Lecture 8- Immunity.ppt

THE IMMUNE SYSTEM
Prof. Khaled H. Abu-Elteen

Terminology
 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.
– 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

 Types of Symbiosis (cont.)
– Parasitism
• A symbiotic relationship in which one
species benefits, and the other species is
harmed
• Generally, the species that benefits (the
parasite) is much smaller than the species
that is harmed (the host)

 Disease and Infectious Disease
– 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
 Antigen
– Any molecule that binds to immunoglobulin or T cell receptor
 Pathogen
– Microorganism that can cause disease
 Antibody (Ab)
– Secreted immunoglobulin
 Immunoglobulin (Ig)
– A glycoprotein produced in response to the introduction of an antigen
 Vaccination
– Deliberate induction of protective immunity to a pathogen
 Immunization
– 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.

Nonspecific Immune Response
 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.

DEFENSES
– Dry
 usual infection sites are wet areas, skin folds, armpit,
groin
– Acidic (pH 3.0- 5.0)
– Temperature less than 37oC
 Some pathogens grow best <37oC
– Lysozyme and toxic lipids
 pore, hair follicles, sweat gland
– Resident microflora
 mainly 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.

SKIN AND MUCOUS
MEMBRANES:1st line of defense
 Mechanical Factors:
 Skin.
 The Epidermis.
 Keratin.
 Mucous Membranes.
 Lacrimal Apparatus ------>
 Cilliary Escalator [ mucocilliary Escalator Action).

Flushing Mechanisms
 Epiglottis.
 Urine and Vaginal secretions.
 Sneezing, coughing, swallowing reflex
 Movement of Fluids across their surfaces
(Saliva)
 Washing action of tears

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.

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 MICRIBIOTAAND
NONSPECIFIC RESISTANCE.
 Microbial Antagonism.
 Commensalism.
 Competitive Exclusion: Opportunistic
pathogens.
 Natural Resistance: Microorganisms has a
host range

Cells of the Immune system:
FORMED ELEMENTS IN BLOOD.
 Many cells of
the immune
system derived
from the bone
marrow
 Hematopoetic
stem cell
differentiation

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.

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).

NEUTROPHILS ( 60% of WBC)
 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)
 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)
 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) .

MONOCYTES.
 Phagocytosis and killing
of microorganisms
– Activation of T cells and
initation of immune
response
 Monocyte is a young
macrophage in blood
 There are tissue-specific
macrophages
 Antigen Presentation

MACROPHAGES.
 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
immunity)
– Cytotoxic T cells
– Helper T cells
 Memory cells

Lymphocytes
 Plasma Cell (in tissue)
– Fully differentiaited B
cells, secretes Ab
 Natural Killer cells
– 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

Mast Cells
 Expulsion of parasites through release
of granules
 Histamine, leukotrienes, chemokines,
cytokines
 Also involved in allergic responses

Other Blood Cells
 Megakaryocyte
– Platelet formation
– Wound repair
 Erythrocyte
– Oxygen transport

Cells, tissues and organs of
the immune system
 Immune cells are bone marrow-derived, & distributed through out
the body
 Primary lymphoid organs:
– Thymus: T cell maturation
– Bone marrow (bursa of Fabricius in birds): B cell maturation
 Secondary lymphoid organs:
– Lymph nodes
– Spleen
– Mucosal lymphoid tissues (lung, gut)

Major Tissues
 Primary Lymph
tissues
– Cells originate
or mature
 Secondary
Lymph Tissues
2º
2º
1º
1º
2º
2º
2º
2º
2º

COMPONENTS OF THE
LYMPHATIC SYSTEM.

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.

Opsonization.
 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.

THE MECHANISM OF
PHAGOCYTOSIS.
 Chemotaxis.
 Adherence.
 Ingestion.
 Digestion.

3. Phagocytosis & oxidative
burst.
 Certain WBCs - phagocytosis.
 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.
 Lysosomes contain enzymes = degrade
biomolecules.
 E.g. acid hydrolases, lysozyme, neutral proteases,
myeloperoxidase, lactoferrin, & phospholipase A.
Human macrophage engulfing the fungus Candida
albicans.

3. Phagocytosis & oxidative burst.
 Engulfed organisms killed in WBC by
“respiratory (oxidative) burst".
 Many pathogens / parasites succeed because avoid
phagocytosis.
Neutrophil
Yeast
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.

 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.

 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).

Inflammation.
 Inflammation - phagocytes & complement
recruited to site tissue invasion.
 Non-specific reaction to tissue damage.
 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.

Types of Immunity
Figure 22.14

Types of immunity
 Innate (natural) immunity
– Phagocytes etc.
– Early, rapid responses, but limited & ‘non-specifc’
 Adaptive (acquired) immunity
– 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 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

Generation of immune response.
 Immunogen = any molecule that stimulates
immune response. Proteins best immunogens >
carbohydrates > nucleic acids. Lipids very poor.
 Antigen = molecule capable of generating
antibody response.
 Antigen = antibody generating.
 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.
 > 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.
 Specifically interact with antigens.
5 classes Antibodies:
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.

Lecture 8- Immunity.ppt

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