Foundations 1a exam 3

3 broad components of the innate immune system

physical/physiological barriers

antimicrobial molecules

sentinel/phagocytic cells

2 antimicrobial molecules produced by epithelial cells and leukocytes

defensins

cathelicidins

what do antimicrobial molecules do (4)

direct toxicity to pathogens/tumor cells

activate/recruit leukocytes

bind/neutralize LPS

stim wound healing

3 sentinel cells and thier functions

mast cell - initiate inflammation

macrophages - inflammation and phagocytosis

dendritic cells - process antigens and start adaptive responses

where are innate immune cells produced

in bone marrow via hematopoiesis

what do myeloid cells become (5)

granulocytes

mast cells

monocytes/macrophages

myeloid dendritic cells

platelets

what do lymphoid cells become (3)

T cells

B cells

NK cells

where does hematopoiesis occur in young animals and adults

young - most skeletal bones

adult - plat bones and proximal ends of humerus and femur

myeloblasts diff into what innate immune cells (5)

basophils

neutrophils

eosinophils

monocytes —> macrophages/meyloid dendritic cells

what color will neutrophils stain

none

eosinophil stain color

pink

basophil/mast cell stain color

blue/purple

function of neutrophils

kills microbes via

• phagocytosis

• degranulation

• neutrophil extracellular traps

which leukocyte is most abundant

neutrophils

which leukocyte is the “first responder”

neutrophils

how long do neutrophils live in blood

a few days

function of eosinophils

kills parasites,

promotes inflammation

involved in hypersensitivity rxns

func of basophils

similar to eosinophils and mast cells

• hypersensitivity rxns

• coagulation

• parasite rejection

which is the largest leukocyte

monocytes

what color is the cytoplasm of monocytes

blue/grey

monocytes are the circulating precursors to (2)

macrophages and Antigen presentinc DCs

macrophage func (3)

inflammation response

Phagocytize cell debris, foreign material, and infectious agents

Secretion of inflammatory cytokines to recruit other inflammatory cells

function of dendritic cells (2)

endo/phagocytosis

antigen presentation

mast cell func (4)

vasodilation

vascular permeability

recs other leukocytes

allergic response

do NK cells need prior sensitization

no

where do NK cells mature

2ndary lymphoid organs

NK cell func (2)

1st line of defense agasint viruses and tumors

secrete cytotoxic granules that drive apoptosis

where do NK cells originate and are they part of the innate or adative immune system

from lymphoid tissue and mature in 2ndary lymph tissue but are part of innate

if we see hella neutrophils is the disease acute or chronic

acute

if we see hella macrophages, lymphocytes, and plasma cellsis the disease acute or chronic

chronic

what is the potential pathogen if we see lymphoccytes

viruses or immune mediated tumors

what is the potential pathogen/disease if we see mast cells/basophils/eosinophils

allergies (alos tumors)

what is the potential pathogen/disease if we see eosinophils

parasites or allergy

what is the potential pathogen/disease if we see macrophages

intracellular bacteria/parasites, fungi, foreign bodies

what is the potential pathogen/disease if we see neutrophils

extracellular bacteria

where are PAMPs located

on pathogens

where are DAMPs located

they are released from damages or dying host cells post injury

where are PRRs located

on host sentinel cells to rec PAMP and DAMP

where are signaling PRRs located

can be located on cell surface, cytoplasm or endosomal

toll like receptors are a type of signaling PRR, where is it located and what does it bind

membranous binds various ligands

NOD like receptors are a type of signaling PRRs where are they located

cytoplasm, binds peptidoglycan and muramyl dipeptide (parts of bacteria)

RIG-1 like receptors are a type of signaling PRR where is it located and what does it bind

cytoplasm - viral dsRNA

all 3 signaling PRRs signal through which two transcription factors to make pro-inflammatory cytokines, chemokines, adhesion molecules, or costimulatory molecules

NF-kB or IRF

function of the inflammasome

rapid inflammation to fight a pathogen by producing proinflammaotry proteins (cytokines) IL-1beta and IL-18

how do inflammasomes get activated

1 rec PAMP/DAMP via PRR and activate NF-kB

2.) activation of NOD-like Receptor to activate enzyme to activate precursor IL-1B and IL-18

for signaling PRRs what happens after phagocyte activation (4)

cytokine production (inflammatory cascade)

chemokine production (leukocyte rec)

expression of adhesion molecules on leukocytes (lets them go from blood → tissue)

production of other mediators to help leukocytes (arachidonic acid, platelet-activating factor)

3 types of phagocytic receptors on neutrophils, macrophages, DCs, and what they recognize

complement receptors - microbes coated with complement proteins (C3b)

FcyR - microbes coated with antibodies (IgG)

mannose receptor - sugar residues on microbes

4 steps of phagocytosis

recognition and attachment of microbe

engulfment (formation of phagosome)

phagosome-lysosome fusion

destruction

what cels contain the phagocytic PRRs

neutrophils, macrophages, DCs

4 ways the phagolysosome kills microbe

acidic pH

oxidative/respiratory burst

generation of reactive nitrogen species

granulation

during maturation pf the phagosome all the steps contain what that are harmful to the microbe

free radicals

do birds and reptiles have myeloperozidase

no

function of NET formed by neutrophils in response to cytokines (IL-8) and PAMPs (LPS)

microbicidal

keeps pathogen in place and starts killing it

function of “major basic protein” in eosinophil

helps fight parasites

2 Rs of NK cells and what it recognizes

activation R - viral proteins, glycoproteins, antibody coated cells

inhibitory R - MHC 1

What happens with NK cells when the activation receptor is active but not inhibitory (no MHC 1 seen) (2)

Perforin inserts into membrane (punches hole)

Granzyme enters pore —> apoptosis

where do complement proteins come from (3)

hepatocytes, manocytes/macrophages GI epithelial cells

complement system nomenclature: inactive comlement

simple number: C1, C2, etc

complement system nomenclature: cleavage product

lowercase suffix: C3a, C3b, etc

for the complement system, what does the complement bind for the alternative pathway, classical pathway, and lectin pathway

alt- directly on pathogen

classical - antibody on path

lectin - lectin binds to mannose on pathogen cell wall

3 final outcomes of the CS

phagocytosis via nuetrophils and macrophages

pathogen killing

inflammatory response

all 3 CS pathways lead to what common complement protein being deposited on microbe

C3b

for the complement system, what is involved for the inflammation pathway

C3a - increases vascular permeability, degranulation of mast cells and basophils

C5a - stimulates neutrophil chemotaxis

for CS, what is involved in the opsonization pathway

C3b on bacterium read by a receptor and causing phagocytosis

For CS, what is involved in the lysis of pathogen pathway

C5-C9 causes polymerization to form MAC that breaks a hole in microbe cell membrane

5 control mechanisms of the complement system

C1- inactivator

CD55, Factor H - prevents complement from attacking host

CD59 - inhibits MAC

complement Rs - ensure removal of antigen-antibody-complement complexes

what are professional APCs

those that present antigen and coordinate response with the adaptive immune system

Dendritic cells, macrophages, B-cells, sometimes neutrophils?

mature vs naive lymphocyte

mature - developed and contains its antigen receptor

naive - lymphocyte that has not encountered specific antigen

what are secondary lymphoid organs and examples

where lymphocytes will activate

-spleen

-lymphatics + nodes

MALT

what part of bone marrow does hematopoiesis occur

red

diferences in TCRs and BCRs

BCRs bind specific protein (antigen) and it doesnt need to be intracellularly processed

TCRs bind processed antigens displayed by MHCs

what happens once B cell and T cells are activated in secondary lymphoid tissue

clonal expansion

does the term humoral relate to B cells or T cells

B cells

does the term cell-mediated relate to B cells or T cells

T cells

function of spleen in terms of adaptive immunity

screens blood

what is occuring at afferent lymph vessels

lymph is being brough in

what is occuring at marginal/medullary sinuses

macrophages and denritic cellls can find antigen while filtering thorugh

what is happening at paracortial region

mature T and B communicate with macrophages/dendritic cells

what is happening at primary folicles

T and B cells located and inactive

what happening at secondary follicles

active B and T cells are responding to antigen and differentiating

whats happening at plasma cells in medullary sinus

antibodies are being released

red vs white pulp of spleen

red - where RBCs and macrophages are

white - lymphoid tissue that surrounds arteriols

3 functions of lymphatic system

collection of excess fluid

transport of fats from GI to bloodstream

enable immune response

fluid component of lymph

plasma-like

electrolytes

small and large molecules contained in lymph

small - proteins

large - microbes

right arm/head drains to where, and where does everything else drain to (lymphatics)

R arm and head → Right subclavian v

everything else → left subclavian v

what two structures does lymph move through as it goes from caudal to cranial

cisterna chylii and thoracic duct

2 ways lymph can move

via skeletal muscle increasing external pressure

or SM cells contracting along lymph vessels

what is an immunogen

an antigen that can induce an immune response (binds to BCR and TCR)

antigen def

any substance that can bind to an antigen receptor

hapten def

an antigen that cant induce an immune resposne on its own, needs a more complex molecule to be immonogenic

epitope definition

part of antigen that is recognized

conformational vs linear determinant for BCR epitopes

conformational - determinant is lost by denaturation

linear - determinant can be denatured or native

MHC 1 vs MHC 2 expression and what it binds to

MHC 1 is on all nucleated cells and presents to CD8+ T cells

MHC 2 is on professional APCs and presents to CD4+ T cells

MHC 1 vs MHC 2, which binds a larger seq of AA peptides

MHC class 2

how many MHC genes does 1 have and how is it expressed

several genes

expressed co-dominantly

peptide source for MLH class 1 (intracellular or extracellular)

intracellular

peptide source for MLH class 2 (intracellular or extracellular)

extracellular (endocytosed, lysosome, endosome)

what blocks the binding groove of MHC class 2 proteins until endosomal compartment binds

invariant chain

for MHC class 1 antigen processing how does the peptide transport into the ER where MHC 1 molecule is present

via TAP