Chapter 14

Host Defenses I

Nonspecific Defenses

Defense Mechanisms of the Host

•       Innate, nonspecific

–      1^st Line of defense (anatomical and physiological barriers)

–      2^nd line of defense (cellular and chemical systems)

•       Acquired, specific

–      3^rd line of defense

•       Naturally acquired

–      Active (Infection)

–      Passive (Maternal antibodies)

•       Artificially acquired

–      Active (Vaccination)

–      Passive (Immune serum)

First Line of Defense

•       Physical factors

–      Skin

–      Mucous membrane

•       Chemical factors

–      Sebum

–      Gastric acid

–      Lysozyme

Skin

Skin consists of two layers:

•       epidermis - outer thinner portion made of     tightly packed cells (upper layer - dead cells)

•       dermis - inner thicker portion; Gives skin strength  

Infection can develop when the epithelial surface is broken

Mucous membranes

•       Mucous membranes line the gastrointestinal, respiratory and genitourinary tracts

•       Epithelial layer secrets the mucus that maintains the surface of the membrane always moist

•       Mucous membranes are more susceptible to infections than skin

Other physical barriers

•       Lacrimal apparatus

–      provides washing action; removal of microbes

•       Ciliary escalator

–      The mucus membrane of the lower respiratory tract is covered with cilia; propel mucus containing microorganisms upward

Chemical Factors

•       Sebum – oily substance produced by skin; contains unsaturated fatty acids – inhibit the growth of certain pathogenic bacteria

•       Gastric juice – mixture of hydrochloric acid, enzymes, and mucus; kills most of bacteria except Clostridium botulinum and Staphylococcus aureus

•       Lysozyme in saliva and tears – enzyme that hydrolyzes the peptodoglycan

Second and Third Line of Defense: Immune system

Responsible for:

•       Surveillance of the body - white blood cells

•       They recognize foreign material – distinguish between “self” and “nonself”

•       Destruction of foreign entities

Systems involved in immune defenses

•       Reticuloendothelial system

•       Extracellular fluid

•       Bloodstream

•       Lymphatic system

Reticuloendothelial system

•       Consists of:

–      Network of connective tissue fibers that surround all organs

–      Phagocytic cells located in reticular connective tissue

–      Interconnects neighboring cells

•       Provides a passageway between tissues and organs

Blood

•       A liquid connective tissue, consists of plasma and blood cells

–      Plasma - a fluid containing: water (92%); proteins (antibodies); fibrinogen, hormones, nutrients, O₂ and CO₂

–      Blood cells:

•       Erythrocytes – red blood cells

•       Leukocytes – white blood cells

•       Thrombocytes – platelets

Formed Elements in Blood

•       Erythrocytes- carry oxygen and carbon dioxide in the blood

•       Platelets- involved in blood clotting

•       Leukocytes- involved in defending the body against invaders

•       Granulocytes

•       Agranulocytes

Agranulocytes

•       Cytoplasm appears uniform under a light microscope

•       2 types

–      Monocytes

–      Lymphocytes- involved in specific immunity

•       B lymphocytes

•       T lymphocytes

Monocytes

•       Produced in bone marrow – discharged into the bloodstream and transformed into macrophages

•       Macrophages are responsible for:

–      Phagocytosis

–      Processing foreign molecules – presenting them to lymphocytes

–      Secreting compounds involved in immune response

Lymphatic system

•       Consists of lymphatic fluid, vessels, and organs

•       Lymphatic fluid is  plasma that moved out of the blood vessels and circulates in the space between the tissue cells

•       Lymphatic vessels collect the lymph and return it to the circulatory system

Lymphoid Organs

•       Lymph nodes

–      Aggregated in armpit, groin, and neck area

–      Filters lymph

•       Spleen

–      Abdominal cavity

–      Filters blood – worn-out erythrocytes

•       Thymus

–      Pharyngeal region

–      T-cell maturation

Second Line of Defense: Inflammation

Inflammation is a body’s response to microbial infection

•       Three stages of inflammation:

–      Vasodilation

–      Edema and pus formation

–      Tissue repair

Vasodilation and increased permeability of blood vessels

•       An increase of diameter of blood vessel – enables increased blood flow to the damaged area

•       Caused by the chemicals released from damaged tissue

–      Histamin - vasodilation

–      Chemical mediators – increase permeability of blood vessels

Edema

•       Accumulation of fluid in the tissue

•       White blood cells (phagocytes) migrate from the blood vessels – diapedesis – they squeeze themselves between the endotelial cells

•       Chemotactic migration towards the site of injury

•       Phagocytosis is followed by formation of pus (cellular debris, bacteria)

Fever

•       Abnormally elevated body temperature in response to an infection

•       Body thermostat (hypothalamus) normally set at 37⁰C

•       Substances called Pyrogens can reset the body thermostat to higher setting

•       Pyrogens

–      Exogenous – products of infectious agents

–      Endogenous (liberated from white blood cells)

•       Benefits of fever

–      Inhibits the growth of temperature sensitive microorganisms

–      Increased production of transferins (decreased availability of iron)

–      Faster tissue repair

•       Complications of fever

–      Tachycardia (accelerated heart rate)

–      Dehydration

–      Electrolyte imbalance

–      Coma

Phagocytosis (eat, cell)

•       Certain types of white blood cells eliminate the microbes by phagocytosis

•       The most important phagocytic cells are macrophages

•       Macrophages either reside in a specific organ or they wander throughout the tissues 

Mechanism of Phagocytosis

There are five phases of phagocytosis

•       Chemotaxis - Phagocytes are attracted by:

–      microbial products

–      damaged tissue cells

•       The plasma membrane of the phagocyte attaches to the microbe and identifies it as “nonself”

•       Ingestion

–      A phagocyte extends the pseudopds that engulf the microbe

–      Inside the phagocyte, the microbe is located within a sac called phagosome

•       Formation of phagolysosyomes

–      Phagosome fuses with lysosome forming a single structure – phagolysosome

•       Digestion

–      Bacteria are killed by reactive oxygen species (H2O2, singlet oxygen) and lysozyme

•       Excretion

–      Bacteria are digested. The waste products discharged outside the cell.

Microbial Evasion of Phagocytosis

•       Some microbes resist the attachment of phagocyte by producing large capsules

•       Microbial toxins can kill a phagocyte

•       Microbial enzyme can lyse phagolysosome

•       Some microbes enter the phagocyte – they either multiply or remain dormant

Antimicrobial substances

The body produces antimicrobial substances:

•       Interferon

–      Interferon alpha and beta (produced by lymphocytes, macrophages, fibroblasts)

–      Interferon gamma (produced by T-cells)

•       The complement system

–      Serum proteins that contribute to destruction of microbes

Interferons

•       Proteins that interfere with viral multiplication.

•       Produced and released by a virus-infected cell 

•       Interferon enters now the neighboring non-infected cell

•       This triggers the cell to produce antiviral proteins (AVPs)

•       Other effects:

–      Defense against other, non-viral microbes

–      Play role in maturation B and T lymphocytes

–      Inhibits cancer cells

Complement proteins

•       The complement system consists of about 30 proteins found in the serum

•       Designated by the letter “C”

•       Act in a cascade (one reaction triggers another)

•       Complement activation occurs in 3 pathways

–      Classical

–      Lectin

–      Alternative

Steps in classical complement pathway

•       Initiation –

–      C1 component binds to antibodies that are bound to a pathogen

•       Amplification

–      C1 activates other components

•       Polymerization

–      The components aggregate and integrate into pathogen membrane

•       Membrane attack

–      The final product is an enzyme that punctures pores in the membrane

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