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Defence on Body Surfaces

Veterinary ImmunologyVeterinary education, 3rd year

31/03/2019

Defence on the Mucosa

Defence on the Mucous Membranes

Physical defences• Skin, mucous membranes, hair/feather, mucous• Movements: palpebra reflex, peristalsis, retroperistalsis• Flushing: saliva, tear, urine, sweating

Chemical barrier• Unfavorable pH for microorganisms• Antimicrobial materials

Biological barrier• Microbiome

Defence of cells• Tight junctions between epithelial cells• Ciliary movement in the upper respiratory tract

Entry of the Pathogens

https://viralzone.expasy.org

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Entry of the Pathogens

Vírusreceptorok: https://viralzone.expasy.org/956?outline=all_by_species

• SALT: skin associated lymphoid tissue• MALT: mucosa associated lymphoid tissue

⁻ BALT: bronchus associated lymphoid tissue

⁻ NALT: nasopharynx associated lymphoid tissue

⁻ GALT: gut associated lymphoid tissue⁻ CALT: conjuctival associated lymphoid tissue⁻ LALT: larynx associated lymphoid tissue⁻ VALT: vulvo-vaginal associated lymphoid tissue⁻ O-MALT: organized associated lymphoid tissue⁻ D-MALT: diffuse associated lymphoid tissue

Terminology

SALT SALT

Keratinocytes• Can be acticated by microbial stimuli, physical influences, UV

radiation, cytokines and neuropeptides• After the activation they produce inflammatory (IL-1α, TNF)

and anti-inflammatory (IL-1Ra, IL-2R2) cytokines and antimicrobial peptides (β-defensin)

• To the effect of IFN they produce chemotactic materials• MHCII-antigens and costimulatory molecules on the

membrane (APC)

Mast cells• Production of cytokines and bioactive materials (leukotrienes,

histamine) based on the activating Atg

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• The proffesional APCs of the skin are Langerhans-cells and dermal DCs

• They migrate to lymph nodes, and presentate in the paracortical part of the cortex

• Liberated cytokines and chemokines enhance expression of adhesion molecules and help the release of NG, Eos and NK-cells

• Some of the circulating memory T-cells carry CLA (Cutaneous Lymphocyte Antigen) epitopes

SALT

• The T-cell mediated immune response in the skin is mainly the IV. type hypersensitivity reaction (Delayed Type Hypersensitivity Reaction – DTH)

• It is generated by low molecular weight soluble antigens or chemicals

• The secretory IgA is also present in the skin secretions and protects against various bacteria

• IgE-mediated hypersensitivity reactions can also take place in the skin, which effector cells are dermal mast cells

SALT

MALT

• MALT: mucosa associated lymphoid tissue⁻ BALT: bronchus associated lymphoid tissue

⁻ NALT: nasopharynx associated lymphoid tissue

⁻ GALT: gut associated lymphoid tissue⁻ CALT: conjuctival associated lymphoid tissue⁻ LALT: larynx associated lymphoid tissue⁻ VALT: vulvo-vaginal associated lymphoid tissue⁻ O-MALT: organized associated lymphoid tissue⁻ D-MALT: diffuse associated lymphoid tissue

• 200-300 m2 surface in an adult• Tonsils, appendix, Peyer's plaques, folliculi• 2/3 of immunoglobulin production of the body

and more lymphocytes as in all other parts of the body

Main task: local immune response• Complete exclusion of various infectious agents

and other antigens in the intestinal lumen• Induction of tolerance

GALT

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GALT

Effector site Inductive siteOrganized lymphoid tissue

Laminapropria

M cell: microfolded cell (Atg transport from the lumen)SED: subepithelial dome (DC: atg transport to the zone

of T-cells)TDA: T-dependent territoryIEL: intraepithelial lymphocyte

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Lymphocytas arrived through HEV. Receptors CCR7 and L-selectin are attractedto kemokines CCR19 and CCR21 wich selected by secunder lymphoid tissues(not just Peyer’s patches).

Naive Cells

Lymphocytasrecirculatethrought HEV

(HEV)

M-Cell

CCL19 és CCL20

Activation of DC-cell–T-cell–B-cell

• Activated lymphocytas homing– Lymphocytes express homing receptors because

of retinol acid produced by DC

– Homing receptors will direct lymphocytes to the lamina propria

– OR the activated lymphocytes leave the Peyer’s patches throught lymphatic ducts to a mesenteric lymph node

• DC presenting an Atg migrates to lymp nodes to activate naive T-cells

Homing of T-cells, B-cells

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Activation of Lymphocytesin a Lymp Node

• B-cell mature to plasma cell in lymp node

• Activated cytotoxic and helper T-cells and IgMproducing B-cells leave the lymp node through the efferent lymphatic duct

• IgM producing plasma cell has class switching to IgA producing plasma cell that is helped by IL5 and IL6 produced by Th-cell

Homing

Lamina Propria

Laminapropria

Epithel cells

CD8+ T-cells

CD4+ T-cells, lotsmemorycell

• Cells migrate from efferent lymphatic ducts to the lamina propria through an artery

• Chemokins and adhesion receptors help this migration from blood vessels to the lamina propria

• Matured cells activate in lamina propria

Cytotoxic T-cell

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Phagocytosis of DC

By opsonisation of IgA Between cells By apoptosis caused by CD8+ cells

DC-cell

DCs rarely reach out to epithelial cells because of the tight junctions

• DC presents antigens also on MHCII!

• Activated DC migrates to a mesenteric lymp node through the efferent lymph duct, than activate naive cells…

• Neutrophil granulocytes also have phagocytotic activation

• IL-10 produced by DC stops the activation of cytotoxic cells

After Activation of DC

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Thank you foryour attention!