The Immune System: Innate and Adaptive Defenses

1st line
Nonspecific

2nd line
Phagocytosis,
cells, chemicals
Inflammation
3rd line

Specific

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B, T cells

Figure 21.1

First Line of Defense: Surface Barriers

Skin, mucous membranes, and their secretions

Skin- Keratin:

Presents a physical barrier to most microorganisms

Is resistant to weak acids and bases, bacterial

enzymes, and toxins

Mucosae provide similar mechanical barriers

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First Line of Defense: Chemical Barriers

Epithelial membranes

Skin acidity (pH of 3 to 5) inhibits bacterial growth

Sebum- chemicals toxic to bacteria

Stomach mucosae-HCl, protein-digesting enzymes

Saliva & lacrimal fluid contain lysozyme, IgA

Digestive & respiratory systems- Mucus & cilia

trap & eject bacteria

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Second Line of Defense: Cells and Chemicals

Phagocytes

Natural killer (NK) cells

Antimicrobial proteins in blood and tissue fluid

Inflammatory response (macrophages, mast cells, WBCs,

and chemicals)

Surface carbohydrates on pathogens serve as

antigens

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Second Line of Defense: Phagocytes

Macrophages, monocytes (in blood), neutrophils

(blood & tissues), mast cells, eosinophils

Free: wander thru tissue in search of cellular debris

Fixed:

Kupffer cells (liver)

Microglia (brain)

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Figure 21.2a

Phagocytosis

1 Microbe adheres to phagocyte.

2 Phagocyte forms pseudopods that
eventually engulf the particle.

Lysosome

Phagocytic vesicle
containing antigen
(phagosome).
3 Phagocytic vesicle is
fused with a lysosome.
Phagolysosome

Acid
hydrolase
enzymes

4 Microbe in fused vesicle

is killed and digested by
lysosomal enzymes within
the phagolysosome, leaving
a residual body.
Residual body
5 Indigestible and
residual material
is removed by
exocytosis.

(b)
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Figure 21.2b

Second Line of Defense: Natural Killer (NK) Cells

Nonspecific

Large granular lymphocytes

Bind targets (recognize as non-self)

Induce apoptosis of targets

Lyse cancer cells, virus-infected cells

Release perforins, other cytolytic chemicals

Enhance inflammation

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Second Line of Defense:Inflammation

Non-specific response to injury

Prevents the spread of damaging agents to nearby tissues

Disposes of cell debris and pathogens

Sets the stage for repair processes

Hallmarks:

1. Red (rubor)
2. Hot (calor)
3. Swollen (tumor)
4. Painful (dolor)
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Toll-like Receptors (TLRs)

Macrophages and cells lining the gastrointestinal

and respiratory tracts bear TLRs

TLRs recognize specific classes of infecting

microbes

Activated TLRs trigger the release of cytokines

that promote inflammation

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Inflammatory Response: Phagocytic

Mobilization
Four main phases:

Leukocytosis neutrophils are released from the

bone marrow in response to leukocytosis-inducing
factors released by injured cells

Margination neutrophils cling to the walls of

capillaries in the injured area

Diapedesis neutrophils squeeze through capillary

walls and begin phagocytosis

Chemotaxis inflammatory chemicals attract

neutrophils to the injury site

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Inflammatory Response: Phagocytic Mobilization

4 Positive
chemotaxis
Inflammatory
chemicals diffusing
from the inflamed
site act as chemotactic
agents
1 Neutrophils enter blood
from bone marrow
2 Margination

Capillary wall

3 Diapedesis

Endothelium
Basement membrane

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Figure 21.4

Second Line of Defense: Inflammation

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Figure 21.3

Homeostatic Imbalance

Inflammation does not clear infection & debris

Abscess (Pus not cleared)

RX: I & D

Granulomas infectious granulomas such as tubercles

containing Mycobacterium tuberculosis

Resistant to digestion by Macrophages

Infected macrophages with fibrous capsule

Can remain asymptomatic until immunocompromised

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Second Line of Defense:Antimicrobial Proteins

Attack microorganisms &/Or inhibit reproduction

Interferon

Complement proteins

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Second Line of Defense:Antimicrobial ProteinsInterferon (IFN)

IFN synthesized by virus infected cells

IFN diffuses to nearby cells, stimulate synthesis of proteins

(PKR) that inhibit viral replication

PKR is nonspecific & inhibits replication of all viruses

Many types of IFN from many different cell types

Alpha IFN used:

As an antiviral drug against hepatitis C virus

To treat genital warts caused by the herpes virus

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Interferon (IFN)

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Figure 21.5

Second Line of Defense:Antimicrobial ProteinsComplement

20+ proteins in 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

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Second Line of Defense: Antimicrobial ProteinsComplement

A cascade of rxns that amplifies inflammation,

nonspecific & specific immune responses

Kills bacteria, cells (punches holes in membranes)

Classical Pathway activates specific immunity by:

Ab binds pathogen

C1 binds to Ag-Ab complex

Alternate Pathway by: factors B, D, P & surface

polysaccharides of microorganisms

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Second Line of Defense: Antimicrobial ProteinsComplement; Pathways

C3b initiates formation of a membrane attack

complex (MAC)

MAC causes cell lysis by interfering with a cells

ability to eject Ca2+

C3b also causes opsonization (> phagocytosis),

and C3a causes inflammation

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Complement Pathways

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Figure 21.6

Second Line of Defense: Antimicrobial Proteins;

C-reactive Protein (CRP)

Produced by liver in response to:

Infection

Inflammation

Used as clinical marker to assess the above

Binds to pathogens & targets them for:

Phagocytosis

Opsonization

Complement activation

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Second Line of Defense: Fever

> body temperature

In response to infection by microorganisms or

exposure to antigens

Moderate fever OK:

Liver, spleen sequester iron & zinc from pathogens

> metabolic rate speeds up tissue repair

Too high, denatures enzymes

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Adaptive Defenses (Specific Immune Response)

Adaptive immune system- functional system :

Recognizes antigens (anything foreign)

Antigen-specific, systemic, and has memory

Acts to immobilize, neutralize, or destroy

foreign substances

Amplifies inflammatory response and

activates complement

Humoral antibody-mediated immunity

Cellular- cell-mediated immunity

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Specific Immune Response : Antigens

Anything the body perceives as foreign; non-self

Autoimmune diseases

Substances that stimulate an immune response

Pathogenicity or virulence is defined as the degree

to which a pathogen can EVADE the immune
response

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Specific Immune Response : Complete Antigens

Functional properties:

Immunogenicity ability to stimulate proliferation

of specific lymphocytes and antibody production

Reactivity ability to react with activated

lymphocytes and the antibodies released in
response to them

Complete antigens- foreign protein, nucleic acid,

some lipids, and large polysaccharides

Usually large molecules

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Specific Immune Response: Haptens (Incomplete

Antigens)

Small molecules; peptides, nucleotides, many

hormones;

not immunogenic

are reactive when attached to protein carriers

Hapten + bodys protein = immune response as in

allergies

Haptens in poison ivy, dander, some detergents,

and cosmetics

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Specific Immune Response : Antigenic Determinants

Immunogenic part of ag

Antibodies and activated lymphocytes bind to

antigenic determinants

Most antigens =numerous antigenic determinants :

Mobilize several different lymphocyte populations

Form different kinds of antibodies against it

Large, chemically simple molecules (e.g., plastics)

have little or no immunogenicity

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Specific Immune Response : Antigenic Determinants

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Figure 21.7

Specific Immune Response: MHC Proteins

Major Histocompatibility Complex- self antigens,

unique to an individual

Class I MHC on all body cells

Class II MHC on certain cells involved in the

immune response

These are the markers that will elicit graft rejection

& transfusion rxns

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Specific Immune Response: Cells of Adaptive Immune

System

1. B lymphocytes or B cells humoral immunity;

ab production
2. T lymphocytes or T cells cell-mediated
immunity

3. Antigen-presenting cells (APCs):

Process all antigens in the same way

Can stimulate > immunity

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Specific Immune Response: Lymphocyte Maturation

Key:

Red bone
marrow

Immature
lymphocytes

Circulation
in blood

Thymus

Bone marrow

2
Immunocompetent,
but still naive,
lymphocyte migrates
via blood

2
Lymph nodes,
spleen, and other
lymphoid tissues

Activated
Immunocompetent
B and T cells
recirculate in
blood and lymph

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= Site of lymphocyte origin

= Site of development of
immunocompetence as
B or T cells; primary
lymphoid organs
= Site of antigen challenge,
activation, and final
diff erentiation of B and
T cells

1 Lymphocytes destined
to become T cells
migrate to the thymus
and develop
immunocompetence
there. B cells develop
immunocompetence
in red bone marrow.
2 After leaving the thymus
or bone marrow as nave
immunocompetent cells,
lymphocytes seed the
lymph nodes, spleen, and
other lymphoid tissues
where the antigen
challenge occurs.
3 Antigen-activated
immunocompetent
lymphocytes circulate
continuously in the
bloodstream and lymph
and throughout the
lymphoid organs of
the body.

Figure 21.8

T Cell Selection in the Thymus- Immunocompetence

Tolerancerecognizes/binds, MHC

Immunocompetence- has
only mild rxn to MHC
after binding; 2%

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Figure 21.9

B Cells- Immunocompetence

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

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Immunocompetent B or T cells
Display unique receptors responds to that antigen

Become immunocompetent before encountering

antigens they attack

Are exported to secondary lymphoid tissue where

encounters with antigens occur

Mature into fully functional antigen-activated cells

upon binding with their recognized antigen

It is genes, not antigens, that determine which

foreign substances our immune system will
recognize and resist

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Antigen-Presenting Cells (APCs)

1. Phagocytose antigens partially digest
2. Presents fragments of antigens on own surfaces

Cell types: Dendritic cells (Langerhans),

macrophages, B cells

Activate specific immune response, usu. in

lymphoid organs, by presenting antigens to T and B
cells;

Can interact with T lymphocytes & become

activated macrophages

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Adaptive Immunity: Summary

Humoral, Cellular

B & T 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

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Humoral Immunity Response

Antigen challenge first encounter between an

antigen and a naive immunocompetent cell

In spleen or other lymphoid organ

B cell receptor binds ag, receptor-mediated

endocytosis of the cross-linked antigen-receptor
complexes, T cell activation/interaction

B cell forms clones of identical cells (clonal

selection)

Specific Ab produced against specific ag

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Primary Response
(initial encounter
with antigen)

B lymphoblasts

Proliferation to
form a clone

Plasma
cells

Antigen
Antigen binding
to a receptor on a
specific B lymphocyte
(B lymphocytes with
non-complementary
receptors remain
inactive)

Memory
B cell

Secreted
antibody
molecules
Secondary Response
(can be years later)

Clone of cells
identical to
ancestral cells

Subsequent
challenge by
same antigen

Plasma
cells
Secreted
antibody
molecules
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Memory
B cells
Figure 21.10

Fate of the Clones

Secreted antibodies:

Bind to free antigens

Mark the antigens for destruction by specific or

nonspecific mechanisms

Clones that do not become plasma cells become

memory cells that can mount an immediate
response to subsequent exposures of the same
antigen

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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

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Immunological Memory

Secondary immune response re-exposure to the

same antigen; amnestic response

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

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Primary and Secondary Humoral Responses

IgM

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IgG

Figure 21.11

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

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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

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Types of Acquired Immunity

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Figure 21.12