LECTURE
2
If you do not
read and study
textbooks………
• Weir & Stewart
Immunology
[S-LEN 599 L098*7;2
• Bauman
• Wood
11/e Chaps 1-4
599 L098*7
Microbiology 2/e
Chap 15
Understanding Immunology
2/e
• P rescott Microbiology 5/e
576 N02*5;25
8th ed ]
616.9 P7
616.07 P16
Part IX
S-LEN 576 N02*5
Any Microbiology/Immunology text after 2008!
616.7
Immunity is
•  ‘Increased resistance to’
not
‘Complete protection from’
•  Innate or Non-specific
- comes with us at birth!
•  Acquired or Specific
- we develop it as we
grow and experience ‘non-self’ substances!
What about plants?
•  Plants have immune-type defence systems
but based on alkaloids and other chemicals
•  One can immunise plants by exposing to a
vaccine e.g. Tobacco mosaic virus
What about animals?
•  Immune systems
become more
complex with higher
phylogenetic rank
Phylogeny
Ontogeny
•  Grow more complex
with ontogenetic
development also
Innate Resistance (inbuilt from birth)
•  Resistance due to physiological barriers
and processes that are incompatible
with those of the pathogen!
–  Suitable chemical receptors not present on
host cells!
–  Temperature, pH and conditions may be
incompatible with those necessary for the
pathogens survival!
•  Provides basic resistance to most
pathogens!
•  Innate immunity depends on genetic
capability we receive plus state of
health and nutrition
Response to Infection
•  Awareness – sensing systems
•  Immediate response - activation, physiological
alterations of blood flow and cell recruitment
•  Delayed response - cell multiplication, induction,
new factors, more specific.
•  Destruction or elimination of pathogen.
•  Trigger repair.
•  Provision of future immunity
3 lines of Defence
External
First Line of Defense barriers and coatings
•  Structures, cells, chemicals, processes
that work to prevent pathogens from
entering the body
•  Non-specific defenses –  Includes the skin and mucous
membranes of the respiratory, digestive,
urinary, and reproductive systems
Epithelial cells
Renewed every 5 weeks
Skin – Barrier
layers
•  Two major layers
–  Epidermis
•  Outer layer of multiple layers of tightly packed cells
»  Few pathogens can penetrate these layers
»  Shedding of dead skin cells removes attached
microorganisms
•  Epidermal dendritic cells (Also termed Langerhans cells)
–  Phagocytize, carry and present pathogens as antigens
–  Dermis
•  Contains protein fibers called collagen
–  Give skin strength and pliability to resist abrasions that
could introduce microorganisms
Skin – Chemical coatings
•  Perspiration secreted by sweat glands
–  Salt- inhibits growth of pathogen by drawing water
from their cells
–  Lysozyme- destroys cell wall of bacteria •  Sebum secreted by sebaceous (oil) glands
–  Helps keep skin pliable and less likely to break or
tear
–  Lowers the pH of the skin to a level inhibitory to
many bacteria
Internal surfaces
Mucous membrane
Mucous Membranes
•  Line all body cavities open to the outside environment
•  Two distinct layers
–  Epithelium
•  Thin, outer covering of the mucous membranes
•  Unlike surface epidermal cells, epithelial cells are living
•  Tightly packed to prevent entry of pathogens
•  Continual shedding of cells carries attached
microorganisms away
–  Deeper connective layer that supports the epithelium
Microbial Antagonism
•  Normal microbiota help protect
the body by competing with
potential pathogens
–  Secrete antimicrobial substances
that limit pathogen growth
–  Consumption of nutrients makes
them unavailable to pathogens
–  Create an environment unfavorable
to other microorganisms by changing
pH
Microbial
Antagonism &
Normal flora
–  Help stimulate the body’s second line of defense
–  Regulate each other by competition
–  Displace any newcomers
–  Promote overall health by providing vitamins to host
Other First-Line Defenses
•  Many body organs secrete chemicals with
antimicrobial properties e.g lysozyme, spermine
•  Lachrymal glands that bathe the eye
Lubricant and antimicrobial secretions
Second Line of Defenses
(inside the tissues)
•  Operates when pathogens succeed in penetrating
the skin or mucous membranes
•  Non-specific defence of cells, antimicrobial
chemicals, and processes but no physical barriers
–  Many of these components are contained or originate
in the blood
Blood
•  Composed of cells and portions
of cells within a fluid called
plasma
–  Plasma is mostly water containing
electrolytes, dissolved gases,
nutrients, and proteins
•  Plasma minus clotting factors is
called serum
•  Other plasma proteins include
complement proteins and antibodies
•  The cells and cell fragments in
plasma are called formed elements
Formed Elements
•  Three types of formed elements
–  Erythrocytes- carry oxygen and carbon dioxide in
the blood
–  Platelets-(not cells) involved in blood clotting
–  Leukocytes- involved in defending the body against
invaders
•  2 groups
–  Granulocytes
–  Agranulocytes
Stem cell
WBC
RBC
Platelets
Granulocytes
Lymphocytes
•  Contain large granules that stain based on dye affinity
•  3 types
–  Basophils- granules stain blue with the basic dye methylene blue
–  Eosinophils- granules stain red/orange with the acidic dye eosin
–  Neutrophils- granules stain poorly
•  Neutrophils and eosinophils can phagocytoze pathogens
•  Neutrophils and eosinophils are capable of diapedesis
Neutrophil 70% of WBC in blood
Also known as a polymorphonuclear leucocyte or PMN
Eosinophil
2-4% of WBC in blood
Basophil or Mast cell - less than 1% of WBC in blood
Agranulocytes (No granules)
•  Cytoplasm appears uniform under a light microscope
•  2 types
–  lymphocytes- most involved in specific immunity
Monocyte - 3-8% of WBC in blood Become macrophages in the tissues
Macrophages
•  Phagocytic cells of the second line of defence
•  Wandering macrophages leave the blood via
diapedesis and phagocytize throughout the body
•  Fixed macrophages do not move throughout the
body and often phagocytoze within a specific
organ
–  Include Langerhans cells (epidermis), alveolar
macrophages (lungs), microglia (central
nervous system), Küpffer cells (liver)
•  All macrophages, both wandering and fixed
constitute the mononuclear phagocytic system
Lab Analysis of Leukocytes
•  The differential white blood cell count can signal
signs of disease
–  Increased eosinophils ……. allergies or parasitic
worm infection
–  increase in leukocytes particularly neutrophils ……
Bacterial diseases
–  increase in lymphocytes………….Viral infections (AIDS is characterised by drop in T lymphocyte (CD4)
count)
Mechanisms of the Second Line of
Defence
• 
• 
• 
• 
• 
Phagocytosis
Extracellular killing by leukocytes
Non-specific chemical defences
Inflammation
Fever
Phagocytosis
•  Cells capable of phagocytosis (certain leukocytes
or their derivatives) are called phagocytes
•  Phagocytosis killing is not completely understood
•  Can be divided into 5 stages
HELP!
Why don’t phagocytes eat our cells?
•  The host’s cells are protected from destruction by
the phagocytes because
–  phagocytes have receptors for bacterial surface
components, such as flagellar proteins or cell wall
components, that are lacking on the host cells
–  Opsonins such as complement and antibody provide
labels or indicators to mark targets for the phagocyte
Extracellular Killing by Leukocytes
Fluke
•  2 Cell types that kill extracellularly
–  Eosinophils
•  Mainly attack parasitic helminths (worms) by attaching to
their surface
•  Secrete toxins that weaken or kill the helminth
•  Eosinophilia, or elevated eosinophil levels, is often
indicative of a helminth infection
Extracellular Killing by Leukocytes
–  Natural killer lymphocytes (NK cells)
•  Secrete toxins onto the surface of virally infected cells and
tumors
•  Trigger apoptosis (self destruction genes)
Nonspecific Chemical Defenses
•  Augment phagocytosis
–  Some attack pathogens directly
–  Some enhance other features of nonspecific
resistance
•  Includes various chemicals
–  Lysozyme
–  Complement
–  Interferons
–  Defensins
Gram positive bacterial cell wall - murein
Complement System
•  Set of serum proteins designated numerically
according to the order of their discovery
•  Complement activation results in inflammatory
signals and ends in lysis or damage of nearby
membranes.
•  It is a cascade pathway which acts as a biological
burglar alarm
•  Complement can be activated in several ways
–  Classical Pathway
–  Alternate Pathway
The complement
pathways
Red cell perforated
by complement.
•  Activated Complement has a short half-life
•  Body’s own cells withstand complement
cascade
–  Membrane-bound proteins on many cells bind
with and break down activated complement
proteins
–  High turnover rate for cell membranes means
any bound membrane attack complexes are
shed or endocytosed before any damage occurs
Interferons
•  Protein molecules released by host cells to
nonspecifically inhibit the spread of viral infections
•  Particularly effective against viruses with RNA
genomes
•  Cause many symptoms typically associated with viral
infections
•  3 Classes
» Alpha (from many cell types)
» Beta (from many cell types)
» Gamma (from T-cells)
•  Alpha and beta interferons are present early in the
infection
•  Gamma interferon appears later in the course of
infection
Interferon Therapy
•  It was thought that this might be a good antiviral
treatment
•  Many viral infections don’t respond to interferon
therapy at all
•  Only a slight effect is seen with those viral
infections that do respond
Defensins
•  Small peptides that function nonspecifically to
protect against a broad range of pathogens
•  Act against pathogens in various ways
–  Punch holes in cytoplasmic membranes
–  Interfere with internal signaling and other metabolic
processes
–  Interfere with the protein that preserves the shape of
bacterial proteins under heat stress
•  In humans, inflammation increases the
production of defensins
Inflammation
•  Nonspecific response by circulatory system to tissue
damage resulting from various causes
•  Characterized by redness, heat, swelling, and pain
•  Two types
–  Acute
–  Chronic
Inflammation
of….
=
- itis
e.g. Tonsilitis
Nephritis
Appendicitis
Acute vs Chronic Inflammation
•  Acute inflammation
–  Develops quickly and is short lived
–  Is usually beneficial
–  Important in the second line of defense
•  Dilation and increased permeability of the blood vessels
•  Migration of phagocytes
•  Tissue repair
•  Chronic inflammation
–  Develops slowly and lasts a long time
–  Can cause damage to tissues
Chemical Mediators of
Inflammation
Fever
•  A body temperature over 37°C
•  Results when chemicals called pyrogens trigger
the hypothalamus to increase the body’s core
temperature
•  Various types of pyrogens
–  Bacterial toxins
–  Cytoplasmic contents of bacteria released by lysis
–  Antibody-antigen complexes
–  Interleukin-I (IL-1)
Fever Production
•  IL-1 causes the hypothalamus to secrete
prostaglandin which resets the hypothalamic
“thermostat” •  Communication with the brain initiates muscle
contractions, increased metabolic activity, and
constriction of blood vessels which raises the
body’s temperature
•  Chills associated with fever are due to the
reduced blood flow of constricted vessels
•  Decrease in IL-1 production results in the body’s
temperature returning to normal
Benefits of Fever
•  Enhances the effects of interferons
•  Inhibits growth of some microorganisms
•  May enhance the performance of phagocytes, cells of
specific immunity, and the process of tissue repair
A Summary of Some Non-specific
Components of the First and Second
Lines of Defense