Immunology Exam 1 Flashcards

father of immunology; studied smallpox

affected anyone and everyone; use cowpox to confer protection (unethical experiment)

bacteria, viruses, parasites, fungi

microorganisms that cause disease only when IS is compromised

microbes that live in a healthy adult

our body's response against infection

the study of the body's physiological defense against invading organisms

anatomic barriers-> complement antimicrobial proteins-> innate immune cells-> adaptive immunity

covering membranes

ex: skin, oral mucosa

present right away in the blood serum; antimicrobial proteins

ex: C3, defensins, RegIIIy

epithelial surfaces immune cells (Neutrophils)

active early, limited in how many pathogens can be recognized.

Rapid response

Ex: macrophages, granulocytes, NK cells, epi cells

developed over time- adapts to the pathogen, highly specific, provides protective immunity- memory

Slow response

ex: B cells/antibodies, t cells

methods to kill or destroy a pathogen.

cells using effector mechanism

bacterial cell surface induces cleavage and activation of complement-> one complement fragment covalently bonds to the bacterium and the other attracts an effector cell-> the complement receptor on the effector cell bind to complement fragment on the bacterium-> effector cell engulfs the bacterium, kills it and breaks it down

surface would introduces bacteria-> activates resident effector cells to secrete cytokines-> vasodilation and increase vascular permeability allow fluid protein and inflammatory cells to leave blood and enter tissue-> the infected tissue becomes inflamed, causing redness, heat, swelling and pain

phagocytose bacteria

make cytokines

messengers that start inflammatory response, communicators

call other immune cells in

lymphocytes- B and T cells

adaptive- lympocytes

only antigen-specific lymphocytes- proliferate and differentiate

only those w receptors for pathogen causing infection will be selected to play a role in adaptive response

multiplication of antigen-specific lymphocytes

clonal selection (progenitor cell gives rise to lg number of lymphocytes each w different specificity-> removal of potentially self reactive immature lymphocytes by clonal detection-> pool of mature lymphocytes)-> clonal expansion (proliferation/ differentiation of activated lymphocytes to form a clone of effector cells)

not yet encountered pathogen

first time the adaptive IS sees a pathogen

second and all subsequent times that the adaptive IS sees a pathogen

memory cells

3-5 days

some lymphocytes persist- long term protection

1. immunological recognition

2. immune effector function

3. immune regulations- control so doesn't attack self

4. immunological memory (adaptive only)

leukocytes (WBC)

bone marrow

development of blood cells

lymphoid, myeloid, erythroid

hematopoietic stem cell

self renew, mulipotent

give rise to lymphoid, myeloid and erythroid lineages

Multiple potential of what they'll become

HSC (bone marrow)-> common lymphoid progenitor (bone marrow)-> B cell, T cell, NK cell, ILC (blood-> lymphoid tissues-> effector cells)

HSC-> common myeloid progenitor-> granulocyte/macrophage progenitor and megakaryocyte/erythrocyte progenitor OR immature DC-> mature DC OR granulocytes then immature DCs and mast cell macrophages

HSC-> common myeloid progenitor-> megakaryocyte/erythrocyte progenitor-> megakaryocyte and erythroblast-> platelets (from megakaryocytes) and erythrocyte (from erythroblast)

myeloid lineage

granulocytese, macrophages, Dendritic cells, mast cells

prominent cytoplasmic granules, single lobed nucleus

neutrophils, eosinophils, basophils

most abundant

phagocytose and kill pathogens and activate bacterial mechanisms

2nd most abundant

defense of parasite and allergens- kill Ab coated parasites

least abundant

defense against parasite/ allergic responses

phagocytosis/bacterial mechanism activation

antigen presentation/ cytokine production

innate but start to inform adaptive

antigen uptake

antigen presentation/ cytokine production

resident in body tissues

release of granules containing histamine and active agents

resident in CT

dendritic ce;;s

migrates through bloodstream, enters tissues

undergoes macropinocytosis

process of ingesting lg amounts of ECF from environment and look for pathogen

mature- able to activate T cells

DCs also called

reside in peripheral tissues and encounter pathogen-> DCs migrate via lymphatic vessels to regional LNs and mature-> mature DCs activate naive T cells in lymphoid organs

activated T cells

adaptive (mostly)

NK cells

not antigen-specific

active against tumor cells and virus infected cells

antigen specific

1 billion constantly circulating

without infection- small and featurelist

common lymphoid progenitor-> B cell-> lymph node B cells-> effector cells- plasma cells

common lymphoid progenitor-> T cell-> lymph node T cells-> effector cells- activated T cell

common lymphoid progenitor-> NK cell-> lymph node NK cell-> effector cells- activated NK cell

humoral

fluid-phase immunity

cell-surface receptor for pathogen- held at surface very early then secreted

plasma cell

secrete soluble Igs or antibodies "Ab factories"

neutralization and opsonization

blocking a toxin

coat surface of bacteria with Abs-> easily recognized by IS

one

cell-mediated immunity

cell contact with the pathogen

cell-surface receptor for pathogen

never secreted- always receptor

cytotoxic, helper, or regulatory T cells

killer T cells

make cytokines; help activate killer T and B cells

help dampen IR-> balance response and controls

specific Ab-> bacterial toxins-> neutralizations-> ingestion by macrophage

specific Ab-> bacteria in extracellular space-> opsonization-> ingestion by macrophage

specific Ab-> bacteria in plasma-> complement activation-> lysis and ingestion

series of serum proteins

ingestion bc complements coats bacteria and make it more recognizable

aggregates of lymphocytes in a framework of non-lymphocytes

lymphocyte generation-> where lymphocytes are made

bone marrow and thymus

in the bone marrow

thymus

naive mature lymphocyte maintenance; adaptive IR initiated

lymph nodes, spleen, MALT (gut, nasal, respiratory, and urogenital)

mucosal-associated lymphoid tissue

small lymphocytes move bw the blood and lymph

lymphocytes continually survey secondary lymphoid organs

stay and start to develop response

in draining lymph nodes; DCs bring pathogens or components of pathogens to the draining LNs

lymphocytes activated by pathogen in LN-> stay

in arterial blood

via afferent lymphatic vessels w/ cytoskeletal changes

naive lymphocytes arrive to LNs in arterial blood and pathogens via lymphatics ->draining LNs-> lymphocytes and lymph return to the blood via lymphocytes-> venous blood-> venous blood returns to the heart-> L subclavian vein

mostly T cells

DCs

B cells to lymphoid follicles if bind to pathogen-> expand-> reproduction, tons of very specific B cells

innate phase, induced innate response, adaptive phase

to kill or weaken pathogen

antimicrobial enzymes, antimicrobial peptides, complement system

digest bacterial cell walls

lyse bacterial cell membranes directly

targets pathogens for lysis and phagocytosis

PAMP recognition, cellular actiation

pathogen-associated molecular patterns

inflammation

Antigen-specific lymphocytes, memory response

pathogen-> containment by an anatomic barrier-> if fails->

Innate phase: infection-> recognition by preformed, nonspecific and broadly specific effectors-> if fails->

Induced Innate response: recruitment of effector cells-> recognition of PAMPs, activation of effector cells and inflammation-> if fails->

adaptive immune response: transport of antigen to lymphoid organs-> recognition by naive B and T cells-> clonal expansion and differentiation to effector cells-> removal of infectious agents

pathogens adhere to epithelium (normal flora, local chemical factors, phagocytes)

-> local infection, penetration of epithelium (wound healing induced, antimicrobial proteins and peptides, phagocytes and complement destroy invading microorganisms->

local infection of tissues (complement, cytokines, chemokines, phagocytes, NK cells; activation of macrophages; DCs migrate to LNs to initiate adaptive; blood clotting helps limit spread of infection)->

adaptive immunity

extracellular and intracellular

most have extracellular component; bacteria, viruses, fungi, parasites

soluble/secrete molecule-> many promote phagocytosis

interstital spaces, blood, lymph, epithelial

interstitial spaces, blood, lymph: complement, phagocytosis, Abs

epithelial: antimicrobial peptides, Abs

some bacteria, viruses

kill infected cells-> epose to the soluble/secreted molecules

cytoplasmic: NK cells, cytotoxic T cells

Vesicular: T-dependent and NK cell-dependent macrophage activation

direct: exotoxin production, endotoxin, direct cytopathic effect

indirect: immune complexes, anti-host Ab, cell-mediated immunity

released by pathogen and act at the surface of host cell; bind to our cell receptors

direct mechanism

part of microbial structure activate phagocytes-> release cytokines-> local and systemic response

direct mechanism

direct damage to infected cell

Ag:Ab complexes-> further activate IR-> tissue damage

Ab that cross react with host cells

indirect mechanism of tissue damage by pathogens

recognize the pathogen and our cell thats similar to

indirect mechanism of tissue damage by pathogens

T cells that kill infected cells

indirect mechanism of tissue damage by pathogens

skin: stratified epi

gut: single cell layer of columnar epi

lungs: upper airway- pseudostratified columnar; lower airway- single cell layer of columnar epi

eyes/nose/oral cavity: pseudostratified columnar

tight junctions

skin/guts: longitudinal flow of air or fluid

lungs: movement of mucus by cilia

eyes/nose/oral cavity: tears, nasal cilia

beta defensins

alpha defensins

alpha defensins

beta defensins

normal microbiota

soluble effector molecules

mammals, insects and plants

constantly secrete at mucosal surfaces

defensins

minutes to disrupt cell membrane of bacteria, fungi and envelopes of some viruses

cationic peptides (35-40 AAs)- positively charged peptides-> how bacteria is effected

amphipathic structure- pos and neg parts

much bigger-> get processed down to smaller

proteolytic processing from propeptides

alpha, beta, sigma

in primary granules of neutrophils

paneth cells of gut

epithelia of skin, respiratory, and urogenital tracts

little to know, inactive to humans

electrostatic attraction and the transmemrane EF bring the defensin into the bilipid layer and form a pore

system of plasma proteins, series of enzymatic reactions

constitutively made by the liver

in blood, lymph, ECF

direct pathogen lysis, phagocytosis, inflammation

discovered the complement of serum that complements the action of Abs

1. pattern-recognition

2. protease cascade

3. targets pathogens

lectin, classical, alternative

all lead to C3 convertase-> phagocytosis, C3b engulfs and destroys pathogen, and formation of MAC

zymogens

inactive form of protease; requires cleavage by another protease to become acive

covalent, C3b

C3a and C3b

anaphylotoxin

chemicals that help recruit phagocytes, make vessels more leaky to allow over and communicate to go

can induce anaohylactic shock

opsonizes pathogen, provides for next stems in the pathway=critical

covalent attachment of C3b (or C4b) to pathogen surface

have recurrent infections

before cleavage by C3 convertase, thioester bond is protected from reacting-> cleavage of C3 releases Ca and C3b with conformational change that allows thioester bond to react with chemical group on pathogen surface making C3b bound

C3b thioester bond inactivated by hydrolysis

microorganisms-> repeating molecular structures-> PAMPs

contain many mannose residues

pathogen associated molecular patterns

carb side chain has sialic acid residues-> lectin pathway will not bind/recognize

C-type lectin

group of carb binding proteins; require calcium

mannose containing carbs of pathogen

1. acts as opsonin- more recognized

2. Triggers lectin pathway- complement activation

trimeric clusters of carb recognition domains by binding with high acidity to mannose and fructose residues

total high binding strength

MBL + MASP1 + MASP2 (all inactive)-> bind to pathogen surface-> conformational change (MASP1)-> activate MASP2-> C4-> Ca and C4b (C4b bound to pathogen surface)-> C4b binds to C2-> MASP2 cleaves into C2b(released) and C2a-> C4b2a (C3 convertase)-> C3 (active)-> cleaved into C3a and C3b

inflammation response

bind pathogen surface

eventual generation of classical C3 convertase

C1 complex- binds to either CRP or Ab-> can recognize

C-reactive protein- can bind to the pathogen surface

C1 complex (C1q, C1s, C1r)-> attach to pathogen surface (C1q is the attachment pt)-> C1r:C1s conformational change-> C1r becomes active-> C1s becomes active-> C1s cleaves C4 (active)-> C4a and C4b-> C4b binds to microbial surface -> binds C2-> C1s cleaves C2 into C2b and C2a-> forms C4b2a (C3 convertase)-> cleaves C3 into C3a and C3b

C3b (pathogen surface)-> bind factor B-> conformational change-> factor D cleaves into Ba (released) and Bb (still bound to C3b)-> C3bBb (alternative C3 convertase)

C3 (H20)-> binds to factor B-> Ba and Bb-> C3(H2O)Bb

C3(H2O)Bb

C4b2a

C3bBb

generate C3 convertase which cleaves C3 leaving C3b bound to microbial surface and releasing C3a-> inflammatory cells recruited, opsonization-> perforation of pathogen surface

C3a and C5a recruit phagocytic cells to site of infection and promote inflammation

C3b coats to make more recognizable, phagocytes with receptors for C3b enguld and destroy the pathogen

generate C5 convertase that leads to formation of membrane-attack complex (MAC)-> disrupts cell membranes

on phagocytes, endothelial cells, mast cells

BVs to increase vascular permeability and cell adhesion molecules

increased permeability- leakage of fluid and complement from BVs-> provide more fuel for response

migration of macrophages, neutrophils and lymphocytes-> increase in microbial activity-> very active when they get there-> combat

CR1-complement receptor 1= bind to C3b-> helps recognize, bring in + destroy

bacterium coated in C3b-> only C3b binds to CR1, bacteria not phagocytosed-> C5a can activate macrophages to phagocytose via CR1

C3b binds C4b2a and C3bBb-> form C5 convertases (C4b2a3b or C3b2Bb)-> C5 cleaved by active C2a or active Bb-> C5a released and C5b

initiate terminal complement complex

loss of cellular homeostasis

disrupt proton gradient

enzymes (lysozymes) enter pathogen

C5b-> bind to C6 (C5b6)-> bind to C7 (C5b67) insert in lipid bilayer-> bind to C8 (C5b678)-> bind to C9 (polymerization of 10-18 C9)-> MAC

properdine (+)

CR1 (-)

DAF (-)

Factor H (-)

stabilize Bb (+)

binds C3b or C4b, displace Bb (-)

competes with factor B, displaces Bb (-)

bind C3b, displace Bb

CR1

Factor I (-)

CD59/protectin (-)

cleaves C3b-> inactive (-)

binds to C8-> prevents C9 recruitment

prevents final complex (-)

direct binding assay for ag or ab, enzyme chemically linked to ab, purpose: quantify how much ag in sample

protein of interest bound to well

blocking-coat rest of plate

abs- primary, secondary...

substrate added-color change

Data-> standard curve

ag-> block-> primary w enzyme

ag-> block-> primary Ab (acts as bridge)-> secondary Ab w enzyme

Ab complement-> ag-> ab

complementary to/ binds ag

binds primary ab

using fluoroflor; must use microscope

tissue is fixed depositing color in T cell; light microscope

look at location of proteins in tissues

ab gets attached to Ag directly

ab of one species bound to ag and ab of other species bound to that one

images- can be quantified

define (size, granularity,protein expression), enumerate populations of cells/collect cells; cell sorting

generate single cell suspension

cells stained with Fluorescence-Abs

cells move by the laser (single-file)

emitted light detected by optical system

computer analysis

selection of subpopulations for analysis

marker on y-axis=marker 2; marker on x-axis= marker 1

upper left: marker 2 pos.

upper right both pos

lower left both negative

lower right marker 1 pos

single cell analysis from complex sample

high-throughput

very specific for rare cell populations

isolation of cells with very high purity

need single cell suspension

limited to less than 20 parameters

technique is not standart

subjective nature

pathogen recognition receptors

free receptors, membrane bound phagocytic and signaling receptors, cytoplasmic signaling receptors

distinguish self from nonself

recognize the cell surface carbs of bacterial cells but not those of human cells

recognize changes at the surface of human cells that are caused by viral infection

myeloid and lymphoid progenitors

cDC and pDC

conventional, classical DC

resident in tissue, pick up pathogen and take back to LN

plasmacytoid, extremely good at viral responses

carbs and lipids

bind to pathogen-> phagocytose pathogen-> phagolysome (destroy)-> phagosome formed with lysosome

recognize carbs on surface of pathogens; target bacteria and fungi

beta glucans (fungi), mycobacterial ligand (bacteria)

bacteria

LPS, LTA, proteins, CpG DNA

damaged, low density lipoprotein

bacteria/fungi

beta glucans(fungi), oligosaccharides and proteins (bacteria)

macrophage receptors that recognize complements of microbial surfaces-> microorganisms bound by phagocytic receptors on the macrophage surface-> microorganisms internalized by receptor-mediated endocytosis-> fusion of the endosome with a lysosome forms a phagolysosome in which microorganisms are degraded

kill

slow down

intracellular or on surface response to form cytokines- some endosomal that recognize nucleic acids

carbs, lipids, proteins, nuceic acids

1. recognize

2. signaling to nucleus

3. gene expression (cytokines)-> bring more immune cells in

controls dorso-ventral gene patterning

controls host defense agains gram pos bacteria and fungus

leucine rich repeat region, recognition domain, horse-shoe shape

toll interleukin/receptor domain, signaling

heterodimer if TLR2 is involved, rest are homodimers

all except TLR3

recognition: TLR dimer forms

MyD88 recruited/scaffold

IRAKs recruited

TRAF6 recruited and activated-> polyubiquitinated

Kinases activated- moce phosphates

IkB phosphorylated and degraded- inhibits NFkB

TF (NFkB) phosphorylated and degraded

no MyD88- use TRIF

phosphorylation/polyubiquitination steps

TF (IRF3)- interferon regulatory factor

transcription, translation, replication,

endosomal TLRs- leads to type 1 interferons

contain RNA helicase like domain and 2 amino terminal CARD domains

recognition, bind to RNA

interact with adaptor proteins to activate signaling pathways

recognizes the unmodified 5' triphosphate end of ssRNA

senses dsRNA

recognize viral nucleic acids; results/leads to production of type 1 interferon

cytoplasm

sense intracellular pathogens and products from intracellular degradation of phagocytosed pathogens

NOD

LRR
CARD

helps oligomerization

NFkB-> nucleus-> gene expression