Elements of

the Immune System and

their Roles in Defense

Chapter 1
Objectives
Distinguish Distinguish innate versus adaptive immune response

Define Define the roles of the cells of the immune system

Summarize Summarize lymphocyte circulation

Identify cells and their function in the draining lymph

Identify node during an adaptive immune response
 Immunology

Terms
Pathogen

Immune
system
• Greatest triumph in immunology
has been immunizations

• Immunization- procedure where

severe disease is prevented by
prior exposure to the infectious
agent in a form that cannot cause
disease

• Smallpox- viral disease caused by

pox virus
– first vaccine
– 1796 Edward Jenner showed
inoculation with cowpox offered
protection against smallpox virus
What is the main goal
of the Immune
System?

protect human body from infectious disease

Immune system overview
1st - innate 2nd - adaptive
immunity immunity
•Physical barrier •Takes time, but
•Chemical is specific
barrier
•Responses
ready and
waiting for
infection
Physical and
Chemical Barriers
• skin and mucous membranes
• skin: barrier of epithelium protected
by keratinized cells
• mucosal surfaces or mucosa: secrete
mucous (glycoproteins, enzymes)
• beating cilia continually remove
mucous
Antimicrobial substances secreted by
epithelial surfaces

sebum (fatty acids and lactic acid)

• inhibit bacterial growth on skin

defensins: antimicrobial peptides

• secreted by macrophage and neutrophils
• permeability in pathogen membrane

lysozyme attacks peptidoglycan

• tears and saliva
• degrade bacterial cell wall

acid pH (stomach, vagina, skin)

• deter pathogen growth
• microbial species that live in healthy human, occupy a
specific niche

Function of commensal organisms:

• Enhance human nutrition

• Protect against disease

• Some bacteria in the gut secrete antibacterial proteins

that prevent other bacteria from colonizing the gut-
some E. coli species secrete colicins
Antibiotic treatment and the colon
Immune system in a
nutshell

https://www.science.org.au/curious/video/immun
e-system-explained
Immune system
overview

Physical barrier

1st - innate
Chemical barrier
immunity

Responses ready
2nd - adaptive
and waiting for
immunity
infection
When barriers are 1. recognize pathogen is present
breached…..innate – Soluble proteins
immune response – Cell surface receptors
jumps into action 2. recruitment of destructive effector
mechanisms
– Kill and eliminate pathogen
INFLAMMATION
Immune system overview
1st - innate immunity
• Physical barrier
• Chemical barrier
• Responses ready and waiting for
infection

2nd- adaptive immunity

Adaptive immune response

• Lymphocytes- increase power and focus of immune

response

• Adapts to specific pathogen

• Long lasting

• Evolved only in vertebrates

Innate vs Adaptive Immunity
• cell-surface receptors used by lymphocytes to recognize
pathogens (receptors used by cells innate immunity are
not specific for a particular pathogen)

• highly pathogen specific (require cutting and gene splicing)

• only cells with pathogen specific receptors participate

• clonal selection and clonal expansion required

Selection
of lymphocytes
by a pathogen
primary immune response
• results in immunological memory and acquired
immunity
secondary immune response
• involves immunological memory
• also called acquired immunity or protective
immunity
• much stronger and faster response
• stops infection with minimal illness

vaccination induces immunological memory

What does the adaptive

immune response look like?
If you had to choose only one arm of the immune
system, which would you choose?

Innate Adaptive
Immunity Immunity
• How do we know
innate immunity is
important?
• What does this say
about vaccine
requirement

• benefit of both innate

and adaptive immunity

• normal individuals clear infecti

on with a combination of both

• innate immunity is required for

an adaptive response

• lack of adaptive response

can lead to failure to
clear infection

• much of medicine is
concerned with small
proportion of infections that
innate immunity fails to
terminate and the spread of
infection results in overt
disease
Site of
Hematopoiesis-

Blood cells are short

lived so they are
continually being
made
MEGAKARYOCYTE/ERYTHROID
PROGENITOR

Magakaryocytes
• Permanent residents of
bone marrow
• Giant nucleus
• Fusion of multiple
precursor cells
• Nuclei have multiple sets
of chromosomes
Platelets
– Membrane
enclosed
cytoplasm of
megakaryocytes
– Maintain
integrity of blood
vessels

Erythroblasts
• Gives rise to RBC
Granulocytes
• Cytoplasmic granules

• Kill microorganisms

• Enhance inflammation
1. Neutrophils
2. Eosinophils
3. Basophils
Neutrophils
• Most abundant granulocyte
• Capture, engulf and kill microorganisms
• Effector cells of innate immunity
• Short lived and die at site of infection (pus)
Eosinophils
• 2nd most abundant granulocyte
• Defends against helminth worms and
other intestinal parasites
Basophils
– Least abundant granulocyte
– defends against parasites
– Extremely rare so not much known about it
Macrophage and dendritic
cell precursor
• Monocyte

• Macrophage

• Dendritic cells
MONOCYTE
• Leukocytes that circulate
in the blood
• Precursor to macrophage
• Bigger than granulocytes
• Distinct indented nucleus
• All look same
MACROPHAGE

• Monocytes which travel in

blood to tissues
• Monocytes mature into
macrophages
• “Large phagocyte”
• Irregularly shaped cells
• Numerous vacuoles with
engulfed material
• Scavenger cells of the body
• Long lived
• Warn other cells
• 1st to sense invading
microorganism
• Secrete cytokines that
recruit neutrophils and
other leukocytes
Macrophage response to pathogen
Dendritic Cells
• In tissues
• Distinct star shaped
morphology
• Cellular messengers that
are sent to call adaptive
immune response
• How?
– Leave tissue with cargo of
intact and degraded
pathogens
– Take to lymphoid organs
that specialize in making
adaptive immune responses
Mast cells
• Found in all connective
tissues
• Granules like basophil
• Blood borne progenitor
unknown
• Activation and degranulation
of mast cells at infection site
major contributor to
inflammation
 Lymphoid progenitor
Natural killer cells (NK cells)
• Effector cells of innate immunity
• Defense against viral infections
• How?
vEnter infected tissue
vKill virus infected cells
vSecrete cytokines that impede viral
replication in infected cells
 Lymphoid progenitor
B cells and T cells
• Cells responsible for adaptive immune
response
• Circulate in quiescent and immature
state (functionally inactive)
• Recognition of pathogen results in
lymphocyte selection, growth and
differentiation
 B-lymphocytes (B-cells)

• Cell surface receptors are immunoglobulins

• Effector B cells are plasma cells
• Plasma cells secrete soluble forms of immunoglobulins
(antibodies)

B cells T-lymphocytes (T-cells)

and T • Cell surface receptors are T-cell receptors

cells • Only expressed as cell-surface receptor, never as soluble

proteins

Antigen- molecule or molecular fragment

that is recognized by an antibody, or B-cell
receptor or T-cell receptor

Antigen receptors- surface

immunoglobulins and T-cell receptors
Tophat
Immunoglobulins and T-cell receptors
• Similar structural molecules
• Product of genes that are cut, spliced and modified
• Each B-cell expresses a single type of immunoglobulin
• Each T-cell expresses a single type of T-cell receptor
• Millions of different immunoglobulins and TCRs represented in
population of small lymphocytes in one human
• Adaptive immune response made against one pathogen provides
no immunity against another pathogen
 B- differentiate
into Ab
cells producing
plasma cells

only effector
function of
B-cells

Differentiation
of B-cells and
T-cells T-
Kill cells infected with virus or
Two main Cytotoxic certain bacteria

effector T-cells
cells functions of
activated T-
cells

Secrete cytokines that help

Helper T- other cells become fully
activated effector cells

cells Macrophage more active in

phagocytosis

B cells to become plasma cells

Regulatory T-cells- control

activity of other T cells
Humoral immunity-

Neutralization

Opsonization

Most important function

of antibodies is to
facilitate engulfment and
destruction of extracellular
microorganisms and toxins by
phagocytes
• Major lymphoid organs
– Bone marrow
– Thymus
– Spleen
– Adenoids
– Tonsils
– Appendix
– Lymph nodes
– Peyer’s patches

• Primary lymphoid tissue

– Bone marrow
– Thymus

• Secondary lymphoid tissue

– All others

B lymphocytes and T lymphocytes

originate from bone marrow
B cells mature in bone marrow
T cells migrate in blood from bone marrow and mature in thymus
 Lymphatics

• Originate in the connective tissues

throughout the body

• Collect plasma that leaks out of blood

vessels and forms extracellular fluid
(lymph)

• Lymph returns to the blood via thoracic

duct into left subclavian vein in neck

• Unlike blood, lymph is not pumped- one

way valves in lymph vessels direct fluid
away from peripheral tissues

• Lymph flow is driven by body movement

• Edema- lymph accumulation in tissues

that results in swelling
 Lymphocyte recirculation
• Mature B and T cells move through body
in blood and lymph

• Leave primary lymph tissue where they

develop and enter blood

• When they reach the capillaries, they

leave blood and enter lymph node

• activated by pathogen - remain in lymph

node

• If not activated - remain for a short time

and then leave via the efferent lymph and
eventually return to blood

*One exception is the spleen- Lymphocytes enter and leave spleen

in the blood
Blood lymphocytes respond to lymph borne
pathogens

• Infection commonly occurs in connective

tissue where a skin wound occurs

• Myeloid dendritic cell carries pathogen to

nearest lymph node

• Draining lymph node

• In lymph node -B cells and T cells are

stimulated to divide and differentiate into
effector cells
• Arriving lymphocytes separate to the T cell area or B cell
area (lymphoid follicle)
• Infected dendritic cells and pathogens enter lymph node via
afferent lymphatic vessel
• Dendritic cells come in and stay
• Pathogens filtered out by macrophages
• Germinal centers formed by pathogen specific B cells that
bind the pathogen and proliferate “swollen glands”
Activation of adaptive
immunity in
draining lymph node

• Macrophage remove free pathogens

and debris

• Dendritic stay in T-cell areas

• Small lymphocytes enter

• Dendritic cells stimulate specific T

cells to become effector cells

• Helper T cells and cytotoxic T cells

leave and go to site of infection

• Other helper T cells stay and activate

B cells

• Plasma cells secrete antibodies

 Spleen

• Defend body against blood borne pathogens

• Macrophage and dendritic cells in the spleen

phagocytize microorganisms

• Stimulate B and T cells arriving in blood.

• Filter out damaged or old RBCs

 Asplenia
• mutations in gene for ribosomal protein SA (component of small subunit of
ribosome)
• Susceptible to infections of bacteria Streptococcus pneumoniae or
Haemophillis influenza
• Encapsulated bacteria not susceptible to phagocytosis, but are susceptible to
Ab. Young kids don’t make Abs to polysaccharides so are more susceptible (6
months-1 year)
• Immunize with vaccines that incorporate capsular polysaccharides of these
bacteria
• Adults who have splenectomy, but have previously been infected with these
pathogens have little problem

Mother child
 Secondary lymph tissue
• Gut associated lymphoid tissue (GALT)
– Tonsils
– Adenoids
– Appendix
– Peyer’s patches- line small intestine

• Bronchial associated lymphoid tissue

(BALT)
– line respiratory epithelium
 Secondary lymph tissue
• Mucosal associated lymphoid tissue
(MALT)
• Pathogens cross mucosa through M cells
• Lymphocytes enter tissue from blood and
if not activated leave lymphatics
• Activated lymphocytes stay within
mucosal system
Tophat