1

Chapter 46
Animal Defenses Against Infections

Chuang Chih-Hung (莊智弘)

Department of Medical Laboratory

Science and Biotechnology (醫技系)

Office: CS604
TEL: 07-3121101 #2351
Lecture Presentation by
Nicole Tunbridge and
Mail: a4132600@gmail.com
Kathleen Fitzpatrick
 Basic immunology Innate immunity
警察系統
海防系統 N K Ce ll

Physical barriers MO WBC

Complement
system

Antigen 傳令兵 Lymphotic

presenting cell system

MHC class II MHC class I 國防系統

Ag Ag
CD4 CD8
Y
Y
Th
Tc 坦克車 Perferin
B cell Y Y /Grazyme
Y Cytotoxic
Helper
T-cells (CD8)
T-cells(CD4)
導彈系統
後勤司令
Humoral immunity Cellular immunity Touch-killing
 Cytotoxic T lymphocytes (Tc cells) 右先鋒

MHC class I Infected &

Ag Cancer cell

口水獸
B lymphocytes (B cells) 左先鋒

Pathogen

WBC

對特定抗原具專一性
然後產生抗體,來抓取抗原
 Types of pathogens
 Pathogens, agents that cause disease, infect
a wide range of animals, including humans
• Bacteria
– Major entry points through direct bodily contact, open
wounds, inhalation, and ingestion
• Viruses
– Nucleic acids enclosed in a protein coat
– Must infect host cell to replicate
– May kill host cell rapidly or lie dormant for a period
– May cause cancer
• Eukaryotic parasites
– Protists, fungi, worms
– Damage host by using host nutrients or secreting toxic
chemicals 5
Recognition and Response
 The immune system recognizes foreign bodies
and responds with the production of immune cells
and proteins
 All animals have innate immunity, a defense
active immediately upon infection
 Vertebrates also have adaptive immunity

© 2014 Pearson Education, Inc.

 Pathogens
Overview of animal Immunity (such as bacteria,
fungi, and viruses)

INNATE IMMUNITY Barrier defenses:

(all animals) Skin
• Recognition of traits Mucous membranes
shared by broad Secretions
ranges of pathogens, Internal defenses:
using a small set of Phagocytic cells
receptors Natural killer cells
• Rapid response Antimicrobial proteins
Inflammatory response

ADAPTIVE IMMUNITY Humoral response:

(vertebrates only) Antibodies defend against
• Recognition of traits infection in body fluids.
specific to particular
pathogens, using a Cell-mediated response:
vast array of receptors Cytotoxic cells defend
against infection in body
• Slower response cells.
© 2014 Pearson Education, Inc.
 Overview of animal Immunity
 Innate immunity is present before any exposure
to pathogens and is effective from the time of birth
 It responds to a broad range of pathogens

 Adaptive immunity, or acquired immunity,

develops after exposure to agents such as
microbes, toxins, or other foreign substances
 It involves a very specific response to pathogens

© 2014 Pearson Education, Inc.

Concept 47.1: In innate immunity, recognition
and response rely on traits common to groups
of pathogens
 Innate immunity is found in all animals and plants
 In vertebrates, innate immunity is a first response
to infections and also serves as the foundation of
adaptive immunity

© 2014 Pearson Education, Inc.

Innate Immunity of Invertebrates
 Innate defenses of Invertebrates include barrier defenses,
phagocytosis, antimicrobial peptides
 In insects, an exoskeleton made of chitin forms the first
barrier to pathogens
 The digestive system is protected by a chitin-based barrier
and lysozyme, an enzyme that breaks down bacterial cell
walls
 Hemocytes circulate within hemolymph and carry out
phagocytosis, the ingestion and digestion of foreign
substances including bacteria
 Insects also have defenses against viruses, based on
recognition of double-stranded RNA
© 2014 Pearson Education, Inc.
Figure 47.3
1 Pseudopodia surround pathogens.
Pathogen

2 Pathogens engulfed by endocytosis.

PHAGOCYTIC
CELL
3 Vacuole forms.
Lysosome
Vacuole containing
enzymes
4 Vacuole and lysosome fuse.

5 Pathogens destroyed.

6 Debris from pathogens released.

© 2014 Pearson Education, Inc.

  Hemocytes also secrete antimicrobial peptides
that disrupt the plasma membranes of fungi and
bacteria
 The immune system recognizes bacteria and fungi
by structures on their cell walls
 Innate immune responses are distinct for different
classes of pathogens (Toll receptor)

antimicrobial
peptides-GFP

© 2014 Pearson Education, Inc.

 100 Wild type

% survival
75
Mutant + drosomycin
50
Mutant Mutant + defensin
25

0
0 24
48 72 96 120
Hours post-infection
Fruit fly survival after infection by N. crassa fungi

100
Wild type Mutant +
% survival

75
defensin
50
Mutant + Mutant
25 drosomycin

0
0 24
48 72 96 120
Hours post-infection
Fruit fly survival after infection by M. luteus bacteria
© 2014 Pearson Education, Inc.
Insects also have defenses against viruses, based on recognition of
double-stranded RNA
Double-stranded viral RNA

Viral infection Host defense 1 Dicer-2

RNA virus enzyme
HOST CELL

Single-stranded Argo
Viral RNA 2
viral mRNA protein
genome complex

HOST CELL

© 2014 Pearson Education, Inc.

Innate Immunity of Vertebrates

 The immune system of mammals is the best

understood of the vertebrates
 Innate defenses include barrier defenses,
phagocytosis, antimicrobial peptides
 Additional defenses unique to vertebrates are
natural killer cells, interferons, and the
inflammatory response

© 2014 Pearson Education, Inc.

Overview of animal
Immunity
• Body surface-Barrier Defenses
– Initial line of defense

– Skin glands secrete antimicrobial molecules (mild acids and

enzymes) (Prevent colonization)
– Skin, Saliva, tears, and mucous secretions (lysozyme/cell wall)

– Mucus is sticky to trap invaders and antimicrobial

– The low pH of skin and the digestive system prevents growth of

many bacteria

– Stomach acids destroy invader highly acidic environments

17
Overview of animal immunity
 Cellular Innate Defenses
• Pathogens entering the mammalian body are
subject to phagocytosis
• Phagocytic cells recognize groups of
pathogens using TLRs, Toll-like receptors
• TLRs recognize fragments of molecules
characteristic of a set of pathogens
 Phagocytic Cells
• Pathogens entering the mammalian body are
subject to phagocytosis
Neutrophils ( 60%-70% WBC)
Engulfing and destroying microbes there self-destruct as they
destroy foreign invaders,

Monocytes, about 5%
into tissues and develop into macrophages

Macrophage
 Eosinophils, about 1.5% (low phagocytic activity)

Contribute to defense against large parasitic invaders

Mast cells release histamine

Dendritic cells
Stimulate the development of acquired immunity.

• Natural killer (NK) cells

Attack virus-infected body cells and cancer cells
Trigger apoptosis in the cells they attack
 Antimicrobial Proteins
• About 30 proteins make up the complement
system
– Which can cause lysis of invading cells (membrane
attack complex (MAC) and help trigger
inflammation

• Interferons
– Provide innate defense against viruses and help
activate macrophages
– Inhibits viral replication inside host cells
 Cellular Innate Defenses
• Groups of pathogens are recognized by TLR, Toll-like receptors
EXTRACELLULAR Lipopolysaccharide
FLUID
Helper
protein Flagellin
TLR4

PHAGOCYTIC CELL
TLR5

Cellular TLR?
CpG
DNA

TLR9
VESICLE Innate immune
responses

dsRNA
TLR3
 Cellular Innate Defenses
• Groups of pathogens are recognized by TLR, Toll-like receptors
Inflammatory response
Redness, swelling, Heat , Pain.

Pathogen Splinter

Movement
of fluid

Signaling Macro-
Mast molecules phage
cell
Capillary Phagocytosis

Red blood cells

Neutrophil

1 Histamines and cytokines 2 Antimicrobial 3 Neutrophils

released. Capillaries dilate. peptides enter tissue. digest pathogens
Neutrophils are and cell debris.
recruited. Tissue heals.
Overview of animal immunity
 Basic immunology Innate immunity
警察系統
海防系統 N K Ce ll

Physical barriers MO WBC

Complement
system

Antigen 傳令兵 Lymphotic

presenting cell system

MHC class II MHC class I 國防系統

Ag Ag
CD4 CD8
Y
Y
Th
Tc 坦克車 Perferin
B cell Y Y /Grazyme
Y Cytotoxic
Helper
T-cells (CD8)
T-cells(CD4)
導彈系統
後勤司令
Humoral immunity Cellular immunity Touch-killing
The lymphatic system: Plays an active role in defending the body from
pathogens Blood
Interstitial fluid
capillary
Adenoid
Tonsils

Lymphatic
vessels
Thymus
Tissue Lymphatic
cells vessel
Lymphatic
Peyer’s Spleen vessel
patches
(in small
intestine) Lymph
nodes
Appendix
(cecum)

Lymph
node Masses of
defensive cells
 The Immune Response Features a Specialized Array of
Cells and Proteins

歐亞書局
• Lymphocytes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

B cells:
Fig. 53.4
Differentiate into plasma cells.

Plasma cells: Secrete antibodies.

Lymphocytes

Cytotoxic T cells:
Attack and kill virus-infected cells,
cancerous cells, and transplanted cells.

Helper T cells:
Assist in the function of B cells and cytotoxic T cells.

Natural killer cells:

Similar to T cells but perform many
nonspecific actions as well.
 3 stages of acquired immune response
HUMORAL CELL-MEDIATED
IMMUNE RESPONSE IMMUNE RESPONSE
1 Encounter and
Antigen
recognize a specific
Antigen
B cell Helper T cell Cytotoxic T cell
遭遇-敵我辨識

2 Lymphocyte activation
and cell division +
(Cytokines) (Cytokines) +
動員-衡山指揮所

Plasma cells Memory B cells Memory T cells Cytotoxic T cells

(effector cells) (effector cells)

Secrete antibodies Directly attack

3 Attack against the that bind to antigens antigen-bearing cells
specific antigen
打擊並記錄
 Antigen Recognition by Lymphocytes
Lymphocytes: B (B cells) and T lymphocytes (T cells).
B or T lymphocyte: 100,000 receptors (same specificity)
a type of genetic recombination

•B cell receptors T cell receptor

Antigen-
Antigen- Antigen- Binding site
Binding
YY
binding site
Disulfide
YY
site
bridge Variable
Light Variable regions
Plasma chain regions
cell Constant
C C regions
Constant
Transmembrane
regions
region

Plasma b chain
membrane a chain
Heavy chains
Disulfide bridge
B cell Cytoplasm of B cell T cell
Cytoplasm of T cell
 Recognition by B cell (BCR)
Antibody binding site: Epitopes
A lymphocyte actually recognizes and binds
To just a small, accessible portion of the antigen called an epitope
 Specific antigen
Antigen binding sites
Antigen

Hinge
Light regions Variable
chain
region
Disulfide
Plasma bond
membrane Constant
of B cell Transmembrane Heavy chain region
domain Fc region

Cytosol
(a) B-cell receptor (b) Secreted antibody

 Variable region – varies among different B cells – specifically

recognizes antigen
• Constant region – Fc domain 34
identical for given class
 Antigen
receptor Antibody

B cell

Antigen Epitope

Pathogen
(a) B cell antigen receptors and antibodies

Antibody C
Antibody A
Antibody B

Antigen

(b) Antigen receptor specificity

The five classes of Immunoglobins/Antibodies.
Class of Immuno-
Distribution Function
globulin (Antibody)

IgM First Ig class Promotes neutraliza-

(pentamer) produced after tion and cross-
initial exposure to linking of antigens;
antigen; then its very effective in
concentration in complement system
the blood declines activation
J chain

Promotes opsoniza-
IgG Most abundant Ig tion, neutralization,
(monomer) class in blood; and cross-linking of
also present in antigens; less effec-
tissue fluids tive in activation of
complement system
than IgM
Only Ig class that
crosses placenta,
thus conferring
passive immunity
on fetus
 Provides localized
IgA Present in defense of mucous
(dimer) secretions such membranes by
as tears, saliva, cross-linking and
J chain mucus, and neutralization of
breast milk antigens
Presence in breast
milk confers
Secretory passive immunity
component on nursing infant
IgE Present in blood Triggers release from
(monomer) at low concen- mast cells and
trations basophils of hista-
mine and other
chemicals that cause
allergic reactions
IgD Present primarily Acts as antigen
(monomer) on surface of receptor in the
B cells that have antigen-stimulated
not been exposed proliferation and
Trans- to antigens differentiation of
membrane B cells (clonal
region selection)
• Immunoglobulin gene rearrangement
The mechanism of Ab diversity
 How to induce the specific immunity
Clonal selection B lymphocytes (B cells) and T lymphocytes (T cells).

Specificity

Memory cells
無敵鐵金剛
無敵鐵金剛
(戰鬥型）
(潛伏型）

T cell same as this model

• Antibody-mediated mechanisms of antigen disposal

Macrophage
Antibody Function
Figure 43.19
 Memory immune response
Naive B or T cells
Y Antigens

Antigen presenting
7 days cells
(10 to 17 days)
(戰鬥型）
Effector cells
(short-lived ) Y Y Y

Memory cells
After clean <1 days (long-lived )
pathogens
(潛伏型）
Death
Apoptosis
The specificity of Immunological memory

Greater affinity for the antigen

Proliferate and differentiate rapidly
Animation: Role of B Cells

© 2014 Pearson Education, Inc.

Concept 47.3: Adaptive immunity defends
against infection of body fluids and body cells
 The defenses provided by B and T lymphocytes
can be divided into humoral immune response and
the cell-mediated immune response
 In the humoral immune response antibodies
help neutralize or eliminate toxins and pathogens
in the blood and lymph
 In the cell-mediated immune response
specialized T cells destroy affected host cells

© 2014 Pearson Education, Inc.

 Basic immunology Innate immunity
警察系統
海防系統 N K Ce ll

Physical barriers MO WBC

Complement
system

Antigen 傳令兵 Lymphotic

presenting cell system

MHC class II MHC class I 國防系統

Ag Ag
CD4 CD8
Y
Y
Th
Tc 坦克車 Perferin
B cell Y Y /Grazyme
Y Cytotoxic
Helper
T-cells (CD8)
T-cells(CD4)
導彈系統
後勤司令
Humoral immunity Cellular immunity Touch-killing
Fig. 43-11

Recognition by T cell (TCR)

MHC + peptide (Antigen)
Top view: binding surface
exposed to antigen receptors
Major histocompatibility
complex (MHC).

Antigen
Class I MHC Antigen
molecule

Plasma
membrane of
infected cell
Displayed
antigen T cell
fragment
T cell antigen
MHC
receptor
molecule

Antigen
fragment

Pathogen

Host cell
(a) Antigen recognition by a T cell

Top view

Antigen
fragment
MHC
molecule
Host cell

(b) A closer look at antigen presentation

 The killing action of cytotoxic T cells
Infected or abnormal cells Perforin: protein forms pores

CD8

TCR

The TC cells kills other cells infected with the same pathogen
The killing of virus-infected cells by cytotoxic T cells
Virus-infected cell Macrophage
Viral antigen
Class II MHC protein
Class I MHC protein Virus IL-1
Viral antigen TNF
CD8
T-cell receptor Helper
Cytotoxic T cell CD4 T cell

Activation and
IL-2 and
proliferation
Other cytokines

Perforin Perforin Perforin Channels

Water
Infected cells 52
Animation: Cytotoxic T Cells

© 2014 Pearson Education, Inc.

 Basic immunology Innate immunity
警察系統
海防系統 N K Ce ll

Physical barriers MO WBC

Complement
system

Antigen 傳令兵 Lymphotic

presenting cell system

MHC class II MHC class I 國防系統

Ag Ag
CD4 CD8
Y
Y
Th
Tc 坦克車 Perferin
B cell Y Y /Grazyme
Y Cytotoxic
Helper
T-cells (CD8)
T-cells(CD4)
導彈系統
後勤司令
Humoral immunity Cellular immunity Touch-killing
Self is distinguished from nonself by the display of peptides
on cell surfaces
MHC (major histocompatibility complex) proteins (呈現抗給T細胞)
Class I MHC
Bind and display peptides derived from cellular proteins.
Recognition targets of the T-cell receptors of the TC cells.
Class II MHC
Occur on the surfaces of macrophages and B lymphocytes. Bind
and display peptides derived from external proteins. Recognition
targets of the T-cell receptors of the TH cells.
T cell receptor and antigen presentation

56
The central role of helper T cells
humoral and cell-mediated immune responses

Plasma cells Active killers.

B cell activation in the humoral immune response

2000Abs/sec
Animation: Helper T Cells

© 2014 Pearson Education, Inc.

 Immunity in Health and Disease
Abnormal immune function can lead to disease
Allergy:
Mast cell & IgE & allergic response

degranulate
 AIDS is an immunodeficiency disease
caused by a virus

Acquired immunodeficiency syndrome

(loss of humoral and cell-mediated immunity)

People with AIDS are susceptible to opportunistic diseases

Basic immunology Innate immunity
警察系統
海防系統 NK c e l l
Physical barriers
MO WBC

Lymph
Antigen presenting cell node
國防系統
MHC class II MHC class I
Ag Ag

Y
Y Tc
Th
HIV Touch-killing
B cell Y Y 口水獸
Y Helper Cytotoxic
T-cells T-cells
無敵鐵金剛
後勤司令
•CD4 functions as the major receptor for the virus.
The stages of HIV infection
 65

Thank you very much

Chuang Chih-Hung (莊智弘)

Department of Medical Laboratory

Science and Biotechnology (醫技系)

Office: CS604
TEL: 07-3121101 #2351
Mail: a4132600@gmail.com
TABLE 5-2

歐亞書局 p.170
Self is distinguished from nonself by the display of peptides
on cell surfaces
MHC (major histocompatibility complex) proteins (呈現抗給T細胞)
Class I MHC
Bind and display peptides derived from cellular proteins.
Recognition targets of the T-cell receptors of the TC cells.
Class II MHC
Occur on the surfaces of macrophages and B lymphocytes. Bind
and display peptides derived from external proteins. Recognition
targets of the T-cell receptors of the TH cells.
MHC proteins present the antigen to the TCR
Class I MHC display peptides derived from cellular proteins
Class II MHC display peptides derived from external proteins