D1 Mucosal immunity Flashcards
Role of mucosal immune system
Discriminate antigens w/ no pathogenic potential (dietary proteins & commensal organisms) from antigens associated w/ potentially harmful microbe
Name Nonspecific (mechanical) immune responses
- Epithelial barrier:
Single cell layer, joined by tight junction proteins - Peristalsis: weep & sweep response: dislodges pathogens
- Diarrhoea
Name humoral (secreted) immune responses (7)
- Gastric acid (pH 1) - some pathogens restricted e.g. Worms - eggs need exposure to acid to hatch
- Lysozyme
- Peroxidase
- Mucin: mucus component
- Anti-microbial peptides
- Defensins
- Trefoil proteins
Define
1. MALT
2. GALT
and where are they located/ what do they contain
1. Mucosal associated lymphoid tissue (MALT) = Lungs, gut & urointestinal tract 2. Gastrointestinal associated lymphoid tissue (GALT) = gut - Mesenteric lymph nodes - Peyer’s patches - Lamina propria - Cryptopatches (mice)
what Ab present in gut lumen
+ name defence mechanism bacterial have against Ab
IgM, IgG and IgE
- IgA is the major class of antibody actively secreted into the gut lumen
- - prevents attachment of bacteria, toxins, viruses, absorption of foreign substances
+ Some bacteria produce proteases against the hinge region of IgA eliminating secondary effector function
Main class of TCR of IEL
- name role
- name unique feature
γδ T cells
- first line of defence
- maintain intestinal homeostasis
- bridge between innate and adaptive responses: dont require antigen processing/ MHC presentation of peptide epitopes
- Can be be triggered by alarm signals (HSP)
Explain how γδ Tc differ from αβ
7
- γδ Tc can develop extrathymically in liver and gut - (αβ tightly regulated w/in thymus
- γδ express RAG-1
- γδ homodimeric for CD8 i.e. αα CD8
- FcεR1γ chain acts as a component of the γδ Tc CD3 complex
- TCR γδ repertoire is polyclonal in newborns
- γδ may be important in mucosal defence early in life before αβ T cell and IgA responses are developed
- γδ Tc are a lot less diverse than αβ
Detailed functions of γδ IEL
- Surveillance of intestinal epithelial layer against microbial invasion & cytotoxicity via lysis of infected cells
- Support of epithelial cell growth & maintenance of epithelial barrier integrity (remove transformed cells)
- promotes/ abrogates OT
Describe normal antigen processing
Antigen presenting cells e.g. Macrophages/ DC –> encounters antigen, processes & breakdown into peptides.
Present by MHC-II to CD4 –> if this cell has received danger signal = upregulation of co-stimulatory molecules –> will activate Tc: produce cytokines
(costim CD80 & CD86)
Role of DC capturing antigen in mucosa
DC can push dendrites through gap of epithelial cells & grab antigen.
Processes –> enter lymph node & present to Tc
Absorbed pathogen can then:
1. go through endotheial venules –> capillaries (activate more Tc)
2. Present to Tc via its MHC
3. pass through epithelial cell to macrophages
How is lymphocyte intestinal tissue homing achieved
Will always try to go back to place of activation
Integrin a4B7 will bind addressin: MAdCAM
How is lymphocyte intestinal tissue homing achieved
Will always try to go back to place of activation
addressin: MAdCAM will bind Integrin: a4B7
((MAdCAM expressed on postcapillary venules in lamina propria & gut associated lymphoid e.g. PP, MLN))