Host Defenses - Adaptive Immunity

Question 1

Define immunogen.

Answer 1

Substance that can elicit an immune response

Question 2

Define immunogenicity.

Answer 2

Ability of a substance to trigger an immune response

Question 3

Define antigen.

Answer 3

Substance that binds specifically to an antibody or a T-cell receptor (TCR)
- All immunogens are antigens, but not all antigens are immunogens

Question 4

Define antigenicity.

Answer 4

Ability of an antigen to trigger an immune response

Question 5

Describe the four factors that influence the immunogenicity of an immunogen.

Answer 5

1. Size
2. Complexity
3. Foreignness, the more distant in phylogeny, more immunogenic
4. Degradability

In descending order of immunogenicity
- Proteins > polysaccharides > lipids > nucleic acids

Question 6

Define intracellular bacterial pathogen and extracellular bacterial pathogen and give one
example for each type.

Answer 6

• Intracellular bacterial pathogen: lives and replicates inside host cells (L. monocytogenes)
• Extracellular bacterial pathogen: lives and replicates outside host cells (S. aureus)

Question 7

Use Fig. 7.7 to describe the MHC class II antigen-presentation pathway for extracellular or
exogenous antigens.

Answer 7

1. APCs phagocytose or
   macropinocytose microbes and engulf them within phagosomes
2. Phagosomes fuse with lysosomes to form a phagolysosome for degradation of the microbial material into peptides
3. Vesicles containing the MHC-II-invariant chain complex bud
   off from the ER to fuse with the peptide-containing phagolysosome
4. The invariant chain disintegrates within the acidic environment, allowing the peptide to load into the
   vacated peptide-binding groove of the MHC class II molecule
5. Exocytotic vesicles containing pMHC-II are transported to the cell surface for display and recognition by the TCRs of CD4+ T cells

Question 8

Use Fig. 7.7 to describe the MHC class I antigen-presentation pathway for intracellular or endogenous antigens.

Answer 8

1. Ubiquitin covalently attaches to cytoplasmic proteins, marking them for enzymatic degradation by the proteasome
2. Proteolytic peptide fragments are transported into the endoplasmic
   reticulum by a heterodimer composed TAP-1 or TAP-2 for possible loading into nascent MHC-I complexes
3. Exocytotic vesicles containing
   pMHC-I are transported to the cell surface for display and recognition by the TCRs of CD8+ T cells

Question 9

Use Fig. 7.15 to describe immunologic memory and explain why a subsequent immune
response to the same pathogen/antigen occurs faster and is more robust.

Answer 9

• Immunologic memory: ability of the adaptive immune system to recall a previous encounter with a microbe and mount an accelerated, enhanced response against it
• Subsequent immune response is faster/more robust because a reservoir of memory B cells is maintained in the bone marrow (immune system doesn’t have to go through the process of producing antibodies again)

Question 10

Use Fig. 7.15 to describe what may happen to a previously established immunologic memory for a specific antigen when the antigen has changed its structure.

Answer 10

The previously established immunologic memory wouldn’t be useful
- Immune system would have to go through a primary response again.

Question 11

Use Fig. 7.1 and Table 7.2 as a guide to draw a typical IgG antibody molecule with the major components labeled and to assign one function to the variable region, the Fab fragment, and the Fc fragment.

Answer 11

Question 12

Define epitope.

Answer 12

Smallest molecular structure recognized by an antibody or a specific receptor

Question 13

Define binding specificity.

Answer 13

Ability to discriminate different epitopes

Question 14

Explain the significance of the variable regions and the constant regions found in antibodies.

Answer 14

• Variable regions only interact with their epitope (recognize different epitopes)
• Constant regions activate the complement system

Question 15

List the five classes of antibodies (Table 7.2).

Answer 15

1. IgM
2. IgG
3. IgA
4. IgD
5. IgE

Question 16

Use Fig. 7.12 to describe the five antibody-mediated host defenses against bacterial infection.

Answer 16

A. Agglutination: Recognition of microbial surface epitopes by antibodies causes a cross-linked lattice formation analogous to the equivalence zone of the quantitative precipitin curve
B. Neutralization: Neutralizing antibodies usually recognize microbial epitopes that would normally interact with molecules on the surface of the host cell and prevent such interaction.
C. Antibody binding to microbial epitopes causes a conformational changes in the Fc portion of the antibody molecule –> FcR recognize and bind –> phagocytosis
D. Complement activation: Antibody binding to a microbial surface may initiate the classical pathway of complement activation and trigger complement-mediated lysis and/or the binding of C3b as an opsonin
E. Antibody binding to microbial epitopes causes a conformational alteration in the Fc portion of the antibody molecule –> FcR recognize and bind –> complex triggers NK cells to release perforins and granzymes

Question 17

Explain whether antibody-mediated defense would be effective against intracellular bacterial
pathogens.

Answer 17

No, because antibodies don’t have access to intracellular bacterial pathogens

Question 18

Use Fig. 7.13 to describe the steps in the activation of macrophages by CD4+ Th1 cells for
killing intracellular bacteria.

Answer 18

1. Previously activated CD4+ Th1 cells become reactivated upon recognition of antigens in the context of pMHC class II on APCs (phagocytes)
2. Reactivated Th1 cells secrete cytokines and chemokines that increase MHC class II expression, degradative enzymes, and reactive oxygen species in macrophages
3. The activated macrophage has increased killing capacity and destroys everything that comes within its “grasp.”

Question 19

Explain why activation of macrophages as shown in Fig. 7.13 can be a double-edged sword.

Answer 19

Because the activated macrophages are not “antigen specific,” they can destroy normal tissue along with infected cells

Question 20

Use Fig. 7.14 to describe how cytotoxic T cells attack and kill intracellular bacteria.

Answer 20

1. Activated CD8+ T cells circulate through body tissues as CTLs, scrutinizing the pMHC class I molecules displayed by nucleated cells
2. On recognition of the appropriate pMHC class I complex, a series of events are initiated by the CTL that ultimately leads to the lysis of the infected “target cell.” Although contact between the CTL and the target cell lasts only a few minutes, the CTL delivers a fatal “kiss of death” to the target cell in the form of perforin granules and granzymes.
3. The perforin granules polymerize and form pores in the cell, creating an electrolyte imbalance, and through which granzymes enter. Both perforins and granzymes conspire in the demise of the target cell by osmotic lysis and apoptosis, respectively.

Question 21

Define mucosal immunity.

Answer 21

Immune responses at the level of mucosal surfaces, usually involving
antibodies (ex. secretory IgA)

Question 22

Define mucosa-associated lymphoid tissue (MALT) and give one specific example.

Answer 22

Networks of lymphocytes and dendritic cells deployed under mucosal surfaces and in tissue-specific lymphoid collections (ex. tonsils, Peyer’s patch)

Question 23

Describe steps in an IgA response to bacterial colonization of the gastrointestinal mucosal
surfaces.

Answer 23

1. Secretion, sIgA
   - Dimeric or polymeric
   - Secretory components
   - Receptors (poly-Ig) on basolateral membranes of epithelial cells
   - Endocytosis and exocytosis to the luminal space (transcytosis)
2. Distribution
   - Mainly in external secretions
   - Breast milk, saliva, tears, and mucus

Question 24

Describe how secretory IgA (sIgA) contributes to the defense of mucosal surfaces against bacterial infection.

Answer 24

sIgA binds to bacteria and prevents them from attaching to mucosal epithelial cells

Question 25

Describe the function of M-cells found in gastrointestinal-associated lymphoid tissue (GALT).

Answer 25

• Sample cells/antigens at the luminal membrane
• Transport them to lymphocytes and macrophages in the lamina propria

Question 26

Describe, step by step, how you would experimentally determine the relative importance of humoral immunity and cellular immunity in host defense against an extracellular bacterial pathogen or an intracellular bacterial pathogen.

Answer 26

1. Get serum from surviving mice
2. Inject serum into one group of mice
3. Infect both groups with the pathogen
4. Serum group should survive

Question 27

Give three examples to illustrate how innate and adaptive defenses work together to clear microbial infection and explain how such a cooperation enhances host resistance (See Table 6.10, Figs. 6.3, 6.5, 7.12).

Answer 27

1. Opsonophagocytosis: antibodies (adaptive) and phagocytes (innate)
2. ADCC: antibody-dependent cell cytotoxicity (macrophages, NK cells, eosinophils)
3. Innate immunity initiates adaptive immune respones

Question 28

Reading assignment: Describe the role of natural IgM in complement activation by S. pneumoniae strain D39 (Fig. 2A).

Answer 28

IgM mediates C3 binding to S. pneumoniae

Question 29

Reading assignment: Describe the role of natural IgM in host resistance to S. pneumoniae infection (Fig. 2B).

Answer 29

IgM increases host resistance to S. pneumoniae