Nonspecific Host Defenses

Host Defenses

l Susceptibility

l Immunity (Resistance)

n    Innate versus Adaptive

Host Defenses

First Line of Defense – Physical Factors

l

       Skin

n  Epidermis

       Keratin

n  Dermis

       Mucous membrane

n  Mucous

       Traps microbes

n  Less protection than skin

       Fluid nature

n  Similar to skin

       Epithelial layer with underlying connective tissue

First Line of Defense

l Physical Factors

n    Lacrimal apparatus

n    Saliva

n    Goblet cells and mucous

lCiliary escalator

n    Epiglottis

n    Urination

n    Vaginal secretions

First Line of Defense

l

       Chemical Factors

n  Sebum

       Produced by sebaceous glands

       Unsaturated fatty acids (hydrophobic)

n  Low pH (3-5) of skin

n  Low pH (3-5) of vaginal secretions

n  Perspiration

       Sweat glands

       Lysozyme and washing effect

n  Gastric juice

       HCl, enzymes and mucous (very low pH:  1.2-3.0)

       C. botulinum, S. aureus, and H. pylori can survive

n  Ulcers and H. pylori

n  Transferins

       Iron binding proteins found in blood

       Reduce amount of available iron

First Line of Defense

l  Normal Flora/Microbiota

n    Microbial antagonism between normal flora and pathogens

l  Preventing the outgrowth of harmful organisms by preventing colonization/invasion

l Competition for nutrients and O₂, pH, and bacteriocins

n   Competitive exclusion

l The flora are called commensal or mutualistic symbionts of the host.

l Ex. Intestinal flora

Formed Elements

l Plasma

n    Formed elements

lErythrocytes (RBCs)

lLeukocytes (WBCs)

lPlatelets

Differential White Cell Count

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

l   Determine stages of infection

l   Leukocytosis (increase) versus leukopenia (decrease)

LEUKOCYTES

l Granulocytes

n    All involved in 2^nd line of defense

n    Granular appearance

n    Types

lNeutrophils:  motile phagocytes; early stages of infection

lBasophils:  not phagocytic; release histamine; important in inflammation and allergic responses

lEosinophils: motile phagocytes; attack helminths; release toxins to destroy before ingesting large helminth

lDendritic cells: Initiate adaptive immunity response

LEUKOCYTES

l Agranulocytes

n    Monocytes:  must mature into macrophages before they are phagocytic (in tissues)

lSecond line of defense

lIn blood and lymphàmonocytes

lIn tissue and lymphàmacrophage

n   Wandering versus fixed macrophage in lymph

lSwelling in lymph nodes due to monocyte maturation during initial infection

lAlso help dispose of old blood cells in lymph

n    Lymphocytes:  not phagocytic

lOccur in lymphoid tissues of lymphatic system (i.e. tonsils, spleen, thymus gland, etc.)

lThird line of defense (Chapter 17)

Second Line of Defense

l Phagocytosis: ingestion of microorganisms causing disease

Phagocytosis

Microbial Evasion

l S. pyrogenes with M protein can prevent adherence of phagocytes

l S. auerus can kill phagocytes with leukocidins

l Listeria monocytogenes can kill phagocytes

l Coxiella burnetii replicate inside a phagolysosome

n    Prefers that low pH in the lysosome

l Shigella can escape phagosome

l HIV can hide in phagocytes

Second Line of Defense

l  Inflammation (local response)

n    Triggered by tissue damage

n    Four signs/symptoms: (edema, pain, heat and redness)

n    Three functions (destroy injurious agent, isolate infection, repair damage)

n    Three stages

l Vasodilation with increased permeability of blood vessels

l Phagocyte migration and phagocytosis

l Tissue repair

VASODILATION

       Increased blood flow

       Increased permeability

       Chemicals released

n  Histamine causes vasodilation and increased permeability of blood vessels

n  Kinins attract phagocytes to area

n  Protaglandins help phagocytes move through capillary walls

n  Leukotrienes attract phagocytes to pathogens and increase permeability

       Clotting àabscess and isolation

Migration and Phagocytosis

l Migration:  Neutrophils then monocytes (immature macrophage)

l Marginationàemigrationàphagocytosis

l Depression of non-specific immune responses

Tissue Repair

l  Extent of repair depends on type of tissue

l  Occurs after all harm removed

l  Stroma and parenchyma of the tissues produces new cells

n    Stroma:  supporting connective tissue

l Stroma reconstructionàscarring

n    Parenchyma:  functional tissue

Second Line of Defense

l Fever (systemic response)

n    Hypothalmus:  body’s thermostat (37°C)

n    Endotoxins can cause resetting of thermostat

n    Raise thermostatàincreased metabolism, shivering, and blood vessel constriction causes body temp. to raise

n    Stage 1: Chillàraise in body temp

n    Stage 2: Crisisà sweating to lower temp.

n    Effects:  Increased repair, increase in interferon effects (decrease in iron available to microbes)

Fever

       Advantages

n  Increases transferrins

n  Increases IL–1 activity

n  Produces Interferon

       Disadvantages

n  Tachycardia

n  Acidosis

n  Dehydration

n  44–46°C fatal

INTERFERONS

l   Antimicrobial substances

l   Made by host to combat viruses

l   Host cell specific, but not viral specific

l   Different types of cells in host produce different IFNs (alpha, beta, and gamma)

l   Alpha and beta

l   Gamma

n    Produced by lymphocytes and causes neutrophils to kill bacteria

l   Advantages:  Low concentration so not toxic to cells, but prevent spread

l   Disadvantages:  No effect on infected cells, effective only short period

Alpha and Beta Interferons (IFNs)