Medical Microbiology/Immune System

normal microbial flora

first line of defense (in the skin, GI tract, upper respiratory tract, reproductive system)

• varies by location

• bacteria, fungi, viruses, that protect us from the “bad” microbes

functions of microorganisms in normal flora

• metabolize food products (digestion)

• provide essential growth factors

• block infections from highly virulent microorganisms

  • clostridium botulinum is unable to grow in a healthy colonized GI tact

• stimulate immune responses (keep immune cells sensitive to microbial products)

origin of normal flora

healthy fetus is sterile in utero until when the mother’s water breaks, you get the first exposure to microorganisms (broken barrier to allow microbe entry)

also have exposure during and after birth

• mother’s genital tract if vaginal birth (first exposure baby has to microorganisms)

• skin and respiratory flora of people handling the infant

• organisms in the environment

cesarean delivery

sterile surgical suite with no vaginal contact

• first species baby is exposed to is staphylococcus from the skin and this is ineffective at GI seeding like lactobacillus can which is found in the mother’s genital tract (can sometimes delay lactation)

**this is an example of an abnormal microbial introduction

normal vaginal flora

6 weeks: pH is acidic due to lactobacilli as a remnant from maternal source and maternal hormones

pre puberty: pH neutral

puberty: pH acidic due to lactobacilli which is critical for development in child bearing

menopause: pH neutral

normal flora of the intestines/colon

lots of different bacteria that are supposed to be there

• ex: e coli, peptococcus, lactobacilli, etc.

**antibiotics can mess up the normal flora bacteria story (these get knocked out which is not good)

opportunistic pathogens

common and not problematic in healthy patients

• no disease except for in immunocompromised patients like those with HIV, cancer, taking steroids

• found in normal flora

ex: staphylococcus epidermis… catheters and artificial joints

strict pathogens

always associated with disease

NOT found in normal flora - if they are present, you will be affected and become ill

ex: mycobacterium tuberculosis, N. gonorrhoaea

facultative pathogens

able to cause disease in healthy patients but doesn’t always

• organisms in between two extremes

• MOST fall in this group, they ARE found in the normal flora

ex: UTI, toxic shock syndrome, MRSA (strong infection, hard to treat), skin/bone infections

entry into the host

• pathogen must gain access to host tissues and multiply BEFORE the disease is caused

  • must penetrate the skin or mucous membrane

• microbes adhere to epithelial cells (these do shed)

  • interaction of microbial adhesions and specific host cell receptors

  • after adhesion - many pathogens INVADE - penetration of host tissues which gives them direct access to blood or lymphatic system (main ways to get in: dry skin that has breaks for species to get in)

virulence factors

increases pathogenicity, an organism’s ability to infect and cause disease (invade immune system)

gram negative virulence

most produce endotoxin (Lipid A of LPS) - all have the potential to make us sick but not all created equal

released when bacterial cells are lysed

responses:

• fever (LPS stimulation causes hypothalamic set point to increase so thermostat is out of whack)

• activation of compliment (protein defense system)

• disseminated intravascular coagulation (random blood clotting to stop flow so bacteria can’t spread)

• decreased peripheral circulation (limits spread but detrimental to host)

all of these responses decrease BP which decreases organ perfusion which causes shock/death

innate

the body’s first line of defense; hard-wired, in your genes, you are born with this already to go

• structures, chemicals, and processes that work to prevent pathogens entering the body OR stop their progress

• skin and mucous membranes of the respiratory, digestive, urinary, and reproductive systems

epidermis

multiple layers of tightly packed cells; few pathogens can penetrate these layers; shedding of the dead skin cells removes microorganisms

• dendritic cells of this skin layer phagocytize pathogens (it’s an innate cell that engulfs foreign items)

dermis

layer of the skin

collagen fibers help resist abrasions that could introduce microorganisms

perspiration role in innate immunity

secreted by sweat glands

• salt inhibits growth of pathogens

• antimicrobial peptides act against microorganisms

• lysozyme destroys cell wall of bacteria

sebum role in innate immunity

secreted by sebaceous (oil) glands

• helps keep skin pliable and less likely to break or tear

• lowers skin pH to a level inhibitory to many bacteria

two layers of mucous membrane

**line all body cavities open to the environment

• epithelium

• deeper connective layer

epithelium

thin, outer covering of the mucous membranes

• cells are living

• tightly packed to prevent entry of many pathogens

• continual shedding of cells to carry away microorganisms

• dendritic cells below phagocytize pathogens

• goblet and ciliated columnar cells help to remove invaders

goblet cells

cells in epithelium that produce mucous

ciliated columnar cells

cells in the upper respiratory epithelium

deeper connective layer

layer of the mucous membrane that supports the epithelium

• produces chemicals that defend against pathogens

lacrimal apparatus

• produces and drains tears

• blinking spreads tears and washes surface of the eye

• lysozyme in tears destroys bacteria (targets bacterial cell wall to cause lysis)

**the eyes are an immunoprivileged area so immune system function is limited there

antimicrobial peptides

• present in skin, mucous membranes, and neutrophils (innate immune cells)

• act against a variety of microbes - targets foreign things only

saliva

digestive enzyme that washes microbes from teeth, gums, tongue, and palate; contains lysozyme which is an antibacterial enzyme

slightly acidic

second line of defense

still innate!

• operates when pathogens penetrate the skin or mucous membranes

• composed of cells, antimicrobial chemicals, and processes

  • many of these components are contains or originate in the blood/lymph

plasma

mostly water containing electrolytes, dissolved gases, nutrients, and proteins

• has serum that remains when all cells and clotting factors are removed

• contains iron binding compounds (iron needed for metabolism)

• also has complement proteins and antibodies

leukocytes

white blood cells

cells with antimicrobial properties located in the blood and lymph

• involved in defending the body against invaders

• divided into granulocytes and agranulocytes

lypmh

fluid that drains from tissues into the lymphatic capillaries then enters the lymphatic system to filter through the lymph nodes

• eventually returns to circulation AFTER filtering via the SVC

lymph nodes

filter the lymph to detect for pathogens

large population of WBCs

one of the sites of the most immune responses

spleen

filters the blood to detect pathogens

one of the sites of the most immune responses

erythrocytes

red blood cell in the plasma

• carries oxygen and carbon dioxide in the blood

platelets

cell fragments from megakaryocytes (WBC trapped in the bone marrow)

• involved in blood clotting

granulocytes

contain large granules that stain different colors

• basophils

• eosinophils

• neutrophils

**innate cells

basophils

stain blue with methylene blue

eosinophils

stain red/orange with acidic dye eosin

neutrophil stain

stain lilac with mix of acidic and basic dyes

neutrophils/eosinophils

phagocytize pathogens

• capable of diapedesis which is movement via a pseudopod extension

agranulocytes

a class of leukocytes that lack visible granules under a light microscope

• can be lymphocytes or monocytes

lymphocytes

type of agranulocyte

• most involved in adaptive immunity (B cells and T cells)

• natural killer lymphocytes (mostly with things like cancer cells)

monocytes

type of agranulocyte; mature into a macrophage, largest immune cell

• leave the blood and mature

• phagocytic cells that devour foreign objects

non specific killing

innate function!!

no memory, it just responds to non human things

• PMNS, monocytes, macrophages - ALL phagocytes

• they engulf via phagocytosis (to kill off the item and present to the adaptive cells to give a memory response)

• very high number of lysosomes to kill

lysosomes

innate function

breaks down peptidoglycan

• contains

  • proteases

  • phosphatases

  • lipases

all help break down cell/viral components

phagocytosis

carried out by phagocytes

divided into six stages

• chemotaxis

• adherence

• ingestion

• maturation

• killing

• elimination

chemotaxis

stage of phagocytosis

movement toward the foreign item

adherence

stage of phagocytosis

attachment via receptor (ex: toll like receptor)

ingestion

stage of phagocytosis

endocytosis

maturation

stage of phagocytosis

phagosome +lysosome = phagolysosome (functional unit)

killing

stage of phagocytosis

done via enzymes

elimination

stage of phagocytosis

presentation to adaptive cells

• some parts of destroyed pathogens are displayed to T cells via MHC to alert and sensitive adaptive system

1st method of killing cells

phagocytes engulf pathogens into membrane bound phagosome (endocytosis)

• phagosomes fuse with the lysosome to form the phagolysosome - microbes usually killed and digested

2nd method of killing cells

oxygen dependent killing

• toxic oxygen compounds generated in the peroxisome (hydrogen peroxide, super oxide anions, hydroxyl radicals, etc.)

• reactions catalyzed by leukocyte enzymes following a respiratory burst of increased oxygen uptake by the leukocyte

• kills the ingested cell

nonphagocytic killing

killing by eosinophils; innate cells with means of killing by other than engulf and eliminate

• attack parasitic helminths by attaching to their surface

• secrete toxins that weaken or kill the helminth