Beruflich Dokumente
Kultur Dokumente
• cellular immune response: CD4 cells, helper T (TH) cells, CD8 cells,
cytotoxic T (TC) cells, regulatory T cells (Treg cells), class I and class
II MHC proteins, antigen binding, T cell antigen receptors (TCRs), co-
stimulation, cytokines, interleukins, perforin, immune surveillance
CHAPTER 21
THE IMMUNE SYSTEM
PART I
Innate
defenses Internal defenses
• Phagocytes
2nd line • Natural killer cells
• Inflammation
• Antimicrobial proteins
• Fever
Humoral immunity
• B cells
Adaptive
defenses 3rd line
Cellular immunity
• T cells
© 2016 Pearson Education, Inc.
Part I – INNATE DEFENSES
1 Phagocyte adheres
to pathogens or debris.
2 Phagocyte forms
pseudopods that
eventually engulf the
Phagosome
particles, forming a
(phagocytic
phagosome.
vesicle)
Lysosome
3 Lysosome fuses
with the phagocytic
vesicle, forming a
phagolysosome.
Acid
hydrolase
enzymes 4 Toxic compounds
and lysosomal
enzymes destroy
pathogens.
5 Sometimes
exocytosis of the
vesicle removes
indigestible and
residual material.
Events of phagocytosis.
Leukocytosis
(increased numbers of white
blood cells in bloodstream)
Arterioles Increased capillary Attract neutrophils,
dilate permeability monocytes, and
Leukocytes migrate to
lymphocytes to
injured area
area (chemotaxis)
Diapedesis
Leaked protein-rich Leaked clotting
(leukocytes pass through
fluid in tissue spaces proteins form
capillary walls)
interstitial clots
that wall off area
to prevent injury to Phagocytosis of pathogens
Heat Redness Pain Swelling surrounding tissue and dead tissue cells
(by neutrophils, short-term;
by macrophages, long-term)
Locally increased Possible temporary Temporary fibrin Pus may form
temperature increases impairment of patch forms
metabolic rate of cells function scaffolding Area cleared of debris
for repair
Healing
Inflammatory
chemicals
diffusing from 4 Chemotaxis.
the inflamed Neutrophils follow
site act as chemical trail.
chemotactic
agents.
Capillary wall
Basement
membrane
Endothelium
Virus
Viral nucleic acid
1 Virus
New
enters cell.
viruses 5 Antiviral
proteins block
viral reproduction.
2 Interferon
genes
switch on.
Antiviral
mRNA
DNA
Nucleus
mRNA for
interferon
4 Interferon
3 Cell binding stimulates
produces cell to turn on genes
interferon for antiviral proteins.
molecules. Interferon
receptor
Interferon
Host cell 1 Host cell 2
Infected by virus; Binds interferon
makes interferon; from cell 1; interferon
is killed by virus induces synthesis of
protective proteins
© 2016 Pearson Education, Inc.
Complement System (complement)
– consists of ~20 blood proteins that circulate in
blood in inactive state
– Includes proteins C1–C9, factors B, D, and P,
and regulatory proteins
– Provides major mechanism for destroying foreign
substances
– Activation enhances inflammation and also
directly destroys bacteria
• Enhances both innate and adaptive defenses
C3
C3a
C3b
C3b
Opsonization: Enhances inflammation:
C5b C5a Stimulates histamine
Coats pathogen
surfaces, which C6 release, increases blood
MAC
enhances phagocytosis vessel permeability,
C7
attracts phagocytes by
C8 chemotaxis, etc.
MACs form from activated
C9
complement components (C5b
and C6–C9) that insert into the
target cell membrane, creating
pores that can lyse the target cell.
Pore
Complement
proteins
(C5b–C9)
Membrane
of target cell
1. Humoral immunity
– Antibodies, produced by lymphocytes, circulate freely in
body fluids
– Bind temporarily to target cell
• Temporarily inactivate
• Mark for destruction by phagocytes or complement
– Humoral immunity has extracellular targets
2. Cellular Immunity
– Lymphocytes act against target cell
• Directly—by killing infected cells
• Indirectly—by releasing chemicals that enhance inflammatory
response; or activating other lymphocytes or macrophages
– Cellular immunity has cellular targets
© 2016 Pearson Education, Inc.
Antigens
Antigen-
Antigenic determinants
binding
sites
Antibody A
Antigen
Antibody B
Antibody C
Lymphocyte 2 Maturation
precursors • Lymphocyte precursors destined to become T cells
migrate (in blood) to the thymus and mature there.
• B cells mature in the bone marrow.
• During maturation lymphocytes develop
Thymus
immunocompetence and self-tolerance.
Red bone marrow
3 Seeding secondary lymphoid organs and
circulation
• Immunocompetent but still naive lymphocytes leave
the thymus and bone marrow.
• They “seed” the secondary lymphoid organs and
Antigen circulate through blood and lymph.
1. Positive Selection
T cells must recognize self major histocompatibility proteins
(self-MHC)
Antigen-presenting Developing
thymic cell T cell
Recognizing self-MHC
results in survival. Immunocompetence
Survivors proceed
to negative selection.
2. Negative Selection
T cells must not recognize self-antigens
Recognizing self-antigen
results in apoptosis. This
eliminates self-reactive
T cells that could cause
autoimmune diseases.
• Clonal selection
– Naive lymphocyte's first encounter with antigen
via antigen receptors selected for further
development
– If correct signals present, lymphocyte will
complete its activation
Antigen receptors:
• Engulf antigens
• Present fragments of antigens to T cells for
recognition T cell activation
• Major types:
– Dendritic cells in connective tissues and
epidermis
– Macrophages in connective tissues and
lymphoid organs
– B cells
• Dendritic cells
– Found in connective tissues and epidermis
– Phagocytize pathogens that enter tissues, then
enter lymphatics to present antigens to T cells in
lymph node
• Most effective antigen presenter known
• Key link between innate and adaptive immunity
• Antigen challenge:
– First encounter between an antigen and a naive
immunocompetent B lymphocyte
– Usually occurs in the lymphoid organs (e.g.
spleen or a lymph node)
– The antigen provokes a humoral immune
response:
• Antibodies are produced
• Activation and differentiation of B cells:
Memory B cell—
primed to respond
to same antigen
Plasma
cells
Secreted
antibody Memory
molecules B cells
104
in plasma (arbitrary units)
103
102
101 Anti-
Anti-
bodies bodies
to A to B
100
0 7 14 21 28 35 42 49 56
- Natural acquired
- Artificially acquired
Figure 21.13 Active and passive humoral immunity.
Humoral
immunity
Active Passive
Antigen-binding site
Hinge region
Stem region
Antigen-antibody
Antigen Antibody
complex
Chemotaxis
Histamine
release
Immature
lymphocyte
Red bone marrow
T cell T cell
receptor receptor
Maturation
Class I MHC
Class II MHC CD8 protein displaying
CD4
protein displaying cell antigen
antigen
cell Thymus
Activation Activation
APC
Memory APC
(dendritic cell)
cells (dendritic cell)
CD4 CD8
Bacterial antigen
1 Antigen
presentation
Class lI MHC Dendritic cell engulfs
protein an exogenous
displaying antigen, processes it,
processed and displays its
bacterial antigen fragments on class II
Dendritic Co-stimulatory MHC protein.
cell molecule
3 Clone formation
Activated CD4 T cells
proliferate (clone), and
become memory and
effector cells.
Memory
CD4 T cell Helper
T cells
Humoral immunity
Adaptive defenses
Cellular immunity
Helper T cells help in humoral immunity Helper T cells help in cellular immunity
Cytotoxic
T cell (TC) 1 TC identifies 2 TC releases 3 Perforin molecules insert into
foreign antigens perforin and the target cell membrane,
on MHC I granzyme polymerize, and form
proteins and molecules from transmembrane pores (cylindrical
binds tightly to its granules by holes) similar to those produced
target cell. exocytosis. by complement activation.
Granule
Perforin
TC cell
membrane
Target
cell
membrane
Target
cell Perforin
pore
Granzymes
Surface Internal
barriers defenses
Free Ags
may directly
Ag-infected activate B cell
body cell engulfed
by dendritic cell Antigen-
activated
Becomes B cells
Memory
Memory
CD4 T cells
CD8 T cells Secrete
Cytotoxic Helper
T cells T cells
Cytokines stimulate
Nonspecific killers
(macrophages and Antibodies (Igs)
Together the nonspecific killers
and cytotoxic T cells mount a NK cells of innate Circulating lgs along with complement
physical attack on the Ag immunity) mount a chemical attack on the Ag