AMERICAN LANGUAGE HUB_Level2_Student'sBook_Answerkey.pdf
Immune Responses To Infectious Disease
1. The Immune Responses to
Infectious Disease
徐北辰
陽明大學醫學院醫學士
中山醫學大學免疫學研究所理學碩士
中興大學生命科學系博士班肄業
前台中榮總過敏免疫風濕科主治醫師
苗栗大千綜合醫院過敏免疫風濕科主治醫師兼內科部主任
仁德醫護管理專科學校兼任講師
950616
2. Three Levels of Defense
Epithelial surface barriers: Clearance and
nonspecific host defenses at skin and mucosal
surfaces
Epithelial barriers
Antibacterial factors (fatty acids, antibactericidal
peptides, lysozymes, phospholipase A2)
Mucociliary activity
Normal flora
Adherence blocking molecules
The innate immune responses
The acquired immune responses
3. The Immune Systems
An organization of cells and molecules with specialized
roles in defending against infection.
The innate immune responses
The acquired immune responses
Innate and acquired responses usually work together to
eliminate pathogens.
Immunobiology Fig. 2.1
4. The innate immune responses
occur to the same extent
No changes after infection
Lack immunologic memory
The cellular components
phagocytic cells: neutrophils, monocytes, and macrophages
cells that release inflammatory mediators: basophils, mast cells,
and eosinophils
natural killer cells
The molecular components
Complement
acute-phase proteins
cytokines such as the interferons.
Specialized cells, called antigen-presenting cells
Macrophage, dendritic cells, B-cells
display the antigen to lymphocytes
To generate the adaptive immune response
5. Macrophages
Derived from blood-borne monocytes
Immune Recognition: discriminate between
“foreign” and “self ” molecules.
Receptors for carbohydrates : such as
mannose
Toll-like receptors
Receptors for antibodies and complement
the coating of microorganisms
enhances phagocytosis.
Phagocytosis
The engulfed microorganisms toxic
intracellular molecules, including superoxide
anion, hydroxyl radicals, hypochlorous acid,
nitric oxide, antimicrobial cationic proteins
and peptides, and lysozyme.
remove the body’s own dead or dying cells.
Figure 2.5.
6. Toll-like Receptors (TLR)
A mammalian homologue of the
drosophila Toll , identified in 1997
TLR family
11 members in humans
A leucine-rich repeat (LRR) domain in
extracelluar domain
A Toll/IL-1 receptor (TIR) domain in
intracellular domain
8. Signalling
pathways by TLRs
in vertebrates &
Drosophila.
Toll-like receptors in the induction of the innate immune response
Alan Aderem & Richard J. Ulevitch
NATURE | 2000 | VOL 406 | 782-787
9. NF-κB activation
pathways
NF-κB family, I-κB
family, IKK complex,
Signaling components
A key player in
controlling both innate
and adaptive immunity
Nature Reviews: Immunology,
Volume 2, October 2002, pp725-734
10. NF-κB proteins TD: C-terminal non-homologous
transactivation domain strongly
RHD: structurally conserved N-terminal Rel-
activate transcription from NFκB-
homology domain : dimerization, nuclear-
binding sites in target genes
localization (N) and DNA binding domains
(p65)
ANK: Ankyrin
Leucine- RELB: no homodimer repeats: protein-
zipper
protein
motif(LZ) interaction
GRR: glycine-
(NF-κB1)
P50 homodimer: rich region
transcriptional
repressor Required for
(NF-κB2)
processing
Main activated form of NFκB: heterodimer of p65 and (p50 or p52)
Transcription of RELB, c-REL and p105: regulated by NF κB
Nature Reviews: Immunology, Volume 2, October 2002, pp725-734
11. IκB Proteins
Ankyrin repeats: 33-amino-acid motif: protein-protein interaction
IκB retain NFκB in the cytoplasm By masking NLSs on NFκB subunits
IκBα:Nuclear-export signal(NES) at N terminus (also IκBε, but not IκBβ)
IκBα:degraded rapidly; NFκB response element in its promoter; intrinsic NLS;
displace NFκB from DNA binding sites; NES post-induction
repression of NFκB function
IκBβ:less sensitive to degradation; not NFκB inducible; no NES; not displace
NFκB from DNA binding sites
Nature Reviews: Immunology, Volume 2, October 2002, pp725-734
12. A model of how NF-κB
phosphorylation regulates
its transactivation
function
Nature Reviews: Immunology,
Volume 2, October 2002, pp725-734
14. Granulocytes
(polymorphonuclear leukocytes, PMN)
Neutrophils
Phagocytic cell
Most numerous and most important cellular
component of innate immune response
Eosinophils
only weakly phagocytic
kill parasites mainly by releasing cationic proteins
and reactive oxygen metabolites into the
extracellular fluid.
secrete leukotrienes, prostaglandins, and various
cytokines.
15. Granulocytes
(polymorphonuclear leukocytes, PMN)
Basophils and mast cells
possess high-affinity receptors for IgE (FcεR)
become coated with IgE antibodies.
secrete inflammatory mediators such as
histamine, prostaglandins, and leukotrienes.
important in atopic allergies such as eczema,
hay fever, and asthma, in which allergen
binding to the IgE cross-links the FcεR.
16. Interferons are antiviral proteins produced
by cells in response to viral infection
Interferons α andβ
induce resistance to viral replication in
uninfected cells by activating genes that cause
the destruction of mRNA and inhibit the
translation of viral and some host proteins.
induce MHC class I expression enhancing
their resistance to NK cells;
induce increased synthesis of MHC class I
molecules in cells that are newly infected by
virus more susceptible to killing by CD8
cytotoxic T cells
activate NK cells, which then kill virus-infected
cells selectively.
17. Erythrocytes and Platelets
Have complement receptors
Play an important part in the clearance of
immune complexes consisting of antigen,
antibody, and components of the
complement system.
18. Natural killer cells
destroy infected and malignant cells.
recognize their targets in one of two ways.
Killer-activating receptors and killer-inhibitory
receptors
Fc receptors that bind IgG (FcγR) IgG-
coated target cells: antibody-dependent
cellular cytotoxicity.
19. A System Used by Natural Killer Cells to Recognize Normal
Cells and Cells That Lack Major-Histocompatibility
Complex Class I Surface Molecules
NEJM, 2000, 343(1), p37
20.
21. interdigitating dendritic cell
Cells of this type, which include
Langerhans’ cells in skin, constantly but
quietly endocytose extracellular antigens.
Pattern-recognition receptors on dendritic
cells
the lipopolysaccharide receptor,
the mannose receptor
Toll-like receptor
22. MHC molecules
class I : HLA-A, B, and C
class II : HLA-DP, DQ, and DR
present the peptides to the T-cell receptor on
the surface of helper T cells.
Dendritic cells are particularly efficient at
initiating (priming) immune responses :
activate so called naive T cells
23. Activated dendritic cells
up-regulate the expression of B7 costimulatory
molecules
provide the signals necessary for lymphocyte
activation in addition to those provided through the
antigen receptor.
Activated dendritic cells migrate to the local
draining lymph node,
The antigen is processed intracellularly into
short peptides by means of proteolytic cleavage
before it is presented by major-
histocompatibility-complex (MHC) molecules on
the surface of dendritic cells.
25. Soluble Factors in Innate Defense
Complement
Acute-phase proteins
Cytokines
26. Complement
first identified as a heat-labile principle in
serum that “complemented” antibodies in
the killing of bacteria.
a system of more than 30 proteins in
plasma and on cell surfaces.
Complement proteins > 3g/L in plasma
15 % of the globulin fraction.
The nomenclature of complement follows
the historical order of discovery of the
proteins
30. Acute Phase Proteins
enhance resistance to infection
promote the repair of damaged tissue
Plasma levels change rapidly in response to infection,
inflammation, and tissue injury.
C-reactive protein Clinical Use
serum amyloid A protein
Mannan-binding lectin ESR
CRP
proteinase inhibitors
coagulation proteins
fibrinogen
31. C-reactive protein
A member of the pentraxin protein family
A multipronged pathogen-recognition
molecule
Binds to the phosphorylcholine portion of
certain bacterial and fungal cell-wall
lipopolysaccharides
Opsonize pathogen
Activate the complement cascade by
binding to C1q
32. Cytokines
act as messengers both within the immune system and
between the immune system and other systems of the
body, forming an integrated network that is highly
involved in the regulation of immune responses.
35. Figure 2.37. The release of
TNF-α by macrophages
induces local protective
effects, but TNF-α can have
damaging effects when
released systemically.
36. The acquired immune responses
Improve on repeated exposure to a given infection.
The proliferation of antigen-specific B and T cells
occurs when the surface receptors of these cells bind to antigen.
B cells
secrete immunoglobulins, the antigen-specific antibodies
responsible for eliminating extracellular microorganisms.
T cells
help B cells to make antibody
eradicate intracellular pathogens by activating macrophages and
by killing virally infected cells.
42. Langerhans' cells can take up
antigen in the skin and migrate to
lymphoid organs where they
present it to T cells
Antigen-presenting cells
Initiate Adaptive Immune
Responses
45. Figure 8.29. The polarization of T cells during specific
antigen recognition allows effector molecules to be
focused on the antigen-bearing target cell
microtubule-
organizing
center
(MTOC)
46. Figure 8.36. Cytotoxic effector proteins
released by cytotoxic T cells
Figure 8.37. Perforin released from the
lytic granules of cytotoxic T cells can
insert into the target cell membrane to
form pores
47. Figure 8.42. The immune response to
intracellular bacteria is coordinated by
activated TH1 cells
48. An Overview of Lymphocyte Responses.
NEJM, 2000, 343(2), p109
49. Role of Antibodies
NEJM, 2000, 343(1), p37
IgA antibody-dependent cellular cytotoxicity.
