Immunological Functions Flashcards by New a

How big is immune system?

approx 10^12 cells

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Features of innate immune system?

Prevents infection + avoids disease
Non-specific
No memory
Mediated by: macrophages, epithelial barriers, secretions

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Features of adaptive immune system?

Responds to infection + prevents disease
Highly specific response to targeted microbe
Memory
Mediated by: lymphocytes, antibodies

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eg of systemic immunity?

Bone marrow, spleen, thymus lymph system, blood circulation

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eg of mucosal immunity?

Mucous membranes : eyes, nose, mouth, lungs, gut, GU

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Features of mucosal immune system?

-Mucosal surfaces: oral, nasal, lacrimal surfaces gastrointestinal tract, bronchial tract, GU, mammary glands
-Colonised by microbes
-Main route of entry for infectious microorganisms
-Large SA specialised for absorption :
gut ~ 200m2 skin ~2m2

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Innate mechanisms of mucosal immune system?

mucin, peristalsis, antimicrobial peptides, proteins

eg lysozyme, lactoferrin, phagocytes

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Adaptive mechanisms of mucosal immune system?

mucosal/secretory immune system

discriminates between harmful pathogens + harmless antigens – foods + commensal bacteria

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eg of innate mucosal barrier?

Natural barriers 
(eg stomach)
Mucin
Peristalsis
Proteolysis
Microvillus membrane or squamous cell

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Immunological of mucosal barrier?

Secretory IgA/IgM

IgG

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Role of gingival crevice?

epithelial layer of the gum that contains immune cells

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Lymphoid cells in gut?

Intra-epithelial lymphocytes
Lymphocytes and macrophages scattered in the lamina propria
Peyer’s patches

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How pathogens get across gut surfaces?

-Breach of epithelium via ulcer so pathogen is getting
into sub-lamina (connective tissue under epithelium)
-Langerhan cell have extensions that go out which sample in gut lumen
*pathogens enter + withdrawn back in macrophage
*pathogens adhere to extension + when macrophage moves off it brings in pathogen
-Peyer’s patches (collection of lymphocytes) that actively sample gut lumen

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How’s peyer’s patch linked to outside lumen?

via M-cell which is doing sampling,

rest of top covered by epithelium

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Diff types of lymphoid cell?

intra-epithelial lymphocytes
lymphocytes
macrophages
=scattered in lamina propria + Peyers patches

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Describe peyer’s patch experiment

-injected antigen into gut area w/o Peyer’s patch, ligated
sides, stitched up
-injected antigen into gut area with a Peyers patch
-w/o Peyers patch = weak antibody response, upstream or downstream also weak response
-Peyer’s patch one = immune response, further up + down gut

Role of M cell?

-Microfold appearance
-Sits on top, samples gut fluid lumen, sends it down to
lymphocyte underneath

What can gain entry via M cells + eg?

Particles + macromolecules eg cholera toxin, latex particles, horseradish peroxidase, ferritin
Viruses eg poliovirus, HIV
Parasites eg Cryptosporidium
Bacteria eg Cholera, salmonella, Campylobacter Yersinia, Shigella, E. coli

Migration of immune cells from Peyer’s Patches?

pathogen + lymphocytes
triggers immune response
B-lymphocyte mature -> B-cell
migrate away from Peyers patch
drain to local lymph node
continue to mature
enter back into lymph circulation back into blood circulation

Diff between mucosal vs systemic immune system?

Systemic immune system lymphocytes stay in blood circulation + produce antibodies
Mucosal lymphocytes come back to mucosal immune system back to gut they originally came from + upstream gut

What’s common mucosal response?

encountering antigen at 1 mucosal site –> immunity across all mucosal sites eg immune response in gut, antibodies in saliva, tears but lymphocytes must move home to a secretory gland before they produce antibodies

What are mucosal antibodies?

Mostly SIgA
Found in all secretions + breast milk
Provide passive immune protection in new-born

Features of IgG in blood?

normal : light + heavy chain

Features of serum IgA?

-Composed of light chain + heavy chain.
mucosal surfaces :
-2 structures dimerized with a joining protein can bind to 4 antigens so difficult for pathogens to burrow via mucosal surface
-Wrapped up by another protein called secretory component protecting antibody from degradation by proteolytic enzymes we produce or produced by bacteria

Mechanisms of action of antibodies IgG in blood?

- Bind to key functional sites on microbes + toxins to blocks its functionality - Agglutination - IgG induces inflammation, by activating complement pathway. - Recruits immune cells.

Mechanisms of action of antibodies IgA in serum?

- Block activity + agglutinate - Dosn't induce inflammation in gut - Doesn't bind immune cells

Approaches to oral immunisation?

``` Attenuated virus (eg polio) Attenuated recombinant bacterial mutants (eg Salmonella typhi) Mucosal adjuvants (eg cholera toxin) Liposomes, microspheres, Capsules Transgenic edible plants ```

Systemic immune response to vaccines?

``` -1st injection produce small antibody response, 1 or 2 weeks to develop, then it would die down -booster injection produce massive response, mediated by IgG --> immunity, years for this antibody response to decline ```

Mucosal immune response to vaccines?

- 2nd vaccine very similar + immunity takes a nosedive after - like having 2 primary responses - no memory - use GM plants for Hep B vaccine

Oral vaccine delivery using GM plants?

- hep B surface antigen gene transferred from yeast into plant cell (potato) - potato plants regenerated from transformed cells - hepatitis vaccine correctly expressed by potato plants - GM potatoes harvested that contain hepatitis vaccine - feed uncooked tubers to animals or humans - analyze immune response

Oral tolerance?

- Orally delivered antigens suppresses systemic immunity - If antigen 1st encountered through mucosal immune system then systemic immune system can be unresponsive (tolerised) to that antigen

Practical considerations of oral tolerance?

- Tolerance to dietary foods, breakdown to food allergy - Oral vaccination + safety - Treatment + prevention of autoimmune diseases

Is oral tolerance a contra-indication for oral immunisation?

1. Tolerance: Soluble antigens Vaccination: Antigen/adjuvant or other formulations 2. Tolerance: Repeated sustained doses Vaccination: Limited number of immunisations 3. Tolerance: High doses (eg 20-500mg bolus) Vaccination: Low dose (usually in μg range)

SUMMARY

- Mucosal immune system stimulated by antigens independently of systemic immune system - 2 immune systems not entirely isolated - Site of stimulation at specialised sites in GALT, BALT, NALT. - Major immunological factor is secretory IgA, which is expressed at all mucosal sites - Most microbial infections start at mucosal sites, but most vaccines are administered systemically