microbio exam 4

hygiene hypothesis

decreasing the diversity and levels of microbes in our normal microbiota may negatively affect immune responses

can happen via antibiotic use, diet changes, or lifestyles changes

innate immunity

the immune response we are born with; always the same, regardless of the pathogen

first-line defenses

help prevent pathogen entry

ex: tears rinse/flush microbes away from the eye; mucus in the respiratory tract traps invaders and the cilia sweeps it away

mechanical barriers

part of first-line defenses

rinse/flush/trap pathogens

ex: tears, mucus membranes, urine, earwax

chemical barriers

part of first-line defenses

create hostile environments for pathogens and/or directly attack pathogens

ex: lysozymes, stomach acids, antimicrobial peptides (AMPs)

physical barriers

part of first-line defense

physically block pathogen entry

ex: main one if epithelial tissue (skin, linings of body organs)

second-line defenses

molecules and cells that actively target pathogens

Lymphatic system organs and tissues that collect, circulate and filter fluid throughout the body before that fluid goes back into the blood

primary lymphoid tissue

part of second-line defense

thymus and red blood marrow that help produce immune system cells

thymus: near the heart

bone marrow: is spongy tissue deep inside bones

secondary lymphoid tissue

part of second-line defense

filter lymph and get fluid back into the body

includes lymph nodes

leukocytes

part of second-line defense

white blood cells that serve generalized immune functions

often release molecules that help control or eliminate pathogens

differential white blood cell count

part of second-line defense

rapid test used to see if leukocytes are overrepresented or underrepresented in the blood

neutrophils

part of second-line defense

most common leukocytes and first responders from bloodstream to injured tissues

look to engulf pathogens

eosinophils

part of second-line defense

uncommon but versatile leukocytes that stain red/orange

basophils

part of second-line defense

rarest leukocyte that releases histamine, which makes blood vessels leaky so more immune cells can respond

mast cells

part of second-line defense

relatively stationary so they act as “lookouts” during potential infection

monocytes

part of second-line defense

eventually leave blood and enter tissues, they mature into macrophages (which are experts at phagocytosis)

dendritic cells

part of second-line defense

leukocytes with cytoplasmic extensions that help them “grab” pathogens for phagocytosis; common near portals of entry

lymphocytes

part of second-line defense

small leukocytes that that directly kill infected/damaged host cells

includes natural killer cells, and adaptive cells like B and T cells

cytokines

part of second-line defense leukocytes

signaling molecules that help immune cells coordinate responses

includes chemokines (attract more leukocytes) and interleukins (stimulate the production of more platelets)

interferons

part of second-line defense leukocytes

“alarm” molecules that can either 1) stop nearby cells from making proteins, 2) trigger nearby cells to die, and 3) activate more leukocytes

iron-binding proteins

part of second-line defense

proteins (like hemoglobin) that tend to bind to free-floating iron so invading pathogens cannot use it

complement cascades

part of second-line defense

Over 30 different proteins work together in a cascade fashion to respond to pathogens.

They all ultimately result in opsonization (tagging pathogens for destruction), the creation of a membrane attack complex (MAC) which bursts pathogens open, and inflammation

classical pathway

part of second-line defense

complement proteins are activated by antibodies that are bound to the pathogen

alternative pathway

part of second-line defense

complement proteins are activated by directly interacting with the pathogen

lectin pathway

part of second-line defense

complement proteins are activated by mannose-binding lectin bound to pathogens

inflammation

part of second-line defense

innate response to infection which recruits immune cells, limits spread of pathogens, and delivers vital nutrients to damaged tissues

this process can damage our own cells, but if it is temporary, it is generally a net benefit

vascular changes phase

phase of inflammation

part of second-line defense

blood vessels enlarge and become porous. these changes are brought about by molecules like histamines or kinins

leukocyte recruitment phase

phase of inflammation

part of second-line defense

molecules called chemoattractants draw leukocytes to the injured tissue

resolution phase

phase of inflammation

part of second-line defense

chemicals signal leukocytes to undergo apoptosis (self-destruction), blood vessels are repaired via angiogenesis, and pus (collection of remnant fluid of dead cells) may form

fever

part of second-line defense

abnormally high systemic body temperature in response to pyrogens (fever-inducing agents that can be molecules, viruses, or cells)

adaptive immunity

idk

third line of defense!

antigen presentation

first stage of adaptive immunity, can be cell-mediated or humoral response

antigen-presenting cells grab up antigens and show them to T cells (B cells just grab antigens directly)

MHC 1

intracellular antigen fragments are carried by MHC 1 to the surface where they bind to T cytotoxic cells

MHC 2

antigen-presenting cells take in extracellular antigens that are broken into fragments. these fragments are carried to the surface where they bind to T helper cells

lymphatic activation

second stage of adaptive immunity, can be cell-mediated or humoral response

cytokines activate leukocytes and activated T cells influence B cell activation

two required steps of activating T cells

aspect of second stage of adaptive immunity, can be cell-mediated or humoral response

1. primary activation signal (MHC)

2. secondary activation signal (co-stimulatory proteins)

superantigens

uniquely potent antigens

they bypass the antigen-presentation process and force a direct link from MHC to T cell receptor, which activates the T cell much faster

lymphocyte proliferation and differentiation

third stage of adaptive immunity, can be cell-mediated or humoral response

activated B and T cells rapidly divide to produce either effector cells that respond to antigens or memory cells that will hang out in tissue for later

antigen elimination/memory

fourth stage of adaptive immunity, can be cell-mediated or humoral response

effector cells work to eliminate antigens (and then die off) while memory cells stick around in tissue

apoptosis

programmed cell death

B cells vs T cells

both are the most important adaptive leukocytes

T cells mature in thymus

B cells mature in bone marrow

antigen

any molecule that can trigger an immune response, meaning they are immunogenic

Molecules generally increase in immunogenicity in the following categories: small molecules, lipids, polysaccharides, proteins.

epitope

specific part of an antigen where B and T cell receptors bind to in order to recognize antigens

T helper cells

these do not directly seek and destroy pathogens, but rather release cytokines that recruit other leukocytes to the area

T 1 helper cell

recruit other T cells, macrophages, and natural killer cells

T 2 helper cell

stimulate B cells to make antibodies

T 3 helper cells

coordinate function of other leukocytes

T cytotoxic cells

the “foot soldiers of adaptive immunity”

they directly destroy infected, damaged, foreign, or cancerous cells

gene shuffling

idk, slide 20

cell mediated response

organized by T helper cells and carried out by T cytotoxic cells

they go through the stages of adaptive immunity

cell-mediated adaptive immunity stages

1. antigen presentation

2. T-cell activation

3. T cell proliferation and differentiation

4. effector and memory cell activity

STEP 1: cell-mediated adaptive immunity stages

antigens are “presented” to T cells via major histocompatibility complexes (MHCs)

STEP 2: cell-mediated adaptive immunity stages

when T cells bind to antigen-presenting cells, this activates them (two required steps)

STEP 3: cell-mediated adaptive immunity stages

activated T cells divide rapidly (mitosis) and will differentiate into types that act as memory cells, recruitment cells, or seek/destroy cells

STEP 4: cell-mediated adaptive immunity

T cytotoxic cells will “seek and destroy” cells displaying specific antigens. T helper cells recruit, stimulate, and coordinate other leukocytes activity

humoral adaptive immunity stages

1. B cells are antigen-presenting cells so they can grab antigens themselves

2. T-independent antigens can fully activate B cells by themselves, whereas T dependent antigens require a helper T cell to fully activate the B cells

3. activated B cells divide rapidly (mitosis) and will differentiate into plasma cells that release antibodies, or memory cells that can assist in future immune responses

4. plasma cells secrete antibodies (immunoglobulins). antibodies bind to pathogen receptors to “block” them, initiate the complement cascade, and increase phagocytotic activity

Immunoglobulin G (IgG)

one of five major isotopes of antibodies

most abundant antibody in blood and can cross placenta to protect the fetus

Immunoglobulin A (IgA)

one of five major isotopes of antibodies

found primarily in mucosal secretions and breast milk

Immunoglobulin M (IgM)

one of five major isotopes of antibodies

created early in infection, but large and cannot migrate quickly

Immunoglobulin E (IgE)

one of five major isotopes of antibodies

involved in allergic reactions and defense against parasitic worms

Imunoglobulin D (IgD)

one of five major isotopes of antibodies

found on B cells, function still poorly understood

Humoral Memory

during primary antigen exposure, IgM is produced first, followed by IgG. due to memory capacity of memory B cells, if secondary antigen exposure occurs, these memory B cells produce tons of IgG very quickly

natural active immunity

immunity from previous infections

natural passive immunity

antibodies pass across the placenta

this is only temporary

artificial active immunity

vaccines used to trigger immune response to make antibodies

artificial passive immunity

patient receives antibodies via antiserums

this is only temporary

immunodeficiency

lack of properly functioning immune system

primary immunodeficiency

genetic errors lead to deficient immunity

secondary immunodeficiency

natural decline in immune function or external causes like infections or medical interventions

ex: leukocytes declines with age

ex: some drugs suppress immune function

ex: some pathogens have virulence factors that limit immune function. some even target immune cells (HIV infects helper T cells)

autoimmunity

immune system attacks healthy self-tissues

systemic vs localized autoimmunity

s: attack tissues throughout body

l: attacks specific type of tissue

hypersensitivity

inappropriate secondary immune response (inappropriate B and T cells activation)

more common in developed countries

hygiene hypothesis

clean food/water and higher antibiotic usage alters the normal healthy microbiota

type 1 hypersensitivity

part of secondary immune response

allergies; immune response to a harmless threat

allergens

antigen that can trigger IgE production and lead to an allergy

sensitization

part of secondary immune response

IgE antibodies attach to mast cells

post-sensitization

part of secondary immune response

antibody-coated mast cells bind to allergen and release pro-inflammatory chemicals like histamine

anaphylaxis

part of secondary immune response

severe and rapid allergic response to an allergen

can be localized (isolated reactions) or systemic (whole-system reactions)

allergen desensitization

part of secondary immune response (type I hypersensitivity)

body shifts its immune response to an allergen. likely due to more IgG antibodies being formed over time than IgE, which limits how much inflammation can occur

type 2 hypersensitivity

part of secondary immune response

cytotoxic reaction

how blood types work

There are four antigen types in blood. Three are carbs (A, B, O) and one is proteins (Rh factor). Rh is denoted by a “+” symbol if it is present and a “-” symbol if it is absent.

a patient can only accept blood types that have the same or fewer antigens present as their own blood

type 3 hypersensitivity

part of secondary immune response

immune complex

IgG or IgM bind to soluble antigens to make an excessive number of antibody-antigen complexes

type 4 hypersensitivity

part of secondary immune response

delayed hypersensitivity

T cells target host cell antigens instead of antibodies. these responses manifest slower than the previous types

ex: 12-72 hours like touching a poisonous plant

vaccine

biological preparation that provides active acquired immunity to a pathogen

herd immunity

enough people in a population are vaccinated so that the pathogen cannot spread effectively among non-vaccinated individuals

live attenuated (active vaccines)

active virus or living cells that have been altered to be non-pathogenic

these vaccines tend to produce the most effective long-lived memory in the immune system

however, these pathogens are the most likely to potentially cause disease or mutate into a form that is pathogenic

vector (vaccine)

genetically modified harmless virus that delivers genetic instructions and information from the pathogen to your body’s cells

whole-agent

inactive vaccine

vaccine contains the entire dead cellular pathogen/whole inactivated virus that has been rendered inactive by heat, chemicals, or radiation

these vaccines are safer but do not necessarily confer as long-term immunological memory

subunit

inactive subunit vaccine

vaccine contains either purified component of the pathogen or genetically engineered components that resemble the pathogen’s components

purified subunit

inactive subunit accine

antigens are a key component

toxoid

inactive subunit vaccine

inactivated protein toxin is the key component

conjugate

inactive vsubunit accine

linked polysaccharides are the key component

mRNA inactive vaccine

vaccine contains mRNA that when translated in host cells produces a protein or antigen that causes an immune response (without actual pathogen present)

mRNA directs the production of a specific protein found in or on the pathogen

Because cells typically only have the mRNA temporarily, additional vaccine administrations are needed to confer effective immunological memory

serology

form of diagnostic testing

study of what is in a patient’s serum (liquid, non-cellular/non-platelet portion of the blood)

serum is obtained vis centrifuge, which spins liquid at high speeds

agglutination

form of diagnostic testing

since antibodies can bind to more than one antigen at one time, they can clump

these tests are used to determine if antibodies are present in a sample

plaque reduction neutralization test (PRNT)

form of diagnostic testing

add viruses to a series of serum samples and then add those samples to a dish with cells

if antibodies are present, plaques (lysed cell residue) will not form. if antibodies re not present, plaques will form

enzyme-linked immunosorbent assays (ELISAs)

form of diagnostic testing

tests that use enzymes to bind to antibodies within antibody/antigen interactions

direct ELISAs

form of diagnostic testing

enzyme-linked antibodies are added to solution in wells that have antigens at the bottom

a substrate is added and if the substrate molecules bind to the antibodies, a signal occurs (light/color)

indirect ELISAs

form of diagnostic testing

similar to direction ELISA while also adding patient antibodies that connect the antigens and enzyme-linked detection antibodies

sandwich ELISAs

form of diagnostic testing

the wells contain a “capture” antibody, patient serum with potential antigens added, and enzyme-linked detection antibodies “sandwich” the antigen between both antibody types