cells and receptors in innate

B cells

create and release antibodies

T cells

dictate immune response and have static receptors

CD4+ “helper” T cells

direct immune response

CD8+ “killer” T cells

elite assassins of adaptive immune system

types of cells in innate immune system

phagocytes, granulocytes, antigen presenting cells

antigen presenting cells (APCs)

tell adaptive immune system something’s wrong

small lymphocytes

b cells (APCs), make antibodies

plasma cells

enhanced golgi apparatus to package and get antibodies around the body

NK cells

non-specific serial killing, essential innate response, cytotoxic

neutrophils

granulocyte and phagocyte, found in pus

eosinophils

granulocyte, allergic responses and parasites

basophils

granulocyte, parasitic infection

mast cells

granulocyte, most POTENT because they contain histamine, anaphylaxis when all granules released at once

DCs

APC, professional activators of T cells, sound alarm for immune response

monocytes

circulating precursor for macrophage

macrophage

BEST phagocyte, phagocytosis and killing of microorganisms, clean stuff, eat stuff and put them into an antigen

healthy neutrophil percentage in leukocytes

40-75%

healthy eosinophil percentage in leukocytes

1-6%

healthy basophil percentage in leukocytes

<1%

healthy monocyte percentage in leukocytes

2-10%

healthy macrophage percentage in leukocytes

20-50%

B cell receptor

surface immunoglobulin, secrete antibodies

Helper T cells

activate and coordinate immune responses, all have CD4

• TH1

• TH17

• TH2

• TFH (T follicular helper cells)

• TREG

perpherin

pokes holes

TH1

activated by macrophages, activate other macrophages, inflammation

TH2

activate basophils, parasitic infection

TH17

responsibe for neutrophil response, activate phagocytosis

C3

central complement protein, cleaved into C3a and C3b by C3 convertase

C3b

complement fixation, Bound to pathogen

C3a

inflammatory molecule, Alerts for pathogen, anaphylotoxin

CR1

used by macrophages and erythrocytes to recognize C3b

C5

binds to C3b, makes C5 convertase which cleaves C5

C5a

inflammation, anaphylotoxin

C5b

tells friends to start killing things, activates last steps of complement

mannose binding lectin (MBL)

recognized microbial carbohydrates containing mannose

Ficolins

recognizes acetylated sugars

C1 complex

must have at least two specific antibodies to be created, IgM, CRP

activates classical pathway

IgM

subset of immunoglobulin, must be in staple formation with arms down

CRP

deposit onto pathogen surface, need multiple

membrane attack complex (MAC)

huge pore, disrupts pathogenn membrane integrity, cell lysis, formed by C5-C9

properdin

stabilizes C3 convertase on microbes

what prevents MAC assembly on host cells?

CD59 and homologous restriction factor (HRF)

Innate Lymphoid cells (ILCs)

kill infected cells (like lymphocytes)

Helper ILCs

strengthem myelois responses via cytokine secretion

ILC1, ILC2, ILC3

Tissue inducer ILCs

oversee development of lymphoid tissue

PRRs

bind molecular motifs on pathogens, trigger intracellular signaling cascades

Toll-like Receptors (TLRs)

recognize extracellular PAMPs or after endocytosis

RIG-I-Like receptors (RLRs)

detect long dsDNA

cytosolic DNA sensors (CDSs)

detect DNA in the cytosol, recognize infection

NOD-like receptors

bind to bacterial surface molecules in cytosol after it’s eaten

which TLRs sense carbs, lipids, and protein ligands on outer microbial surfaces?

TLR1, TLR2, TLR4-6, TLR10

which TLRs sense nucleic acid features common in viral and intracellular bacterial infections?

TLR3, TLR7-9

which TLRs sense repeated 20-29 amino acid motifs rich in leucine?

Leucine-rice repeat (LRR) domain

which TLRs recruit adaptor proteins to initiate downstream signalling?

toll/interleukin-1 receptor domain, adaptor proteins

adaptor proteins

relay signals to kinases and regulatory complexes

tumor necrosis factor receptor-associated factor 6 (TRAF6)

conveys signals from adaptor complexes to activate NFkB

nuclear factor kB (NFkB)

master switch, family of transcription factors, regulate genes for cytokines, adhesion molecules, and immune responses, synthesize and secrete IL-6, TNF-a, and pro-IL-1B

Interferon regulatory factors (IRFs)

regulate type 1 interferon and other innate gene expression, more induced during viral infections

LPS

structure variation on bacteria lead to alterations in immune response strength, signals macrophage to induce inflammation

scavenger receptors (SRs)

wide range of ligands, modified self-molecules, microbial patterns, mediate endocytosis, phagocytosis, adhesion, signaling for removal of non-self or altered-self

scavenger receptor class A1 (SR-A1)

expressed primarily on macrophages

MARCO

binds LPS, whole bacteria, apoptotic cells

mannose receptor

scavenger receptor with 8 c-type lectin domains

c type lectin domain

calcium coordinated protein binding carbohydrates found in lectin-type scavenger receptors

dectin-1

recognizes fungalo and some bacteria surfaces

RIG-1

cytosolic RNA helicase-like receptor

melanoma differentiation-associated protein 5 (MDA-5)

structurally similar RNA helicase receptor

caspase-recruitment domains (CARDs)

protein interaction domains on RIG-1 and MDA-5, caspases drive apoptosis

cyclic GAMP synthase (cGAS)

binds abnormal cytosolic DNA

second messenger cyclic GMP-AMP (cGAMP)

activated by cGAS, binds and activates STING

CXCL8

signals neutrophil migration from the blood and directs them to the infected tissue

bradykinin

lowers BP, dilates vessels, relaxes smooth muscle, promotes inflammation

protease inhibitors

plasma proteins that neutralize microbial proteases

defensins

family of AMPs, broadly antimicrobial, immunomodulatory

a-defensins

found in neutrophils granules, act during innate immune response

b-defensins

many in nature, few understood

pentraxins

plasma proteins the circulate, bind to pathogens, and deliver them to phagocytes via targeting

serum amyloid A

inflammatory signaling protein, associates with HDL in blood

C-reactive protein

bind phosphocholine on bacteria to opsonize

Pathogen-associated molecular patterns (PAMPs)

mpolecular motifs on microbes detected by PRRs, indicte infection

damage-associated molecular patterns (DAMPs)

molecules expressed by host cells during cellular stress/damage (not always infection)

IL-1B

activates macrophage, clocks to surface receptor of macrophage, allow macrophage to release TNF-a

TNF-a

induces blood vessels to be more permeable, enabling cells, fluids, and soluble effectors to enter infected

IL-6

induces fat and muscle cells to metabolize, generate heat, and raise the temperature in the infected tissue

CCL2

recruits monocytes from them to the infection tissue

IL-12

recruits and activates natural killer cells to secrete cytokine that strengthen macrophages’ response to infection

ICAM1 and ICAM2

most important adhesion molecules, bind to integrins

IL-1B, IL-6, and TNF-a effects on liver

acute phase proteins CRP and MBL, activate complement, opsonization

IL-1B, IL-6, and TNF-a effects on bone marrow

mobilize neutrophils, pus, phagocytosis

IL-1B, IL-6, and TNF-a effects on hypothalamus

increase body temperature, decrease viral and bacterial replication

IL-1B, IL-6, and TNF-a effects on fat/muscle

metabolism increases body temperature, decreases viral and bacterial replication

pyrogens

trigger fever

NOD 1

detect degraded peptidoglycan from gram-negative bacteria

NOD 2

detect degraded peptidoglycan common to most bacteria

ROS

superoxide radical, hydrogen peroxide

RNS

nitric oxide

Type 1 macrophage

attack mode, eat things, cause inflammation, and eliminate the pathogen before calling type 2 macrophages

type 2 macrophages

secrete chemicals to allow for cleanup and rebuilds cells to normal tissue

plasmacytoid dendritic cells (pDCs)

specialize in type 1 interferon production, secrete 1000x more interferon than other cells, extensive ER to synthesize massive amounts of interferon, highly antiviral

neutrophil granules

• azurophilic

• specific

• gelatinase

• secretory vesicles