Week16-02 (Lec) Micro 20 ( Innate immunity).pptx

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Chapter 14

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Overview of Host Defense

Mechanisms (1 of 2)

• Innate, natural defenses: present at birth,

provide nonspecific resistance to infection

• _{Adaptive immunities}_{: specific, must be}

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Overview of Host Defense

Mechanisms (2 of 2)

TABLE 14.1 General Features of Host Defenses

Line of

Defense AcquiredInnate/ NonspecificSpecific or

Development of Immunologic

Memory Examples

First Innate Nonspecific No

Physical barriers: skin, tears, coughing, sneezing

Chemical barriers: low pH, lysozyme, digestive enzymes

Genetic barriers: resistance inherent in genetic makeup of host (pathogen cannot invade)

Second Innate Mostly _nonspecific No Phagocytosis, inflammation, fever, _{interferon, complement}

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Defense Mechanisms of the Host

• To protect the body against pathogens, the

immune system relies on a multilevel network of physical barriers, immunologically active cells, and a variety of chemicals

– First line of defense – any barrier that blocks invasion at the portal of entry – nonspecific

– Second line of defense – protective cells and fluids; inflammation and phagocytosis – nonspecific

– Third line of defense – acquired with exposure to foreign substance; produces protective antibodies and creates memory cells – specific

• The lines of defense do not work separately, most

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1st Line of Defense: Barriers at the

Portal of Entry

• A number of defenses are a normal part of

the body’s anatomy and physiology

• These are inborn (innate), nonspecific

defenses

• They can be divided into three categories:

1. Physical or anatomical barriers at the body surface

2. Chemical defenses

3. Genetic resistance to infection

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Physical or Anatomical Barriers

(1 of 4)

• Built-in defenses in skin

– Outermost layer of skin with epithelial cells

cemented together, and impregnated with keratin

– Flushing effect of sweat

• Mucous membranes

– Coating of digestive, genitourinary, and respiratory tracts

– Blinking and tear production

– Flow of saliva

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Physical or Anatomical Barriers

(3 of 4)

• Mucous membranes

– Mucous coat impedes attachment and entry of bacteria

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Physical or Anatomical Barriers

(4 of 4)

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Nonspecific Chemical Defenses

(1 of 2)

• From skin and mucous membranes

– Sebaceous secretions

– Antimicrobial secretions from specialized glands (meibomian glands)

• Other defenses in tears, saliva and skin:

– Lysozyme, an enzyme that hydrolyzes the cell wall of bacteria

– Defensins, peptides that lyse bacteria and fungi

– High lactic acid and electrolyte concentration in sweat

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Nonspecific Chemical Defenses

(2 of 2)

• Hydrochloric acid in stomach

• Digestive juices and bile of intestines

• _{Semen contains an antimicrobial chemical}

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Genetic Defenses

• Some hosts are genetically immune to the

diseases of other hosts

– _{“Humans can’t acquire distemper from cats,}

and cats can’t get mumps from humans”

• Viruses have great specificity for their host

receptors

• Some genetic differences in susceptibility exist

for other pathogens, including differences

within members of the same species

– Humans carrying a gene or genes for sickle-cell

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Structure and Function of the Organs

of Defense and Immunity (1 of 3)

• Immunology

: study of the body’s 2

nd

and 3

rd

lines of defense

• Primary functions of a healthy immune

system:

1. Surveillance of the body

2. Recognition and differentiation of normal versus foreign material

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Structure and Function of the Organs

of Defense and Immunity (2 of 3)

• White blood cells (leukocytes) – innate

capacity to recognize and differentiate any

foreign material

– _{Nonself – foreign material}

– Self – normal cells of the body

• Pathogen-associated patterns (PAMPs) –

molecules shared by microorganisms

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Structure and Function of the Organs

of Defense and Immunity (3 of 3)

• All this is mainly carried our by

white blood

cells (leukocytes)

– innate capacity to

recognize and differentiate any foreign

material

– Nonself – foreign material

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How do White Blood Cells Work?

• Pathogen-associated patterns (PAMPs) – molecules shared by microorganisms

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Components and Connections of the

Immune System

• The immune system is a large, complex, and

diffuse network of cells and fluids that penetrate into every organ and tissue

• _{Body compartments that participate in immune}

function:

1. Reticuloendothelial system (RES) 2. Extracellular fluid (ECF)

3. Bloodstream

4. Lymphatic system

• _{For effective immune responsiveness, the activities}

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Origin, Composition, and Functions

of Blood (1 of 2)

• Whole blood: plasma and formed elements

(blood cells)

– Serum: liquid portion of blood after a clot has formed (minus clotting factors)

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Origin, Composition, and Functions

of Blood (2 of 2)

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A Survey of Blood Cells

• Hemopoiesis

(or

hematopoiesis

)–

production of blood cells

• Stem cells – undifferentiated cells, precursor

of new blood cells

• Primary cell lines:

– Platelets (thrombocytes)

– Red blood cells (RBCs)

– _{Leukocytes or white blood cells (WBCs),}

responsible for immune function

 Granulocytes: lobed nucleus

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Granulocytes (1 of 4)

• Neutrophils

– 55-90% - lobed nuclei with

lavender granules; phagocytes

• Eosinophils

– 1-3% - orange granules and

bilobed nucleus; destroy eukaryotic

pathogens

• Basophils

– 0.5% - constricted nuclei, dark

blue granules; release potent chemical

mediators

– Mast cells: nonmotile elements bound to

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Granulocytes (2 of 4)

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Granulocytes (3 of 4)

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Granulocytes (4 of 4)

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Agranulocytes (1 of 3)

• Lymphocytes – 20-35%, specific immune

response

– B (humoral immunity): activated B cells produce antibodies

– T cells (cell-mediated immunity): activated T cells modulate immune functions and kill foreign cells

• Monocytes, macrophages – 3-7% - largest of

WBCs, kidney-shaped nucleus; phagocytic

– Macrophages: final differentiation of monocytes

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Agranulocytes (2 of 3)

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Agranulocytes (3 of 3)

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Leukocytes (1 of 2)

TABLE 14.2 Characteristics of Leukocytes

Cell Type Prevalence in _Circulation Primary Function Features Appearance*

Neutrophils 55%-90% of white blood cells

General

phagocytosis

Life span of 2 days, with only 4-10 hours spent in the

circulation

Multilobed nuclei; small purple granules

containing digestive enzymes

Eosinophils 1%-3% of white _{blood cells}

Destruction of parasitic worms; mediators of allergy

Found in much higher numbers in the spleen and bone marrow

Bilobed nucleus with large orange granules

containing toxic

proteins, inflammatory mediators, and digestive enzymes

Basophils 0.5% of white _{blood cells}

Active in allergy, inflammation, parasitic infections Cytoplasmic granules contain histamines, prostaglandins, and other chemical mediators of the allergic response.

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Leukocytes (2 of 2)

The “TABLE 14.2” continues on this slide.

Cell Type Prevalence in _Circulation Primary Function Features Appearance*

Monocytes 3%-7% of white blood cells Phagocytosis, followed by final differentiation into macrophages and dendritic cells

Monocytes also secrete several chemicals that moderate the

functions of the immune system.

Largest WBC; nuclei large, ovoid, and often indented-no cytoplasmic

granules visible using a light microscope

Lymphocytes 20%-35% of white blood cells

Specific (acquired) immunity

Two types of

lymphocytes exist. T cells are responsible for cell-mediated immunity, whereas B cells are responsible for humoral immunity.

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Erythrocytes and Platelet Lines

• Erythrocytes

: develop from bone marrow

stem cells, lose nucleus, simple biconcave

sacs of hemoglobin

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Lymphatic System (1 of 2)

• Provides an auxiliary route for return of

extracellular fluid to the circulatory system

• Acts as a drain-off system for the

inflammatory response

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Lymphatic Fluid

• Lymph

is a plasma-like liquid carried by

lymphatic circulation

• Formed when blood components move out of

blood vessels into extracellular spaces

• Made up of water, dissolved salts, 2-5%

proteins

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Lymphatic Vessels (1 of 2)

• Lymphatic capillaries

permeate all parts of

the body except the CNS, bone, placenta, and

thymus

• Thin walls easily permeated by extracellular

fluid which is then moved through contraction

of skeletal muscles

• Functions to return lymph to circulation; flow

is one-direction – toward the heart –

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Classification of Lymphoid Organs

and Tissues (1 of 2)

• Primary organs

– Sites of lymphocytic origin and maturation

 Thymus gland

 Bone marrow

• Secondary organs and tissues

– Circulatory-based locations

 Lymph nodes

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Classification of Lymphoid Organs

and Tissues (2 of 2)

– Collections of cells distributed throughout skin

and mucous membranes

 MALT—mucosal-associated lymphoid tissue

 SALT—skin-associated lymphoid tissue

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Lymphoid Organs (1 of 2)

• Thymus

– High growth and activity until puberty, then begins to shrink

– Site of T-cell maturation

• Lymph nodes

– Small, encapsulated, bean-shaped organs along lymphatic channels and large blood vessels of the thoracic and abdominal cavities

• Spleen

– Nestled below the diaphragm and left of the stomach

– Structurally similar to lymph node; filters

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Second-Line Defenses: Inflammation

• Mechanisms that play important roles in host

defenses:

– _Recognition

– Inflammation

– Phagocytosis

– Interferon

– _Complement

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Inflammatory Response (1 of 2)

• Reaction to any traumatic event in the tissues

that attempts to restore homeostasis

• _{Helps to clear away invading microbes and}

cellular debris left by immune reactions

Redness – increased circulation and vasodilation in

response to chemical mediators

Warmth – heat given off by the increased blood

flow

Swelling – increased fluid in the tissue as blood

vessels dilate – edema; WBC’s, microbes, debris, and fluid collect to form pus; prevents spread of infection

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Major Inflammatory Events (1 of 4)

a) Injury/Immediate Reactions: Blood vessels

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Major Inflammatory Events (2 of 4)

b) Vascular Reactions: Nearby blood vessels dilate;

increased blood flow; increased vascular

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Major Inflammatory Events (3 of 4)

c) Edema and Pus Formation: Collection of fluid;

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Major Inflammatory Events (4 of 4)

d) Resolution/Scar Formation: Macrophages

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Fever: An Adjunct to Inflammation

(1 of 2)

• Initiated by circulating

pyrogens

which reset

the hypothalamus to increase body

temperature; signals muscles to increase

heat production and vasoconstriction

– Exogenous pyrogens – products of infectious agents; endotoxin

– Endogenous pyrogens – liberated by

monocytes, neutrophils, and macrophages

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Fever: An Adjunct to Inflammation

(2 of 2)

• Benefits of fever:

– Inhibits multiplication of temperature-sensitive

microorganisms

– _{Impedes nutrition of bacteria by reducing the}

available iron

– Increases metabolism and stimulates immune

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Second-Line of Defenses:

Phagocytosis (1 of 2)

• General activities of phagocytes:

1. To survey tissue compartments and discover microbes, particulate matter, and dead or

injured cells

2. To ingest and eliminate these materials

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Second-Line of Defenses:

Phagocytosis (2 of 2)

• Major categories of phagocytes:

– Neutrophils – general-purpose; react early to

bacteria and other foreign materials, and to damaged tissue

– Eosinophils – attracted to sites of parasitic

infections and antigen-antibody reactions

– _{Macrophages – derived from monocytes;}

scavenge and process foreign substances to prepare them for reactions with B and T

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Development of Monocytes and

Macrophages (1 of 2)

• After leaving the bloodstream and entering

the tissue, monocytes are transformed by

inflammatory mediators into macrophages or

dendritic cells

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Phagocytic Recognition

• Protein receptors within cell membrane of

macrophages, called Toll-like receptors (TLRs)

• _{Detect foreign molecules and signal the}

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Mechanisms of Phagocytosis (1 of 2)

• Chemotaxis, binding and ingestion

– Phagocytes migrate to inflammation following

a gradient of stimulant products

– Using TLRs they bind pathogen-associated

molecular pattern (PAMPs) receptors

• Phagolysosome formation

– _{Phagocyte extends pseudopods that enclose}

pathogen in a vacuole called a phagosome

– In a short time, lysosomes with antimicrobial

substances fuse with the phagosome to form

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Mechanisms of Phagocytosis (2 of 2)

• Destruction and elimination

– Oxygen-dependent system (respiratory

burst)

– _{Liberation of lactic acid, lysozyme, and nitric}

oxide

– Undigestible debris are released from the

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Sequential Events in Phagocytosis

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Interferon (1 of 2)

• Small protein produced by certain WBCs and

tissue cells

• Three major types of IFNs:

– Interferon alpha – product of lymphocytes and macrophages

– Interferon beta – product of fibroblasts and epithelial cells

– _{Interferon gamma}_{– product of T cells}

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Interferon (2 of 2)

• All three types bind to cell surfaces and

induce expression of antiviral proteins and

inhibit expression of cancer genes

• IFNs alpha and beta stimulate phagocytes

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Complement

• Consists of 26 blood proteins that work in

concert to destroy bacteria and viruses

• Complement proteins are activated by

cleavage (cascade reaction)

• Pathways

– Classical – activated by the presence of

antibody bound to microorganism

– Lectin pathway – nonspecific reaction of a host

serum protein that binds mannan

– Alternative – begins when complement

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4 Stages in the Complement

Cascade

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Membrane Attack Complex (MAC)

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Overview of the Major Host Defenses

(1 of 3)

The figure of “Classification of Host Defenses.”

• HOST DEFENSES

– _{Innate, nonspecific}

 First line of defense

o Physical barriers

o Chemical barriers

o Genetic barriers

The first line of defense is a surface protection

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Overview of the Major Host Defenses

(2 of 3)

The figure of “Classification of Host Defenses” continues on this slide.

 Second line of defense

o Inflammatory response

o Interferons

o Phagocytosis

o Complement

The second line of defense is a cellular and

chemical system that comes immediately into play if infectious agents make it past the surface

defenses. Examples include phagocytes that

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Overview of the Major Host Defenses

(3 of 3)

The figure of “Classification of Host Defenses” continues on this slide.

– Acquired, specific (See chapter 15)

 Third line of defense

o B and T lymphocytes, antibodies, cytotoxicity

The third line of defense includes specific host

defenses that must be developed uniquely for each microbe through the action of specialized white

blood cells. This form of immunity is marked by its activity toward specific pathogens and

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