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Unit 1: Basic Concepts in Immunology > Section 3: Innate Immunity (Recognition and Response) > Flashcards

Section 3: Innate Immunity (Recognition and Response) Flashcards

1
Q

defensins

A

are antimicrobial peptides that contribute to the innate immune response
-there are two classes alpha and beta
-their molecular structure allows them to penetrate microbial membranes and disrupt their integrity
-the set of defensins made by a person is highly variable in the population

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2
Q

a-defensins

A

expressed by neutrophils and Paneth cells

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3
Q

b-defensins

A

expressed by a broad range of epithelial cells

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4
Q

pathogen associated molecular pattern (PAMP)

A

pathogenic microorganisms have fundamental, structural, and biochemical differences that set them apart from eukaryotic cells
-set of conserved motifs that exist on bacterial cell walls or part of viral replication (ex: double-stranded RNA)
-macrophages express a variety of receptors that recognize these differences
-many of the ligands for these receptors are carbohydrates and lipids of microorganisms

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5
Q

receptor mediated endocytosis

A

the binding of macrophage receptors to their microbial ligands initiates engulfment

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6
Q

endosome/phagosome

A

pathogen internalized into a membrane bound vesicle

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7
Q

phagolysosomes

A

the phagosomes fuse with cellular organisms called lysosomes to form these and result in the destruction of the pathogen

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8
Q

Innate-surface receptors

A

-initiate receptor mediated endocytosis
-transduce signals to the nucleus causing gene activation and the release of cytokines

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9
Q

Toll-like receptor (TLR)

A

-example of an innate-surface receptor
-are expressed by a variety of cells and recognize numerous PAMPS
-not all located on the surface some are in vesicles
-activation of TLR during these initial stages of infection is not only important to the innate immune response but also provides the conditions necessary for the adaptive immune response

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10
Q

TLR4

A

-specifically binds to lipopolysaccharide (LPS), a key component of the gram negative cell wall
-upon binding LPS sends signals into the cell nucleus activating genes to release inflammatory cytokines

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11
Q

What are some inflammatory cytokines

A

-in sensing a pathogen by innate immune receptors resident macrophages are stimulated to secrete a variety of cytokines depending on the signal transduced
-can determine immune response
1. IL-1 (interleukin)
2. IL-6
3. CXCL8 (chemokine ligand 8)
4. IL-12
5. Tumor necrosis factor-a (TNF-a)

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12
Q

What are some antiviral type I interferons?

A
  1. IFN-a
  2. IFN-b
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13
Q

IL-6 systemic effects**

A
  • fever
  • induces acute phase protein production by hepatocytes
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14
Q

TNF-a local effects (tumor-necrosis factor)**

A

-activates vascular endothelium and increases vascular permeability, which leads to the increased entry of complement and cells to tissue and increase fluid drainage to lymph nodes
-best way of knocking down inflammation used in a lot of medicine
-main thing responsible for inducing shock when you get septic infection

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15
Q

TNF-a systemic effects**

A

-fever
-mobilization of metabolites
-shock

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16
Q

IL-1B local effects

A

-activates vascular endothelium, activates lymphocytes, local tissue destruction, increase access of effector cells

17
Q

IL-1B systemic effects

A

-fever
-production of IL-6

18
Q

CXCL8 local effects

A

-chemotactic factor , recruits neutrophils and basophils to site of infection

19
Q

IL-12 local effects

A

activates NK cells

20
Q

Tumor necrosis factor alpha (TNF-a)

A

-released by macrophages in response to TLR activation/stimulation
-helps to limit local infections but if the infection spreads leading to sepsis, TNF-a can have bad results

21
Q

acute phase response

A

further systemic effect of IL-6, IL-1, and TNF-a changing the spectrum of plasma proteins secreted by the liver (acute phase proteins)
-MBL
-CRP
- fibrinogen (helps with clotting)
* proteins made in response to the cytokines

22
Q

leukocyte extravasation

A

inflammatory cytokines mobilize populations of circulating neutrophils to the site of infection (homing)
-occurring initially from inflammation and neutrophils are big player that move across in that manner

23
Q

Neutrophils

A

-a specialized phagocytic cell that use innate immune receptors top phagocytose invading pathogens
-they use a battery of degradative enzymes to destroy pathogens that are contained in internal granule
-depend on enzyme NADPH oxidase which is crucial to the production of several toxic oxygen species
(respiratory burst)
-big primary innate responders
-cells can be induced to change into other cells like monocytes –> dendritic cell (there is plasticity) `

24
Q

chronic granulomatous disease

A

people who posses defective mutations in the NADPH oxidase gene have a severe disease state

25
Q

neutrophil innate receptors

A

-neutrophils express receptors for many bacterial and fungal constitutes
-they bind bacteria, engulf them, and destroy them with toxic contents of the neutrophil granules
-they have all these receptors that help them phagocytose or endocytosis

26
Q

macrophage innate receptor

A

-the macrophage expresses several receptors specific for bacterial constituents
-bacteria bind to macrophage receptors
-engulf and digest bound bacteria

27
Q

Neutrophil and respiratory burst

A
  1. bacteria is phagocytosed by neutrophil
  2. phagosome fuses with azurophilic and specific granules
  3. pH of phagosome rises , antimicrobial response is activated and bacterium is killed
  4. pH of phagosome decreases, fusion with lysosome allows acid hydrolases to degrade the bacterium completely
  5. neutrophil dies by apoptosis and is phagocytosed by macrophage
28
Q

Type I interferons

A

are proteins that are produced when a cell is infected by a virus (intracellular pathogen)
-interferon- a (INF-a)
- interferon- b (INF-b)
-these proteins immediately start to interfere with viral replication and signal other cells to the viral replication
-stimulate NK cells which are innate immune cells specialized in killing virus-infected cells

29
Q

interferon-producing cells (IPCs)

A

are specialized cells that produce large amounts of IFNs
-eventually, these cells differentiate and mature into plasmacytoid dendritic cells
-important to the initial innate immune response

30
Q

What is the interferon response?

A
  1. induce resistance to viral replication in all cells
  2. increased expression of ligands for receptors on NK cells
  3. activate NK cells to kill virus-infected cells (provide early response)
    - IFN-a, b, TNF-a, and IL-12 activate and trigger proliferation of NK cells
    -the NK cell response bides time until the adaptive T cell response can clear the infection
    - has an autocrine and paracrine response
    -tells the neighbors I’m infected you should shut down but also produce more interferons to make a zone of warning
31
Q

toll-like receptors: signaling

A

-TLR4 can send signals two ways either through the TRIF-TRAM pathway or MYD88-IRAK4 pathway
-NFkB can lead to the secretion and synthesis of TNF-a and other inflammatory cytokines (MYD88-IRAK4 pathway)
-IRF3 can lead to the synthesis and secretion of type I interferons: IFN-a and IFN-b (for viral and anti-viral)

32
Q

IL-1/IL-6/TNF-a response in liver

A

-acute phase proteins (CRP, MBL)
-activation of complement
-oposination

33
Q

IL-1/IL-6/TNF-a response in bone marrow endothelium

A

-neutrophil mobilization
-phagocytosis

34
Q

IL-1/IL-6/TNF-a response in hypothalamus

A

-increased body temperature
-decreased viral and bacterial replication

35
Q

IL-1/IL-6/TNF-a response in fat. muscle

A

-protein and energy mobilization to generate an increased body temperature
-decreased viral and bacterial replication

36
Q

primary granules

A

-primary (azurophilic)- pre-formed waiting around

37
Q

secondary granules

A

-secondary (specific)- need to be induced, more potent

38
Q

enzymatic reactions involving superoxide and hydrogen peroxide

A

NADPH + 2 O2 –NADPH oxidase–>NADPH + 2 O2- + H+

2 H+ +2 O2—superoxide dimutase–> H2O2 + O2

2 H2O2 –catalase–> 2 H2O + O2

39
Q

Natural killer cells are

A

-main innate response to viral infection
-involved in modulating some innate immune response (ex: T-regulatory cells)
-provide early response to virus infection
-NK cell goes around and bops on cells and pick who to bind to determine healthy cells from not
-when it goes on an infected cell the ligands are expressed by that cell and the NK cell sends a signal

Unit 1: Basic Concepts in Immunology (6 decks)

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