Main problems of clinical

immunology and
allergology. Principes of
the function of the
immune system.
Evaluation of the immune
state.
ASSESMENT OF THE
IMMUNE SYSTEM
What is the immune
system?
 The body’s defense against disease
causing organisms, malfunctioning
cells, and foreign particles
 Immunity
Definition ;
It is a homeostatic condition in which the
body maintains protection against infection and
tumor growth.

Function – major defense against infectious organisms &

abnormal or damaged cells
Defends against bacteria, viruses, fungi & parasites
Removes & destroys damaged/dead cells
Identifies & destroys malignant cells
Three Characteristics
Unique to the Immune
System
 Self-regulation
 Specificity
 Memory
Three Biological Defense
Mechanisms That Protect
the Body
 First line of defense (anatomic/biochemical barrier)
– Skin and mucous membranes
 Second line of defense (mechanical clearance)
– Skin sloughing, respiratory cilia, and urination
 Third line of defense (immune response)
– Long-lasting and sometimes permanent protection
– Structures
 Thymus

 Red bone marrow

 Spleen

 Lymph nodes, vessels, and tissues

 Skin
 The First Line of Defense
~Skin~

- The dead, outer layer of

skin, known as the
epidermis, forms a
shield against invaders
and secretes chemicals
that kill potential
invaders
- You shed between 40 –
50 thousand skin cells
every day!
Figure 8.6

Defensins (epithelium)
 Progression of Immunity

At least three cell types reside within or beneath the epithelium

and induce inflammation in response to trauma or microbial
products: Macrophages, Mast Cells, and Langerhan’s cells (a
skin dendritic cell)
 The First Line of Defense
~Mucus and Cilia~

- As you breathe in,

foreign particles and
bacteria bump into
mucus throughout
your respiratory system
and become stuck
- Hair-like structures
called cilia sweep this
mucus into the throat
for coughing or
swallowing
 The First Line of Defense
~Saliva~
What’s the first thing you do when you
cut your finger?
- Saliva contains many
chemicals that break down
bacteria
- Thousands of different types
of bacteria can survive these
chemicals, however
 The First Line of Defense
~Stomach Acid~

- Swallowed bacteria are

broken down by incredibly
strong acids in the
stomach that break down
your food
- The stomach must produce
a coating of special mucus
or this acid would eat
through the stomach!
Escherichia coli
is common and plentiful in all
of our digestive tracts.

- These bacteria are

technically outside the
body and aid in digesting
material we cannot
- Only if E.Coli are
introduced in an unnatural
manner they can break
through the first line of
defense and harm us
Defenses
 Phagocytic immune response

 Humoral/antibody response

 Cellular immune response

 Chemical Response

14
 Histamine- source: basophils, mast cells, platelets
Chemical Immune
– causes vasodilation and  vascular permeability
Response
 Kinins- source: precursor factor from clotting
system
– causes vasodilation and  vascular permeability
as well as pain receptors stimulated

 Fibrinopeptides- source: activation of clotting

system
–  vascular permeability and stimulates
Chemotaxis

 Prostaglandins/leukotrienes- source: substances

synthesized from the phospholipids of cell
membranes of most body tissues
  vascular permeability and stimulates
Chemotaxis

15
 Complement
 Consists of approx 25 enzymes that work with antibodies to help with puncturing
bacterial cell walls to destroy (during humoral response)
 Circulating plasma proteins, know as complement, are made in the liver and are
activated when an antibody connects with and antigen.

Complement System
 Three major physiologic functions
– Defending the body against bacterial infection
– Bridging natural and acquired immunity
– Disposing of immune complexes and the byproducts associated with inflammation

 The proteins that comprise the complement system interact sequentially

 Three ways to active:

– Classic pathway
– Alternative pathway
– Lectin pathway
Complement pathways

Fig 7.27 Parham

~Interferon~

- Virus-infected body
cells release
interferon when
an invasion occurs
 Fig 8.7

Effects of interferon


Effects on viral Improved recognition Increased innate

growth by adaptive immunity immune activity
Blood Cells
Development of Cells of the
Immune System

21
 Phagocytic Immune
Response
 WBC’s (leukocytes) participate in both, natural and
acquired immunity
 Granulocytes (granular leukocytes) release
mediators (such as histamine, bradykinin and
prostaglandins) and engulf antigen
 (includeneutrophils, eosinophils and
basophils)
 Neutrophils- first cells to arrive on scene

– Nongranular leukocytes
 Monocytes or macrophages (called Histiocytes
when they enter the tissue spaces)- ingest and
destroy greater number of foreign
bodies/toxins that granulocytes do. 22
Phagocytes

 Produced throughout life by the bone

marrow.
 Scavengers – remove dead cells and
microorganisms.
Circulating and Tissue
Effector Cells
 Neutrophils - Early phagocytosis and killing
of microbes
 Mast Cells - Release of inflammatory
granules
 Macrophages - Efficient phagocytosis
and killing of microbes: cytokines
 Eosinophils - Nasty toxic cells designed to
kill helminths (worms)
 Natural killer (NK) cells - Lysis of infected
cells, activation of macrophages
 ~White Blood Cells~ Neutrophil

- If invaders actually get

within the body, then
your white blood cells
(WBCs) begin their attack
- WBCs normally circulate
throughout the blood, but
will enter the body’s
tissues if invaders are
detected
 Neutrophils

 60% of WBCs
 ‘Patrol tissues’ as they squeeze out of the
capillaries.
 Large numbers are released during
infections
 Short lived – die after digesting bacteria
 Dead neutrophils make up a large
proportion of puss.
Figure 8.8
LPS receptor:
CD14
toll-like receptor-4
CR3,4:
Complement (C’)
receptors (C3b)
Scavenger receptor:
sialic acid-bearing
protein
Mannose receptor:
Binds mannose on
bacteria, activates C’
Glycan receptor:
Polysaccharides
Figure 1.6ef
Express some of the
same receptors found
on macrophages.
These cells are
specialized in killing
and swallowing
microbes

Effective against
worm infections.
Granules contain
mediators-smooth
muscle contraction
and worm toxicity
 Mast cells are also found in the tissues
Figure 1.14

TNF

Mast cells can

release histamines Redness, swelling Neutrophils and
which induce (erythema, edema) monocytes are
inflammation
recruited
 Basophil
~The Inflammatory Response~

- Injured body cells release

chemicals called
histamines, which begin
inflammatory response
- Capillaries dilate
- Pyrogens released, reach
hypothalamus, and
temperature rises
- Pain receptors activate
- WBCs flock to infected area
like sharks to blood
Figure 1.6gh
Function in disease, not entirely
understood
Contains high affinity receptors
for IgE, and preformed granules
that contain inflammatory
mediators including: histamine;
heparin; TNF; chondroitin
sulfate; neutral proteases; and
other.
Mast cells can also secrete:
cytokines to induce
inflammation; chemokines to
induce infiltration by monocytes,
and neutrophils, leukotriences to
induce muscle contraction and
increase vascular permeability
Mast cells are capable of
inducing an inflammatory
cascade
Macrophages
 Larger than neutrophils.
 Found in the organs, not the blood.
 Made in bone marrow as monocytes,
called macrophages once they reach
organs.
 Long lived
 Initiate immune responses as they
display antigens from the pathogens to
the lymphocytes.
Figure 1.6ij

Macrophages are
important first
responders to
infection and tissue
damage.

Alveolar macrophages
(lung)
Histiocytes (connective
tissue)
Kupffer cells (liver)
Mesangial cells (kidney)
Microglial cells (brain)
Tissue macrophage
Figure 1.13
Macrophages phagocytose
and degrade foreign particles,
bacteria and dead (and dying)
host cells.

Receptors on
Macrophages:
LPS receptor-CD14
Toll-like receptors
Fc receptors
Mannose receptor
Complement
receptors
IFN receptor
Chemokine
receptors
Phagocytosis
Macrophages
 Phagocytosis

 If cells are under attack they release histamine.

 Histamine plus chemicals from pathogens mean
neutrophils are attracted to the site of attack.
 Pathogens are attached to antibodies and
neutrophils have antibody receptors.
 Enodcytosis of neutrophil membrane  phagocytic
vacuole.
 Lysosomes attach to phagocytic vacuole 
pathogen digested by proteases
White Blood Cells
~T-Cells~
 T-Cells, often called
“natural killer” cells,
recognize infected human
cells and cancer cells
 T-cells will attack these
infected cells, quickly kill
them, and then continue
to search for more cells
to kill
 Natural Killer Cells
play several
interesting roles in the
immune system. One
is to monitor cells for
identification. If a cell
doesn’t reveal its
identity papers, it is
killed.

Dendritic cells are the

most important
antigen presenting
cells (APCs) in the
immune system

Figure 1.6cd
Two Divisions of the
Immune System
- The efforts of the WBCs known as
phagocytes and T-cells is called the
cell-mediated immune system.
- Protective factor = living cells
- Phagocytes – eat invaders
- T-cells – kill invaders
Two Divisions of the
Immune System
 The other half of the immune system
is called antibody-mediated immunity,
meaning that is controlled by
antibodies
 This represents the third line of
defense in the immune system
Cellular Components of
Immune Response
 Lymphocytes
– Primary cells concerned with the development
of immunity
– Have the ability of self-recognition, specificity,
and memory
– Two types
 B lymphocytes (B cells) (humoral immune response)
 T lymphocytes (T cells) (cell-mediated immune
response)
Cell-Mediated Immune
Response
 When presented with an antigen,
helper T cells produce signaling
substances such as interferon,
interleukin, and tumor necrosis factor
 Inflammation and other body activities
are promoted
 Lymphocytes
 Produce antibodies
 B-cells mature in bone marrow then
concentrate in lymph nodes and spleen
 T-cells mature in thymus
 B and T cells mature then circulate in the
blood and lymph
 Circulation ensures they come into contact
with pathogens and each other
 T-Lymphocytes
 Mature T-cells have T cell receptors which
have a very similar structure to antibodies
and are specific to 1 antigen.
 They are activated when the receptor
comes into contact with the Ag with
another host cell (e.g. on a macrophage
membrane or an invaded body cell)
 Cell-Mediated Immune
Response
 Comprised of a variety of T cells
 Th (helper T)
– Exhibits TCR receptors
– CD (clusters of differentiation) markers
– Interacts with macrophage antigen-presenting cell (APC)
– Causes binding of entire Th to antigen
– Produces signaling substances
 Interleukins, interferon, and tumor necrosis factor
– Tc and B cells (and others) stimulated
Lymphocytes are
entirely involved with
acquired immunity.
These come in two
types: T lymphocytes (T
cells) that differentiate
in the thymus and B
lymphocytes or B cells
that differentiate in the
bone marrow.

B cells can further

differentiate after
antigen-activation to
plasma cells that
produce antibodies
Humoral Immune
Response
 Initiated when an antigen binds with
the antibody receptors on the surface
of the mature B cell
 Triggers a sequence of events that
results in production of plasma cells
that secrete antibodies
(immunoglobulin molecules)
 T-Lymphocytes
 After activation the cell divides to form:
 T-helper cells – secrete CYTOKINES
 help B cells divide
 stimulate macrophages
 Cytotoxic T cells (killer T cells)
 Kill body cells displaying antigen
 Memory T cells
 remain in body
Humoral Immune
Response
 Primary
– First exposure to antigen
– Latent period
 Secondary
– Rapid production of large amounts of
antibodies
– Immediate response; may last for several
years
Humoral Immune
Response
 Comprised of B cells
– Assisted in the beginning by Th cells
 Plasma cells are produced and secrete
antigen-specific antibodies
 Memory cells
– Long lives
– React swiftly to specific antibodies
B -Lymphocytes
 There are near 10 million different B-
lymphocytes, each of them produces a
different antibody.
 The huge variety is caused by genes
coding for abs changing slightly during
development.
 There are a small group of clones of
each type of B-lymphocyte

Lymphocytes
B lymphocytes mature in the bone marrow; T lymphocytes
mature in the thymus where they also differentiate into cells
with various functions

55
B -Lymphocytes
 At the clone stage antibodies do not leave the
B-cells.
 The abs are embedded in the plasma
membrane of the cell and are
called antibody receptors.
 When the receptors in the membrane
recognise and antigen on the surface of the
pathogen the B-cell divides rapidly.
 The antigens are presented to the B-cells by
macrophages
B -Lymphocytes
 Some activated B cells  PLASMA CELLS
these produce lots of antibodies,
 The antibodies travel to the blood,
lymph, lining of gut and lungs.
 The number of plasma cells goes down
after a few weeks
 Antibodies stay in the blood longer but
eventually their numbers go down too.
B -Lymphocytes
 The Third Line of Defense
~Antibodies~

- Most infections never make

it past the first and second
levels of defense
- Those that do trigger the
production and release of
antibodies
- Proteins that latch onto, damage,
clump, and slow foreign particles
- Each antibody binds only to one
specific binding site, known as an
antigen
 Antibody Production

- WBCs gobble up invading

particles and break them up
- They show the particle pieces
to T-cells, who identify the
pieces and find specific B-
cells to help
- B-cells produce antibodies
that are equipped to find that
specific piece on a new
particle and attach
 Antibodies
 Also known as immunoglobulins
 Globular glycoproteins
 The heavy and light chains are polypeptides
 The chains are held together by disulphide
bridges
 Each ab has 2 identical ag binding sites –
variable regions.
 The order of amino acids in the variable region
determines the shape of the binding site
 How Abs work
 Some act as labels to identify
antigens for phagocytes
 Some work as antitoxins i.e. they block toxins for
e.g. those causing diphtheria and tetanus
 Some attach to bacterial flagella making them less
active and easier for phagocytes to engulf
 Some cause agglutination (clumping together) of
bacteria making them less likely to spread
Humoral Immune
Response
 Five classes of immunoglobins
(MADGE is acronym to aid memory)
– IgM
– IgA
– IgD
– IgG
– IgE
Different
Immunoglobulins
 Five types of Ig
 IgA, IgG and IgM respond to viral
and bacterial invasion.
 IgD may assist in B cell binding
with antigen
 IgE is present during inflammatory
responses and causes allergic
response
Type Number of Site of action Functions
ag binding
sites
IgG 2 Blood Increase

Tissuefluid macrophage activity

CAN CROSS Antitoxins

PLACENTA Agglutination

IgM 10 Blood Agglutination

Tissue fluid

IgA 2 or 4 Secretions (saliva, Stop bacteria

tears, small intestine, adhering to host
vaginal, prostate, cells
nasal, breast milk) Prevents bacteria
forming colonies on
mucous membranes
IgE 2 Tissues Activate
mast cells
 HISTAMINE
Worm response
Role of Antibodies
 Agglutination- (clumping of antigens)
– Helps clear the body of the invading organism by
facilitating phagocytosis
 Opsonization- the antigen-antibody molecule is coated
with a sticky substance to facilitate phagocytosis

 Promote release of vasoactive substances; activation of

complement system and phagocytosis
 Act in concert with other components of the immune
system

 Types of immunoglobulins: IgA, IgD, IgE,IgG, and IgM

67
Immune Function
 Natural immunity: nonspecific response to any foreign
invader
– White blood cell action: release cell mediators such
as histamine, bradykinin, and prostaglandins, and
engulf (phagocytize) foreign substances
– Inflammatory response
– Physical barriers, such as intact skin, chemical
barriers, and acidic gastric secretions or enzymes in
tears and saliva
 Acquired immunity: specific against a foreign antigen
– Result of prior exposure to an antigen
– Active or passive

68
Types of Immune
Response
 Cell-Mediated – occurs when antigen lives
within the body cell (bacteria, virus, fungus,
cancer)
 Macrophages identify antigen & T cells
(killer T’s, cytoxic cells) & defend against it.
 Delayed response- graft rejection,
hypersensitivity reactions, tumor immunity,
immunity against bacteria, virus & fungus
 Antigen specific – Antigen must be present
on cell surface
What is immunity?

- Resistance to a disease causing

organism or harmful substance
- Two types
- Active Immunity
- Passive Immunity
 Passive Immunity
 You don’t produce the
antibodies
– A mother will pass
immunities on to her
baby during pregnancy
– These antibodies will
protect the baby for a
short period of time
following birth while its
immune system develops.
 Variables That Affect
Immune System Function
 Age and gender
 Nutrition
 Presence of conditions and disorders: cancer/neoplasm, chronic illness,
autoimmune disorders, surgery/trauma
 Allergies
 History of infection and immunization
 Genetic factors
 Lifestyle
 Medications and transfusions: see Table 50-6
 Pyschoneuroimmunologic factors

ALTERED IMMUNE RESPONSES

 Immunoincompetance
– Severe infection, immunodeficiency diseases, malignancy
 Overactive System
– hypersensitivities

73
 Health History and Physical
Examination: Key Assessments
 Disorders and diseases
– Autoimmune disease
– Neoplastic disease
– Chronic illness
– Surgery
 Pain
 Medication
 Blood transfusions
 Lifestyle, stress, and other factors
 Age
 Nutrition
 Recent infections
 Immunization status
 Allergies
 Weight changes, skin lesion, rashes, or impaired healing.
 Activity intolerance, frequent sore throats, URI, swollen glands, easy brusing,
joint pain, swelling, enlarged lymph nodes.
 Acute: erythema, local heat, pain
Assessment – chronic
allergy
 Skin – rashes, itching
 – conjunctivitis, dark circles under
eyes, excessive rubbing/ blinking,
recurrent ear infection, diminished
hearing, nasal voice rhinitis, pale,
swollen mucous membranes, throat
clearing, swollen lips/ tongue,
enlarged lymph nodes
Tests to Evaluate Immune
Function
 WBC count and differential
– Bone marrow release more neutrophils, may
release “bands” which are immature cells to
keep up. “shift to the left” means acute
bacteria infection. (mature
neutrophils=segmented neutrophils)
 Bone marrow biopsy
 Phagocytic cell function test
 Complement component tests
 Hypersensitivity tests
 Specific antigen–antibody tests
 HIV infection tests 76