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Immunology > Innate Immunity (Ch 2) > Flashcards

Innate Immunity (Ch 2) Flashcards

1
Q

Where are pattern recognition receptors located?

A
  • On plasma membrane - target extracellular microbes
  • In vesicles/endosomes - target microbes that get engulfed
  • In cytoplasm - detect cytoplasmic microbes
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2
Q

Specific TLRs

A

CELL SURFACE = Bacterial/Extracellular

  • TLR-2 - bacterial and parasitic glycolipids and peptidoglycans
  • TLR-4- bacterial LPS (endotoxin)
  • TLR-5 - flagellan; bacterial flagella protein

IN ENDOSOMES= VIRAL/Intracellular
- TLR-3/7/8- viral dbl stranded DNA
- TLR-9 - unmethylated cPG DNA
(**in endosomes - where the microbes ingested - DNA exposed)

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3
Q

NOD Proteins (3 specifics)

A
  • In epithelium cytoplasm - bind nucleotides and then activate caspases
    • NOD-1- bind glutamyl diaminopimelic acid (most bacteria)
    • NOD-2- muramyl dipeptide (gram negative bacteria)
    • NLRP3 (Nod-like receptor protein 3) - recognizes microbial products; substances that indicate cell damage (ATP) K+ conc changes, uric acid crystals and excessive amounts of endogenous substances (ex- free FAs); THEN oligomerizes with an adaptor protein and and inactive caspase 1 —> IL-1 —> acute inflammation and fever

***Responsible for gout

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4
Q

Inflammasome

A

complex of NLRP3 + adaptor + caspase

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5
Q

2 Paths of Macrophage Activation

A
  • Classic Path of Activation - induced by TLRs and IFN-gamma - destroy microbes and inc inflammation
  • Alternate Pathway of Activation - IL4 IL13- tissue repair and TERMINATE inflammation
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6
Q

How are natural killer cells activated?

A
  • Activation determined by balance b/n activating and inhibiting receptor engagement
  • Activating receptors have immunoreceptor tyrosine­-based activation motifs—>when bind lingered the tyrosine is phosphorylated —> activate tyrosine kinases —> signal pathways —> cytotoxic granule exocytosis and IFN-gamma production
  • Inhibiting receptors bind class I MHC molecules so that NK do not kill healthy human cells
  • immunoreceptor tyrosine­-based activation motifs—>when bind lingered the tyrosine is phosphorylated —> activate tyrosine phosphatases —> remove phosphates from the components of the activator pathway so counteract it
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7
Q

4 Limited Diversity Lymphocytes of Innate Immunity

A
  • γδ T cells are present in epithelia
  • NK­T cells express TCRs with limited diversity and surface molecules typically found on NK cells; in epithelial and lymphoid organs; recognize microbial lipids bound to MHC-related molecule (CD1)
  • B-1 cells - in mucous and epithelial tissues; make “natural antibodies” (against mainly carbs of bacterial cell walls)
  • Marginal­ zone B cells- at edges of lymphoid follicles in the spleen; rapid antibody responses to blood­borne polysaccharide­ rich microbes
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8
Q

3 Paths of Complement Acivation

A
  • 1- Alternate - activated on microbes membrane (not controlled b/c microbes do not have control proteins); innate response
  • 2- Classical - triggered by microbe or antigen-bound antibody; in humoral response
  • 3- Lectin - triggered when mannose-binding lectin protein bind mannose residues on microbe —> activates proteins of classical path BUT no antibody present so part of innate response
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9
Q

C3a
C3b
C5a
C6-C9

A
  • C3a/C5a - inflammation
  • C3b - opsonization and phagocytosis
  • C6-C9 - lysis of microbe (form membrane attack complex AKA MAC)
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10
Q

Acute Phase Response (+ 3 examples)

A
  • Protective circulation of a number of proteins; made by LIVER; including…
  • MBL- mannose binding lectin - can coat microbes and activate complement via lectin path
  • Surfactant proteins in lung - protect airway
  • CRP - C reactive protein - binds CRP receptors on microbes for opsonization/ phagocytosis; can also activate classical path of complement
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11
Q

4 Mechanisms of Phagocyte Microbe Killing

A
  • Phagocyte oxidase: oxygen —> superoxide (ROS)
  • NO synthase: arginine —> NO
  • Lysosomal proteases: breakdown microbial proteins
  • Dying neutrophils create extracellular traps w/ antimicrobial contents (NETs)
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12
Q

How does innate immunity activate adaptive immunity?

A
  • Naive T and B cells require 2 signals for activation; ensures they only react to infectious agents
    • 1- antigen itself
    • 2- innate immune response to microbe
      • Examples…
        • Co-stimulators on activated dendritic cells (T cell act)
        • IL1, IL6 or IL12 secreted by macrophages or dendritic cells (T cell act)
        • C3d of complement (B cell act)
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13
Q

2 Mechanisms of Innate Immunity Negative Feedback

A
  • IL-10 - anti-inflammatory cytokine

- SOCS- suppressor proteins activated by TLR signaling by blocking cell responses to cytokines

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14
Q

What are the major players of antiviral reaction?

A
  • infected cells (esp plasmacytoid dendritic cells) release type I IFNs —> bind receptors of nearby infected or uninfected cells —> signal paths to inhibit viral replication and destroy viral genomes
  • Natural Killer Cells- kill virus infected cells
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15
Q

TNF

A

From macrophages, T cells and mast cells

Endothelial cells - inflammation/coagulation/expression of ICAM/VCAM
Activate neutrophils
Hypothalamus - fever
Liver- synthesis of acute phase reactants
Muscle/fat- catabolism (cachexia)
Apoptosis of many cell types

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16
Q

IL-1

A

From macrophages, dendritic cells, endothelial cells, some epithelial cells, mast cells

Endothelial cells - inflammation/coagulation/expression of ICAM/VCAM
Hypothalamus - fever
Liver- synthesis of acute phase reactants
T cells - Th17 differentiation

17
Q

Chemokines

A

From macrophages, dendritic cells, endothelial cells, T cells, fibroblasts, platelets

Stim leukocytes- inc integrin affinity, chemotaxis, activation

18
Q

IL-12

A

From dendritic cells and macrophages

NK cells/T cells- stimulate IFN-gamma production and cytotoxic activity
T cells- Th1 differentiation

19
Q

IFN-gamma

A

From T cells and NK cells

Activate macrophages; stem some antibody response

20
Q

Type 1 IFNs

A

alpha - from dendritic cells and macrophages; beta - from fibroblasts

Activate NK cells; inc MHC expression and viral-state of all cells

21
Q

IL-10

A

From macrophages, dendritic cells, T cells

Target other macrophages and dendritic cells to dec cytokine production and dec class 2 MHC display (FEEDBACK)

22
Q

IL-6

A

From macrophages, endothelial cells, T cells

Liver - prod of acute phase reactants
B cell - proliferate antibody producing cells

23
Q

IL-15

A

From macrophages + others

Proliferation of NK cells and T cells

24
Q

IL-18

A

From macrophages

NK and T cells- IFN-gamma production

25
Q

TGF-beta

A

From many cell types

inhibit inflammation
T cells- differentiation of Th17, regulatory T cells

26
Q

IL-8 (AKA CXCL8)

A

From macrophages and dendritic cells

Chemoattractant of neutrophils

Immunology (14 decks)

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