Intro, innate adaptive, infection and vaccination

Question 1

Which of the following IS a phagocyte:

A. B cell.

B. CD4 T cell.

C. Activated macrophage.

D. Eosinophil.

E. CD8 T cell.

Answer 1

C

Question 2

Which of the following is NOT a secondary lymphoid organ?

A. Spleen.

B. Liver.

C. Tonsils.

D. Brachial lymph node.

E. Cervical lymph node.

Answer 2

B
Primary lymphoid organs:
foetal liver
bone
marrow
thymus

Secondary lymphoid organs:
Lymph nodes (eg tonsils)
• Spleen
• Mucosal lymphoid tissues

Question 3

Which of the following BEST describes Pathogen Associated Molecular Patterns (PAMPs)?

A. Conserved molecules shared by broad classes of microbes

B. Released by uninfected human cells when damaged

C. Different types of bacteria

D. Bind to B cell receptors

E. Activate T cells

Answer 3

A

Question 4

Which of the following immune cells utilize reactive oxygen species to kill microbes

A. B cells.

B. Cytotoxic T lymphocytes.

C. CD4+ T cells.

D. Macrophages.

E. NK cells.

Answer 4

D
dendritic cells, macrophages and neutrophils via PRRs on their surface (C-type lectins (CLR) e.g dectin 1 & 2 and TLRs e.g TLR2).
Phagocytosis and killing via production of reactive oxygen species

Small granules in NK cell cytoplasm contain cytotoxic proteins such as
perforin and proteases such as granzymes
• Upon release in close proximity to a target cell, perforin forms pores in
the cell membrane, creating an aqueous channel through which the
granzymes and associated molecules can induce programmed cell death
(apoptosis)

Question 5

Which of the following is MOST true of B cells

A. Express the B cell receptor.

B. Express CD3.

C. Develop in the thymus in adults.

D. Are part of the innate immune system.

E. Phagocytic

Answer 5

A

Question 6

which of the following is LEAST true of dendritic cells

A. Transport antigen to lymph nodes.

B. Prime CD4 and CD8 T cell responses.

C. Are found in the skin.

D. Are professional antigen presenting cells.

E. Kill bacteria.

Answer 6

E

Question 7

Which of the following molecules is NOT required for the activation of T cells into an effector T cells?

A. Cytokine

B. Peptide-MHC molecule complex

C. Costimulatory molecule

D. T cell Receptor

E. Complement receptor

Answer 7

E
Signal 2:tcr, cytokine and costim
Signal 1:mhc peptide

Question 8

Following infection with influenza A, which is the MOST likely mechanism that will protect against future infection with the same virus?

A. Type I interferon.

B. Lytic antibodies specific for influenza B.

C. NK cells.

D. Neutralizing antibody specific for Influenza A virus.

E. Neutrophils.

Answer 8

D

Question 9

Under which circumstances would a live attenuated vaccine NOT be recommended?

A. For a boy.

B. For a child with eczema.

C. For someone who is overweight.

D. For an immunodeficient patient.

E. For a nervous patient.

Answer 9

D

Question 10

Which of the following is a potential disadvantage for live attenuated vaccines?

A. May be given orally

B. Few side effects

C. Ease of transport and handling

D. Activates all elements of the immune system

E. The pathogen might mutate and regain virulence

Answer 10

E

Question 11

Which of the following immune effector mechanisms is the MOST likely mechanism that will protect against the parasitic worm infection with Schistosoma mansoni?

A. Killing by NK cells

B. Phagocytosis

C. Killing by cytotoxic T lymphocytes

D. Killing by membrane attack complex

E. Antibody-dependent cellular cytoxicity

Answer 11

E
worm is extracellular parasite/helmith.
Eosinophils are better at killing helminths than are other
leukocytes; the Th2 (helper T) response and IgE (antibody) provide a mechanism for bringing eosinophils to helminths and activating the cells via Antibody dependent cell cytotoxicity (ADCC): A process by which natural killer (NK) cells are targeted to IgG-coated cells, resulting in the **lysis of the antibody-coated cells. **A specific receptor for the constant region of IgG, called FcγRIII (CD16), is expressed on the NK cell membrane and mediates the binding to the IgG.

option A: Natural killer (NK) cells: A subset of bone marrow-derived lymphocytes, distinct from B and T cells, that function in innate immune responses to kill microbe-infected cells and to activate phagocytes by secreting interferon-γ. NK cells do not express clonally distributed antigen receptors like immunoglobulin or T cell receptors, and their activation is regulated by a combination of cell surface stimulatory and inhibitory receptors, the latter recognizing self MHC molecules.

Question 12

Which of the following is not TRUE about NK cells?

A. Natural killer cells are activated by type I interferon

B. Natural killer cells are critical for the defense against extracellular pathogens

C. Natural killer cells are critical for the defense against intracellular pathogens

D. Natural killer cells kill the infected cells via the release of granzyme and perforin

E. Natural killer cells exert their function in early phase of infection

Answer 12

B
Critical in host defence against
intracellular pathogens: herpes
viruses, parasite Leishmania and
bacteria Listeria monocytogenes

Type one IFN are alpha and beta.

Granzyme and perforin in slide 19 of #3

Question 13

Which of the following is not TRUE about CD4+ T cells?

A. They recognize an antigen presented via MHC class I molecule

B. They can help other immune cells through the production of cytokines

C. They recognize an antigen presented via MHC class II molecule

D. They can inhibit immune cell responses through the production of cytokines

E. They can differentiate into effector CD4+ T cells or memory CD4+ T cells

Answer 13

A
MHC I is presented to CD8 T cells

Question 14

Tut 1

1) What may be the cause of a high white blood cell count? A low white blood cell count?

Answer 14

A high white blood cell count may the sign of:
- Inflammation
- Infection
- Leukemia (blood cancer, abnormal growth of white blood cells in bone marrow)
- Some myeloproliferative disorders (neutrophilic, eosinophilic)
- Medical reaction, e.g certain drugs, such as colony-stimulating factors
- Stress, allergies or tissue injury
- Post-transplantation of organs

A low white blood cell count may be the sign of:
- Viral infection
- Severe bacterial infection
- Bone marrow suppression caused by treatments like chemotherapy or radiation therapy
- Bone marrow diseases e.g immunodeficiencies
- Autoimmune disease (lupus, rheumatoid arthritis)
- Blood donation

Question 15

Tut 1

2) The table below represents the result of full blood count and differential counts of a 6 months-old baby.
a) which parameter is abnormal in this baby?
b) which additional test can be performed to confirm the result of full blood count?
c) This abnormal white blood cell count may render the baby more
susceptible to infection. To which type of infection?

table in pdf

Answer 15

a) Neutrophils. Conditions called neutropenia
b) histological test
c) Bacteria infection. Neutrophils are known to be very important to fight against bacteria and fungi. The baby should not have any problem to fight against viral infection

Question 16

Tut 2

A 35year-old woman with no previous significant medical history becomes infected with Influenza A H1N1 2009. She is given symptomatic treatment and told to rest at home. Over the next 2-3 days, her symptoms get worse, but she subsequently improves and makes an uneventful recovery by day 8.

Describe some mechanisms of innate immunity against influenza

Answer 16

• Barrier defences: epithelial barriers, ciliated epithelium, coughing, sneezing, secretion of mucus at sites of exposure to
  pathogen in upper respiratory tract.
• Detection of the virus by Airway Dendritic cells, macrophages and epithelial cells through their Toll-like receptors (TLR7 and 8) –> secretion of Type I interferons
• Clearance / digestion of viruses by lung macrophages.
• Release of proinflammatory cytokines (IL-1, IL-6, TNF) to initiate fever response.
• NK cell activation by DC and macrophage-derived cytokinesà kill infected cells

Question 17

Tut 2

A 35 year-old woman with no previous significant medical history becomes infected with Influenza A H1N1 2009. She is given symptomatic treatment and told to rest at home. Over the next 2-3 days, her symptoms get worse, but she subsequently improves and makes an uneventful recovery by day 8.

Discuss how influenza antigen from infected tissues of the upper respiratory tract is processed and transported to the draining lymph nodes for antigen presentation.
-Migration of ___ cells from respiratory tract into mediastinal ___ (that drain the airways).

How are naïve T cells specific for influenza
antigens activated?
- Presentation of viral antigens on ___ molecules to circulating naive T cells.
Recruitment of ___ and ___ __cells that have antigen receptors (TCRs) specific for virus-derived peptides displayed on MHC class I or MHC class II respectively.

Answer 17

Migration of dendritic cells from respiratory tract into mediastinal lymph-nodes (that drain the airways).
Presentation of viral antigens on MHC molecules to circulating naive T cells.
Recruitment of CD8 and CD4 T cells that have antigen receptors (TCRs) specific for virus-derived peptides displayed on MHC class I or MHC class II respectively.

diagram in pdf

Question 18

Tut 2

A 35year-old woman with no previous significant medical history becomes infected with Influenza A H1N1 2009. She is given symptomatic treatment and told to rest at home. Over the next 2-3 days, her symptoms get worse, but she subsequently improves and makes an uneventful recovery by day 8.

Describe the mechanisms of host protection mediated by influenza-specific antibodies.

Answer 18

Mainly neutralization: neutralization describes covering a virus (pathogens) surface with antibodies to block binding to its target host cell receptors.

This is principally mediated by IgG (as opposed to other subclasses) induced by interferon gamma

When immune response takes place in mucosal tissue (ex respiratory tract),** secretory IgA** is secreted on the mucosal surface and can also neutralize the virus.

Question 19

Tut 2

A 35year-old woman with no previous significant medical history becomes infected with Influenza A H1N1 2009. She is given symptomatic treatment and told to rest at home. Over the next 2-3 days, her symptoms get worse, but she subsequently improves and makes an uneventful recovery by day 8.

Depict the time course of the adaptive immune response to influenza virus. Discuss this in relation to the time course of the woman’s illness (she gets worse for 2-3 days, but subsequently improves)

Answer 19

Infection can be defined as a pathogen breaking through our innate immune defenses. The recovery of the patient is coincident with the ‘early’ stages of an adaptive response (by day 8). It takes this long to mobilize the adaptive immune response because of the relatively small number of virus-specific CD4/8 T cells and B cells. Our immune system has to identify and recruit these cells into the response.

By day 6, the IgM response is strong and the IgG response is also getting going. You only need trace amounts of pathogen-specific antibodies and small numbers of mobilized pathogen-specific T cells to mediate the protective effects. This is why the virus is already being cleared from our circulation by this time point. The latter stages (>5-6 weeks) of the adaptive response are about generating strong immunological memory.

Question 20

Tut 2

A 35year-old woman with no previous significant medical history becomes infected with Influenza A H1N1 2009. She is given symptomatic treatment and told to rest at home. Over the next 2-3 days, her symptoms get worse, but she subsequently improves and makes an uneventful recovery by day 8.

What happens if this person is exposed to the same strain of virus a second time several months later?

Answer 20

In theory, the memory response generated by the first exposure to the pathogen ensure that the individual has large numbers of influenza H1N1-specific antibodies, and virus-specific memory T cells and B cells in their
circulation. Under these circumstances, the person will usually be completely protected.

Question 21

VA say impt: Pathogen Associated Molecular Patterns (PAMPs)

endotoxin/lipopolysaccharide (LPS), flagellin, nucleic acid

Endotoxin/ lipopolysaccharide (LPS):
- A component of the __ of gram-___ bacteria which is released from ___ bacteria.
- stimulates many ___ immune responses, including the secretion of cytokines and induction of ___ activities of ___ and the expression of ___ ___ for leukocytes on endothelium.
- Endotoxin contains both ___ components and ___ (polysaccharide) moieties,
- recognized by Pattern Recognition Receptors known as ___ expressed by effector cells.

Pathogen Associated Molecular Patterns (PAMPs) are conserved molecular patterns shared by broad classes of pathogens (normally absent in a sterile environment). These are not shared with their host; are shared by many related
pathogens; are relatively invariant; that is, do not evolve rapidly

in their context of action (inflammation, infection, isotope switching..

Answer 21

Endotoxin/ lipopolysaccharide (LPS):
conserved molecular patterns shared by broad classes of pathogens (normally absent in a sterile environment). These are not shared with their host; are shared by many related pathogens; are relatively invariant; that is, do not evolve rapidly
- A component of the cell wall of gram-negative bacteria which is released from dying bacteria. / Conserved molecules shared by broad classes of microbes heh
- stimulates many innate immune responses, including the secretion of cytokines and induction of microbicidal activities of macrophages and the expression of adhesion molecules for leukocytes on endothelium.
- Endotoxin contains both lipid components and carbohydrate (polysaccharide) moieties,
- recognized by Pattern Recognition Receptors known as Toll-like receptors (TLRs) expressed by effector cells.

Question 22

VA says impt: Examples of Pattern Recognition Receptors (PRRs)

mannose receptor, toll like receptors/TLRs
TLRs: Cell surface receptors on ___ and other cell types that act as pattern recognition receptors important in the ___ immune response to ___ and other microbial products. Toll-like receptors share structural homology and signal transduction pathways with the type I ___ receptor.

Mannose receptor (a ___ receptor in phagocytosis): directly bind to ___ on microbes

in their context of action (inflammation, infection, isotope switching..

Answer 22

Examples of Pattern Recognition Receptors (PRRs) (mannose receptor, toll like receptors/TLRs):

TLRs: Cell surface receptors on phagocytes and other cell types that act as pattern recognition receptors important in the innate immune response to lipopolysaccharides (LPS) (a PAMP) and other microbial products. Toll-like receptors share structural homology and signal transduction pathways with the type I interleukin-1 receptor.

Mannose receptor (a membrane receptor in phagocytosis): directly bind to polysaccharides on microbes

Question 23

VA say impt: Opsonin receptor in phagocytosis

1. Fc receptors:
   - __ of antibody-coated (opsonized) microbes
   other roles: A cell surface receptor specific for the carboxy-terminal constant region of an __ molecule. Fc receptors are typically __ protein complexes that include Ig-binding components and signaling components. Fc receptors mediate many of the effector functions of antibodies, including phagocytosis of antibody-coated (opsonized) microbes, antigen-induced activation of mast cells, and activation of natural killer cells.
2. Complement receptors:
   Each complement pathway consists of a cascade of proteolytic enzymes that generate __ mediators and opsonins and leads to the formation of a ___ complex that inserts in cell membranes.

in their context of action (inflammation, infection, isotope switching..

Answer 23

Fc receptors – phagocytosis of antibody-coated (opsonized) microbes
other roles: A cell surface receptor specific for the carboxy-terminal constant region of an Ig molecule. Fc receptors are typically multichain protein complexes that include Ig-binding components and signaling components. Fc receptors mediate many of the effector functions of antibodies, including phagocytosis of antibody-coated (opsonized) microbes, antigen-induced activation of mast cells, and activation of natural killer cells.

Complement receptors: Each complement pathway consists of a cascade of proteolytic enzymes that generate inflammatory mediators and opsonins and leads to the formation of a lytic complex that inserts in cell membranes.

Question 24

molecules VA say impt

Defensins and lysozyme
1. Defensins:
- Cysteine-rich peptides produced in epithelia and neutrophil granules, which act as __ antibiotics that kill a wide variety of bacteria and fungi.
- Originally isolated from frog skin based on their ability to kill bacteria
- Small polypeptides (<10kDa) secreted at mucosal surfaces by __cells and ___, ___, ___ cell
- Direct bacteriocidal properties
- Insertion into biological membranes leading to ___ of target cells

2. Lysozyme:
   - Enzyme
   - Present in ___ and other secretions
   - Found in high concentrations inside ___, ___, ___ cell
   - ___ polysaccharide component of bacterial and yeast cell walls

in their context of action (inflammation, infection, isotope switching..

Answer 24

Defensins:
- Cysteine-rich peptides produced in epithelia and neutrophil granules, which act as broad-spectrum antibiotics that kill a wide variety of bacteria and fungi.
- Originally isolated from frog skin based on their ability to kill bacteria
- Small polypeptides (<10kDa) secreted at mucosal surfaces by epithelial
cells and macrophage, neutrophil, dendritic cell
- Direct bacteriocidal properties
- Insertion into biological membranes leading to lysis of target cells

Lysozyme:
- Enzyme
- Present in tears and other secretions
- Found in high concentrations inside macrophage, neutrophil, dendritic cell
- Hydrolyses polysaccharide component of bacterial and yeast cell walls

Question 25

VA: Molecules involved in Antigen presentation and lymphocyte activation

signal 1 you should know MHC I or II + antigens

signal 2 costimulatory molecules B7/CD28, CD40/CD40L

in their context of action (inflammation, infection, isotope switching..

Answer 25

1. signal 1: MHC I or II + antigens

binding of native antigen to surface IgM/IgD BCR on naïve follicular B cell, B cell internalizes antigen and presents peptide-MHC II to antigen-specific effector T helper cell = **antigen specific T cell-B cell interaction **

2. signal 2: costimulatory molecules B7/CD28, CD40/CD40L + cytokines

TCR triggering up-regulates on costimulatory molecule, CD40L, on T cell and CD40 signaling **promotes B cell activation **

*T cell activation into effector T cells requires signal 1 (peptide/MHC) and signal 2 (costimulatory molecules and cytokines)

Question 26

common cytokines

Adaptive immunity associated cytokines:
1. IFN-γ: A cytokine produced by __ lymphocytes and __ cells whose principal function is to ___ __ in both innate immune responses and adaptive cell-mediated immune responses. (In the past, IFN-γ was also called immune or type __ interferon).

2a. IL-4: A cytokine produced mainly by the ___ subset of ___ cells. Functions include inducing differentiation of TH2 cells from naive CD4+ precursors, stimulation of __ production by __ cells, and suppression of __-dependent macrophage functions.

2b. Interleukin-5 (IL-5): A cytokine produced by __ subset of __ cells and activated __, which stimulates the growth and differentiation of ___ and activates mature ___ (same).

3.IL-10: A cytokine produced by activated ___ and some ___cells. major function is to inhibit activated ___ and therefore maintain ___ control of ___ and ___ immune reactions.

in their context of action (inflammation, infection, isotope switching..

Answer 26

1. IFN-γ: A cytokine produced by T lymphocytes and natural killer cells whose principal function is to activate macrophages in both innate immune responses and adaptive cell-mediated immune responses. (In the past, IFN-γ was also called immune or type II interferon).

2a. IL-4: A cytokine produced mainly by the TH2 subset of CD4+ helper T cells. Functions include inducing differentiation of TH2 cells from naive CD4+ precursors, stimulation of IgE production by B cells, and suppression of interferon-γ-dependent macrophage functions.

2b. Interleukin-5 (IL-5): A cytokine produced by TH2 subset of CD4+ helper T cells and activated mast cells, which stimulates the growth and differentiation of eosinophils and activates mature eosinophils.

3.IL-10: A cytokine produced by activated macrophages and some helper T cells. major function is to inhibit activated macrophages and therefore maintain homeostatic control of innate and cell-mediated immune reactions.

Question 27

common cytokines

Innate immunity associated cytokines:
1. type I interferon (IFN-α, IFN-β): have potent ___ actions. The major source of IFN-α is mononuclear ___, and IFN-β is produced by many cells, including fibroblasts. Both IFN-α and IFN-β bind to the same cell surface receptor and induce similar biologic responses.

Type I IFNs inhibit __ replication, increase the lytic potential of ___ cells, increase expression of class __major histocompatibility complex molecules on virus-infected cells, and stimulate the development of ___cells, especially in humans.

2. IL-1: A cytokine produced mainly by activated mononuclear ___ whose principal function is to mediate host inflammatory responses in innate immunity. There are two forms of IL-1 (α and β) that bind to the same receptors and have identical biologic effects, including __ of __ cell adhesion molecules, stimulation of ___ production by ___ cells and ___, stimulation of synthesis of ___-phase reactants by the ___, and __.
3. IL-6: A cytokine produced by many cell types including activated mononuclear ___, endothelial cells, and fibroblasts, which functions in both innate and adaptive immunity. IL-6 stimulates the synthesis of ___ phase proteins by hepatocytes and stimulates the growth of ___ B lymphocytes.
4. Tumor necrosis factor (TNF-α): A cytokine produced mainly by activated mononuclear ___ that functions to stimulate the recruitment of ___ and __ to sites of infection and to activate these cells to eradicate microbes. TNF stimulates vascular ___ cells to express adhesion molecules and induces ___ and ___ cells to secrete ___. In severe infections, TNF is produced in large amounts and has systemic effects, including induction of ___, synthesis of ___-phase proteins by the ___, and __ (wasting). When very large amounts of TNF are produced, it can cause intravascular ___ and shock (the clinical syndrome of septic shock).

in their context of action (inflammation, infection, isotope switching..

Answer 27

1. type I interferon (IFN-α, IFN-β): A family of cytokines, all of which have potent antiviral actions. The major source of IFN-α is mononuclear phagocytes, and IFN-β is produced by many cells, including fibroblasts. Both IFN-α and IFN-β bind to the same cell surface receptor and induce similar biologic responses.

Type I IFNs inhibit viral replication, increase the lytic potential of natural killer cells, increase expression of class I major histocompatibility complex molecules on virus-infected cells, and stimulate the development of TH1 cells, especially in humans.

2. IL-1: A cytokine produced mainly by activated mononuclear phagocytes whose principal function is to mediate host inflammatory responses in innate immunity. There are two forms of IL-1 (α and β) that bind to the same receptors and have identical biologic effects, including induction of endothelial cell adhesion molecules, stimulation of chemokine production by endothelial cells and macrophages, stimulation of synthesis of acute-phase reactants by the liver, and fever.
3. IL-6: A cytokine produced by many cell types including activated mononuclear phagocytes, endothelial cells, and fibroblasts, which functions in both innate and adaptive immunity. IL-6 stimulates the synthesis of acute phase proteins by hepatocytes and stimulates the growth of antibody-producing B lymphocytes.
4. Tumor necrosis factor (TNF-α): A cytokine produced mainly by activated mononuclear phagocytes that functions to stimulate the recruitment of neutrophils and monocytes to sites of infection and to activate these cells to eradicate microbes. TNF stimulates vascular endothelial cells to express adhesion molecules and induces macrophages and endothelial cells to secrete chemokines. In severe infections, TNF is produced in large amounts and has systemic effects, including induction of fever, synthesis of acute-phase proteins by the liver, and cachexia. When very large amounts of TNF are produced, it can cause intravascular thrombosis and shock (the clinical syndrome of septic shock).

Question 28

Tut 3

What are the advantages and disadvantages of a live attenuated vaccine, compared to an inactivated virus vaccine?

Answer 28

Advantages:
* mimic natural infection
* produce a large antigenic stimulus
* generally induce T&B lymphocyte responses
* provide long‐lasting protection

Disadvantages:
* may retain some pathogenicity
* may revert to virulence
* may not be safe enough to vaccinate immuno‐compromised
subjects
* inadvertent transmission of vaccine strains to susceptible contacts
of vaccinees
* require a good cold chain

Question 29

tut 3

How does the immune response to natural poliovirus infection differ from the immune response to the Salk vaccine (inactivated virus, administered as an intramuscular injection)?

Answer 29

immune response to natural poliovirus:
- Induction of mucosal immunity
- Duration and quality : stronger immune response, both T and B cell responses and long lasting response.

Question 30

tut 3

Which of the two vaccines provides protection against poliovirus infection? Which protects against polio disease? Why is this so?

Answer 30

Oral polio vaccine protects against poliovirus infection because infection of the gut by the live attenuated virus generates mucosal IgA that will block natural infection by neutralizing the virus before it can infect the
host cells
The inactivated vaccine generates systemic IgG but no mucosal immunity, so poliovirus can still infect the gut. But systemic IgG in vaccinated individuals prevents viraemia and CNS infection, and so protects against
paralytic disease.

Question 31

tut 3

The oral polio vaccine was originally part of Singapore’s National Childhood Immunisation Programme. The Ministry of Health is considering a switch to injectable inactivated polio vaccines.
What might be some reasons for this change now?

Answer 31

Advantages of oral polio vaccine (OPV):
In poorly developed countries with poor vaccine coverage, government usually starts with OPV - cheap, no need trained medics to inject, protect from polio infection and so reduces circulating wild-type virus.

What is herd immunity? The purpose of providing vaccines is 2-fold. To protect the individual, and to protect the population from disease.
In countries with poor vaccine coverage and low herd immunity, giving inactivated polio vaccine (IPV) protects the individual. But since the immunised individual can still be infected (protected from disease,
not infection) with wild type polio, such infected individuals can transmit wild type polio to unprotected individuals in this population with low herd immunity.
On the other hand, OPV can be passed out in stools. Circulation of OPV benefits population with good vaccine coverage because it dilutes out wild-type virus in the environment.
Herd immunity: resistance to the spread of an infectious disease within a population that is based on pre-existing immunity of a high proportion of individuals as a result of previous infection or vaccination

As the incidence of wild polio diminishes and herd immunity increases, nations transition from use of the oral vaccine to the injected vaccine because:
- Effective in preventing wild type infections, but now the low frequency of polio is caused by the vaccine strain.
The direct risk of iatrogenic vaccine-associated paralytic poliomyelitis (VAPP) due to OPV outweighs the indirect benefit of immunization via subclinical transmission of the vaccine strain to non-immune
individuals.
In immunodeficient children, the risk of VAPP is almost 7,000 times higher, particularly for persons with B-lymphocyte disorders (e.g., agammaglobulinemia and hypogammaglobulinemia), which reduce the
synthesis of protective antibodies. OPV can also be transmitted to immunocompromised.

• Spread of OPV among humans also increases the chances of reversion to wild-type
• The risk of transmission of wild-type virus by IPV vaccinees decreases because few in the population remain susceptible with good herd immunity.
• Injectable vaccines can be combined with other injected childhood vaccines (5-in-1, or 6-in-1 vaccines) to reduce the overall number of injections and visits to the doctor

Question 32

osmosis

The nurse is preparing to describe the physiology of T lymphocytes to a nursing student. Which statement(s) should the nurse include? Select all that apply.
A. “Fragments of a pathogen that have been engulfed by antigen-presenting cells form a major histocompatibility complex class II on the antigen-presenting cell’s surface.”
B. “Once a naive T-helper cell is exposed to an antigen, it will recognize the antigen and release cytokines to enhance the immune response.”
C. “Perforin is an enzyme released by killer T cells causing pores to form in the cell membrane affected by an antigen.”
D. “Regulatory T cells specialize in eliminating cells in the body that have become abnormal.”
E. “When a cell is invaded by a virus, some of the virus is broken down and the fragments form an antibody-antigen complex.”
F. “Cytokines attract immune cells to the area of the pathogens and cause the blood vessel walls to become leaky.”

Answer 32

A, B, C, F
D wrong: killer T cells not regulatory!
E wrong: An antigen-antibody complex refers to an antibody bound to an antigen. When a virus invades a cell, some of the virus is broken down, and the fragments will be presented on the cell’s surface via major histocompatibility complex class II (MHC-II) proteins. This is then referred to as a histocompatibility complex.

Question 33

osmosis

The nurse reviewed the physiology of antibody production with a group of nursing students. Which student statement(s) indicate(s) an understanding of the teaching? Select all that apply.

A. “T helper cells activate B cells, which causes them to differentiate into malignant cells.”
B. “Central tolerance causes immature T cells in the thymus and B cells in the bone marrow to self-destruct if they react to any self-antigens.”
C. “T-cell receptors recognize antigens on the antigen-presenting cells and activate specific B cells.”
D. “After antigen-presenting cells engulf and digest pathogens, the fragments are presented on the cell’s surface via proteins.”
E. “When complement proteins encounter an antigen-antibody complex, the complement cascade is activated.”
F. “Undifferentiated hematopoietic stem cells in the bone marrow differentiate into various types of white blood cells.”

Answer 33

B, C, D, E, F

Question 34

osmosis

The nurse suspects the client is experiencing a type II hypersensitivity reaction. Which is the best description of this type of hypersensitivity reaction?
A. This reaction is mediated by immune-complexes
b. This reaction is mediated by antibodies that activate cellular cytotoxicity
c. This reaction is mediated by immunoglobulin E (IgE)
d. This reaction is mediated by T-cells

Answer 34

B
Type II hypersensitivity:
antibody-mediated autoimmune diseases
A wrong: type III
C wrong: IgE is for type I
D is type IV

Question 35

osmosis

Describe Type IV hypersensitivity reaction
A type IV hypersensitivity reaction occurs when ___ cells or
___cells overreact to exogenous or endogenous ___ and over proliferate. A ___ than normal immune response occurs if the antigen is encountered again. T helper cells will attract other immune cells like ___ and ___ to cause damage to the tissue where the antigen is found, while killer T cells will attack the cells of the tissue directly.

Answer 35

A type IV hypersensitivity reaction occurs when ✅ T helper cells or
✅killer T cells overreact to exogenous or endogenous ✅ antigens and over proliferate. A ✅ larger than normal immune response occurs if the antigen is encountered again. T helper cells will attract other immune cells like ✅Macrophages and ✅ neutrophils to cause damage to the tissue where the antigen is found, while killer T cells will attack the cells of the tissue directly.

Question 36

1. intro summary

• Immune system is a remarkably versatile defense system that has
  evolved to protect us from invading ___ microorganisms,
  c___ and other harmful substances.
• Major immune functions: r___, a___ and e___ mechanisms
• Immune system is organized into __ and __ immunity
• Collections of -__ with __ functions form
  organs (l__ n___, s__) that are critical for normal immune
  function
• The ___ produces various immune cells, which are
  specialized to defend against particular microbes
• Intercellular communication in the immune system is achieved
  using both s__* and __-___ factors

Answer 36

• Immune system is a remarkably versatile defense system that has
  evolved to protect us from invading pathogenic microorganisms,
  cancer and other harmful substances.
• Major immune functions: recognition, activation and effector
  functions
• Immune system is organized into innate and adaptive immunity
• Collections of immune cells with specialized function form
  organs (lymph nodes, spleen) that are critical for normal immune
  function
• The bone marrow produces various immune cells, which are
  specialized to defend against particular microbes
• Intercellular communication in the immune system is achieved
  using both soluble and membrane-bound factors

Question 37

2. innate adaptive summary

1. T cells express ___ that recognize antigen presented by ___

Answer 37

1. T cells express receptors (TCR) that recognize antigen presented by MHC molecules

Question 38

2. innate adaptive summary

2. Antigen is processed into ___

Answer 38

2. Antigen is processed into peptides

Question 39

2. innate adaptive summary

3. CD__ T cells recognize ___ peptide (from extracellular antigens)
4. CD_ T cells recognize *___ peptide (**intracellular **antigens)

Answer 39

3. CD4+ T cells recognize MHC II + peptide (from extracellular antigens)
4. CD8+ T cells recognize MHC I + peptide (**intracellular **antigens)

Question 40

2. innate adaptive summary

5. T cell activation into effector T cells requires signal 1 (___/___) and signal 2(costimulatory ___ and __-)

Answer 40

5. T cell activation into effector T cells requires signal 1 (peptide/MHC) and signal 2(costimulatory molecules and cytokines)

Question 41

2. innate adaptive summary

6. Effector functions of CD4+ T helper cells vs effector function of CD8+ T cells

Answer 41

6. Effector functions of CD4+ T helper cells: activation of other immune cells via production of cytokines;
   effector function of CD8+ T cells (cytotoxic cells): kill infected cells

Question 42

2. innate adaptive summary

7. B cells express ___ (surface Ig) that recognize ___ antigens

Answer 42

7. B cells express BCR (surface Ig) that recognize native antigens

Question 43

2. innate adaptive summary

8. Outcome of activation of B cells by T cell help (3)

Answer 43

8. Outcome of activation of B cells by T cell help: plasma cells, isotype switching and memory B cells

Question 44

2. innate adaptive summary

5 antibody types and functions:
** IgM, IgD, IgA, IgG, IgE**

Answer 44

9. 5 antibody isotypes:** IgM, IgD, IgA, IgG, IgE**
   IgG: neutralise microbes and toxins. antibody-dependent cellular toxicity. activate classical pathway of complement
   IgM: activate classical pathway of complement
   IgA: mucosal immunity
   IgE: mast cell degranulation. defence against parasites /helmiths

Question 45

2. innate adaptive summary

effector functions of antibodies (5)

Answer 45

10. Effector functions of antibodies: opsonisation, neutralization of microbe/toxin, antibody dependent cellular cytotoxicity, complement activation, mast cell degranulation

Question 46

3 vaccination summary points

Define immunization
It’s the deliberate provocation of a/an ___ immune response by introducing ___ in the body. It’s a procedure designed to increase concentrations of ___ and/or ___ cells which are reactive against infection

Answer 46

Immunization: receiving the vaccine and becoming immune to a disease as a result of being vaccinated.
It’s the deliberate provocation of an adaptive immune response by introducing antigen in the body. It’s a procedure designed to increase concentrations of antibodies and/or effector T-cells which are reactive against infection

confers active OR passive immunity

Question 47

3 vaccination summary points

Define vaccination

Answer 47

The administration of antigenic material

Question 48

What is an ideal vaccine? (3 points)
- To produce the ___ __ ___ which usually follows ___ infection but withour causing __
- To generate ___-___ immunity
- To interrupt ___ of ___

Answer 48

• To produce the same immune protection which usually follows natural infection but without causing disease
• To generate long-lasting immunity
• To interrupt spread of infection

Question 49

Immunological principles of vaccination:
1) Adaptive immunity established ___ infection
2) Immunity that is induced must be ___ and durable
enough in order to be clinically relevant, but induce ___ disease symptoms.
3) Immunological mechanisms of protection:

I. Protective ___
* major mechanism for protection by most current vaccines
* block infection and/or spread of infection

II. __ cell responses (Memory)
* ___- enhance antibody response and
formation of CTL memory
* ___- anti-viral immunity

vaccines contain double A:
1) ___: any protein, peptide, substance, etc., that
stimulates an immune response. Antigen is specific to the
pathogen of interest.
2) ___: a substance that enhances the immune response
to a weakly immunogenic antigen. Adjuvant is ___ to the pathogen. It can also allow ___ release of antigen to allow time for memory response to form

Answer 49

1) Adaptive immunity established before infection
2) Immunity that is induced must be robust and durable
enough in order to be clinically relevant, but induce little or
no disease symptoms.
3) Immunological mechanisms of protection:
I. Protective antibodies
* major mechanism for protection by most current vaccines
* block infection and/or spread of infection
II. T cell responses (Memory)
* CD4 helper T cells- enhance antibody response and
formation of CTL memory
* CD8 CTL- anti-viral immunity

Vaccines generally contain:
1) Antigen(s): any protein, peptide, substance, etc., that
stimulates an immune response. Antigen is specific to the
pathogen of interest.
2) Adjuvant: a substance that enhances the immune response to a weakly immunogenic antigen. Adjuvant is non-specific to
the pathogen. It can also allow slow release of antigen to allow time for memory response to form

Question 50

3 vaccination summary points

Aims of immunisation programmes:
1) To protect individuals at ___ ___ (selective immunisation strategy)
2) To reduce ___ and __ of cases in the population (mass immunisation strategy)
- Reduce risk of infection in population
- Reduce contact of susceptible to cases
- Lengthening of epidemic cycle -> eradication in the world/elimination from an area/control infections in an area

Answer 50

Aims of immunisation programmes
1) To protect individuals at high risk (selective immunisation strategy)
2) To reduce size and number of cases in the population (mass immunisation strategy)
- Reduce risk of infection in population
- Reduce contact of susceptible to cases
- Lengthening of epidemic cycle -> eradication in the world/elimination from an area/control infections in an area

Question 51

3 vaccination summary points

features of effective vaccines:
balance ___ and ____

Answer 51

balance of efficacy and safety:
* safe
* protective
* sustained protection
* induce neutralising antibody
* induce protective T cell
* practical considerations: low cost per dose, biological stability, ease of administration, few side effects)

Question 52

3 vaccination summary

Why Vaccinate?
* Prevent diseases
* 6 Disease Factors to consider
* Cost effective

Answer 52

• Prevent diseases
• Disease Factors to consider :
  – incidence (how common)
  – severity (how sick, hospitalization, deaths)
  – frequency of complications
  – any effective treatment
  – how long does protection last?
  – is it safe (short and long term)
• Cost effective?

Question 53

3 vaccination summary points

list 6 Different types of vaccines

Answer 53

1. Inactivated ( Killed) vaccines
2. Attenuated (Live) vaccines
3. Toxoids
4. Conjugated vaccines
5. Subunit vaccines
6. mRNA vaccines

Question 54

3 vaccination summary

Inactivated (Killed) vaccines:
* Inactivation through __ or ___ fixation
* Need multiple injections in initial course (___, ___ and tertiary immune response)
* Usually need b__
* May be ___ (ex: toxins from killed bacteria)
* Need for a___
* Cell mediated immunity -___
- examples? (5)

Answer 54

Inactivated (Killed) vaccines:
* Inactivation through heat or chemical fixation
* Need multiple injections in initial course (primary, secondary and tertiary immune response)
* Usually need boosters
* May be toxic (ex: toxins from killed bacteria)
* Need for adjuvant
* Cell mediated immunity -poor
Examples
* Cholera, plague, Influenza, Rabies, Polio (Salk)

Question 55

3 vaccination summary

Live (attenuated) vaccines:
* Attenuation: Passage of virulent human viruses in ___ host - influenza virus in ___ eggs

Examples (8)

Advantages:
* mimic ___ infection
* produce a large ___ stimulus
* generally induce ___ and ___ lymphocyte responses
* provide ___-___ protection

Disadvantages:
* may retain some ___
* may revert to ___
* may not be safe enough to vaccinate ___ subjects
* inadvertent transmission of vaccine strains to ___ __of vaccinees
* require a good ___ ___

Answer 55

Live (attenuated) vaccines:
* Attenuation: Passage of virulent human viruses in non human host - influenza virus in embryonic eggs

Examples
* Polio (oral vaccine, Sabin), Mumps, Measles and Rubella (MMR), Yellow fever, Chickenpox, BCG,Typhoid

Advantages:
* mimic natural infection
* produce a large antigenic stimulus
* generally induce T&B lymphocyte responses
* provide long‐lasting protection
Disadvantages:
* may retain some pathogenicity
* may revert to virulence
* may not be safe enough to vaccinate immunocompromised subjects
* inadvertent transmission of vaccine strains to susceptible contacts of vaccinees
* require a good cold chain

Question 56

3 vaccination summary

Toxoid - Inactivated ___:
* Toxoid: a chemically modified toxin from a ___ microorganism, which is no longer ___ but is still __ and can be used as a vaccine.
* ___ (a poisonous substance secreted by certain bacteria) inactivated, either by ___ or ___
* Intended to build immunity against the ___ and not the ___ that produce the toxins

Examples? (2)

Answer 56

Toxoid - Inactivated exotoxins:
* Toxoid: a chemically modified toxin from a pathogenic microorganism, which is no longer toxic but is still antigenic and can be used as a vaccine.
* Exotoxins (a poisonous substance secreted by certain bacteria) inactivated, either by heat or chemicals
* Intended to build immunity against the toxins and not the bacteria that produce the toxins

Examples:tetanus toxoid and diphtheria toxoid

Question 57

3 vaccination summary

Conjugated vaccines:
* Certain materials are not very ___ and require to be conjugated to a protein to be a good vaccine
* Examples (2): polysaccarides from ___ and ___ capsules

• Polysaccharides from ___
  – stimulated low levels of Ig__
  – no memory
  – when conjugated to tetanus toxoid - high titers of Ig___, protective

Answer 57

Conjugated vaccines:
* Certain materials are not very immunogenic and require to be conjugated to a protein to be a good vaccine
* Examples: Polysaccharides from Pneumococcus and meningococcal capsules
* Polysaccharides from Pneumococcus
– stimulated low levels of IgM
– no memory
– when conjugated to tetanus toxoid - high titers of IgG, protective

Question 58

3 vaccination summary points

Subunit vaccines:
- subunit= antigen is a ___ of pathogen
- example (1)

Advantages
*Cannot revert back to ___
*Safe for ___ patients
*Can withstand changes in conditions (e.g. ___-, ___, ___)

Disadvantages
*Reduced ___ compared to attenuated vaccines
*Require ___ to improve immunogenicity
*Often require multiple doses (___ doses) to provide long-term immunity
*Can be difficult to isolate the specific ___
*__

Answer 58

• antigen is a fragment of the pathogen.
• Example: hepatitis B vaccine (yeast vector)

Advantages
*Cannot revert back to virulence
*Safe for immunocompromised patients
*Can withstand changes in conditions (e.g. temperature, light exposure, humidity)

Disadvantages
*Reduced immunogenicity (ability of a foreign substance to provoke an immune response in the body) compared to attenuated vaccines
*Require adjuvants to improve immunogenicity
*Often require multiple doses (booster doses) to provide long-term immunity
*Can be difficult to isolate the specific antigen(s)
*Cost

Question 59

3 vaccination summary points

RNA vaccines:
-uses a copy of the ___ encoding the ___ of interest to produce an immune response.
-3 types:
a. non replicating mRNA (mRNA encoding antigen + ___)
b. in vivo self-replicating mRNA (mRNA encoding antigen + the viral RNA ___ ___)
c. in vitro (lab) dendritic cell non-replicating mRNA vaccines (__ cell transfected with mRNA encoding antigen)

Advantages:
*___: RNA vaccines are not made with pathogen particles or inactivated pathogen, so are ___. RNA does not integrate itself into the host genome and the RNA strand in the vaccine is ___ once the protein is made.
*___: vaccines can be produced more rapidly in the laboratory in a process that can be standardised

Disavantages:
* May elicit an ___ reaction. To minimise this the mRNA vaccine sequences are designed to mimic those produced by ___ cells.
* ___: free RNA in the body is quickly ___. Strategies: the RNA strand is incorporated into a ___ molecule to help ___ it and/or packaged into ___ or ___.
* Storage: need to be ___ or ___.

Answer 59

RNA vaccines:
-uses a copy of the mRNA encoding the antigen of interest to produce an immune response.
-3 types:
a. non replicating mRNA (mRNA encoding antigen + liposome)
b. in vivo self-replicating mRNA (mRNA encoding antigen + the viral RNA replication machinery)
c. in vitro dendritic cell non-replicating mRNA vaccines (DC transfected with mRNA encoding antigen)

Advantages:
*Safety: RNA vaccines are not made with pathogen particles or inactivated pathogen, so are non-infectious. RNA does not integrate itself into the host genome and the RNA strand in the vaccine is degraded once the protein is made.
*Production: vaccines can be produced more rapidly in the laboratory in a process
that can be standardised

Disavantages:
* May elicit an unintended immune reaction. To minimise this the mRNA vaccine sequences are designed to mimic those produced by mammalian cells.
* Delivery: free RNA in the body is quickly degraded. Strategies: the RNA strand is incorporated into a larger molecule to help stabilise it and/or packaged into particles or liposomes.
* Storage: need to be frozen or refrigerated.

Question 60

3 vaccination summary points

Role of adjuvant:
___ the recipient’s immune response
___ to pathogen
allows ___ release of antigen

Answer 60

Adjuvant - pharmacological or immunological agent that modifies the effect vaccine. They are often included to enhance the recipient’s immune response
(to a weakly immunogenic antigen).
Adjuvant is non-specific to the pathogen. It can also allow slow release of antigen to allow time for memory response to form

Question 61

3 vaccination summary points

Challenges faced by vaccines:
1. Vaccine responses at the extremes of __
2. Emerging & ___ infections
3. ___ variation
4. ___ & risk
5. ___to vaccines (antivaxxers)

Answer 61

challenges faced by vaccines:
1. Vaccine responses at the extremes of age
2. Emerging & re-emerging infections
3. Antigenic variation
4. Safety & risk
5. Opposition to vaccines

Question 62

Primary lymphoid organs (3)

Secondary lymphoid organs (3)

Answer 62

Primary lymphoid organs:
foetal liver
bone marrow (b cell hometown)
thymus (t cell hometown)

Secondary lymphoid organs:
Lymph nodes (eg tonsils)
* Spleen
* Mucosal lymphoid tissues