INNATE IMMUNITY:

NONSPECIFIC DEFENSES OF
THE HOST
Microbiology: An Introduction. 13th Ed.
[Gerard J. Tortora_Berdell R.
Part 1 Funke_Christine L. Case] Chapter 16 pp.
445 – 472
GROUP 2

MEMBERS:
Rafaela Gaye Dela Cruz
Chrystian Mae Balut
Angelica Jiana Marabut
Renee Dwi Messakaraeng
Maica Janice Banaag
TOPICS:

A. THE CONCEPT OF IMMUNITY

B. FIRST LINE OF DEFENSE: SKIN AND
MUCOUS MEMBRANES
B.1. Physical Factors
Continuation…TOPICS

B.2. Chemical Factors

B.3. Normal Microbiota and Innate
Immunity
C. SECOND LINE OF DEFENSE
C.1. Formed Elements in Blood
C.2. The Lymphatic System
Continuation…TOPICS

C.3. Phagocytes
C.4. Inflammation
C.5. Fever
C.6. Antimicrobial Substances
C.6.a. The Complement System
C.6.b. Interferons
Continuation…TOPICS

C.6.c. Iron-binding Proteins

C.6.d. Antimicrobial Peptides
C.6.e. Other Factors
A. THE CONCEPT OF IMMUNITY

❑ Immunity, also called resistance, is the ability to ward off

diseases caused by microbes.
 Susceptibility- lack of immunity
Continuation…A. THE CONCEPT OF IMMUNITY

 Types of Immunity:
Innate immunity refers to the defenses that are
present at birth. They are always available to
provide rapid responses to protect us against
diseases.

Adaptive immunity is based on a specific

response to a specific microbe once a microbe has
breached the innate immunity defenses.
Continuation…A. THE CONCEPT OF IMMUNITY

 Responses of the innate system are activated by

protein receptors in the plasma membranes of
defensive cells.
⮚ Toll-like receptors (TLRs) attach to various
components on pathogens called pathogen-
associated molecular patterns (PAMPs)

⮚ Cytokines (cyto- = cell; -kinesis = motion) are

proteins that regulate the intensity and duration
of immune responses.
B. FIRST LINE OF DEFENSE: SKIN AND
MUCOUS MEMBRANES

 The skin and mucous membranes are the body’s first

line of defense against environmental pathogens.
This function results from both physical and
chemical factors.
B.1. Physical Factors

 Physical factors include barriers to entry and

processes that remove microbes from the body’s
surface.
Continuation…B. 1. Physical Factors

 Skin
 The intact skin is the human body’s
largest organ in terms of surface area
and weight and is an extremely
important component of the first line of
defense.

*Keratin: a protective protein that makes the skin more rigid and
durable.
Continuation…B. 1. Physical Factors

 EPIDERMIS OF SKIN:
 The periodic shedding of the top layer helps
remove microbes at the surface.
 The structure of the skin provides such a
formidable barrier to the entrance of
microorganisms.
 The dryness of the skin is a major factor in
inhibiting microbial growth on the skin.
Continuation…B. 1. Physical Factors

 MUCOUS MEMBRANES and MUCUS

 The epithelial layer of a mucous membrane secretes a
fluid called mucus.
 Mucus prevents the tracts from drying out and traps
many of the microorganisms that enter these tracts.

*Mucous membranes: membranes that line various cavity in the body.

*Mucus: a slightly viscous (thick) glycoprotein produced by goblet cells of a mucous membrane.
Continuation…B. 1. Physical Factors

 LACRIMAL APPARATUS

 a group of structures that

manufactures and drains tears.

 Tears contain a substance called

lysozyme, which has an antibacterial
action, and works to prevent
invasion and infection of microbes.
Continuation…B. 1. Physical Factors

 SALIVA

 Salivary glands produce saliva

 Saliva helps dilute the numbers of

microorganisms and wash them
from the surface of the teeth and the
mucous membrane of the mouth.
Continuation…B. 1. Physical Factors

 MUCUS-COATED HAIRS

 The mucous membrane of the nose

has mucus-coated hairs that filter
inhaled air and trap particles.
Continuation…B. 1. Physical Factors

 CILIA

 Together with mucus form a ciliary

escalator, which traps and removes
microbes from lower respiratory
tract.
Continuation…B. 1. Physical Factors

 EPIGLOTTIS

 Microorganisms are also prevented

from entering the lower respiratory
tract by a small lid of cartilage
called the epiglottis, which covers
the larynx (voicebox) during
swallowing.
Continuation…B. 1. Physical Factors

 EARWAX (cerumen)

 help prevent microbes, dust,

insects, and water from entering the
ear.
Continuation…B. 1. Physical Factors

 URINE
 Cleansing of the urethra is by the
flow of urine, which prevents
microbial colonization in the
genitourinary tract.

 VAGINAL SECRETIONS

 Vaginal secretions likewise move

microorganisms out of the female
body.
Continuation…B.1. Physical Factors

 Peristalsis, defecation, vomiting, and diarrhea

Expel microbes from the body
Peristalsis: series of coordinated contractions that propels food along the
gastrointestinal tract.
Defecation: result of mass peristalsis of large intestinal contents into the rectum
Vomiting: upward, vigorous contractions of the muscles of the gastrointestinal tract, in
response to microbial toxins
Diarrhea: loose, watery stool (bowel movement); when you get an infection caused by
microbes, your GI systems doesn't absorb nutrients and fluids adequately and it passes
through your body more quickly than it should, leading to frequent, watery bowel
movements.
B.2. Chemical Factors

 Certain chemical factors also play important roles

against microbial invasion.
Continuation…B.2. Chemical Factors

 Sebaceous (oil) glands of the skin produce an oily

substance called sebum that prevents hair from
drying and becoming brittle.
It also forms a protective film over the surface of the
skin.
Unsaturated fatty acids (component of sebum)
inhibit the growth of certain pathogenic bacteria and
fungi.
Continuation…B.2. Chemical Factors

The low pH of the skin, between pH 3 and 5, is caused

in part by the secretion of fatty acids and lactic acid.
The skin’s acidity discourages the growth of many
other organisms.
Continuation…B.2. Chemical Factors

 Certain bacteria commonly found on the skin

metabolize sebum, and this metabolism forms free
fatty acids that cause the inflammatory response
associated with acne.
Isotretinoin can be a treatment for severe type of
acne called CYSTIC ACNE.
Continuation…B.2. Chemical Factors

 The sweat glands of the skin produce

PERSPIRATION, which helps maintain body
temperature, eliminate wastes, and flush
microorganisms from the surface of the skin.
Perspiration contains LYSOZYME, an enzyme that
breaks chemical bonds on peptidoglycan, which
destroys the cell walls; and is found in tears, saliva,
nasal secretions, tissue fluids, and urine where it
exhibits its microbial activity.
Continuation…B.2. Chemical Factors

 The EARWAX is a physical barrier functioning also as

a chemical protectant.
The secretions are rich in fatty acids, giving the ear
canal a low pH, which inhibits the growth of many
pathogenic microbes.
Continuation…B.2. Chemical Factors

 SALIVA has a number of substances that inhibit

microbial growth (e.g. Lysozyme, urea and uric acid)
Ph of saliva (6.55-6.85) also inhibits some microbes
Contains an antibody (IgA) that prevents attachment
to microbes.
Immunoglobulin A ( IgA, or 11S): a dimeric antibody found in both serum and external
secretions such as tears, saliva colostrums, and intestinal secretions.
Continuation…B.2. Chemical Factors

 GASTRIC JUICE is produced by the glands of the

stomach.
High acidity of gastric juice can destroy bacteria:
• Mixture of hydrochloric acid, enzymes, mucus
• Helicobacter pylori (neutralizes stomach acid)
• Growth of bacterium triggers an immune
response of gastritis and ulcers
Continuation…B.2. Chemical Factors

 VAGINAL SECRETIONS play a role in antibacterial

activity.
Lactobacillus spp. breaks down glycogen into lactic
acid, which creates an acidic pH (3–5) that inhibits
microbes.

URINE contains lysozyme and has an acidic pH

(average 6) which inhibits microbes.
B.3. NORMAL MICROBIOTA AND INNATE
IMMUNITY

 Certain microbes establish more or less permanent

residence (colonization) in and on the body but
normally do not produce disease (Chapter 14).
 This symbiotic relationship is called
commensalism.
Continuation…B.3. NORMAL MICROBIOTA AND INNATE IMMUNITY

 Play an important role in preventing the overgrowth

of harmful microbes.
 The normal microbiota are not normally considered
as part of the innate immune system.
They afford considerable protection for the body.
Continuation…B.3. NORMAL MICROBIOTA AND INNATE IMMUNITY

The normal microbiota provide resistance in three

principal ways:

 They adapt well to a limited number of

attachment sites.
 Normal microbiota produce substances that
inhibit or kill pathogens.
 Development of immune system is dependent on
the presence of microbiota even before birth.
Continuation…B.3. NORMAL MICROBIOTA AND INNATE IMMUNITY

Probiotics are live microbial cultures applied to or

ingested that are intended to exert a beneficial effect.

Prebiotics are chemicals that selectively promote the

growth of beneficial bacteria.
commensalism: is a symbiotic relationship wherein one organism uses the body of a
larger organism as its physical environment and may make use of the body to obtain
nutrients. In commensalism, one organism benefits while the other is unaffected.
opportunistic pathogens: are microorganisms that are normally commensal or does not
cause disease but becomes harmful or pathogenic when their environmental conditions
change or when the body’s immune system is impaired and unable to fight off infection.
competitive exclusion: a principle which states that two species cannot coexist in the
same ecological niche for very long without one becoming extinct or being driven out
because of competition for limited resources.
C. SECOND LINE OF DEFENSE

 When microbes penetrate the first line of defense,

they encounter a second line of defense that includes
phagocytic cells, inflammation, fever, and
antimicrobial substances.
Many of these components are contained or
originate in the blood.
C.1. FORMED ELEMENTS IN BLOOD

 Composed of cells and portions of cells within a

fluid called plasma.
 The cells and cell fragments in plasma are called
formed elements.
Continuation… C.1. FORMED ELEMENTS IN BLOOD

 Three types of Formed Elements:

1. Erythrocytes- red blood cells; carry oxygen and

carbon dioxide in the blood
2. Leukocytes- white blood cells; involved in
defending the body against invaders
• Granulocytes
• Agranulocytes
3. Platelets- thrombocytes; involved in blood clotting
 Continuation… C.1. FORMED ELEMENTS IN BLOOD

 Hematopoieses

 A process where formed

elements are created in
red bone marrow by
stem cells.
Continuation… C.1. FORMED ELEMENTS IN BLOOD

Pluripotent stem cells- are master cells. They’re able to make cells from all three basic
body layers, so they can potentially produce any cell or tissue the body needs to repair
itself. Pluripotent stem cells are also able to self-renew, meaning they can perpetually
create more copies of themselves.

Myeloid stem cells- they undergo differentiation to produce precursors of erythrocytes,

platelets, dendritic cells, mast cells, monocytes, and granulocytes.

Lymphoid stem cells- lymphoid stem cells give rise to a class of leukocytes known as
lymphocytes, which include the various T cells, B cells, and natural killer (NK) cells, all of
which function in immunity.
Continuation… C.1. FORMED ELEMENTS IN BLOOD

 Leukocytes: GRANULOCYTES

 Category of white blood cells characterized by the

presence of large granules in their cytoplasm.
1. Neutrophils
2. Basophils
3. Eosinophils
Continuation… C.1. FORMED ELEMENTS IN BLOOD

 Neutrophils

 Stain pale lilac with a mixture of

acidic and basic dyes.
 Most abundant white blood cells
 Highly phagocytic and motile, and
they are active in the initial stages of
an infection.
Continuation… C.1. FORMED ELEMENTS IN BLOOD

 Basophils

 Least common granulocyte

 Stain blue-purple with the basic dye
methylene blue
 When activated, it release histamine
that are important in inflammation
and allergic responses.
Continuation… C.1. FORMED ELEMENTS IN BLOOD

 Eosinophils

 Main effector cells in allergic

responses & asthma
 Stain red or orange with the acidic
dye eosin
 Main function is to kill certain
parasites, such as helminths
Continuation… C.1. FORMED ELEMENTS IN BLOOD

 Leukocytes: AGRANULOCYTES
1. Dendritic Cells
2. Monocytes
3. Lymphocytes
a) Natural Killer (NK) cells
b) T cells
c) B cells
Continuation… C.1. FORMED ELEMENTS IN BLOOD

 Dendritic Cells

 Dendritic cells are especially

abundant in the epidermis of the
skin, mucous membranes, the
thymus, and lymph nodes.

 They destroy microbes by

phagocytosis and initiate adaptive
immune response.
Continuation… C.1. FORMED ELEMENTS IN BLOOD

 Monocytes

 Leave the blood and mature into

macrophages (phagocytic cells of the
second line of defense)
Continuation… C.1. FORMED ELEMENTS IN BLOOD

 Lymphocytes

 Include natural killer cells, T

cells, and B cells.
Continuation… C.1. FORMED ELEMENTS IN BLOOD

 Natural Killer (NK) cells

 Found in blood and in the spleen,

lymph nodes, and red bone marrow
 Play a major role in the host-rejection of
both tumors and virally infected cells
 The binding of NK cells to a target cell
causes the release of toxic substances
from lytic granules.
Lytic granules- secretory organelle unique to NK cells
Perforin- a protein which inserts into the plasma membrane of the target cell and creates channels
in the membrane.
Cytolysis- a process where extracellular fluid flows into the target cell and the cell bursts.
Granzymes- a protein-digesting enzymes that induce the target cell to undergo self-destruction.
Continuation… C.1. FORMED ELEMENTS IN BLOOD

T cells

 B cells and T cells

 They are not usually phagocytic but

play a key role in adaptive immunity.
 They occur in lymphoid tissues of the
lymphatic system and also circulate in
blood.

B cells
Continuation… C.1. FORMED ELEMENTS IN BLOOD

 Differential White Blood Cell Count

 calculation of the percentage of each kind of white
cell in a sample of 100 white blood cells, which
detects an increase or decrease in leukocytes
(WBC)
Continuation… C.1. FORMED ELEMENTS IN BLOOD

 Leukocytosis
 Increased levels of leukocytes in the blood

 Leukopenia
 Decreased levels of leukocytes in the blood
C.2 THE LYMPHATIC SYSTEM

❑ The lymphatic system consists of a fluid called

lymph
❑ Lymphoid tissue contains large numbers of
lymphocytes, including T cells, B cells and
phagocytic cells that participate in immune
responses.
❑ Lymph nodes are the sites of activation of T
cells and B cells, which destroy microbes by
immune responses
Continuation… C.2. THE LYMPHATIC SYSTEM

 Lymphoid tissues and organs are scattered

throughout the mucous membranes that line the
gastrointestinal, respiratory, urinary, and
reproductive tracts.

⮚ They protect against microbes that are ingested

or inhaled.
Continuation… C.2. THE LYMPHATIC SYSTEM

 Lymphoid tissues are located in specific parts of the

body:

 These include the tonsils in the throat

 Peyer’s patches in the small intestine.
 The spleen contains lymphocytes and
macrophages that monitor the blood for microbes.
 The thymus serves as a site for T cell maturation.
C.3. PHAGOCYTES

 Phagocytosis is the ingestion of microorganisms or

particulate matter by a cell.
Continuation…C.3. PHAGOCYTES

 Phagocytes are cells that perform phagocytosis.

 When an infection occurs, both granulocytes

(neutrophils and eosinophils) and monocytes
migrate to the infected area or tissues.
 Monocytes enlarge and develop into
macrophages.

*Macrophage: a large phagocytic cell found in stationary form in the tissues or

as a mobile white blood cell, especially at sites of infection.
Continuation…C.3. PHAGOCYTES

 FIXED MACROPHAGES (HISTIOCYTES)

• Fixed macrophages are resident in certain tissues

and organs of the body.
• They are found in the liver (Kupffer’s cells),
lungs (alveolar macrophages), nervous system
(microglial cells), bronchial tubes, spleen
(splenic macrophages), lymph nodes, red bone
marrow, and the peritoneal cavity surrounding
abdominal organs (peritoneal macrophages).
Continuation…C.3. PHAGOCYTES

 FREE (WANDERING) MACROPHAGES

• Macrophages that are motile, which roam the
tissues and gather at sites of infection or
inflammation.
Continuation…C.3. PHAGOCYTES

 During the course of an infection, a shift occurs in the

type of white blood cell that predominates in the
bloodstream.
 Granulocytes, especially neutrophils, dominate
during the initial phase of bacterial infection, at
which time they are actively phagocytic.
 As the infection progresses, the macrophages
(monocytes) dominate; they scavenge and phagocytize
remaining living bacteria and dead or dying bacteria.
Continuation…C.3. PHAGOCYTES

 MECHANISM OF PHAGOCYTOSIS:

 It has four phases: chemotaxis, adherence,

ingestion, and digestion.
Continuation…C.3. PHAGOCYTES (MECHANISM OF PHAGOCYTOSIS)

1. CHEMOTAXIS
 Chemotaxis is the chemical attraction of
phagocytes to microorganisms.
Continuation…C.3. PHAGOCYTES

2. ADHERENCE
 Adherence is the attachment of the phagocyte’s
plasma membrane to the surface of the
microorganism or other foreign material.
 Adherence is facilitated by the attachment of
pathogen-associated molecular patterns (PAMPs) of
microbes to receptors, such as Toll-like receptors
(TLRs), on the surface of phagocytes.
Pathogen-associated molecular patterns (PAMPs): diverse set of microbial molecules
that share a number of different general “patterns,” or structures, that alert immune
cells to destroy intruding pathogens.
Toll-like receptors (TLRs): class of proteins that play a key role in the innate immune
system. They are single-pass membrane-spanning receptors usually expressed on
sentinel cells such as macrophages and dendritic cells, that recognize structurally
conserved molecules derived from microbes.
Continuation…C.3. PHAGOCYTES

3. INGESTION
 The plasma membrane of the phagocyte extends
projections called pseudopods that engulf the
microorganism.
 Once the microorganism is surrounded, the pseudopods
meet and fuse, surrounding the microorganism with a
sac called a phagosome, or phagocytic vesicle.
Continuation…C.3. PHAGOCYTES

4. PHAGOLYSOSOME FORMATION AND

DIGESTION
 Next, the phagosome pinches off from the plasma
membrane and enters the cytoplasm, where it
contacts lysosomes that contain digestive enzymes
and bactericidal substances.
 On contact, the phagosome and lysosome
membranes fuse to form a single, larger structure
called a phagolysosome.
Continuation…C.3. PHAGOCYTES

4. PHAGOLYSOSOME FORMATION AND

DIGESTION
 After enzymes have digested the contents of the
phagolysosome brought into the cell by ingestion,
the phagolysosome contains indigestible material
and is called a residual body.
 This residual body then moves toward the cell
boundary and discharges its wastes outside the
cell.
C.4. INFLAMMATION

 Body’s tissues local defensive response:

P- AIN
R- EDNESS
I- MMOBILITY
S- WELLING
H- EAT
Continuation…C.4. INFLAMMATION

 FUNCTIONS:
destroy the injurious agent
walling off the injurious agents and its byproducts
repair or replace tissue
Continuation…C.4. INFLAMMATION

Classifications of inflammation:
ACUTE INFLAMMATION- the signs and symptoms
develop rapidly and usually last for a few days or
even a few weeks.
CHRONIC INFLAMMATION- signs and symptoms
develop more slowly and can last for up to several
months or years.
Continuation… C.4. INFLAMMATION

 VASODILATION- responsible for the redness and

heat with inflammation

 INCREASED PERMEABILITY- permits defensive

substances retained in the blood

 EDEMA- accumulation of fluid in an inflammation

Continuation… C.4. INFLAMMATION
Continuation…C.4. INFLAMMATION

 TISSUE REPAIR( final stage of inflammation)

Stroma (supporting connective tissue)
Parenchyma ( functioning part of the tissue)

 FIBROSIS (process that forms scar tissue)

C.5. FEVER

 Fever is one of the most important systemic response

characterized by an abnormally high body
temperature, a third component of the second line of
defense.
 The most common cause of fever is infection from
bacteria or viruses.
Continuation…C.5. FEVER

The body’s thermostat (hypothalamus) is normally set

at 37º C (98.6º F).

 The hypothalamus sets a higher temperature

when affected by certain substances such as
cytokines (Figure 15.6).
Continuation…C.5. FEVER

Figure 15.6. Endotoxins and the pyrogenic response (page 434).

cytokines: are proteins that are crucial in controlling the growth and activity of other
immune system cells and blood cells. When released, they signal the immune system to
do its job.
prostaglandins: are lipid compounds found in almost every tissue in humans and other
animals. They play an important role in the regulation of body temperature. They also
control processes such as inflammation, blood flow, the formation of blood clots and the
induction of labor.
endotoxins: are toxins produced within the microorganism and released only when the
cell disintegrates or ruptures.
pyrogenic response: is a febrile phenomenon caused by infusion of solution
contaminated, and commonly manifested by cold, chill and fever. “Pyrogenic” indicates
that a molecule can trigger a fever response, and cytokines are a broad class of peptide
signaling molecules used in the immune system.
Continuation…C.5. FEVER

As infection subsides, heat-losing mechanisms such as

vasodilation and sweating go into operation.
 This phase is called crisis, which indicates that the
body temperature is falling.
Continuation…C.5. FEVER

High body temperature intensifies the effect of

antiviral interferons and increases production of
transferrins.
 Higher body temperature also speeds up the
body’s reactions and may slow the growth rate of
some bacteria.
Continuation…C.5. FEVER

Among the complications of fever are tachycardia

(rapid heart rate), increased metabolic rate, dehydration,
electrolyte imbalances, seizures, delirium and coma.

 As a rule, death results if the body temperature

rises above 44º to 46ºC (112º to 114ºF).
vasodilation: is the widening of blood vessels as a result of the relaxation of the blood
vessel's muscular walls. Vasodilation is a mechanism to enhance blood flow to areas of
the body that are lacking oxygen and/or nutrients.
sweating: is the act of secreting fluid from the skin by the sweat (sudoriferous) glands. It
is also known as perspiration.
interferons: is a class of proteins produced by certain animal cells, such as lymphocytes
and macrophages.
transferrin: is an iron-binding protein found in blood and tissue fluids which functions to
transport and store iron. Low transferrin can impair hemoglobin production and may
eventually lead to anemia–a condition in which the body lacks adequate healthy red
blood cells to carry adequate oxygen to your body's tissues.
delirium: is a serious disturbance in mental abilities that results in confused thinking
and reduced awareness of the environment. The start of delirium is usually rapid —
within hours or a few days.
C.6. ANTIMICROBIAL SUBSTANCES

 The body produces certain antimicrobial substances, a

final component of the second line of defense, in
addition to the chemical factors mentioned earlier
Among these are the proteins of the complement
system, interferrons, iron-binding proteins, and
antimicrobial peptides.
C.6.a. THE COMPLEMENT SYSTEM

 Consists of a group of serum proteins that activate

one another to destroy invading microorganisms.
Continuation…C.6.a.THE COMPLEMENT SYSTEM

 The complement system is not adaptable, never

changing over a person’s lifetime.

 Therefore, it is considered part of the innate

immune system.

 However, it can be recruited into action by the

adaptive immune system.
Continuation…C.6.a.THE COMPLEMENT SYSTEM

 Complement proteins are inactive until split into

fragments, which activates them.
 Complement proteins are usually designated by an
uppercase letter C and are numbered through C1
and C9.

 Activated fragments are indicated by lowercase

letters a and b.
Continuation…C.6.a.THE COMPLEMENT SYSTEM

 Complement proteins act in a cascade, where one

reaction triggers another.

 The cascade of complement proteins that occurs

during an infection is called complement
activation.
Continuation…C.6.a.THE COMPLEMENT SYSTEM

 PATHWAYS OF COMPLEMENT
ACTIVATION:
The Classical Pathway
• Begins with an antigen-antibody
reaction.
Continuation…C.6.a.THE COMPLEMENT SYSTEM

 PATHWAYS OF COMPLEMENT
ACTIVATION:
The Alternative Pathway
• Begins by contact between certain
complement proteins and a
pathogen; it doesn’t involve
antibodies.
Continuation…C.6.aTHE COMPLEMENT SYSTEM

 PATHWAYS OF COMPLEMENT
ACTIVATION:
The Lectin Pathway
• Lectin binds to mannose on the
surface of a microbe.
Lectin- a type of protein that binds to certain carbohydrates.

Mannose- a sugar of the hexose class of carbohydrates which occurs as a component of

many natural polysaccharides.
Continuation…C.6.aTHE COMPLEMENT SYSTEM

 OUTCOMES OF COMPLEMENT ACTIVATION

Cytolysis

• occurs when a cell bursts due to an osmotic

imbalance that has caused excess water to
diffuse into the cell.

• Cytolysis of microbial cells involves the

membrane attack complex (MAC)
Membrane attack complex (MAC): a complex of proteins typically formed on the
surface of pathogen cell membranes as a result of the activation of the host's
complement system.

C3 or complement component 3: a protein of the immune system. It plays a central role

in the complement system and contributes to innate immunity.
Continuation…C.6.a. THE COMPLEMENT SYSTEM

 OUTCOMES OF COMPLEMENT ACTIVATION

Opsonization

• Or immune adherence, promotes attachment of

a phagocyte to a microbe.
Continuation…C.6.a. THE COMPLEMENT SYSTEM

 OUTCOMES OF COMPLEMENT ACTIVATION

Inflammation

• Immune system's response to harmful stimuli,

such as pathogens, damaged cells, toxic
compounds, or irradiation.
Continuation…C.6.a.THE COMPLEMENT SYSTEM

 Regulation of Complement

 Once complement is activated, its destructive

capabilities usually cease very quickly to
minimize the destruction of host cells.
 One example of a regulatory protein is CD59,
which prevents the assembly of C9
molecules to form the MAC
CD59: inhibits the formation of MAC pores in the membranes of expressing cells. It is a
‘suicide inhibitor’, locking onto C8 in the forming MAC to block the recruitment of C9
into the complex.
Continuation…C.6.a.THE COMPLEMENT SYSTEM

 Complement and Disease

 Complement deficiencies can result in an

increased susceptibility to disease.
Continuation…C.6.a.THE COMPLEMENT SYSTEM

 Complement and Disease

 C1, C2, or C4 deficiencies cause collagen vascular

disorders that result in hypersensitivity.
 C3 deficiency, results in increased susceptibility
to recurrent infections with pyogenic microbes.
 C5 through C9 defects result in increased
susceptibility to Neisseria meningitidis and N.
gonorrhoea infections.
C.6.b. INTERFERONS

❑ One way an infected host cell counters viral infections

is with a family of cytokines called interferons (IFNs).
Continuation… C.6.b. INTERFERONS

❑ There are three main types of human interferons:

1) Alpha interferon (IFN-a)
2) Beta interferon (IFN-b)
3) Gamma interferon (IFN-g)
Continuation… C.6.b. INTERFERONS

⮚ Both IFN-α and IFN-β are produced by virus-infected

host cells only in very small quantities that diffuse to
uninfected neighboring cells.
⮚ Gamma interferon is produced by lymphocytes and
induces neutrophils and macrophages to kill bacteria.
Continuation… C.6.b. INTERFERONS

 Interferons would seem to be ideal antiviral

substances, but certain problems do exist.
 When injected, interferons have side effects such as
nausea, fatigue, headache, vomiting, weight loss,
and fever.
Continuation… C.6.b. INTERFERONS

• High concentrations of interferons are toxic to the

heart, liver, kidneys, and red bone marrow.
• The importance of interferons in protecting the body
against viruses, as well as their potential as anticancer
agents, has made their production in large quantities a
top health priority.
Continuation… C.6.b. INTERFERONS

⮚ Intron® A is approved in the United States for treating

several virus-associated disorders. One is Kaposi’s
sarcoma. Other approved uses: treating hepatitis B and
C, malignant melanoma, and hairy cell leukemia.
⮚ Betaseron® slows the progression of multiple sclerosis
(MS) and lessens the frequency and severity of attacks.
Also used to treat osteoporosis.
Kaposi’s sarcoma (KS): is a cancer that develops from the cells that line lymph or blood
vessels. It usually appears as tumors on the skin or on mucosal surfaces such as inside
the mouth.

Other approved uses:

Hepatitis B: a vaccine-preventable liver infection caused by the hepatitis B virus (HBV).
Hepatitis B is spread when blood, semen, or other body fluids from a person infected
with the virus enters the body of someone who is not infected.
Hepatitis C: a liver infection caused by the hepatitis C virus (HCV). Hepatitis C is spread
through contact with blood from an infected person. Today, most people become
infected with the hepatitis C virus by sharing needles or other equipment used to
prepare and inject drugs.
Malignant Melanoma: A melanoma is a tumor produced by the malignant
transformation of melanocytes. Melanocytes are derived from the neural crest;
consequently, melanomas, although they usually occur on the skin, can arise in other
locations where neural crest cells migrate, such as the gastrointestinal tract and brain.
hairy cell leukemia: a rare, slow-growing cancer of the blood in which your bone
marrow makes too many B cells (lymphocytes), a type of white blood cell that fights
infection. These excess B cells are abnormal and look "hairy" under a microscope.
multiple sclerosis (MS): Multiple sclerosis (MS) is a condition that can affect the brain
and spinal cord, causing a wide range of potential symptoms, including problems with
vision, arm or leg movement, sensation or balance.
C.6.c. IRON-BINDING PROTEINS

❑ Humans and pathogens require iron to survive.

Thus, an infection creates a situation where pathogens
and humans compete for available iron.
Continuation… C.6.c. IRON-BINDING PROTEINS

 The concentration of free iron in the human body is

low because most of it is bound to iron-binding
proteins— molecules such as transferrin, lactoferrin,
ferritin, and hemoglobin—whose function is to
transport and store iron.
Continuation… C.6.c. IRON-BINDING PROTEINS

 Transferrin is found in blood and tissue fluids.

 Lactoferrin is found in milk, saliva, and mucus.

 Ferritin is located in the liver, spleen, and red bone

marrow.

 Hemoglobin is located within red blood cells.

 The iron-binding proteins do not only transport and

store iron but also, by doing so, deprive most pathogens
of the available iron.
Continuation… C.6.c. IRON-BINDING PROTEINS

 To survive in the human body, many

pathogenic bacteria obtain iron by secreting
proteins called siderophores, which compete
to take away iron from iron-binding proteins
by binding it more tightly.
 Once the iron–siderophore complex is
formed, it is taken up by siderophore
receptors on the bacterial surface and
brought into the bacterium; then the iron is
split from the siderophore and utilized.
*Siderophores: small molecules that are produced and secreted by
microorganisms in order to mediate the uptake of essential iron into
the cell from the extracellular environment.
Continuation… C.6.c. IRON-BINDING PROTEINS

 A few pathogens do not use the siderophore

mechanism to obtain iron:
 Neisseria meningitidis produces receptors on its
surface that bind directly to human iron-binding
proteins. Then the iron-binding protein, along with
its iron, is taken into the bacterial cell.
 Streptococcus pyogenes, release hemolysin, a protein
that causes the lysis (destruction) of red blood cells.
The hemoglobin is then degraded by other bacterial
proteins to capture the iron.
Hemoglobin: comprises one-third of a red blood cell’s volume and is responsible for the
cell’s red color. Each hemoglobin molecule consists of four protein chains (globin) and
four heme groups. Each heme contains one iron itom.
C.6.d. Antimicrobial Peptides

 Antimicrobial peptides are one of the most important

components of the innate immunity.
Were first discovered in the skin of frogs, the lymph
of insects, and human neutrophils

Antimicrobial peptides: short peptides that consists of a chain of about 12-50 amino acids
synthesized on ribosomes.
Continuation… C.6.d. Antimicrobial Peptides

 MODE OF ACTIONS:
inhibiting cell wall synthesis
forming pores the plasma membrane that cause lysis
destroying DNA and RNA
Continuation… C.6.d. Antimicrobial Peptides

 ANTIMICROBIAL PEPTIDES (AMPs) produced by

humans:
DERMCIDIN- produced by sweat glands
DEFENSINS and CATHELICIDINS- produced by
neutrophils, macrophages, and epithelium
THROMBOCIDIN- produced by platelets
Continuation… C.6.d. Antimicrobial Peptides

 Scientists are especially interested in AMPs for the

following reasons:
broad spectrum of antimicrobial activities
shown synergy (working together) with other
antimicrobial agents
very stable over a wide range of pH
microbes don’t appear to develop resistance even
though the microbes are exposed to them for a long
period of time
Continuation… C.6.d. Antimicrobial Peptides

AMPs also participate in a number of other immune

functions:
 vigorously attract dendritic cells
 recruit mast cells, which increase vessel
permeability and vasodilation
C.6.e. Other Factors

 Genetic resistance is an inherited trait in a person’s

genome that provide resistance to a disease. It
confers a selective survival advantage.
Continuation…C.6.e. Other Factors

 Individuals who have sickle cell trait are relatively

protected against Plasmodium falciparum malaria.

 A naturally occurring variant of a human prion has

been found that completely protects against
spongiform encephalopathy (prion diseases).
sickle cell trait: Sickle cell trait (SCT) is not a disease, but having it means that a person
has inherited the sickle cell gene from one of his or her parents. People with SCT usually
do not have any of the symptoms of sickle cell disease (SCD) and live a normal life.
Plasmodium falciparum malaria: severe malaria caused by a parasite of the genus
Plasmodium (P. falciparum) and marked by irregular recurrence of paroxysms (sudden
attacks or reemergence of symptoms) and usually prolonged or continuous fever.
human prion: an abnormal form of a normally harmless protein found in the brain that
is responsible for a variety of fatal neurodegenerative diseases.
encephalopathy: a disease that affects the function or structure of your brain.
spongiform encephalopathy: a family of rare progressive neurodegenerative brain
disorders that affect both humans and animals. They have long incubation periods,
progress rapidly once symptoms develop and are always fatal.
Continuation…C.6.e. Other Factors

 With respect to age, the very young and the elderly

are more susceptible to disease.

 Observing healthy protocols also provide resistance

to infection.

 Examples: Proper handwashing, controlling

sneezing, employing standard precautions, safe
sex practices, and avoiding cross-contamination
and fecal-oral transmission.
Continuation…C.6.e. Other Factors

Cross contamination and fecal-oral transmission

https://www.sciencedirect.com/science/article/pii/S1879625716301687