Transcript Lecture 8- Immunity

THE IMMUNE SYSTEM
Prof. Khaled H. Abu-Elteen
Terminology
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Types of Symbiosis ( Living togathers)
- Amensalism
A symbiotic relationship in which one species is
harmed, but it isdifficult to see how the other species
benefit.
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Mutualism
 A symbiotic relationship in which both species benefit
Commensalism
 A symbiotic relationship in which one species benefits,
and the other species is neither helped nor harmed
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Types of Symbiosis (cont.)
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Parasitism
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A symbiotic relationship in which one
species benefits, and the other species is
harmed
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Generally, the species that benefits (the
parasite) is much smaller than the species
that is harmed (the host)
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Disease and Infectious Disease
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Disease
 Any deviation from a condition of good
health and well-being
Infectious Disease
 A disease condition caused by the presence
or growth of infectious microorganisms or
parasites
Immunology lingo
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Antigen
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Pathogen
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A glycoprotein produced in response to the introduction of an antigen
Vaccination
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Secreted immunoglobulin
Immunoglobulin (Ig)
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Microorganism that can cause disease
Antibody (Ab)
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Any molecule that binds to immunoglobulin or T cell receptor
Deliberate induction of protective immunity to a pathogen
Immunization
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The ability to resist infection
TYPES OF IMMUNITY.
Nonspecific: Skin and mucous membranes,
Phagocytosis, Inflammation, and The
Complement System.
 Specific: Humoral(Antibody-Mediated) and
Cell-Mediated.
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Nonspecific Immune Response
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Physical and Mechanical Barrier’s
Chemical Factor’s
Biological Factor’s
Phagocytosis and Associated with Blood and
lymph
Defenses that protect from ANY pathogen
regardless of type and species( Bacteria, Fungi,
Protozoa, etc).
Physical and Mechanical Barrier’s
THE SKIN: First Line Of Defense.
 Repels many organisms: difficult to get
through.
 Epithelium lines all body systems exposed to
external environments including the respiratory,
digestive and urinary systems.
 Secretes liquid which are mildly acidic which
hinder bacterial growth.
 Lack of nutrition for microbial growth.
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DEFENSES
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Dry
 usual
infection sites are wet areas, skin folds, armpit,
groin
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Acidic (pH 3.0- 5.0)
Temperature less than 37oC
 Some
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Lysozyme and toxic lipids
 pore,
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pathogens grow best <37oC
hair follicles, sweat gland
Resident microflora
 mainly
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G+
Skin-associated lymphoid tissue (SALT)
Tears and saliva contain lysozymes which
dissolve the wall of bacteria.
 Cilia of respiratory tract trap bacteria in
mucus.
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SKIN AND MUCOUS
MEMBRANES:1st line of defense
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Mechanical Factors:
Skin.
The Epidermis.
Keratin.
Mucous Membranes.
Lacrimal Apparatus ------>
Cilliary Escalator [ mucocilliary Escalator Action).
LACRIMAL APPARATUS.
CILIARY ESCALATOR.
Flushing Mechanisms
Epiglottis.
 Urine and Vaginal secretions.
 Sneezing, coughing, swallowing reflex
 Movement of Fluids across their surfaces
(Saliva)
 Washing action of tears
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CHEMICAL FACTORS.
Sebum and fatty acids in skin ( e.g.
unsaturated fatty acids as Olic acid).
 Gastric Juice (Low pH stomach ).
 Lyzozyme: degrade the bacterial cell wall
 Antimicrobial peptides (β Lysine) with high
quantity of Lysine or Arginine. Act by
disruption of plasma membrane of
microorganisms.
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Complement:complex
of 17 proteins
(Glycoproteins) present in normal serum) C1,
C2, C3 …..etc. Function: Lysis of microbes,
Neutralization of viruses, Enhancement of
phagocytosis, Damage of plasma membrane,
Recruitment of Phagocytes,
Interferons
: Family of Glycoproteins that
block Viral Replication by rendering host cells,
NORMAL MICRIBIOTA AND
NONSPECIFIC RESISTANCE.
Microbial Antagonism.
 Commensalism.
 Competitive Exclusion: Opportunistic
pathogens.
 Natural Resistance: Microorganisms has a
host range
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Cells of the Immune system:
FORMED ELEMENTS IN BLOOD.
Many cells of
the immune
system derived
from the bone
marrow
 Hematopoetic
stem cell
differentiation
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Components of blood
Serum vs. Plasma
 Serum: cell-free liquid, minus the
clotting factors
 Plasma: cell-free liquid with clotting
factors in solution (must use an
anticoagulant)
 Contain protein: Albumin, Globulin
and Fibrinogen.
Components of blood
LEUKOCYTES.
Divided into two main categories based on
their appearance under the light microscope:
 Granulocytes Versus Agranulocytes.
 Granulocytes: Neutrophils(stain lilac),
Basophils (stain blue-purple), and
Eosinophils (stain red or orange).
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NEUTROPHILS ( 60% of WBC)
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Commonly called
polymorphonuclear
leukocytes (PMNs).
Multinucleated.
Highly phagocytic and
motile.
Active in the initial stages
of infection.
Short life span (hours)
Very important at
“clearing” bacterial
infections
Innate Immunity
BASOPHILS (1% of WBC)
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Role is not clear.
Release substances,
such as histamine, that
are important in
inflammation.
Might be “blood Mast
cells’
Important in allergic
reactions
Eosinophils ( 3% of WBC)
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Somewhat phagocytic.
Have the ability to leave
the blood.
Major function is to
produce toxic proteins
against certain parasites
such as worms.
Involved in allergic
inflammation
Double Lobed nucleus
Orange granules contain
toxic compounds
AGRANULOCYTES.
Monocytes ( 5% of all WBC).
 Macrophages.
 Lymphocytes ( 30% of all WBC) .
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MONOCYTES.
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Phagocytosis and killing
of microorganisms
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Activation of T cells and
initation of immune
response
Monocyte is a young
macrophage in blood
There are tissue-specific
macrophages
Antigen Presentation
MACROPHAGES.
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Maturation and
proliferation of is one
factor that is
responsible for the
swelling of lymph
nodes during an
infection.
Lymphocytes
Many types:
 B-cells produce
antibodies( Humoral
immunity)
 T- cells (Cellular
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immunity)
– Cytotoxic T cells
– Helper T cells
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Memory cells
Lymphocytes
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Plasma Cell (in tissue)
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Fully differentiaited B
cells, secretes Ab
Natural Killer cells
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Kills cells infected with
certain viruses
Both innate and adaptive
Antigen presentation
TH cells play a central role in the immune system
Antigen
Presenting
Cell
Dendritic Cells
Activation of T cells and
initiate adaptive immunity
 Found mainly in
lymphoid tissue
 Function as Antigen
Presenting Cells (APC)
 Most potent stimulator of
T-cell response
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Mast Cells
Expulsion of parasites through release
of granules
 Histamine, leukotrienes, chemokines,
cytokines
 Also involved in allergic responses
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Other Blood Cells
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Megakaryocyte
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Platelet formation
Wound repair
Erythrocyte
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Oxygen transport
Cells, tissues and organs of
the immune system
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Immune cells are bone marrow-derived, & distributed through out
the body
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Primary lymphoid organs:
– Thymus: T cell maturation
– Bone marrow (bursa of Fabricius in birds): B cell maturation
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Secondary lymphoid organs:
– Lymph nodes
– Spleen
– Mucosal lymphoid tissues (lung, gut)
2º
2º
1º
2º
2º
Major Tissues
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2º
2º
2º
1º
Primary Lymph
tissues
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Cells originate
or mature
Secondary
Lymph Tissues
COMPONENTS OF THE
LYMPHATIC SYSTEM.
Dendritic cell
(sentinel)
The bursa of Fabricius in birds
ACTION OF PHAGOCYTIC
CELLS.
Wandering macrophages.
 Fixed macrophages.
 Mononuclear phagocytic
(reticuloendothelial) system.
 During the initial infection, granulocytes,
especially neutrophils are many and they
dominate.
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Opsonization.
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Opsonization - coating micro-organisms with
plasma proteins – aids phagocytosis.
Complement binds to antibody-antigen targets.
Promotes adhesion between opsonized cell &
macrophages.
Opsonin binds to receptors on phagocyte
membrane.
PHAGOCYTOSIS: 2ND LINE
OF DEFENSE.
Cell Eating.
 Phagocytes: Cells that perform
phagocytosis.
 Are mostly types of white blood cells or
derivatives of white blood cells.
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THE MECHANISM OF
PHAGOCYTOSIS.
Chemotaxis.
 Adherence.
 Ingestion.
 Digestion.
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3. Phagocytosis & oxidative
burst.
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Certain WBCs - phagocytosis.
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Chemotactically attracted to disease / tissue
damage foci.
Stages:
1.
Engulfment of particulate matter into phagosome.
(e.g. bacteria, virions, cell debris, etc.).
2.
Phagosome fuses with lysosomes =
phagolysosome.
3. Phagocytosis & oxadative
burst.
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Lysosomes contain enzymes = degrade
biomolecules.
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E.g. acid hydrolases, lysozyme, neutral proteases,
myeloperoxidase, lactoferrin, & phospholipase A.
Human macrophage engulfing the fungus Candida
albicans.
3. Phagocytosis & oxidative burst.
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Yeast
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Engulfed organisms killed in WBC by
“respiratory (oxidative) burst".
Many pathogens / parasites succeed because avoid
phagocytosis.
Neutrophil
Human neutrophil kills yeast cell using
oxidative burst.
Dye shows extent of reactions.
INFLAMMATION: Second line
of defense.
Inflammatory response results in increased
blood flow to infection; chemical attractants
and flow of fluid to wound ( vasodilation).
 Together these cause swelling, heat, and
pain.
 Fluids include histamine and serotonine
(causes arterioles to dilate), and plasma
(contains clotting factors to wall off area.
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Kinins: cause vasodilation and increased
permeability of blood vessels.
 Prostaglandins: released by damaged cells,
and intensifies the effects of histamin and
kinins.
 Leukotrienes: produced by mast cells and
basophils- Cause increased permeability,
and attract phagocytes to pathogens.
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Vasodilation and increased permeability of
blood vessels also help to deliver clotting
elements to injured area.
 Blood clots prevent microbe from
spreading, so a localized collection of pus
results(abcess).
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Inflammation.
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Inflammation - phagocytes & complement
recruited to site tissue invasion.
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Non-specific reaction to tissue damage.
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Cell damage initiates inflammation.
Inflammation.
• Vasodilation - swelling.
• Adhesion of leukocytes to
endothelial cells & migration
phagocytes into tissues.
• Redness (blood flow).
• Pain (prostaglandins).
• Heat (pyrogens).
• Inflammation localised to area
infection / injury and give pus.
•Once organisms destroyed
inflammation resolves.
Inflammation
Figure 22.13
Types of Immunity
Figure 22.14
Types of immunity
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Innate (natural) immunity
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Phagocytes etc.
Early, rapid responses, but limited & ‘non-specifc’
Adaptive (acquired) immunity
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Lymphocytes (B & T cells)
Take time but powerful - ‘specificity + memory’
Measles attacks & immunological memory
Vaccination protects us from infection by
inducing the adaptive immune response, but
bypassing the need for a primary infection
B Cells
work chiefly by secreting
soluble substances known
as antibodies (Ab)
Ab basic structure
domains
Ab V and C regions
Fab
region
Antigen
binding
site
Fc region
Activate of
Complement
Figure 22.21 Antibody Structure
Figure 22.21a
Figure 22.21 Antibody Structure
Figure 22.21b-d
Actions of antibodies include:
Neutralization
 Agglutination and precipitation
 Activation of complement
 Attraction of phagocytes
 Opsinization
 Stimulation of inflammation
 Prevention of adhesion
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Generation of immune response.
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Immunogen = any molecule that stimulates
immune response. Proteins best immunogens >
carbohydrates > nucleic acids. Lipids very poor.
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Antigen = molecule capable of generating
antibody response.
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Antigen = antibody generating.
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Haptan= Ag incapable of stimulating immune
response. Need carrier molecules for stimulating
immune response
Generation of immune response.
~ 4-7 days to generate immune response.
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> 7 days get primary immune response.
1st IgM produced then IgG.
After ~3 weeks primary immune response turned
off.
Ab producing cells & memory B cells formed.
Memory B cells secrete ab when same agent
encountered again.
This is secondary immune response.
Memory lasts weeks / years.
Classes of Immunoglobulins
Large globular glycoproteins released by B cells
in the serum of blood tissue fluids and some
secretions.
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Specifically interact with antigens.
5 classes Antibodies:
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1. IgM – largest & 1st Ab made. Neutralisation,
fix complement, agglutinate & immobilise ags.
2. IgG - main serum Ab. Able to crosses placenta.
Synthesized during secondary immune response.
All functions. Smallest ab.
3.
IgA - mucosal / secretory ab , present in mother
milk.
4.
IgD - receptor ab found on surface
immunocompetent cells.
5.
IgE - binds surface mast cells = degranulation &
histamine release. Allergies.
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The End