Innate Immunity

most common route of entry

respiratory tract

defenses in lungs

goblet cells, mucus glands, ciliated cells

goblet cells

secrete mucus, traps pathogens

ciliated cells

move mucus

what impairs ciliated cells’ function

cold weather, smoke, low humidity

lower airways primary defense

alveolar macrophage

defenses in GI tract

lysozyme, stomach acid, intestine alkalinity, digestive enzymes, bile salts, detergents

features of viruses that infect GI tract

resistant to pH extremes, proteases, and detergents

alimentary viruses structures

not enveloped because the envelope is susceptible to damage by detergents and bile salts

M cells

likely site of virus entry where viruses are sent to Peyer’s patches

Paneth cells

release defensins to disrupt bacterial cell walls

primary sites of infection in eye

epithelial sclera and conjuctiva

what makes up tears

antibodies and lysozyme

types of tears

basal (normal), psychic (emotion/stress), reflex (noxious irritants with more antimicrobial factors)

barriers of urogenital tract

low pH and mucus

common sites of infection in urogenital tract

urethra (women and men) and vagina

how do viruses spread in urogenital tract?

tears or abrasions

keratin layer

outer layer of dead keratinized skin that cannot support viral replication

skin barriers

dry, acidic, normal bacterial flora

placental infections transmission

vertical

TORCH infections

toxoplasma, rubella, cytomegalovirus, and herpes simplex (all serious for fetus)

primary protection for fetus

syncytiotrophoblast cells

syncytiotrophoblast cells

separate maternal and fetal blood, relatively resistant to viral infections

PRRs

TLRs (proteins and nucleic acids), RNA helicases (dsRNA), PKR (dsRNA)

TLRs

recognize PAMPs, induce transcription factor activation, on cell surface or endosomes

what are some transcription factors that TLRs induce

NFkB, IRF

activation of NFkB by TLR signaling

recognizes RSV F protein, causes IkB degradation, NFkB translocation to nucleus, transcription of inflammatory response genes

cytoplasmic receptors that sense viral nucleic acid

RIG-I (5’ triphosphates, dsRNA), MDA-5 (dsRNA), produce type I interferon

PKR activation

recognizes dsRNA, halts protein synthesis

how is cytoplasmic DNA detected?

induce type I interferon and cytokines (cGAS-STING pathway)

Interferons

type I (IFN alpha/beta) and type II (IFNgamma)

type I IFN

heterodimer, general anti-viral defense and sometimes cell death, create viral “firebreak” and activates immune cells

type II IFN

macrophage activation

IRF transcription factors

recognize IFNa/b-stimulated response elements (ISREs) in nucleus to stimulate transcription of 300 genes

apoptosis process

nuclear condensation, Caspase activation and protein degradation, DNA fragmentation (non-inflammatory), PS flips to outer membrane, membrane blebbing and macrophage engulfment

2 pathways of apoptosis

intrinsic (mitochondrial-cell stress) and extrinsic (signaling)

intrinsic apoptosis

viral infection within cell

things that can alter innate immune responses

stress, corticosteroids, hormones, age, malnutrition, smoking

first line innate immune cell defense

macrophages and monocytes

macrophages

ingest pathogen, acidification in endosome, release chemokines

PMNs

neutrophils that ingest pathogens using NO and reactive oxygen species and have short half-life

Sentinel cells

DCs and macrophages that lead to adaptive response by presenting Ag

complement overview

over 30 proteins, recognize pathogen surfaces or Ab molecules, help kill enveloped viruses or infected host cells

how does complement kill non-enveloped viruses?

coat them with C3b to stimulate phagocytosis

outcomes of complement

inflammation, opsonization, membrane-attack complex

what is self?

cells that exhibit MHC class I and possibly class II

what cells express class II HLA?

DCs, macrophages, and B-cells (APCs)

MHC function

present foreign Ags to body

what cells do NK cells recognize

ones missing class I (not self)

how do some viruses try to escape immune responses?

diminish MHC class I on cell surface (NK cells recognize this)