Immunity in the Gut Flashcards
2 branches of immune defenses
- Innate
2. Adaptive
Innate
- immediate
- physical, chemical, cellular barriers
- cells of the innate
- recognition of pathogenic associated molecular patters (PAMPS)
Adaptive
- Learned
- Antigen specific: B cells (antibodies) & T cells (cellular)
- immunological memory
Innate response time
Minutes/hours
Innate immunity diversity
a limited number of germ line encoded receptors
innate memory responses
none
innate self/nonself discrimination
perfect (doesn’t accidently recognize self as bad)
- no microbe specific patterns in host
innate soluble components of blood or tissue fluids
many antimicrobial peptides and proteins
innate major cell types
Phagocytes (monocytes, macrophages, neutrophils)
- killer (NK) cells
- dandritic cells
Adaptive immunity response time
days
adaptive specificity
- highly specific discriminates even minor difference in molecular structure
- details of microbial or nonmicrobial structure recognized with high specificity
adaptive memory responses
-persistent memory with faster response of greater magnitude on subsequent infection
adaptive self/nonself discrimination
- very good
- occasional failures of self/nonself discrimination result in autoimmune disease
adaptive soluble components of blood or tissue fluids
antibodies
adaptive major cell types
- T cells
- B cells
- antigen-presenting cells
Innate Immunity: Barriers
- Skin
- Mouth and upper alimentary canal
- stomach
- small intestine
- large intestine
- airway and lungs
Innate Immunity barriers: Skin
Antimicrobial peptides, fatty acids in sebum
Innate Immunity barriers: Mouth and upper alimentary canal
enzymes, antimicrobial peptides, and sweeping surface by directional flow of fluid toward stomach
Innate Immunity barriers: stomach
Low pH
- digestive enzymes
- antimicrobial peptides
- fluid flow toward intestine
Innate Immunity barriers: small intestine
- digestive enzymes
- antimicrobial peptides
- fluid flow to large intestine
Innate Immunity barriers: large intestine
- normal intestinal flora compete with invading microbes
- fluid/feces expelled from rectum
Innate Immunity barriers: airway and lungs
- cillia sweek mucus outward
- coughing
- sneezing expel mucus
- macrophages in alveoli of lungs
Innate Immunity: Beyond the first line of defense
- Complement System
- Recognition of pathogens by antigen presenting cells (APC)
- A-specific (non-specific) killing of pathogens
Complement system
protein complex lysing bacteria
Recognition of pathogens by antigen presenting cells (APC)
- monocytes/macrophages
- Dendritic cells
- B cells (also in adaptive immunity)
A-Specific (non-specific) killing of pathogens
- natural killer (NK) cells
- Neutrophils, mast cells, eosinophils
Cytokines
- 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
What are cytokines secreted from
monocytes, macrophages, T cells
-innate and adaptive
Examples of cytokines
- Tumor necrosis factor
- interleukin-1 (IL-1)
- interleukin-6 (IL-6)
Dendritic cell
- Antigen presenting cell
- have chemokine receptors to guide them –> chemokines (cytokines that attract)
- can present to B or T cells
Antigen-presenting cell
- 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
Adaptive or acquired immune system
- specific
- second line of defense
- humoral (B cells, antibodies)
- Cell-mediated (T cells)
Adaptive system cells
- T cells (T lymphocytes)
- T lymphocyte-antigen recognition (TCR)
T lymphocyte-antigen recognition
- 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
Adaptive system cells functionally divided into…
-T helper
-T cytotoxic
T regulatory Suppressor
T Helper Cells
- Activated by MHC on antigen-presenting cell - also need co-stimulatory receptor (CD4)
- Directs immune system action via cytokines
- Marker CD4 predominates
What does T Helper do?
- stimulates B lymphocytes to differentiate
- activates Tc and natural killer cells
- recruits and activates macrophages
B cells (B lymphocytes)
- Made in bone marrow
- recognize antigens to produce antibodies
- differentiate into plasma cells & memory cells
- Antibody (immunoglobulin)
Antibody (immunoglobulin)
- protein secreted by plasma cells
- membrane-bound on memory cells
- identifies and neutralizes foreign objects
- activate complement pathway
What are the different types of antibodies?
- IgM
- IgA
- IgG
- IgE
- IgD
IgM
1st produced
-precursor and changes to other antibodies
IgA
- Mucosal surfaces
- secreted in Breast Milk
IgG
- 75% of Ig in circulation, important in fetus/infant food sensitivity
- test for specific foods but not always helpful
IgE
- Primary antibody in allergies
- produced in response to allergen
IgD
levels increase in chronic infections
How b cell recognizes antigens
- B cell and antigen have to interact
- B cell makes a receptor
- T cell activates B cell
- B cell releases antibody
T cell responses –>
determine the type of immunoglobulin plasma cells produced
TH1 vs TH2 responses
- TH1 = intracellular antigens: bacteria, viruses, fungi, tumor cells
- TH2 = extracellular antigens: parasites, food and environmental antigens
TH1 mediated disease
-IgG Rheumatoid arthritis -Chrons disease -Multiple sclerosis -DM1
Multiple Sclerosis
- Autoimmune disease
- immune system attacts the central nervous system (identify self as nonself)
- Damages myelin, myelin-producing cells, and nerve fibers
Examples of Th2 mediated disease
- allergens: egg, peanut, ragweed, dust mites
- extracellular antigen- environmental and food allergens
- IgE
Th1 & Th2 similarities
-both promote an appropriate immune response to different types of infectious organisms
Eosinophilic esophagitis (EoE) cause
-genetic and environment
EoE presentation
- dysphagia
- heartburn
- food impaction
EoE diagnosis
15+ eosinophils per high-power field
EoE treatment
Dietary elimination and corticosteroids
EoE elemental formula
- Neocate
- ~90% effective (histological remission)
- difficult to follow
EoE dietary treatment
- elemental formula
- skin allergy test - directed elimination diet (25% histological remission)
- empirical elimination diet based on common food allergens (75% histological remission)
T Cytotoxic cells (Tc)
activated by MHC on antigen presenting cell (also need co-stimulatory receptor (CD8)
How is Tc activated
activated by Th cell through cytokines
-once activated - becomes cytotoxic T lymphocyte (CTL)
What does Tc eliminate?
Eliminates any cells that display antigen
- Tumor cells
- virus-infected cells
- tissue graft cells
Regulatory T cells (Tr)
- suppress immune system
- discriminate between self and non-self
- transforming growth factor-B and inerleukin-10 (anti-inflam)
- important in gut immunity
Primary lymphoid system
- Bone Marrow - B cells
- Thymus - T cells
Secondary lymphoid organs
- Lymph node, spleen, MALT, GALT
Tollerance vs. Inflammation
- 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
How do we balance between pathogenic protection and tolerance?
- Oral tolerance: systemic nonresponsiveness to oral antigens
- antigenic ignorance (barrier function)
- active tolerance (T regulatory cells)
Cells in the Intestine
- Epithelial cells
- paneth cells
- goblet cells
- enteroendocrine cells
- Intraepithelial lymphocytes (GALT)
Epithelial cells
Barrier and express PRR (TLR4)
Paneth cells
secrete anti-microbial peptides (SI)
Goblet cells
-produce mucus (LI)
Enteroendocrine cells
- CCK
- GLP-1
- PYY
Intraepithelial lymphocytes (GALT)
- mostly T cells
- 10-15 per 100 epithelial cells
Gut-Associated Lymphoid Tissue (GALT)
- gut barrier
- Follical-Associated Epithelium –> M cells & intraepithelial lymphocytes
- Dendritic cells
- Peyer’s patches
- Solitary lymphatic follicles
- Vermiform appendix
- Mesenteric lymph nodes
GALT Cells
- T cells
- B cells
- Macrophages (DC)
- IEL
Gut Barrier Components
- Commensal Bacteria
- Antimicrobial peptides (AMP)
- Follicle-associated epithelium (M cells, IEL)
- Dendritic Cells
- IgA secretion
Follicle Associated Epithelium
- Epithelium covering peyer’s patches, single lymphoid follicles
- Membranous Epithelial Cells (M cells (antigens continuously taken up transepithelially)
Dual humoral immune reaction
local secretion of antibodies (IgA)
-suppression of systemic immunologic responses to ingested antigens (oral tolerance)
M Cells
- 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(
Gut Immunity: Routes of Entry
- 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
Peyer’s Patch
- Aggregates of lymphoid tissue
- B cells
- Ileum
- Lamina propria to submuccosa
Transport od IgA into Gut lumen
- 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)
Solitary Lymphatic Follicles
- Smaller individual follicles
- line small bowel and colon
Vermiform Appendix
- Blind-ended tube located at the cecum
- rich in lymphocytes
Mesentery Lymph nodes
- Between layers of mesentary
- 100-150 lymph nodes
- lymphocytes migrate here from rest of GALT
- GALT stimulation can be systemic
