Chapter 14

Innate Defenses

our internal bodies must strive to maintain a sterile environment in a world full of microbes

  • first-line defenses

  • cells of the immune system

  • cell communication

  • Sensor Systems

  • phagocytosis

  • Inflammation

  • Fever

Innate immunity - host defenses (anatomical barriers, sensor systems, and phagocytic cells)

Pattern recognition - what sensor systems are used to detect certain microbes

  • LPS and peptidoglycan

  • molecules that envoke immune response are called antigens

Adaptive immunity - immunity that comes from exposure to microbes and is a specialized defense system of vertebrates

First Line Defenses

Barriers make it difficult for microbes to get to our insides

Barriers are in direct contact with the outside environment

Anatomical barriers - skin and mucous membranes

provide a physical barrier and have innate antimicrobial properties such as antimicrobial secretions and benefits from normal flora

Physical Barriers

all exposed surfaces are lined with epithelial cells tightly packed resting on a thin fibrous basement membrane

Skin

  • most difficult to penetrate - two layers

  • Dermis - tightly woven fibrous connective tissue

  • Epidermis - layers of epithelial cells becoming progressively flattened toward the exterior

  • outermost layers consist of dead cells with water

    • repelling Keratin protein creating an arid environment

    • Dead cells come off and take microbes with them

mucous membranes

  • Digestive, respiratory and genitourinary tract

  • Constant mucous or other secretions to wash away microbes

  • some can use cilia (respiratory tract) or peristalsis (digestive tract) to propel microbes toward areas of easy elimination or in the case of the genitourinary tract the flow of urine

Antimicrobial Substances

substances on skin and mucous membranes that inhibit or kill microbes

  • Sweat - High Salt

  • Lysozyme - degrades peptidoglycan in tears, saliva, mucus

    • also inside phagocytic cells, blood, and fluid surrounding tissues

  • peroxidase enzymes - Saliva and milk. Break down hydrogen peroxide producing harsh oxidizing compounds

    • catalase-producing bacteria less susceptible

  • Lactoferrin - Saliva, mucus, Mild (Transfirin in blood and tissue fluids.)

    • Iron-binding protein effectively sequesters iron thereby withholding it from Microbes

  • Defensin - Short antimicrobial Peptides produced by neutrophils and epithelial cells. insert into bacterial membrane-making pores that disrupt cell integrity

Normal Microbiota/ Flora

competitive exclusion of pathogens

covering attachment Sites

consuming available nutrients

Toxic compound production

Disruption of normal microbiota can predispose a person to infections

essential for immune system development in infants

Cells of the Immune System

Travel through the body's circulatory system moving from one part of the body to another

some of these cells are in both innate and adaptive immune response

Always found in blood, numbers increase during infection

reserves found in bone Marrow. All blood cells come from hematopoietic Stem cell

Three General Categories

Red blood cells - erythrocytes, carry oxygen

platelets - megakaryocytes, clotting

white blood cells - leukocytes: hosts defenses

Cytokines - colony-stimulating factors cause stem cells to develop into different kinds of blood cans. Some cars mature and others differentiate as they enter tissues

Polymorphonuclear Leukocytes - PMN

  • Granulocytes

    • cytoplasmic granules containing biologically active chemicals

  • neutrophils

    • phagocytize (engulf) and destroy foreign material.

    • Granules contain antimicrobial substances and degrative enzymes

      • most abundant

  • Basophils

    • Allergic reactions and inflammation.

    • Granules contain histamine and other chemicals that increase capillary permeability

    • similar to mast ceil but found in blood

  • Eosinophils

    • Thought to function in expelling parasitic worms

    • involved in allergic reactions - causing and alleviating symptoms

    • Granules contain antimicrobial substances and histaminase

Leukocytes

Mononuclear Phagocytes - MPS

monocytes circulate in the blood for a few days then enter tissues and differentiate into macrophages or dendritic cells

  • Macrophages

    • differentiated form of monocyte

    • phagocytic cells in almost all tissues but abundant in the liver, spleen lymph nodes, lungs, abdominal cavity

    • names change based on tissue

    • survives for months

  • Dendritic Cells

    • usually differentiated from monocyte

    • function as scouts in various tissues

    • engulf material in tissues and bring it to adaptive immune cells for inspection

  • lymphocytes

    • responsible for adaptive immunity

    • Two major groups

      • B cells and T cans

        • great septicity in antigen recognition

        • Generally resid in lymph nodes

      • Natural killer- not specific

Cell Communication

Immune System Cells need to communicate with each other and their environment to Successfully combat invasion or trauma

Surface Receptors

  • proteins that generally span the membrane

    • eyes and ears

  • enable inside of the cell to sense and respond to what is outside the cell

  • receptors are specific to a certain ligand compound

  • when a ligand binds, the receptor potion becomes modified in some ways, causing a cell response

  • cells can change the winds and amounts of receptors they make to adjust conditions

Cytokines

  • protiens made for the purpose of communication.

    • voices

  • Bind Cytokine receptors on the surface of the internal cans that the cytokines regulate

  • can cause changes in cell growth, differentiation, movement or cause cell death

  • Doesn't last long, take many to produce large effect.

    • can act locally or systemically

    • often act together or in a sequence cascade

    • pro-inflammatory cytokines CTNF-Alpha, IL-1, IL-6 and others) contribute to inflamation

    • often involved in antibody response

Adhesion Molecules

  • one cell surface and allow cen to adhere to other cells or to 'gras certain cells as they pass by

  • when tissues need phagocytic cells, the cells that line the blood vessels synthesize adhesions that adhere to passing phagocytic cells

  • other adhesion molecules allow cells to create direct contact whereby cytokines or other molecules can be delivered to a particular cell

Sensor systems

complement system

  • series of proteins always circulating in the blood and tissue fluid that work in conjunction with "complement the adaptive immune response.

  • circulate in their inactive form, activation sets of a cascade of events that cooperate with host defense systems to remove and destroy invading microbes

    • Activation of one complement proton allows it to become enzymatically active, Cleaving and activating millions of the next protein in the cascade. Each of those activates multiple Molecules of the next proteion in the cascade

      • stringent controls at various points

  • three pathways lead to a complement system

    • Alternative Pathway

    • Lectin pathway

    • Classical pathway

Complement System - 3 Outcomes

Inflammation

  • compliment components C3a and C5a induce changes in epithelial cells that line blood vessels leading to vascular permeability associated with inflammation

  • C5 is a chemoattractant living phagocyte in the area

Lysis of Foreign Cells

  • complexes of (Sb, 16, CG molecules spontaneously assemble in the membrane of foreign ceils producing structures called Membrin attack complex (mac) creating pores in the membrane and interfering with the integrity of the cell

    • Gram + cells peptidoglycan kyer makes them less susceptible but Gram-bacteria outer layer is sensitive

Opsonization

  • C3b binds foreign material making them sensitive to phagocyte ingestion because they have C3b receptors on their surface

  • C3b coated material is opsonized - prepared for eating

    • C3b is an opsonin

Inflammation

Inflammatory response triggered when tissues have been damaged

  • skin penetrated, invasion

Cardinal signs of inflammation: swelling, redness, heat, pain, loss of fiction

The purpose is to contain the site of damage, localize response, eliminate invaders, and restore tissue function

Macrophages and eosinophils at the Site of damage, neutrophils, and monocytes recruited

Acute Infection - short-term inflammation, characterized by neutrophils

chronic inflammation - long-term inflammation, occurs when acute inflammation is insufficient to limit infection, characterized by macrophages, giant cells, and granulomas

Inflammatory processes

Dilation of small blood vessels

  • greater blood flow, slower rate

  • leakage of fluids

migration of leukocytes from the bloodstream to tissues

  • endothelial cells "grab" phagocytes, slow them down

  • phagocytes squeeze between cells of vessel - diapedesis

Clotting factors wall off-site of infection

Dead neutrophils, tissue debris accumulate as pus

Outcomes of Inflammation

can help prevent a problem but causes damage doing it

Toxic substances from dead phagocytes can be released

damage inflicted by these effects vary in severity based on length of inflammation and where inflammation occurs

Fever

Important host defense of vertebrates

Temperature regulated by the brain

  • during infection, the regulator changes its setting achieving higher temperatures than normal

pro-inflammatory cytokines released by macrophages signal to the brain

Fever-inducing substances are called pyrogens

  • endogenous pyrogens - produced by the body-cytokines

  • exogenous pyrogens - produced externally by microbial products

fever inhibits the growth of many pathogens by

  • exceeding microbes’ temperature range for growth

  • Activating and Speeding up other host defenses

Sensors that Detect Long dsRNA

most cans do not contain ds RNA greater than 30bp

usually a sign of Viral infection

  • RNA viruses, retroviruses, DNA viruses

Long ds RNA induce alpha-beta interferon synthesis and secretion.

  • Attach to receptors on infected cells and their neighbors using the expression of several inactive antiviral protiens

iAVPs are activated by dsRNA and become AVP which degrades RNA, stop protien synthesis, leads to apoptosis

  • only infected cells are sacrificed

Phagocytosis

Cells that engulf and digest material

Pattern recognition receptors on phagocytes determine which particles to engulf

Macrophages handle Butine situations with a few bacteria, is too many - produce cytokines to attract phagocytes

Process of Phagocytosis

medically important because bacteria often evolve to evade one of them

Chemotaxis

  • chemoattractants recruit phagocytes to the Site of tissue damage or infection.

    • Chemical stimuli include products of microorganisms, complement component CSa, and phospholipids released by damaged host cells

Recognition and Attachment

  • phagocytic cells have receptors to bind to invading microbes

  • Direct binding occurs through pattern recognition receptors identifying microbe compounds

    • bind to mannose

  • Indirect binding occurs when the particle is first opsonized which increases a phagocytic ability to attach and engulf

    • bind to opsonins

Engulfment

  • phagocytotic cell engulfs creating a membrane-bound vacuole called a phagosome - which does not destroy

    • pseudopods form around material

Fusion of Phagosome with Lysosome

  • phagosome transported along the Cytoskeleton to fuse with the lysosome

  • lysosome filled with digestive enzymes

    • phagolysosome

Destruction of Pigestion

  • Involves aerobic respiration of sugars creating oxygen diproducts.

    • ph decreases, enzymes degrade, detentions damage membrane of invader, lactoferrin ties up iron

Exocytosis

  • membrane-bound vesicle l fuses with can membrane dumping contents out of a cell

Attributes of Macrophages

scavengers of dead cells and debris

  • function as a first response

  • call for reinforcements

can live for weeks or months

  • alwas present in tissues

TLRs on their surface allow them to detect microbes, then produce pro-inflammatory cytokines to stimulate other cans of the immune system

gain assistance from certain T cells

  • activate macrophages

upon chronic infection, macrophages form giant cells

  • form granulomas with t cells

  • quarantine organisms

Attributes of Neutrophils

Critical during the early stages of inflammation, first cell type recruited from the bloodstream to of damage

only live 1-2 days in tissues but have more destructive power than macrophages

kill microbes through phagocytosis and can lay traps

  • can reless the content of their granules and DNA

  • DNA Shares microbe a and granule contents digest them