The Immune System

                                                               

Dr. Anuar Sani 17 July 2007

FPSK USIM Y1 FPSK USIM 2007/08
http://apc.ucc.ie
 Components of Whole Blood

Plasma
(55% of whole blood)

Buffy coat:
leukocyctes and
platelets
(<1% of whole blood)
Formed
elements
Erythrocytes
1 Withdraw blood 2 Centrifuge (45% of whole blood)
and place in tube

Figure 17.1
 Protection
• Blood prevents infection by:
– Synthesizing and utilizing antibodies
– Activating complement proteins
– Activating WBCs to defend the body against
foreign invaders
 Leukocytes (WBCs)
• Leukocytes, the only blood components that
are complete cells:
– Are less numerous than RBCs
– Make up 1% of the total blood volume
– Can leave capillaries via diapedesis
– Move through tissue spaces
• Leukocytosis – WBC count over 11,000 per
cubic millimeter
– Normal response to bacterial or viral invasion
 Granulocytes
• Granulocytes – neutrophils, eosinophils,
and basophils
– Contain cytoplasmic granules that stain
specifically (acidic, basic, or both) with
Wright’s stain
– Are larger and usually shorter-lived than RBCs
– Have lobed nuclei
– Are all phagocytic cells
 Neutrophils

• Neutrophils have two types of granules that:

– Take up both acidic and basic dyes
– Give the cytoplasm a lilac color
– Contain peroxidases, hydrolytic enzymes, and
defensins (antibiotic-like proteins)
• Neutrophils are our body’s bacteria slayers
 Eosinophils

• Eosinophils account for 1–4% of WBCs

– Have red-staining, bilobed nuclei connected via a
broad band of nuclear material
– Have red to crimson (acidophilic) large, coarse,
lysosome-like granules
– Lead the body’s counterattack against parasitic
worms
– Lessen the severity of allergies by phagocytizing
immune complexes
 Basophils

• Account for 0.5% of WBCs and:

– Have U- or S-shaped nuclei with two or three
conspicuous constrictions
– Are functionally similar to mast cells
– Have large, purplish-black (basophilic) granules
that contain histamine
• Histamine – inflammatory chemical that acts as a
vasodilator and attracts other WBCs (antihistamines
counter this effect)
 Agranulocytes

• Agranulocytes – lymphocytes and

monocytes:
– Lack visible cytoplasmic granules
– Are similar structurally, but are functionally
distinct and unrelated cell types
– Have spherical (lymphocytes) or kidney-shaped
(monocytes) nuclei
 Lymphocytes
• Account for 25% or more of WBCs and:
– Have large, dark-purple, circular nuclei with a thin
rim of blue cytoplasm
– Are found mostly enmeshed in lymphoid tissue
(some circulate in the blood)
• There are two types of lymphocytes: T cells and
B cells
– T cells function in the immune response
– B cells give rise to plasma cells, which produce
antibodies
 Monocytes

• Monocytes account for 4–8% of leukocytes

– They are the largest leukocytes
– They have abundant pale-blue cytoplasms
– They have purple-staining, U- or kidney-shaped
nuclei
– They leave the circulation, enter tissue, and
differentiate into macrophages
 Monocytes

• Macrophages:
– Are highly mobile and actively phagocytic
– Activate lymphocytes to mount an immune
response
Summary of Formed Elements

Table 17.2
Summary of Formed Elements

Table 17.2
 Production of Leukocytes
• Leukopoiesis is hormonally stimulated by two
families of cytokines (hematopoietic factors) –
interleukins and colony-stimulating factors (CSFs)
– Interleukins are numbered (e.g., IL-1, IL-2), whereas
CSFs are named for the WBCs they stimulate (e.g.,
granulocyte-CSF stimulates granulocytes)
• Macrophages and T cells are the most important
sources of cytokines
• Many hematopoietic hormones are used clinically
to stimulate bone marrow
Formation of Leukocytes

Figure 17.11
 The Immune System
Defends body against pathogens
Can distinguish between self and non-self

General Defence System (innate) Specific Defence System (adaptive)

Non-specific = acts against all pathogens
Rapid

1. First line of general defence

Skin = barrier. Sweat (acidic pH)
Clotting = also helps protect skin
Lysozyme = enzyme in saliva, sweat, tears. Attacks bacterial cell walls
Mucous (respiratory, digestive, urinary & reproductive tracts) = traps pathogens
Cilia = little hairs that help clear mucous (and pathogens) from respiratory tract
Alimentary canal = lysozyme in saliva, stomach HCl kills many pathogens, specialised
immune areas in the GI tract, very high turnover of epithelial cells, antibodies
 2. Second line of general defence
Phagocytic white blood cells (leukocytes) = destroy pathogens that enter
Complement
Inflammation

Phagocytes – (Phago= eat; cyte=cell)

attracted to a site of infection (chemotaxis) by chemicals released by injured cells
Three types – neutrophils (short lived),
monocytes (short-lived..in blood) and macrophages (long-lived..in tissue)
Immune organs Macrophages – very large white cells that can move
around body, or remain in certain tissues. Long lived,
act as scavengers
 2. Second line of general defence cont.
Complement
• set of 30 proteins found in plasma that are activated by
infection
• complicated chain reaction that leads to the bursting of
viruses and bacteria
• made in the liver

Interferons
• set of proteins produced by virally infected cells cells to limit the spread of viral
infections, by inducing a state of resistance in healthy cells.
• induced by viruses, bacteria and other signals from the immune system

Inflammation
• infected cells (mast cells) release histamine, which is a vasodilator. This causes
localised swelling, redness, heat, pain. Can also cause high temperature.
• brings white cells to the area of infection
• Anti-histamines
Complement Pathways

Figure 21.5
Interferon (IFN)

Figure 21.4
Inflammatory Response: Phagocytic
Mobilization

4 Positive
chemotaxis
Inflammatory
chemicals
diffusing from
the inflamed
site act as
chemotactic
1 Neutrophils agents
enter blood
from bone 3 Diapedesis
marrow 2 Margination

Endothelium
Capillary wall
Basal lamina
Figure 21.3
 Immunocompetent B or T cells
Red Key: = Site of lymphocyte origin
bone marrow
= Site of development of immunocompetence
as B or T cells; primary lymphoid organs
= Site of antigen challenge and final
Immature differentiation to activated B and T cells
Circulation in lymphocytes
1
blood
1 1 Lymphocytes destined to become T
Thymus cells migrate to the thymus and
develop immunocompetence there. B
Bone
marrow cells develop immunocompetence in
red bone marrow.

2 2 After leaving the thymus or bone

Immunocompetent,
marrow as naive immunocompetent
but still naive, Lymph nodes,
spleen, and other cells, lymphocytes “seed” the lymph
lymphocyte
lymphoid tissues nodes, spleen, and other lymphoid
migrates via blood
tissues where the antigen challenge
occurs.

3 Mature (antigen-activated)
3 3 immunocompetent lymphocytes
circulate continuously in the
Activated bloodstream and lymph and
immunocompetent throughout the lymphoid organs of
B and T cells the body.
recirculate in blood
and lymph

Figure 21.8
 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
 Specific Defence System (Adaptive Immune System)

Antigens – foreign molecules that

generate antibody production

Antibodies (immunoglogulins) – proteins

produced by lymphocytes in response
to antigens

Monocytes – develop into macrophages which phagocytose foreign particles (antigens)

Lymphocytes -
 Classes of Antibodies
• IgD – monomer attached to the surface of B cells,
important in B cell activation
• IgM – pentamer released by plasma cells during the
primary immune response
• IgG – monomer that is the most abundant and diverse
antibody in primary and secondary response; crosses the
placenta and confers passive immunity
• IgA – dimer that helps prevent attachment of pathogens to
epithelial cell surfaces
• IgE – monomer that binds to mast cells and basophils,
causing histamine release when activated
Mechanisms of Antibody Action

Figure 21.13
Major Types of T Cells

Figure 21.14
 T-lymphocytes
Mature in Thymus, which is most active just before and after birth.
The thymus starts to shrink during puberty.

Helper T-Cells Killer T-Cells Suppressor T-Cells Memory T-Cells

•Recognise antigens on Also called cytotoxic •Control the •Can survive a long time
surface of leukocytes, •Destroy abnormal body immune system and give lifelong
especially macrophages cells, e.g. virus infected when the immunity from
•Enlagre and form a or cancer cells antigen /pathogen infection
clone of T-helper cells •Stimulated by cytokines has •Can stimulate memory
•Secrete interferon and (THcells) been destroyed B-cells to produce
cytokines which •Release perforin, which •Only recently antibodies
stimulate B-cells and forms pores in target discovered so •Can trigger production
stimulate killer -cells cells. This allows water little is known of killer T cells
•Can be infected by HIV and ions in = lysis about them
 Killer T-cell How T-cells work…
Abnormal cell e.g recognises antigen
cancer cell, infected cell

Antigen
X
Killer T-cells release
perforin pores
Clones of killer T-cell
attach to antigen

X
Normal cell

Helper T-cell stimulates

correct killer T-cell to
multiply
X
Helper T-cell also
Abnormal cell gains
water, swells and
stimulates B-cells bursts
to make antibodies

Memory T-
cells stay in
Suppressor T-cells
circulation
turn off immune
response
Duration of immunity
Memory B-cells circulate for a long time. If the same pathogen infects the
body again, these B-cells can produce large amounts of specific antibody
very quickly. This is why you usually don’t suffer from the same infection
twice.
Memory T-cells survive a long time and trigger an immune response

Immune disorders
•Sometimes the body produces antibodies against its own tissues e.g. autoimmune
diseases e.g. rhumatoid arthritis, Crohn’s disease, SCID (bubble boy disease),
asthma

•Allergies occur when the body reacts to materials which should not
be antigenic e.g. peanuts

•Tumours – in most cases the body recognises tumours as being bad, because they
express abnormal molecules on the cell surface. However sometimes the body doesn’t
notice and cancers can develop
 Induced Immunity

Active immunity Passive immunity

Production of a person’s own An individual is given antibodies by another
antibodies. Long lasting Short-term resistance (weeks- 6months)

Natural Active Artificial Active Natural Passive Artificial Passive

When pathogen Vaccination – usually Baby in utero Gamma globulin
enters body in the contains a safe antigen (placenta) injection
normal way, we from the pathogen. Breast-fed babies Extremely fast, but
make antibodies Person makes short lived (e.g. snake
antibodies without venom)
becoming ill

yummy

Edward Jenner
Overview of the Immune Response