Immunology

Chapter 3a
Elements of the Immune
Systems
Cells of the Immune
System
Morphology and lineage of cells involved in the immune response.
Cells of the Immune System
Structures and
Functions of
Granulocytes
Antigen – Presenting Cells
Lymphoid lineage
 Lymphocytes/Lymphoid Cells

• Three major populations:

a. B lymphocytes (B cells);
b. T lymphocytes (T cells), and
c. Natural killer (NK) cells

✓ In humans, approximately a trillion

(1012) lymphocytes circulate
continuously through the blood and
lymph and migrate into the tissue
spaces and lymphoid organs.
Natural Killer cells (NK cells)
Non-specific Defense
Mechanisms
(Innate Response)
 Innate immunity

✓ Most primitive type of immune response

✓ Nonspecific defenses of the host; always present and active
✓ Defenses that are present at birth
✓ Immediate and rapid
✓ No prior exposure to antigen is needed
✓ Same every time; no “memory” as found in the adaptive
immune system
✓ Physical and chemical barriers
✓ Cellular defense
Components of Innate Immunity
 ESSENTIAL FUNCTIONS OF
INNATE IMMUNITY

1. Initial response to microbes

2. Eliminate damaged cells and initiate the
process of tissue repair
3. Stimulates adaptive immune response
 Four types of defensive barriers of
innate immunity
1. Anatomic barriers – skin and mucous
membranes
2. Physiologic barriers – temperature, low pH,
chemical mediators
3. Phagocytic/endocytic barrier – neutrophils,
macrophages, etc
4. Inflammation barriers
 ANATOMICAL BARRIERS:
Mucous Membranes
➢ Found in the conjunctive and alimentary, respiratory and
urogenital tracts
➢ Consist of an outer epithelial layer and an underlying
layer of connective tissue.
➢ Saliva, tears and mucous secretions (mucus)act to wash
away potential invaders and also contain antibacterial or
antiviral substances
➢ It is covered by cilia (respiratory tract)
➢ Normal flora
 Second Line of Defense

1. Phagocytic cells - macrophages

2. Inflammation
3. Fever (physiological barrier)
4. Antimicrobial substances (physiological
barrier)
5. Complement System
 A. Cells involved in the innate
immune system
a. Monocytes
b. Macrophages
c. Polymorphonuclear granulocytes
(polymorphonuclear neutrophils (PMNs),
basophils and eosinophils)
d. NK cells
e. Mast cells
f. Platelets
 PHAGOCYTIC BARRIER

➢ Phagocytosis - ingestion of
extracellular particulate material

➢ Endocytosis – the general term

for the uptake by a cell of
material from its environment.
a. Receptor – mediated
endocytosis
b. Pinocytosis
 Role of Phagocytes in Innate
Immunity
➢ Order of events in infection
1. Entry of pathogen
2. Recognition of pathogen
3. Phagocytosis and killing of a pathogen (macrophages)
➢ Reactive oxygen species (ROS), nitric oxide (NO) and lysosomal enzymes
4. Induction of inflammation
➢ Production of pro-inflammatory cytokines (TNF, IL-1, chemokines)
5. Attraction of cells to infection site
➢ Adhesive molecules (selectins and integrins) and chemokines
 Role of Phagocytes in Innate Immunity
➢ Order of events in infection
6. Pathogen elimination and/or adaptive immunity activation
7. Tissue repair and remodeling
➢ Enzymes and cytokines (growth factors, metaloproteinases
5. Attraction of cells to infection site
➢ Adhesive molecules (selectins and integrins) and chemokines
Steps in phagocytosis of a bacterium
 Natural Killer Cells
• play a vital role in innate
immune responses to
infection;
• they express activation
receptors that recognize
virus-infected cells.
• Highly related to receptors
recognizing tumor cells - the
activation receptors trigger
cytotoxicity and cytokine
production
 B. Inflammation

Inflammation is the body’s response to tissue damage or microbial invasion. The way
the body responds depends on:
1. What has caused the damage
2. Its location
3. Its severity

Damage can be caused by physical means or by infection. If an infection is present, the

body’s innate systems for limiting damage and repairing tissues work in concert with the
adaptive immune responses. This involves a number of overlapping stages, which
typically take place over a number of days or weeks.

Hallmarks of inflammation:
• Influx of fluid (edema)
• Increased temperature (hyperthermia)
• Decreased oxygenation (local hypoxia)
• Influx of white blood cells (extravasation)
➢Chemical mediators – acute-phase proteins
1. Histamine - vasodilation, increased permeability of
blood vessels
2. Kinins - vasodilation, increased permeability of blood
vessels
3. Prostaglandins – intensify the histamine and kinin
effect
4. Leukotrienes - increased permeability of blood
vessels, phagocytic attachment
5. Cytokines
Process of inflammation

a. Damage to tissue
b. Vasodilation and
increased permeability of
blood vessels
c. Phagocyte migration and
phagocytosis
d. Repair of damaged tissue
 Functions of Inflammation
1. Destroy the injurious agent
2. If destruction is not possible, to limit the effects
on the body by confining or walling off the
injurious agent and its by – products
3. To repair or replace tissue damaged
 Physiologic Barrier
➢ Include temperature, pH and various soluble and cell-associated
molecules.

a. lysozyme – hydrolytic enzyme found in mucous secretions and tears

✓ Able to cleave the peptidoglycan layer of the bacterial cell wall
b. Interferon – comprises a group of proteins produced by virus-infected cells.
✓ It has the ability to bind to nearby cells and induce a generalized antiviral
state
c. Complement – a group of serum proteins that circulate in an inactive state
 a. Complement System
➢ a system of plasma proteins
that can be activated directly by
pathogens or indirectly by
pathogen-bound antibody,
leading to a cascade of
reactions that occurs on the
surface of pathogens and
generates active components
with various effector functions
➢Also known as complement
cascade
 Complement system
➢ an alarm and a weapon against infection, and is
especially important against bacterial infections.
➢ The complement system is activation depends on the
type of pathways:
a. alternative or properdin pathway - directly by
bacteria and bacterial products
b. mannose-binding protein - by lectin binding to
sugars on the bacterial or fungal cell surface
c. classical pathway - by complexes of antibody and
antigen
Comparison of the different complement pathways
 General Properties of Complement

a. Primary role is cell lysis.

b. Activity of complement destroyed by heating sera to 56 C for 30
minutes.
c. IgM and IgG are the only immunoglobulin capable of activating
complement (classical pathway).
d. Complement activation can be initiated by complex
polysaccharides or enzymes (alternative or properdin pathway).
e. Portions of the complement system contribute to chemotaxis,
opsonization, immune adherence, anaphylatoxin formation, virus
neutralization, and other physiologic functions
BIOLOGIC EFFECTS OF COMPLEMENT
SYSTEM
a. Cytolysis of foreign organisms (e.g. bacteria)
b. Opsonization and phagocytosis of foreign organisms
c. Activation of inflammation and directed migration of
leukocytes
d. Solubilization and clearance of immune complexes
e. Enhancement of humoral immune response
BIOLOGIC EFFECTS
OF COMPLEMENT
SYSTEM
Source:Seghal N. et al.
http://epgp.inflibnet.ac.in/epgpdata/uploads/epgp_content/S000035ZO/P001308/M016709/ET/1466399838ComplementSystemQuad1.pdf
 C. FEVER
✓ An abnormally high body temperature
✓ 3rd component of the second line of defense
✓ Controlled by the hypothalamus
(sometimes called as the body’s thermostat)

➢ Substances that stimulate the

production of fever are called
pyrogens or pyrogenic substances
FEVER as defense against disease

1. Stimulate white blood cells (leukocytes) to deploy and

destroy invaders
2. Slow down the rate of growth of certain pathogens and
can even kill some especially fastidious pathogens
3. Reduce available free plasma iron
4. Induce the production of IL-1
5. Help in body tissues repair
D. Antimicrobial Proteins and Peptides