T-cell dependent – after more time of more circulation after exposure
Peaks at 10-14 days

Question 11

What antibody is T-cell independent and what is the significance?

Answer 11

IgM can be, but not always, T-cell independent – less time of less circulation after exposure
Peaks at 3-5 days

Question 12

How does exposure to microbes cause changes in phenotype and function of B cells?

Answer 12

• Increased survival, proliferation of B cells
• Increased expression of B7-1/B7-2
• Increased expression of cytokine receptors IL-4 and IL-2 (survival signal)
• Increased expression of CCr7 & migration from follicle to T cell areas

Question 13

Describe the pathway of activated B cells clonally expanding

Answer 13

Activated B cell → clonal expansion
→ become plasma cell + IgM → antibody secretion
→ IgG-expressing B cell+ IgG → isotype switching
→ high-affinity Ig-expressing B cell + high affinity IgG → Memory B cell

Question 14

Describe T and B cell interactions in lymph nodes (where abouts are they)?

Answer 14

T cells migrate to edge of T cell zone; B cells migrate to edge of follicle & into T cell zone
T cells activate B cells which then migrate back to follicle (to germinal center)
Activated → enlargement of lymph node

Question 15

Is isotype class switching dependent on T cells

Answer 15

YES! AND CYTOKINES
Isotype class switching is dependent T cell interactions and cytokines
	Antigen presentation to helper T cell → activation of T cell, expression of CD40 ligand 			and cytokine secretion → activation of B cell by cytokines & CD40 ligation 			→ B cell proliferation & isotype switching induced by cytokines

Question 16

What are the general sequential phases of the adaptive immune response?

Answer 16

Recognition of antigen by specific lymphocytes → activation of lymphocytes (proliferation & differentiation into effector cells) → effector phase of elimination of antigens
Response declines as antigen is eliminated & most of the antigen-stimulated lymphocytes die by apoptosis
Antigen-specific cells that survive are responsible for memory

Question 17

Describe what is unique about IgA for dentists

Answer 17

IgA is the most prevalent antibody isotype in the mouth
Must be secreted onto mucosal surfaces
Dimer, connected by J chain& cleaved once in lumen

Question 18

How do antibodies lead to lysis, phagocytosis, or inflammation?

Answer 18

(IgM, IgG, IgA) → neutralization of microbes & toxins
Bound IgG → opsonization & phagocytosis of microbes
→ Antibody-dependent cellular cytotoxicity via NK cells
IgM, IgG, IgA → complement activation → lysis, phagocytosis or inflammation

Question 19

Where do antibody producing plasma cells reside?

Answer 19

Bone Marrow

Question 20

Where do memory B cells reside?

Answer 20

In secondary lymph nodes

Question 21

Describe active immunization

Answer 21

Induces adaptive immunity, immunological memory & protection
Involves ‘live’ or killed vaccines
Wide range of antigenic preparations is in use

Question 22

Describe passive immunization

Answer 22

Passive immunization is accomplished by the passive injection of preformed antibodies
(Or passage to fetus from mother)

Question 23

What are the 3 kinds of Live vaccines

Answer 23

1. Attenuated
2. Heterologous
3. Recobinant

Question 24

Describe Live attenuated vaccines

Answer 24

Live attenuated organisms – organisms whose virulence has been artificially reduced
Replication of the vaccine strain in the host reproduces many of the features of wild type infection, without causing clinical disease
Most successful viral vaccines belong to this group

Question 25

Describe Heterologous vaccines

Answer 25

Heterologous vaccines – closely related organism of lesser virulence witch shares many antigens with the virulent organism
Eg. Cowpox & vaccinia virus are closely related to variola virus, causative agent of smallpox; use of vaccinia virus as a vaccine has lead to eradication

Question 26

Describe Live Recombinant vaccines

Answer 26

Live recombinant vaccines – using genetic engineering, a gene coding for an immunogenic protein form one organism is placed in the genome of another
Recombinant – organism expressing a foreign gene

Question 27

Describe the 4 attributes of live vaccine: immune response, safety, stability, expense

Answer 27

Good immune response – induces T cells & antibody and immunity is long lived; usually a single dose is all that is required
Safety – danger of reversion to virulence; can’t be used in immunocompromised patients
Stability – organisms must remain viable in order to infect & replicate in; sensitive to storage condition; maintenance of the cold chain is important
Expense – inexpensive to prepare

Question 28

What are killed inactivated vaccines?

Answer 28

Made when safe live vaccines have not been developed or when reversion to the wild type is common; radiated
The organism inactivated with either β-propiolactone or formaldehyde
Are not infectious & are therefore relatively safe

Question 29

What are the two types of killed inactivated vaccines?

Answer 29

1. Subcellular fractions

2. Recombinant proteins

Question 30

Describe Subcellular fractions as killed inactivated vacccines

Answer 30

Subcellular fractions – may be possible to use a purified preparation of a microbial protein as a vaccine; protein is purified from the culture suspension
Sage & fewer local reactions occur at the injection site

Question 31

Describe Recombinant proteins as killed inactivated vaccines

Answer 31

Recombinant proteins – immunogenic proteins of virulent organisms may be synthesized artificially by introducing the gene coding for the protein into an expression vector (E. coli or yeast)
Protein can be extracted from lysates of expression vector, then concentrated & purified fro use
Eg. hepatitis B vaccine

Question 32

Describe the 4 attributes of killed vaccines: immune response, safety, stability, expense

Answer 32

Immune response – poor, primarily an antibody response (little cell-mediated)
Short lived & multiple doses are needed
May be enhanced by incorporation of adjuvants into vaccine
Safety – inactivated therefore cannot replicate in the host & cause disease
Local reaction at the site of injection may occur
Stability – efficacy does not rely on viability
Tend to withstand more adverse storage conditions
Expense – more expensive to prepare

Question 33

In what 4 ways do vaccines induce protective antibody response?

Answer 33

Antibody blocks binding of microbe & infection of cell, blocks infection of adjacent cell and blocks binding of toxin to cellular receptor
Antibodies can neutralize microbes or toxins
Antibodies can opsonize microbes to facilitate phagocytosis
Opsonization by IgG → biding of opsonized microbes to phagocyte Fc receptors → Fc receptor signals activate phagocyte → phagocytosis of microbe
Antibody-dependent cellular cytotoxicity
IgG onto surface antigen of antibody coated cell → binding of low-affinity FcγRIII of NK to IgG → killing of antibody-coated cell

Question 34

What antibodies are T-cell dependent?

Answer 34

IgM, IgG, IgA, and IgE

Question 35

What antibody is T-cell independent?

Answer 35

IgM