Download Immune System

The
Immune
System
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Overview
• Barriers = 1st line of defense against pathogens
• Immune system recognizes foreign bodies
 responds with the production of leukocytes
and proteins
• 2 kinds of defense:
– innate immunity
– acquired immunity
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Pathogens
(microorganisms
and viruses)
INNATE IMMUNITY
• Recognition of traits
shared by broad ranges
of pathogens, using a
small set of receptors
• Rapid response
ACQUIRED IMMUNITY
• Recognition of traits
specific to particular
pathogens, using a vast
array of receptors
• Slower response
Barrier defenses:
Skin
Mucous membranes
Secretions
Internal defenses:
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response:
Antibodies defend against
infection in body fluids.
Cell-mediated response:
Cytotoxic lymphocytes defend
against infection in body cells.
Innate immunity
• present from birth
• recognition and rapid response rely on
shared traits of pathogens
• nonspecific responses to pathogens
– external barriers
– internal cellular defense
– chemical defenses
– inflammation
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Barriers
• Skin - continuous keratinized stratified
squamous layers of epithelium
• Mucus traps and allows for the removal of
microbes
• Saliva, mucus, and tears are hostile to
microbes (hydrolytic enzymes, high salinity)
• low pH of skin and digestive system prevents
microbial growth
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Cellular Innate Defenses
• Phagocytic
leukocytes engulf
pathogens in the
body
• Groups of
pathogens are
recognized by TLR,
Toll-like receptors
of leukocytes
EXTRACELLULAR
Lipopolysaccharide
FLUID
Helper
Flagellin
protein
TLR4
WHITE
BLOOD
CELL
TLR5
VESICLE
CpG DNA
TLR9
TLR3
ds RNA
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Inflammatory
responses
Phagocytic Cells
4 types:
– Neutrophils engulf and destroy microbes
– Macrophages (of lymphatic system) and are
found throughout the body
– Eosinophils discharge destructive enzymes
– Dendritic cells stimulate acquired immunity
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Chemical Defenses
• Proteins and enzymes attack microbes directly
or impede their reproduction
• Interferon proteins:
– innate defense against viruses
– activate macrophages
• ~ 30 proteins form the complement system:
lysis of invading cells, trigger inflammation
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Inflammatory Response
• Following an injury, mast cells release
histamine:
 Dilates blood vessels
 increase local blood supply
 more phagocytes and antimicrobial proteins
enter tissues
• Pus, a fluid rich in white blood cells, dead
microbes, and cell debris, accumulates at the
site of inflammation
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Inflammatory Response
• Fever
– 100 – 102 Fahrenheit = beneficial
– Slows growth and reproduction of microbes
• denature their proteins
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Pathogen
Splinter
Chemical Macrophage
signals
Mast cell
Capillary
Red blood cells Phagocytic cell
Fluid
Phagocytosis
Natural Killer Cells
• All cells in the body (except red blood cells)
have a class 1 MHC protein on their surface
(major histocompatibility complex)
• Cancerous or infected cells lack this protein;
natural killer (NK) cells attack these damaged
cells
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Innate Immune System Evasion by Pathogens
• Some pathogens avoid destruction by
modifying their surface to prevent recognition
or by resisting breakdown following
phagocytosis
• Ex. Tuberculosis (TB);
– kills more than a million people/year
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Acquired immunity
• develops after exposure to foreign substances
• specific responses
– Antibody-mediated
– Cell-mediated response
• Slower
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Lymphocyte-Dependent
• lymphocytes recognize, remember, and
respond to antigens, foreign molecules
• Cytokines, secreted by macrophages and
dendritic cells, recruit and activate lymphocytes
• T cells Lymphocytes mature in the thymus
above the heart
• B cells mature in bone marrow
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
B and T-cell Specificity
• Each lymphocyte is specialized to recognize
ONE specific type of antigen (foreign body)
• A single B cell or T cell has about 100,000
identical antigen receptors
• B cells give rise to plasma cells, which secrete
proteins called antibodies or
immunoglobulins (Ig) specific to the antigen
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 43-9
Antigenbinding
site
Antigenbinding site
Antigenbinding
site
Disulfide
bridge
C
C
Light
chain
Variable
regions
V
V
Constant
regions
C
C
Transmembrane
region
Plasma
membrane
Heavy chains
 chain
 chain
Disulfide bridge
B cell
(a) B cell receptor
Cytoplasm of B cell
Cytoplasm of T cell
(b) T cell receptor
T cell
The Role of Antibodies
• Neutralization occurs when a pathogen can no
longer infect a host because it is bound to an
antibody
• Opsonization occurs when antibodies bound to
antigens increase phagocytosis
• Antibodies together with proteins of the
complement system generate a membrane
attack complex and cell lysis
Animation: Antibodies
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 43-10
Antigenbinding
sites
Antigen-binding sites
Antibody A Antigen Antibody C
C
C
Antibody B
Epitopes
(antigenic
determinants)
Primary Immune Response
• The first exposure to an antigen
• Slow response
– B cells called plasma cells are generated,
– T cells are activated
• In secondary immune response, B-cell
memory facilitate a faster, more efficient
response
Animation: Role of B Cells
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Two branches of Acquired immunity
• Humoral (antibody-mediated) immune
response
– activation and clonal selection of B cells,
resulting in production of secreted
antibodies
• Cell-mediated immune response
– activation and clonal selection of cytotoxic T
cells
• Helper T cells aid both responses
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 43-16
Humoral (antibody-mediated) immune response
Cell-mediated immune response
Key
Antigen (1st exposure)
+
Engulfed by
Gives rise to
Antigenpresenting cell
+
Stimulates
+
+
B cell
Helper T cell
+
Cytotoxic T cell
+
Memory
Helper T cells
+
+
+
Antigen (2nd exposure)
Plasma cells
Memory B cells
+
Memory
Cytotoxic T cells
Active
Cytotoxic T cells
Secreted
antibodies
Defend against extracellular pathogens by binding to antigens,
thereby neutralizing pathogens or making them better targets
for phagocytes and complement proteins.
Defend against intracellular pathogens
and cancer by binding to and lysing the
infected cells or cancer cells.
Active Immunity
• Active immunity develops naturally in
response to an infection
• It can also develop following vaccination
– a nonpathogenic form of a microbe or part
of a microbe is used to initiate a primary
immune response and immunological
memory
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings