First Line of Defense – Skin and Mucous

-     Physical factors

-     Chemical factors

-     Microbiota

 

Second Line of Defense – Defense cells and reactions

-     Formed elements of blood

-     Lymph system and phagocytosis

-     Inflammation

-     Fever

-     Antimicrobial substances – the compliment system

 

The Concept of Immunity

-     Susceptibility: Lack of resistance to a disease

-     Immunity: Ability to ward off disease

-     Innate immunity: Defenses against any pathogen

-     Adaptive immunity: Immunity, resistance to a specific pathogen

-     Host Toll-like receptors (TLRs) attach to

-     Pathogen-associated molecular patterns (PAMPs)

-     TLRs induce cytokines that regulate the intensity and duration of immune responses

 

Physical Factors

-     Skin

-     Epidermis consists of tightly packed cells with

-     Keratin, a protective protein

 

Physical Factors

-     Mucous membranes

-     Mucus: Traps microbes

-     Ciliary escalator: Microbes trapped in mucus are transported away from the lungs

 

Physical Factors

-     Lacrimal apparatus: Washes eye

-     Saliva: Washes microbes off

-     Urine: Flows out

-     Vaginal secretions: Flow out

 

Chemical Factors

-     Fungistatic fatty acid in sebum

-     Low pH (3–5) of skin

-     Lysozyme in perspiration, tears, saliva, and urine

-     Low pH (1.2–3.0) of gastric juice

-     Low pH (3–5) of vaginal secretions

 

Normal Microbiota and Innate Immunity

-     Microbial antagonism/competitive exclusion: Normal microbiota compete with - pathogens or alter the environment

-     Commensal microbiota: One organism (microbe) benefits and the other (host) is unharmed

-     May be opportunistic pathogens

 

Formed Elements in Blood

-     See Table 16.1

 

Differential White Cell Count

-     Percentage of each type of white cell in a sample of 100 white blood cells

= Neutrophils = 60-70%

= Lymphocytes = 20-25%

 

The Lymphatic System

 

Phagocytosis

-     Phago: From Greek, meaning eat

-     Cyte: From Greek, meaning cell

-     Ingestion of microbes or particles by a cell, performed by phagocytes

 

Phagocytosis

-     Neutrophils

-     Fixed macrophages

-     Wandering macrophages

 

Microbial Evasion of Phagocytosis

-     Inhibit adherence: M protein, capsules

-     Streptococcus pyogenes, S. pneumoniae

-     Kill phagocytes: Leukocidins

-     Staphylococcus aureus

-     Lyse phagocytes: Membrane attack complex

-     Listeria monocytogenes

-     Escape phagosome

-     Shigella, Rickettsia

-     Prevent phagosome-lysosome fusion

-     HIV, Mycobacterium tuberculosis

-     Survive in phagolysosome

-     Coxiella burnettii (Q fever)

 

Inflammation

-     Acute-phase proteins activated (complement, cytokine, and kinins)

-     Vasodilation (histamine, kinins, prostaglandins, and leukotrienes)

-     Redness

-     Swelling (edema)

-     Pain          

-     Heat

 

Functions

-     Destroy agent causing injury (and remove its by-products)

-     Limit effects of agent on body by containing the damage

-     Repair damage from agent or its by-products

 

Steps in inflammation

-     Vasodilation and blood vessel permeability

-     Phagocyte migration and phagocytosis

-     Tissue repair

 

Chemicals Released by Damaged Cells

-     Histamine - Vasodilation, increased permeability of blood vessels

-     Kinins - Vasodilation, increased permeability of blood vessels

-     Prostaglandins - Intensity histamine and kinin effect

-     Leukotrienes - Increased permeability of blood vessels, phagocytic attachment

 

Fever

-     Abnormally high body temperature

-     Hypothalamus normally set at 37íC

-     Gram-negative endotoxin cause phagocytes to release interleukin–1 (IL–1)

-     Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature

-     Body increases rate of metabolism and shivering which raise temperature

-     Vasodilation and sweating: Body temperature falls (crisis)

-     Advantages

-     Increases transferrins

-     Increases IL–1 activity

-     Produces Interferon

-     Disadvantages

-     Tachycardia

-     Acidosis

-     Dehydration

-     44–46íC fatal

 

The Complement System

-     Serum proteins activated in a cascade

-     Activated by

-     Antigen-antibody reaction

-     Proteins C3, B, D, P and a pathogen

-     C3b causes opsonization

-     C3a + C5a cause inflammation

-     C5b + C6 + C7 + C8 + C9 cause cell lysis

 

Effects of Complement Activation

-     Opsonization or immune adherence: Enhanced phagocytosis

-     Membrane attack complex: Cytolysis

-     Attract phagocytes

 

Some Bacteria Evade Complement

-     Capsules prevent C activation

-     Surface lipid-carbohydrates prevent membrane attack complex (MAC) formation

-     Enzymatic digestion of C5a

 

Interferons (IFNs)  

-     IFN-a and IFN-b: Cause cells to produce antiviral proteins that inhibit viral replication

-     Gamma IFN: Causes neutrophils and macrophages to phagocytize bacteria

 

Innate Immunity

-     Transferrins = Bind serum iron

-     Antimicrobial peptides = Lyse bacterial cells