Microbiology Exam 3

what is a pathogen?

a microbe that causes disease in its host

what is an infection?

when a microbe invades the body and multiplies

what is a disease?

tissue damage due to an infection

what is pathogenesis?

the molecular and cellular events that cause tissue damage and disease

what determines pathogenicity?

the microbe and immune response

what are the functions of the immune system?

prevent/limit infection

identify and eliminate damaged/abnormal cells

prevent inadvertent damage to host

prepare for future exposure to previous pathogen

how does our immune system know what is “self?”

Major Histocompatibility Complex I (MHC I) proteins

how do MHC I proteins tell our immune system what is “self?”

distinguish between normal “self” cells and potentially dangerous “non-self” invaders

every nucleated cell in our body expresses MHC I molecules except for RBCs

what are the three lines of defense against pathogens?

barriers

innate immune response

adaptive immune response

what are examples of barriers?

strongest/fastest

physical barriers, mechanical barriers, chemical factors, normal microbiome

what are examples of innate immune response?

takes hours to days

Phagocytes, complement proteins, inflammation and fever, innate immune cells

what are examples of adaptive immune response?

slowest, takes weeks to years

B cells and antibodies, T cells, complement proteins

what do physical barriers do?

block pathogens from entering the body

ex: skin, mucous membranes, epiglottis, eyelids, tight junctions between epithelial cells

what do mechanical barriers do?

mechanical actions that remove microbes and debris

ex: shedding of skin cells, cilia movement in lower respiratory tract, sneezing, vomiting, tears, defecation

what do chemical factors do?

proteins and other compounds produced by the body that inhibit/kill microbes

ex: gastric juices, sebum, antimicrobial peptides produced by barriers

what does normal flora do?

microorganisms that are not pathogenic and are found all over the human body

how does the epidermis protect against infection?

skin in the primary barrier to infection?

has all four types of barriers

what does the immune system do?

protects body against pathogenic microbes

recognizes our cells as “self,” therefore we do not destroy them

respond to pathogen re-infection in the same way (innate)

respond to re-infection faster/better/stronger (adaptive)

where are all blood cells generated?

in bone marrow through the process hematopoiesis

what are the three main components of the immune system?

proteins, cells, and tissues/anatomy

what/where are immune cells derived from?

common myeloid progenitors

includes RBCs, mast cells, monocytes, macrophages, and granulocytes 

what are the two types of innate cells?

phagocytes and granulocytes

what do phagocytes do?

innate cell

surround and engulf microbes, small particles, etc.

neutrophils, macrophages, dendritic cells

what do granulocytes do?

innate cell

prepackaged to release enzymes and toxins into microbial invaders when activated

neutrophils, basophils, eosinophils, mast cells

what are the types of granulocytes?

neutrophils, eosinophils, basophils, and mast cells

what do neutrophils do?

granulocyte

most abundant, always the first cell on scene of an infection

rapidly migrate to site of infection and inflammation

as they die, they release DNA to trap bacteria to limit dissemination

• DNA forms sticky nets in process called netosis, these nets trap pathogens

key source of pus when dying

what do eosinophils do?

granulocyte

high in parasitic worm infections and allergy

amplify immune response

express cytokines that amplify immune responses and cytoplasmic granules containing enzymes that are harmful to cell walls of parasites

activated by cell-cell adhesion receptors and cytokines 

what do basophils do?

granulocyte

interface with environment during response by using secreting antibodies

what do mast cells do?

granulocyte

rapidly secrete pro-inflammatory factors

activated when IgE binds antigen and releases histamine causing inflammation in other immune cells 

what is an antigen?

any substance that can stimulate an immune response

what are antigen presenting cells (APC) and what do they do?

key to initiated, amplifying, and tuning the adaptive immune response (typically done by promoting T cell responses)

macrophages and dendritic cells

how do APCs amplify immune responses?

detect and engulf pathogens through phagocytosis 

pathogen is digested into peptide fragments and loaded onto MHC molecules

antigen-MHC complexes are displayed on APC surface, allowing T cells to recognize and respond to specific antigen

tells immune system there must be a response

what do dendritic cells do?

APCs

reside in all tissues = everywhere throughout the body

use dendrites to sample their environment and capture antigens

after antigen is captured, dendritic cell migrates from tissue to lymph node to present antigen to lymphocytes

what do macrophages do?

APCs

long lived phagocytes residing in all tissues, but not blood

phagocytose pathogens and activate T cells and phagocytose dying cells and promote wound healing

what are (antigen-specific) lymphocytes?

adaptive cells

includes B and T cells which each have a unique surface receptor that responds to a specific antigen due to hundreds of antibodies covering the cell surface

what does it mean for a B/T cell to be naive?

they have not encountered their specific antigen

once they do, it becomes an activated lymphocyte

what do natural killer (NK) cells do?

innate lymphoid cells

destroy virally infected cells through antibody-dependent cell-mediated cytotoxicity

what are the protein component of the immune system?

receptors and ligands

antimicrobial peptides (AMP)

antibodies (Abs)

what do receptors and ligands do?

receptors on cells receive the ligands

receptor is specific for each ligand

what do antimicrobial peptides (AMP) do?

small secreted proteins that poke holes (pores) in microbial surfaces

defensins and cathelicidins, histatins, lectins, lysozyme

what do antibodies (Abs) do?

secreted version of B cell antigen receptor

do not directly kill, they tag foreign antigens for removal by other immune cells/protein factors

are a critical component of immune response

how do antibodies contribute to immunity?

neutralization

opsonization

complement activation

what is neutralization?

antibodies surround pathogen and bind on its surface

their binding neutralizes the pathogen so it cannot bind to its target cell

what is opsonization?

microbe is surrounded and covered by antibody which tags microbe for phagocytosis

what is complement activation?

enzymatic cascade that results in the holes forming in surface of pathogen

what is the complement system?

a pathogen with antigens on its surface gets into your system

these antigens are recognized by an antibody which trigger it to bind to the antigen

this causes C1 to bind to the antigen-antibody and gets activated which causes C2 and C4 to split into two, forming C3 which then splits into two, forming C3a and C3b

what is the classical pathway of the complement system?

C3a (Chemical Attractant) diffuses out and attracts other phagocytes into the area to eat the pathogens

C3b binds to the surface of the pathogen, tagging it for destruction

C3b causes C5 to split into C5a and C5b

C5b forms with C6-C9 to form the membrane attack complex which attaches to the membrane of the pathogen and makes a hole in it so water rushes in and breaks the cell apart

what is the alternative pathway of the complement system?

antibody-independant

starts with C3 which gets activated by binding directly to the pathogen itself

this binded C3 interacts with other proteins which causes C3 to split into C3a and C3b

C3b causes C5 to split into C5a and C5b 

C5b forms with C6-C9 to form the membrane attack complex which attaches to the membrane of the pathogen and makes a hole in it so water rushes in and breaks the cell apart 

what do cytokines do?

responsible for cell-to-cell communication during immune response

regulate immune response by altering differentiation and function of other innate and adaptive immune cells

some amplify immune response, others suppress immunity

what does chemokineses do?

direct traffic

draw immune cells toward sites of infection/inflammation

what are the three main functions of the innate immune response?

detect and kill pathogens

sound the alarm

activate the adaptive immune response

why do barriers fail?

breach of intact skin

virulence factor of microbe

immunosuppression

loss of normal flora

what triggers the innate immune response?

if/when barriers break down

what does the innate immune system do to recognize pathogens?

keeps organisms with no capsule in check

recognize PAMPs and DAMPs

do not detect specific pathogens

pathogens with capsules are harder to control until adaptive immunity gets activated 

how does the innate immune system recognize microbes and damaged tissue?

Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs)

what are pathogen-associated molecular patterns (PAMPs)?

cell wall lipids = LPS and LTA

what is a PRR?

pattern recognition receptors

proteins of innate immune system that detect PAMPs

how does PRR engagement cause phagocytosis?

when certain PRRs recognize PAMPs, the microbe is ingested and destroyed 

how does PRR engagement cause signaling?

when certain PRRS recognize PAMPs, certain cell signaling pathways are activated and the alarm is sounded

leads to production/release of cytokines, chemokines, and antimicrobial peptides

what do toll-like receptors (TLRs) do?

activates cell signaling

TLR-4 binds LPS

TLR-2,6 binds LTA

what do Fc receptors do?

activates phagocytosis

when antibodies coat a pathogen (opsonization), Fc portion sticks out and Fc receptor can bind to exposed Fc regions which triggers phagocytosis 

what do complement receptors (C3b receptor) do?

activated phagocytosis

complement proteins opsonize bacteria

complement receptor on phagocyte recognizes complement protein

what phagocytes carry out phagocytosis?

neutrophils, macrophages, dendritic cells

what are the mechanisms of phagocytosis in order?

chemotaxis

adherence

ingestion and phagosome formation

phagolysosome formation

digestion

exocytosis

what is chemotaxis?

1st step of phagocytosis

phagocytes recognize:

• chemicals produced by bacteria

• agitated complement proteins

• chemokines/cytokines

what is adherence?

2nd step of phagocytosis

phagocytes bind to PAMPs

opsonization enhances phagocytes adherence to pathogen

(opsonins: C3b, IgM, IgG)

what is ingestion and phagosome formation?

3rd step in phagocytosis

cytoplasmic membrane forms extensions called pseudopods that wrap around microbes

two pseudopods fuse to form a phagosome

what is phagolysosome formation?

4th step of phagosytosis

phagosome fuses with lysosome vesicle that contains hydrolytic enzymes (proteases, nucelase, lysozyme, myeloperoxidase)

some bacteria express proteins that prevent phagosome-lysosome fusion

what is digestion?

5th step in phagocytosis

hydrolytic enzymes and myeloperoxidase break down pathogens into bits (peptides) inside phagolysosome

what is exocytosis?

6th step in phagocytosis

phagolysosome fuses with cytoplasmic membrane and peptide contents are expelled

expelled peptides become source of antigen for other phagocytes

what occurs if a phagocyte is an antigen presenting cell (APC)?

MHC II is found on antigen presenting cells

phagolysosome peptides get loaded onto MHC II (major histocompatibility complex 2) instead of being expelled

APC presents to peptide/MHC II complex on its surface

APC proceeds to nearest lymph node to present the peptide to a CD4 T helper cell that matches

what in inflammation?

process by which circulating leukocytes and plasma proteins are brought into sites of infection/tissue damage and are activated to destroy and eliminate the offending agents

what is inflammation a reaction to?

tissue damage and cell death

infection of pathogens

accumulation of abnormal substances in cells in tissues

what are the four signs of inflammation?

redness, pain, heat, swelling

how is inflammation activated?

bacteria enters wound

damaged tissue releases inflammatory chemicals (DAMPs)

sentinel cells (mast cells and macrophages) release inflammatory mediators

TNF-alpha increases vascular permeability and promotes migration of leukocytes from blood to infection site

what is a fever?

a systemic response to an infection

how is a fever activated?

phagocytes detect bacteria using PRRs

phagocytes release cytokines IL-1 beta and IL-6 which travel through the bloodstream to the brain to the hypothalamus

hypothalamus produces prostaglandin E2 which increases body temperature