Chapter 17: Innate Host Defenses

Question 1

two parts of the immune system of mammals

Answer 1

innate or nonspecific immunity

adative or specific immunity

innate immunity is a pre-existing (pre-infection) system of cells, tissues and organs and molecules

Question 2

Physical Barriers - SKin

Answer 2

3 layers to the skin: epidermis, dermis and hypodermis

epidermis is dead cells, dermis and hypodermis are living cells

hypodermis is the connective tissue and fats

dermis is live cells (approx 15 layers) that pass up, and dessicate upwards at the same time as filling up keritin. (add lipids for waterproofing)
=> kerritin is very hard for fungi and bacteria to digest

Question 3

immune system in bacteria

Answer 3

restriction enzymes and crisper

Question 4

Physical barriers

Answer 4

skin

mucous membranes

endothelia

bacteria cannot penetrate through intact skin

only exception is S. aureus causes scalded skin syndrom => produciton of enzyme that can cut the connective fibres that holds the layers of skin together, give them access to breach this physical barrier.

fungi can cause superficial skin infections in tropical climates

Question 5

Epidermis

Answer 5

consists of dead cells filled with the protien keratin and lipids

resistant to mechanical attack - bacteria and viruses cannot penetrate it

mostly dry, salt, and acidic - inhibits bacteria, especially gram-negatives

dessicated epidermis is not very nutritious

fatty acids secreted onto skin are toxic (from lipases)
=>

secretion of lysozyme (breaks down peptidoglycan)

Question 6

desquamaiton

Answer 6

skin cells slouphing off

help to get rid of bacteria on the surface of your skin

Question 7

dry skin vs wet skin

Answer 7

there is 100-1000fold more bacteria that live on wet skin than on dry skin per square centimeter

Question 8

sweating

Answer 8

increases salt conc. on skin to dessicate the microbes

especially helps to inhibit gram negative bacteria

Question 9

What kind of bacteria moslty live on skin

Answer 9

mostly gram negatives, and a few gram positives

salty sweat to inhibit the growth of gram negative bacteria

Question 10

Dermis

Answer 10

contains hair follicles, sweat and oil glands and blood/ lymphatic vessels (carry immune cells to skin)
=> the dermis contains parts of the adaptive immune system as well

the hypodermis contains fat and connective tissue

Question 11

Mucosal membranes

Answer 11

usually a single layer of epitheliad cells covered with a thick (or thin) layer of mucus which trap debris and microorganisms

lines the respiratory tract, difestive tract and urinary tract

mucus is mobile, flushes away trapped microorganisms, in respiratory tract ciliated epitheliad cells propel the mucus (cilia plus peristalsis from the muscular movements) => especially important in the respiratory tract. With out this cilia you can become much more susceptible to streptococcus pneumoniae

Question 12

Endothelia

Answer 12

epitheial cells line the urogential tract, blood vessesl, and lymphatic system vessels

tight junctions between cellst to prevent bacteral and fungi from passsing through (prevent bacteria from entering capillaries)

also forms the blood-brain barrier to protect CNS

Question 13

Mechanical defenses

Answer 13

shedding (exfoliation) of skin cells

expulsion of mucus from lungs and movement of mucus in gastrointestinal tract

flushin of urine (low pH)

Tears (also contain lysozyme)

hairs in nose, design of upper respiratory tract (nose hairs, and 90 degree bend of throat to nasal cavity to incoming air hits the back of the throat)

Question 14

Chemical defenses

Answer 14

olic acid

Lactoperoxidase system

acidic skin

defense in depth
=> not just one single defense
=> reduces the likelyhoood that any one microorganism can get through

Question 15

lactoperoxidase system

Answer 15

lactoperoxidase oxidises oxidises iodide, bromide, and thiocyanate using hydrogen peroxide to produce hypoiodide, hypobromite, and hypothiocyanite (IO-, BrO-, OSCN-) which in turn oxidize proteins in pathogens

hydrogen peroxide is produced by glucose oxidase

found in saliva, mucus, and milk

Question 16

Oleic acid

Answer 16

produced by skin microorganisms from sebum lipids
=> low pH and toxicity of long chain fatty acids

sebum is cleaved into a glycerol and long chain fastty acids like oleic acids, (long chain fatty acids are fairly toxic to microorganisms)

Question 17

lysozyme

Answer 17

an enzyme whihc hydrolyzes the glycosidic bond between NAG and NAM in peptidolygan

effective agaisnt most gram positive bacteria
=> some bacteria modify their peptidoglycan to become resistant to lysozyme (prevents the enzyme form binding to it)
=> other enzymes are also present to attack peptidoglycan like proteases and such

found in tears, saliva, mucus, on skin
=> why milk is naturally semi-antibiotic, unfortunately, pasturization denatures this enzyme activity

Question 18

Lactoferrin

Answer 18

a protien which binds to and sequesters iron

lack of iron inhibits the growth of most microorganisms
(important because iron is needed in relativly high abundance in cells)
=> why bacteria perform haemolysins and synthesis sidirophores to trap iron

found in tears, saliva and muscus

Question 19

Lactic acid

Answer 19

fermentation of glycogen in urinary tract to lactic acid

glycogen is secreted into the urinary tract

lactic acid bacteria ferment this

lactic acid or really protonated organic acid is toxic// antibacterial

Question 20

Surfactants

Answer 20

produced in the alveoli by type II cells (at the bottom of the respiratory tracts, bottom of alvioli?)

breaks surface tension

consist of lipoproteins and phospholipids

phopholipids act as detergents, include dipalmityoulphophatidycholic, phosphatidylcholine, phosphatidylglycerol and cholesterol

lipoproteins SP-A and SP-D are collectins, they bind to the surface of bacterial cells and activate the complement system
=> collectins make bacteria sticky? and help macrophages eat them

Question 21

Transportation of antibiotics into Gram negative cells

Answer 21

use a siderophore that a Gram negative produces, covalently ligate it to an antibiotic. The bacteria will take up the siderophore, and trojan hore antibiotic is brought into the Gram-negative cells

not needed with Gram positives because their is not an outer membrane you have to worry about

Question 22

antimicrobial peptides

AMPs

Answer 22

a number of different short protiens or poptides that are produced by all mammals and many other organsims
=> short protiens, 30 aa or 60aa

generally contain positively charged aa and hydrophobic aa and so AMPs are amphiphilic

usually act on the membraneand cause pores to form
(not all do this tho)

broad spectrum (the positive charges are important here. Positive charged AMPs attack negativley charge bacterial cell walls. Whereas they are repelled by our neutral to slightly positive cell membranes, usually)

some have other roles to inhibit microorgansims from the inside = proteins/ cell wall synthesis, DNA daamage
=> or can collapse proton gradients and such

some have dual functions

secreted by skin, epitheliad cells, marcrophage and neutrophils

Question 23

Two classes of AMPs

Answer 23

defensins and cathelicidins

Question 24

Cathelicidin

Answer 24

in humans, LL-37, a peptide of 37aa and 2 adjecent leucines

L-37 disrupts membranes and is effective against bacteri, fungi and viruses

Question 25

Defensins

Answer 25

are bount 30aa, cationic peptides with many cysteines, also disrupt membranes and is effective against bacteria , fungi and viruses (viruses with lipid membranes)

less active agaisnt mammalian cell membranes

Question 26

Acute phase proteins

Answer 26

generally antibacterial

secreted by liver cells and circulate in the blood, increase in response to inflammaiton and infection (in the blood)

C-reactive protiens (CRP)

ferritin and transferrin
= iron binding proteins

mannose-binding lectin (MBL)

lectins are proteins that bind carbohydrates

Question 27

AMPs as theraputics

Answer 27

trying to use them as antibiotics

hard for a microorganism to become generally resistant to AMPs

problem = you own body will degrade foreign AMPs

Question 28

Complement system

Answer 28

a number of protiens found in the blood which become activated by certain triggers and have antibacterial activity

most important are the C1 to C9 protiens

cleavage of a C protein into Ca, Cb leads to activation and the cascade

3systems of complement activation = classical, alternate, and lectin binding

Result i the formaiton of the membrane attack complex (MAC) which creates pores in membranes

Question 29

Other functions of complement system

Answer 29

opsonization, inflammation, and chemotaxis

Opsonization is the process of attaching a compound/ protein to the surface of a bacterium which allow macrophage to detect and phagocytize them more quickly

Question 30

Cytokines

Answer 30

small soluable protein or peptide messengers

produced by immune system cells but also other cells types and usually activate other immune system cells

BInd to receptors on cell surfaces
=> interleukins secreeted by WBCs and act moslty on other leukocytes
(IL-1, IL-2, IL-6…)

Chemokines attract cells to the sites of infecitons (inflammaiton)
=> CXC-x, CC-x, RANTES, MIP, MCP-1

Question 31

Interferons

Answer 31

primarily anti-viral defense

TYPEW 1 interferons (a and b) are produced by cells infeced with a virus and act on neighbouring cells

stop these cells from making RNA and DNA and protien which are the components of viruses

Type II IFN gamma is an immune system cell activaotr and an inflammatory agent

Question 32

Two cell lineages

Answer 32

myeloid and lymphoids

both derived form pluripotent hematopoietic stem cells

Lymphoid stem cells produce NK cells, and T and B lymphocytes

Question 33

Myeloid stem cells

Answer 33

myeloid stem cells produce megakaryocytes which produce platelets and also erythrocytes, mast cells and myeloblasts

myeloblasts give rise to basophils, neutrophils, eosinophils, and monocytes which give rise to macrophage and DCs

Question 34

Neutrophils (polymorphonuclear neutropils, PMN)

Answer 34

pphagocytose bacteria in blood stream and in tisuse

granules contain antibacterial compounds, can be released our of the cells

create extracellular DNA meshes or traps which contain lactoferrina nd myeloperoxidase

Question 35

eosinophils

Answer 35

mostly for defense against protozoa and multi-cellular parasites

Question 36

basophils

Answer 36

release substances (histamine) which promote inflammation

Question 37

mast cells

Answer 37

also release substances whcih promote inflammation

migrate into the tissues

Question 38

Natural killer cells

Answer 38

drecognize and kill abnormal cells including those infected with viruses and macteria

induce abnormal cells to udnergo apoptosis using perforin and granzymes

do not need activation

Question 39

Monocytes

Answer 39

macrophages and Dendritic cells

macrophage leave bloodstram and enter tissue (unlike neutrophils) where they differentiate into tissue-specific (tissue resident) macrophage, often have different names

Neutrophils also have multi-lobed nuclei

macrophages also help to get rid of cellular debris, M2 type is anti-inflammatory
(M1 is pro inflammatory)

phagocytic and produce cytokines

DC capture antigens and present them to leukocytes

Question 40

Extravasation or Diapedesis

Answer 40

passage of leukocytes from the bloodstream into tissues

cytokines and complement protien C5a attract the leukocytes and cause capillary endothelial cells to produce molecules which the leukocytes attach to

when leukocytes reach an endothelial cell-cell junction they bind, flatten out and squeese through the junction into the tissue
=> Transendothelial migration

Question 41

Pathogen recognition

Answer 41

pathogen associated molecular pattens (PAMPs)

overall types or categories of macromolecules, not specific

found on the surface of bacteria and fungi

• peptidoglycan
• flagellin
• lps
• nucleic acids, = dsRNA

Recognized by pattern recognition receptors (PRR) which are protiens on or inside phagocytic cells (and othe cell types)

Question 42

PRR activation

Answer 42

PRRs are activated by PAMPs (or DAMPs)

PRRS are protiens on or inside phagocytic cells and other cell types

upon binding of PAMP to PRR, the phagocyte is activated

also allows phagocytes to recognize damaged cells and remove them

Question 43

Pathogen degredation

Answer 43

phagocytosis is the engulfment of a particle (pathogen) by a macrophage or neutrophil

forms a membrane enclosed phagosome

lysomes are membrane enclosed vesicles containing antibacterial enzymes and compounds
lysosomes fuse with phagosomes to form phagolysomes and the pH drops activating the antibacteral enzymes
=> lysozyme, phospholipase and proteases

respiratory burst

Question 44

Respiratory burst

Answer 44

increases in oxygen uptake to produce ROS such as H2O2, O2* and *OH

Question 45

Inflammation and fever

Answer 45

due to increased permeability of the blood vessels
=> histamine released by mast cells
=> fluid enters tissue(ie swelling = edema)

Cells migrate into tissue
=> macrophages and neutrophils
=> They can release proinflammatory compounds

Also redness (erythema), heat, pain and altered function

Question 46

Chronic inflammaiton

Answer 46

inflammation usually only lasts a few days, if longer it is chronic

due to the presence of pathogens or abnormal regulation of inflammation

may lead to formation of granulomas which wall off pathogens
=giant multinuclear macrophage cells
=> other cells including fibroblasts
=> Formation of collagen fibres and caalcium deposition

Question 47

Chronic inflammaiton and alterations to tissue

Answer 47

formation of collagen fibres

remodelling of tissue

(chronic inflammation activates leukocytes which secreate proteases, thus preventing tissue repair and remodelling)

also prevents M1 => M2 conversion, M2 cells promote angiogenesis

Question 48

Fever

Answer 48

increase in body temperature due to exogenous pyrogens (LPS) and or endogenous pyrogens (IL-1 and TNF)

may help in slowing virus replication

may help in immune cell functiona nd replicaiton