Innate Immunity Flashcards

1
Q

Innate immunity

A

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

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2
Q

Skin

A

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

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3
Q

Mucus membranes

A

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

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4
Q

Physiological barriers

A
Acid pH of lactic acid
Fatty acids in sweat
Sebaceous sections
Acid pH of stomach
Fever repsonse
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5
Q

Antimicrobial peptide

A

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

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6
Q

Lysozyme

A

Mucosal/glandular secretion: tears, saliva, resp tract

Cleaves glycosidic bonds of peptidoglycan

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7
Q

Lactoferrin

A

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

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8
Q

Secretory leukocyte protease inhibitor

A

Skin, mucosal/glandular secretions

Block epithelial infection by bacteria, fungi, virus

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9
Q

S100 proteins

A

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

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10
Q

Defensins

A

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

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11
Q

Cathelicidin

A
Mucosal epithelia (resp, uro)
Disrupts membranes
Toxic intracellularly affects
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12
Q

Surfactant protein

A

Resp
Block bacterial surface components
Promotes phagocytosis

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13
Q

Phagocytic barriers

A

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

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14
Q

Pathogen recognition mechanism

A

TLR and NOD receptors

Recognize structural motifs (PAMPs)

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15
Q

PAMPs

A

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

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16
Q

Soluble innate immune recognition elements

A

Mannose-binding lectin
C reactive protein
Complement
Interferons

17
Q

Cellular receptors in innate immune cells

A
Toll-like receptors (TLR)
NOD receptors (nucleotide binding oligomerization domain)
18
Q

Toll-like receptors

A

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

19
Q

Inflammation promoting genes regulated by NF-cappaB

A

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

20
Q

Dendritic cell maturation

A

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

21
Q

Collectins

A

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

22
Q

Serum

A

Contains interferons, which are antiviral agent

Contains complement

23
Q

Interferons

A

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

24
Q

Complement

A

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

25
Q

Lectin pathway

A

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

26
Q

Alternative pathway

A

Innate

Microbial cell wall components

27
Q

Classical pathway

A

Adaptive immunity

Antibody-antigen complexes

28
Q

Membrane attack complex

A

MAC

Leads to cell lysis

29
Q

Opsonin

A

C3b

Facilitates phagocytosis of microbes

30
Q

Anaphylatoxins

A

C3a, C5a

Facilitate immune cell activation/recruitment

31
Q

Acute phase response

A

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

32
Q

Innate immunity to viral infections

A

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)

33
Q

Plasmacytoid dendritic cells

A

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