Innate Immunity

Question 1

Innate immunity

Answer 1

First line of defence, slow growth of infectious agents until adaptive immune responses can develop
Immediate effector function
Does not differentiate between particulate proteins but classes of pathogens
Include:
1. Anatomic barriers
2. Physiologic barriers
3. Soluble factor based and chemical barriers
4. Phagocytosis

Question 2

Skin

Answer 2

Epidermis and dermis
Mechanical barrier, impermeable to most infectious agents
First line of defence
Several layers of epithelial cells
Outermost layer is dead cells filled with keratin
Antimicrobial peptides, lysozyme, fatty acids in sebum

Question 3

Mucus membranes

Answer 3

Lining interiors surface of body
Secrete mucus which traps foreign particles and prevents them from adhering
Cilia, sneezing, coughing, swallowing
Bacterial flora prevents other pathogenic bacteria (gut commensals: colicins)
GI: enzymes, antimicrobial peptides, normal flora
Resp: mucus, cilia, alveolar macrophages
Uro: mucus, fluid flow

Question 4

Physiological barriers

Answer 4

Acid pH of lactic acid
Fatty acids in sweat
Sebaceous sections
Acid pH of stomach
Fever repsonse

Question 5

Antimicrobial peptide

Answer 5

Short cationic peptides with amphipathic structure
Defensins (intestinal paneth cells, epithelial cells, neutrophils, macrophages)
Active against bacteria, fungi, enveloped viruses
Bind to negative microbial structures
disrupt membrane, inhibit DNA, RNA, protein synthesis

Question 6

Lysozyme

Answer 6

Mucosal/glandular secretion: tears, saliva, resp tract

Cleaves glycosidic bonds of peptidoglycan

Question 7

Lactoferrin

Answer 7

Mucosal/glandular secretion: milk, intestinal mucus, nasal/resp, uro
Binds/sequesters iron, limiting growth of bacteria and fungi, disrupts microbial membranes, limits viral infectivity

Question 8

Secretory leukocyte protease inhibitor

Answer 8

Skin, mucosal/glandular secretions

Block epithelial infection by bacteria, fungi, virus

Question 9

S100 proteins

Answer 9

Psoriasin, calprotectin
Skin, mucosal epithelia (mouth, intestine, nasal, resp, uro)
Disrupts membranes, killing cells
Binds and sequesters divalent cations

Question 10

Defensins

Answer 10

alpha, beta
Skin, mucosal epithelia (mouth, intestine, nasal, resp, uro)
Disrupts membranes
Toxic intracellularly effects

Question 11

Cathelicidin

Answer 11

Mucosal epithelia (resp, uro)
Disrupts membranes
Toxic intracellularly affects

Question 12

Surfactant protein

Answer 12

Resp
Block bacterial surface components
Promotes phagocytosis

Question 13

Phagocytic barriers

Answer 13

Neutrophils, macrophages
Killed by reactive O and N, enzymes
Inducible nitric oxide synthase

Question 14

Pathogen recognition mechanism

Answer 14

TLR and NOD receptors

Recognize structural motifs (PAMPs)

Question 15

PAMPs

Answer 15

Pathogen associated molecular patterns
Highly conserved and usually necessary for survival
Absent from host cells

Question 16

Soluble innate immune recognition elements

Answer 16

Mannose-binding lectin
C reactive protein
Complement
Interferons

Question 17

Cellular receptors in innate immune cells

Answer 17

Toll-like receptors (TLR)
NOD receptors (nucleotide binding oligomerization domain)

Question 18

Toll-like receptors

Answer 18

Contain membrane spanning receptors with leucine rich repeats form ligand-binding domain
TIRAP and/or MyD88 function as interior signalling domain
Signalling activates MAP kinase pathway, interferon regulatory factor 3/7, and/or NF-cappaB

Question 19

Inflammation promoting genes regulated by NF-cappaB

Answer 19

Inflammatory cytokines (TNF-alpha, IL1, IL6, IL12, GM-CSF, IFN-alpha/beta)
Chemokine’s (IL8, MCP, RANTES, eotaxin)
Adhesion molecules (ICAM1, VCAM1, Eselectin, Pselectin)
Immune effector molecules (iNOS, defensives)
Costimulatory molecules (CD40, CD80/86 on dendritic cells)
Anything that blocks NF-cappaB is a good anti-inflammatory

Question 20

Dendritic cell maturation

Answer 20

TLR are direct inducers of DC maturation, including expression of CD80, 86, 40, up regulation of MHCII and IL12
Can be induced indirectly by TNF and IL1
Mature DC up regulate CCR7 (chemokine receptor) and migrate to lymph node

Question 21

Collectins

Answer 21

Small proteins that are able to kill certain bacteria by cell wall disruption
Cause bacteria to aggregate, enhancing phagocytosis

Question 22

Serum

Answer 22

Contains interferons, which are antiviral agent

Contains complement

Question 23

Interferons

Answer 23

Alpha produced by leukocytes
Beta produced by fibroblasts
Gamma produced by T and NK cells

Question 24

Complement

Answer 24

20+ serum proteins that act in combination and sequence
Both innate and adaptive
C3 is most important
Cascade to membrane damaging reaction
Activated by: Alternative, lectin, classical

Question 25

Lectin pathway

Answer 25

Innate Mannose-binding lectin (protein in tissue fluid and plasma) binds mannose residues on glycoproteins and carbohydrates of bacteria, fungi, viruses Humans have sialic acid residues that cover and hide mannose residues Activates complement cascade C-reactive protein (in fluid and plasma) binds phosphatidylcholine and pneumococcal polysaccharide to active complement cascade

Question 26

Alternative pathway

Answer 26

Innate | Microbial cell wall components

Question 27

Classical pathway

Answer 27

Adaptive immunity | Antibody-antigen complexes

Question 28

Membrane attack complex

Answer 28

MAC | Leads to cell lysis

Question 29

Opsonin

Answer 29

C3b | Facilitates phagocytosis of microbes

Question 30

Anaphylatoxins

Answer 30

C3a, C5a | Facilitate immune cell activation/recruitment

Question 31

Acute phase response

Answer 31

Responsible for production of innate immune effector cells and soluble molecules Results in production of certain cytokines (IL6, TNF) Effect on hypothalamus (prostaglandins cause fever) Adrenal cortex makes corticosteroids that cause production of acute phase proteins in the liver

Question 32

Innate immunity to viral infections

Answer 32

Induction of Type 1 Interferons (IFNalpha/beta) Presence of viral RNA/DNA activated production via TLR stimulation Interferons induce antiviral response leading to mRNA degradation and inhibition of protein synthesis NK cells are activated and kill virally infected cells (dual receptor with MHC1 and activating receptor, MHC1 missing on virally infected cells)

Question 33

Plasmacytoid dendritic cells

Answer 33

Produce 100-1000x more type 1 interferon upon contact with viruses Do not need a productive viral infection in order to up regulate type 1 interferon genes Recognize mechanism for viral infection is most likely TLR7/8 that recognizes viral ssRNA Drive NK response