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Metabolics > Immunity in the Gut > Flashcards

Immunity in the Gut Flashcards

1
Q

2 branches of immune defenses

A
  1. Innate

2. Adaptive

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2
Q

Innate

A
  • immediate
  • physical, chemical, cellular barriers
  • cells of the innate
  • recognition of pathogenic associated molecular patters (PAMPS)
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3
Q

Adaptive

A
  • Learned
  • Antigen specific: B cells (antibodies) & T cells (cellular)
  • immunological memory
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4
Q

Innate response time

A

Minutes/hours

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5
Q

Innate immunity diversity

A

a limited number of germ line encoded receptors

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6
Q

innate memory responses

A

none

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7
Q

innate self/nonself discrimination

A

perfect (doesn’t accidently recognize self as bad)

- no microbe specific patterns in host

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8
Q

innate soluble components of blood or tissue fluids

A

many antimicrobial peptides and proteins

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9
Q

innate major cell types

A

Phagocytes (monocytes, macrophages, neutrophils)

  • killer (NK) cells
  • dandritic cells
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10
Q

Adaptive immunity response time

A

days

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11
Q

adaptive specificity

A
  • highly specific discriminates even minor difference in molecular structure
  • details of microbial or nonmicrobial structure recognized with high specificity
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12
Q

adaptive memory responses

A

-persistent memory with faster response of greater magnitude on subsequent infection

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13
Q

adaptive self/nonself discrimination

A
  • very good

- occasional failures of self/nonself discrimination result in autoimmune disease

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14
Q

adaptive soluble components of blood or tissue fluids

A

antibodies

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15
Q

adaptive major cell types

A
  • T cells
  • B cells
  • antigen-presenting cells
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16
Q

Innate Immunity: Barriers

A
  • Skin
  • Mouth and upper alimentary canal
  • stomach
  • small intestine
  • large intestine
  • airway and lungs
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17
Q

Innate Immunity barriers: Skin

A

Antimicrobial peptides, fatty acids in sebum

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18
Q

Innate Immunity barriers: Mouth and upper alimentary canal

A

enzymes, antimicrobial peptides, and sweeping surface by directional flow of fluid toward stomach

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19
Q

Innate Immunity barriers: stomach

A

Low pH

  • digestive enzymes
  • antimicrobial peptides
  • fluid flow toward intestine
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20
Q

Innate Immunity barriers: small intestine

A
  • digestive enzymes
  • antimicrobial peptides
  • fluid flow to large intestine
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21
Q

Innate Immunity barriers: large intestine

A
  • normal intestinal flora compete with invading microbes

- fluid/feces expelled from rectum

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22
Q

Innate Immunity barriers: airway and lungs

A
  • cillia sweek mucus outward
  • coughing
  • sneezing expel mucus
  • macrophages in alveoli of lungs
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23
Q

Innate Immunity: Beyond the first line of defense

A
  • Complement System
  • Recognition of pathogens by antigen presenting cells (APC)
  • A-specific (non-specific) killing of pathogens
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24
Q

Complement system

A

protein complex lysing bacteria

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25
Q

Recognition of pathogens by antigen presenting cells (APC)

A
  • monocytes/macrophages
  • Dendritic cells
  • B cells (also in adaptive immunity)
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26
Q

A-Specific (non-specific) killing of pathogens

A
  • natural killer (NK) cells

- Neutrophils, mast cells, eosinophils

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27
Q

Cytokines

A
  • protein chemical messengers
  • can regulate cell in which produced or other cells
  • changes activity of target cell through binding to receptors
  • impacts multiple immune cells
  • Measure to identify level of inflammation
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28
Q

What are cytokines secreted from

A

monocytes, macrophages, T cells

-innate and adaptive

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29
Q

Examples of cytokines

A
  • Tumor necrosis factor
  • interleukin-1 (IL-1)
  • interleukin-6 (IL-6)
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30
Q

Dendritic cell

A
  • Antigen presenting cell
  • have chemokine receptors to guide them –> chemokines (cytokines that attract)
  • can present to B or T cells
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31
Q

Antigen-presenting cell

A
  • process antigen material and present it on the surface to other cells of the immune system
  • macrophages are APC to T cells and B cells
  • is required for T-cell antigen recognition
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32
Q

Adaptive or acquired immune system

A
  • specific
  • second line of defense
  • humoral (B cells, antibodies)
  • Cell-mediated (T cells)
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33
Q

Adaptive system cells

A
  • T cells (T lymphocytes)

- T lymphocyte-antigen recognition (TCR)

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34
Q

T lymphocyte-antigen recognition

A
  • T lymphocytes recognize antigen via peptides or antigen presenting cells (macrophages)
  • receptors are antigen specific
  • antigens have to be “presented”
  • happens at site of major histocompatibility complex or cluster
35
Q

Adaptive system cells functionally divided into…

A

-T helper
-T cytotoxic
T regulatory Suppressor

36
Q

T Helper Cells

A
  • Activated by MHC on antigen-presenting cell - also need co-stimulatory receptor (CD4)
  • Directs immune system action via cytokines
  • Marker CD4 predominates
37
Q

What does T Helper do?

A
  • stimulates B lymphocytes to differentiate
  • activates Tc and natural killer cells
  • recruits and activates macrophages
38
Q

B cells (B lymphocytes)

A
  • Made in bone marrow
  • recognize antigens to produce antibodies
  • differentiate into plasma cells & memory cells
  • Antibody (immunoglobulin)
39
Q

Antibody (immunoglobulin)

A
  • protein secreted by plasma cells
  • membrane-bound on memory cells
  • identifies and neutralizes foreign objects
  • activate complement pathway
40
Q

What are the different types of antibodies?

A
  • IgM
  • IgA
  • IgG
  • IgE
  • IgD
41
Q

IgM

A

1st produced

-precursor and changes to other antibodies

42
Q

IgA

A
  • Mucosal surfaces

- secreted in Breast Milk

43
Q

IgG

A
  • 75% of Ig in circulation, important in fetus/infant food sensitivity
  • test for specific foods but not always helpful
44
Q

IgE

A
  • Primary antibody in allergies

- produced in response to allergen

45
Q

IgD

A

levels increase in chronic infections

46
Q

How b cell recognizes antigens

A
  • B cell and antigen have to interact
  • B cell makes a receptor
  • T cell activates B cell
  • B cell releases antibody
47
Q

T cell responses –>

A

determine the type of immunoglobulin plasma cells produced

48
Q

TH1 vs TH2 responses

A
  • TH1 = intracellular antigens: bacteria, viruses, fungi, tumor cells
  • TH2 = extracellular antigens: parasites, food and environmental antigens
49
Q

TH1 mediated disease

A 
-IgG
Rheumatoid arthritis
-Chrons disease
-Multiple sclerosis
-DM1
50
Q

Multiple Sclerosis

A
  • Autoimmune disease
  • immune system attacts the central nervous system (identify self as nonself)
  • Damages myelin, myelin-producing cells, and nerve fibers
51
Q

Examples of Th2 mediated disease

A
  • allergens: egg, peanut, ragweed, dust mites
  • extracellular antigen- environmental and food allergens
  • IgE
52
Q

Th1 & Th2 similarities

A

-both promote an appropriate immune response to different types of infectious organisms

53
Q

Eosinophilic esophagitis (EoE) cause

A

-genetic and environment

54
Q

EoE presentation

A
  • dysphagia
  • heartburn
  • food impaction
55
Q

EoE diagnosis

A

15+ eosinophils per high-power field

56
Q

EoE treatment

A

Dietary elimination and corticosteroids

57
Q

EoE elemental formula

A
  • Neocate
  • ~90% effective (histological remission)
  • difficult to follow
58
Q

EoE dietary treatment

A
  • elemental formula
  • skin allergy test - directed elimination diet (25% histological remission)
  • empirical elimination diet based on common food allergens (75% histological remission)
59
Q

T Cytotoxic cells (Tc)

A

activated by MHC on antigen presenting cell (also need co-stimulatory receptor (CD8)

60
Q

How is Tc activated

A

activated by Th cell through cytokines

-once activated - becomes cytotoxic T lymphocyte (CTL)

61
Q

What does Tc eliminate?

A

Eliminates any cells that display antigen

  • Tumor cells
  • virus-infected cells
  • tissue graft cells
62
Q

Regulatory T cells (Tr)

A
  • suppress immune system
  • discriminate between self and non-self
  • transforming growth factor-B and inerleukin-10 (anti-inflam)
  • important in gut immunity
63
Q

Primary lymphoid system

A
  • Bone Marrow - B cells

- Thymus - T cells

64
Q

Secondary lymphoid organs

A
  • Lymph node, spleen, MALT, GALT
65
Q

Tollerance vs. Inflammation

A
  • 80% of all Ig (antibody)-producing cells are in the intestinal mucosa
  • 20% of all cells in the epithelial layer of the intestine are lymphocytes
66
Q

How do we balance between pathogenic protection and tolerance?

A
  • Oral tolerance: systemic nonresponsiveness to oral antigens
  • antigenic ignorance (barrier function)
  • active tolerance (T regulatory cells)
67
Q

Cells in the Intestine

A
  • Epithelial cells
  • paneth cells
  • goblet cells
  • enteroendocrine cells
  • Intraepithelial lymphocytes (GALT)
68
Q

Epithelial cells

A

Barrier and express PRR (TLR4)

69
Q

Paneth cells

A

secrete anti-microbial peptides (SI)

70
Q

Goblet cells

A

-produce mucus (LI)

71
Q

Enteroendocrine cells

A
  • CCK
  • GLP-1
  • PYY
72
Q

Intraepithelial lymphocytes (GALT)

A
  • mostly T cells

- 10-15 per 100 epithelial cells

73
Q

Gut-Associated Lymphoid Tissue (GALT)

A
  • gut barrier
  • Follical-Associated Epithelium –> M cells & intraepithelial lymphocytes
  • Dendritic cells
  • Peyer’s patches
  • Solitary lymphatic follicles
  • Vermiform appendix
  • Mesenteric lymph nodes
74
Q

GALT Cells

A
  • T cells
  • B cells
  • Macrophages (DC)
  • IEL
75
Q

Gut Barrier Components

A
  • Commensal Bacteria
  • Antimicrobial peptides (AMP)
  • Follicle-associated epithelium (M cells, IEL)
  • Dendritic Cells
  • IgA secretion
76
Q

Follicle Associated Epithelium

A
  • Epithelium covering peyer’s patches, single lymphoid follicles
  • Membranous Epithelial Cells (M cells (antigens continuously taken up transepithelially)
77
Q

Dual humoral immune reaction

A

local secretion of antibodies (IgA)

-suppression of systemic immunologic responses to ingested antigens (oral tolerance)

78
Q

M Cells

A
  • Presentation of enteric antigens to immune system (follicle)
  • No microvilli
  • Attach to regular absorptive cells by tight junctions
  • Form latticework with many intraepithelial lymphocytes
  • Transport antigenic material (viruses(
79
Q

Gut Immunity: Routes of Entry

A
  • M cells - Dendritic cells to T cells to peyers patches. - B cells to peyer’s patches
  • Dendritic cells between cells - peyer’s patches. - Mesenteric lymph nodes
  • paracellular leak
  • signaling from lumen 0 not really entry
80
Q

Peyer’s Patch

A
  • Aggregates of lymphoid tissue
  • B cells
  • Ileum
  • Lamina propria to submuccosa
81
Q

Transport od IgA into Gut lumen

A
  • Important in defense and tolerence (immune exclusion/barrier to entry)
  • secreted from plasma cell
  • Response to stimulation by dendritic cells (antigen presentation to T cells)
82
Q

Solitary Lymphatic Follicles

A
  • Smaller individual follicles

- line small bowel and colon

83
Q

Vermiform Appendix

A
  • Blind-ended tube located at the cecum

- rich in lymphocytes

84
Q

Mesentery Lymph nodes

A
  • Between layers of mesentary
  • 100-150 lymph nodes
  • lymphocytes migrate here from rest of GALT
  • GALT stimulation can be systemic

Metabolics (4 decks)

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