Structure and functions of

immune system
 Immunity
 Immunity

 The ability of the body to fight infection and/or foreign invaders

by producing antibodies or killing infected cells.
 Immune System

 The system in the body responsible for maintaining

homeostasis by recognizing harmful from nonharmful
organisms and produces an appropriate response.
Immune system
 Immunity: Two Intrinsic Defense Systems
• Innate (nonspecific) system responds quickly
and consists of:
• First line of defense – intact skin and
mucosae prevent entry of microorganisms
• Second line of defense – antimicrobial
proteins, phagocytes, and other cells
• Inhibit spread of invaders throughout the
body
• Inflammation is its hallmark and most
important mechanism
 Immunity: Two Intrinsic Defense Systems

 Adaptive (specific) defense system

Third line of defense – this is a specific
response to a specific pathogen/antigen.

Takes longer to react than the innate

system
Works in conjunction with the innate
system
Types of Acquired Immunity
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
 Surface Barriers

 Keratin in the skin:

Presents a formidable physical barrier to most
microorganisms
Is resistant to weak acids and bases, bacterial
enzymes, and toxins

 Mucosae provide similar mechanical barriers

 Epithelial Chemical Barriers

 Epithelial membranes produce protective

chemicals that destroy microorganisms
Skin acidity (pH of 3 to 5) inhibits bacterial
growth

Stomach mucosae secrete concentrated HCl

and protein-digesting enzymes
Saliva and lacrimal fluid contain lysozyme

Mucus traps microorganisms that enter the

digestive and respiratory systems
 Internal Defenses: Cells and Chemicals

 The body uses nonspecific cellular and

chemical devices to protect itself
Phagocytes and natural killer (NK)
cells
Antimicrobial proteins in blood and
tissue fluid

Inflammatory response enlists macrophages,

mast cells, WBCs, and chemicals

 Harmful substances are identified by surface

 Phagocyte
s
 Macrophages are the chief phagocytic cells
 Free macrophages wander throughout a region in
search of cellular debris
 Kupffer cells (liver) and microglia (brain) are fixed
macrophages
 Neutrophils become phagocytic when encountering
infectious material
 Eosinophils are weakly phagocytic against parasitic
worms
 Mast cells bind and ingest a wide range of bacteria
 Mechanism of Phagocytosis

 Microbes adhere to the phagocyte

 Pseudopods engulf the particle (antigen) into a

phagosome
 Phagosomes fuse with a lysosome to form a
phagolysosome

 Invaders in the phagolysosome are digested by

proteolytic enzymes

 Undigestible and residual material is removed

by exocytosis
Mechanism of Phagocytosis
 Antimicrobial Proteins

The most important antimicrobial proteins are:

Interferon

Complement proteins
 Interferon (IFN)

 Genes that synthesize IFN are activated when

a host cell is invaded by a virus

 Interferon molecules leave the infected cell and

enter neighboring cells

 Interferon stimulates the neighboring cells to

activate genes for PKR (an antiviral protein)

 PKR nonspecifically blocks viral reproduction in

the neighboring cell
Interferon (IFN)
 Interferon Family

 Interferons are a family of related proteins each

with slightly different physiological effects

 Lymphocytes secrete gamma () interferon, but

most other WBCs secrete alpha () interferon
 Fibroblasts secrete beta () interferon

 Interferons also activate macrophages and

mobilize NKs
 Cytokines

IFN-α ІL-10

ІL-6 TNF-α
 Complement

 20 or so proteins that circulate in the blood in

an inactive form
 Proteins include C1 through C9, factors B, D,
and P, and regulatory proteins

 Provides a major mechanism for destroying

foreign substances in the body
 Complement

 Amplifies all aspects of the inflammatory

response
 Kills bacteria and certain other cell types (our
cells are immune to complement)

 Enhances the effectiveness of both nonspecific

and specific defenses
 Complement Pathways
 Complement can be activated by two pathways:
classical and alternative
 Classical pathway is linked to the immune
system
Depends on the binding of antibodies
to invading organisms
Subsequent binding of C1 to the antigen-
antibody complexes (complement
fixation)
 Alternative pathway is triggered by interaction
among factors B, D, and P, and polysaccharide
molecules present on microorganisms
 Complement Pathways

 Each pathway involves a cascade in which

complement proteins are activated in an orderly
sequence and where each step catalyzes the next
 Both pathways converge on C3, which cleaves into
C3a and C3b
 C3b initiates formation of a membrane attack complex
(MAC)
 MAC causes cell lysis by interfering with a cell’s ability
to eject Ca2+
 C3b also causes opsonization, and C3a causes
inflammation
Complement Pathways
Membrane attack complex
 C-reactive Protein (CRP)

 CRP is produced by the liver in response to

inflammatory molecules
 CRP is a clinical marker used to assess for:
The presence of an acute infection
An inflammatory condition and its response to
treatment
 Functions of C-reactive Protein

 Binds to PC receptor of pathogens and

exposed self-antigens

 Plays a surveillance role in targeting damaged

cells for disposal

 Activates complement
C-reactive protein
 Adaptive (Specific) Defenses

 The adaptive immune system is a functional

system that:
Recognizes specific foreign substances

Acts to immobilize, neutralize, or destroy

foreign substances
Amplifies inflammatory response and activates
complement
 Adaptive Immune Defenses

 The adaptive immune system is antigen-

specific, systemic, and has memory

 It has two separate but overlapping

arms
Humoral, or antibody-mediated
immunity
Cellular, or cell-mediated immunity
 Antigens

 Substances that can mobilize the immune

system and provoke an immune
response

 The ultimate targets of all immune responses

are mostly large, complex molecules not
normally found in the body (nonself)
 Complete
Antigens
 Important functional properties:
Immunogenicity – the ability to stimulate
proliferation of specific lymphocytes
and antibody production

Reactivity – the ability to react with the

products of the activated lymphocytes and the
antibodies released in response to them

 Complete antigens include foreign protein,

nucleic acid, some lipids, and large
polysaccharides
 Haptens (Incomplete
Antigens)

 Small molecules, such as peptides,

nucleotides, and many hormones, that are not
immunogenic but are reactive when attached to
protein carriers
 If they link up with the body’s proteins, the
adaptive immune system may recognize them
as foreign and mount a harmful attack (allergy)

 Haptens are found in poison ivy, dander, some

detergents, and cosmetics
 Antigenic Determinants

Only certain parts of an entire antigen are

immunogenic
Antibodies and activated lymphocytes bind
to these antigenic determinants
Most naturally occurring antigens have
numerous antigenic determinants
that:
Mobilize several different lymphocyte
populations
Form different kinds of antibodies
Antigenic Determinants
 Antibody Types

 IgG

 IgM

 IgA

 IgD

 IgE
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Functions of
Antibodies

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 IgG

 Most common antibody

type
 Only antibody that crosses placenta

 Prime mediator of secondary immune response

 Principal defender against bacteria, viruses, and

toxins
 IgM

 Macroglobulin
 Confined to bloodstream

 First antibody to appear in response to presence

of antigen

 Agent of primary immune response

 IgA

 Secretory antibody
 Found in saliva, tears, respiratory secretions, GI
tract secretions

 Frontline bacterial, viral defense

 IgD

 Role not fully

understood
 Low serum levels

 High concentrations on B-cells

 May act as receptors that trigger production of

other antibodies
 IgE

 Very low serum levels

 Primarily bound to mast cells in tissues

 Controls allergic response

 Prevents parasitic infections

Antibody Production

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

Antibodies

 Y-shaped protein molecule.

 Made up of variable and
constant regions.
 Made up of Heavy and
Light chains.
 Produced by plasma cells
 Function: Recognize
antigens, bind to and
deactivate them.
 Note: Variable region
recognizes the antigens.
Different Immunoglobulins
 Self-Antigens: MHC Proteins

 Our cells are dotted with protein molecules

(self-antigens) that are not antigenic to us but
are strongly antigenic to others
 One type of these, MHC proteins, mark a cell
as self
 The two classes of MHC proteins are:
Class I MHC proteins – found on virtually
all body cells
Class II MHC proteins – found on certain
cells in the immune response
 MHC Proteins

 Are coded for by genes of the major

histocompatibility complex (MHC) and are
unique to an individual
 Each MHC molecule has a deep groove that
displays a peptide, which is a normal
cellular product of protein recycling

 In infected cells, MHC proteins bind to

fragments of foreign antigens, which play a
crucial role in mobilizing the immune system
Class I MHC Molecule Class II MHC Molecule
 Cells of the Adaptive Immune System

 Two types of lymphocytes

B lymphocytes – oversee humoral immunity
T lymphocytes – non-antibody-producing cells
that constitute the cell-mediated arm of
immunity
 Antigen-presenting cells (APCs):
Do not respond to specific antigens
Play essential auxiliary roles in immunity
 Lymphocytes

 Immature lymphocytes released from bone

marrow are essentially identical

 Whether a lymphocyte matures into a B cell or

a T cell depends on where in the body it
becomes immunocompetent
B cells mature in the bone marrow

T cells mature in the thymus

 T Cells

 T cells mature in the thymus under negative

and positive selection pressures
Negative selection – eliminates T cells that are
strongly anti-self
Positive selection – selects T cells with a weak
response to self-antigens, which thus become
both immunocompetent and self-tolerant
 B Cells

 B cells become immunocompetent and self-

tolerant in bone marrow
 Some self-reactive B cells are inactivated
(anergy) while others are killed

 Other B cells undergo receptor editing in which

there is a rearrangement of their receptors
 Antigen-Presenting Cells (APCs)

 Major rolls in immunity are:

To engulf foreign particles
To present fragments of antigens on their own
surfaces, to be recognized by T cells
 Major APCs are dendritic cells (DCs),
macrophages, and activated B cells
 The major initiators of adaptive immunity are
DCs, which actively migrate to the lymph nodes
and secondary lymphoid organs and present
antigens to T and B cells
 Macrophages and Dendritic Cells

 Secrete soluble proteins that activate T cells

 Activated T cells in turn release chemicals that:

Rev up the maturation and mobilization of DCs

Prod macrophages to become activated

macrophages, which are insatiable phagocytes
that secrete bactericidal chemicals
 Immune Response Explained

1. Antigen infects cells.

2. Macrophage ingests antigen and displays portion on its surface.
3. Helper T- Cell recognizes antigen on the surface of the macrophage
and becomes active.
4. Active Helper T-Cell activates Cytotoxic T-Cells and B-Cells.
5. Cytotoxic T-Cells divide into Active Cytotoxic T-cells and Memory T
– Cells.
6. Active Cytotoxic T-Cells kill infected cells.
7. At the same time, B-Cells divide into Plasma Cells and Memory
B- Cells.
8. Plasma cells produce antibodies that deactivate pathogen.
9. Memory T and Memory B cells remain in the body to speed up the
response if the same antigen reappears.
10. Supressor T-Cells stop the immune response when all antigens
have been destroyed.
 The Pathway of Specific Immune Response

Step 1
Pathogens eaten by Macrophage

Step 2
Displays portion of Pathogen
on surface

Step 3

Pathogens

Helper-T cell recognizes

Pathogen
Activates Cytotoxic Activates B- Cell

T- Cell

Memory B-Cell
Memory T-Cell

Antibodies
Kills Infected Cells
T cell dependent B cell activation, computer artwork. Invading pathogens (gold ovoids) are phagocytosed
(engulfed) by macrophages, a type of white blood cell. Fragments of protein (antigen) from the pathogen are
displayed on the macrophage's surface. The antigen is recognised by helper T lymphocytes (purple), which
secrete chemicals to activate other immune cells, including B lymphocytes (blue spiky cells). The B lymphocytes
differentiate into plasma cells (large blue cells), which produce large numbers of antibodies (red) that recognise
the antigen. The antibodies either neutralise the pathogen or flag it for destruction by other cells.
Cell-mediated immune response, computer artwork. This type of immune response is most often used
against intracellular pathogens, such as viruses. The viruses (gold) are phagocytosed (engulfed) by
macrophage cells (green), a type of white blood cell. Fragments of viral protein (antigen) are displayed on the
macrophage's surface. The antigen is recognised by a helper T lymphocyte (purple, centre and right), which
secretes chemicals to activate other immune cells, including cytotoxic T lymphocytes (purple, left). The
cytotoxic cells release chemicals that cause the macrophages to disintegrate and die, killing the viruses inside
as well.
 Immune Response Summary
Displays copy of antigen
onDisplays
surface ofcopy
cell of
antigen on surface of
cell
Antigen

Macrophage

Helper T - Cell Antibody

Cellular Immunity
Immunity
Cellular Immunity

Active Cytotoxic T-Cell Active B-Cell

Antibody Immunity

Kills Infected Cells Memory T- Cell Plasma Cell Memory B-Cell

Antibodies

Deactivates Antigens
 Adaptive Immunity: Summary

 Two-fisted defensive system that uses

lymphocytes, APCs, and specific molecules to
identify and destroy nonself particles

 Its response depends upon the ability of its cells

to:
Recognize foreign substances (antigens)
by binding to them
Communicate with one another so that the
whole system mounts a response specific to
those antigens
 Humoral Immunity Response

 Antigen challenge – first encounter between an

antigen and a native immunocompetent cell

 Takes place in the spleen or other lymphoid

organ
 If the lymphocyte is a B cell:

 The challenging antigen provokes a

humoral immune response

 Antibodies are produced against

the challenger
 Immunological Memory

 Primary immune response – cellular

differentiation and proliferation, which occurs on
the first exposure to a specific antigen
Lag period: 3 to 6 days after antigen challenge

Peak levels of plasma antibody are

achieved in 10 days
Antibody levels then decline
 Immunological Memory

 Secondary immune response – re-exposure to

the same antigen
Sensitized memory cells respond within
hours

Antibody levels peak in 2 to 3 days at

much higher levels than in the primary
response
Antibodies bind with greater affinity, and their
levels in the blood can remain high for
weeks to months
Primary and Secondary Humoral
Responses
 Active Humoral Immunity

 B cells encounter antigens and produce

antibodies against them
Naturally acquired – response to a bacterial
or viral infection
Artificially acquired – response to a vaccine of
dead or attenuated pathogens
 Vaccines – spare us the symptoms of disease,
and their weakened antigens provide
antigenic determinants that are immunogenic
and reactive
 Passive Humoral Immunity

 Differs from active immunity in the antibody source and the

degree of protection
 B cells are not challenged by antigens
 Immunological memory does not occur
 Protection ends when antigens naturally degrade in the
body

Naturally acquired – from the mother to her fetus via the
 placenta

Artificially acquired – from the injection of serum, such as gamma

globulin