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III > WK 7- MUCOSAL IMMUNOLOGY > Flashcards

WK 7- MUCOSAL IMMUNOLOGY Flashcards

1
Q

What are the 4 compartments that make up the immune system- describe why they are immune barriers

A
  1. Peripheral lymph nodes and spleen-> contain B and T cells
  2. Skin protects against external environment
  3. MALT-> protects internal surfaces of the body, includes GALT (gut), BALT (bronchus), genitourinary tract and NALT (nasal)-> all have immune cells within the tissues
  4. Body cavities-> eg peritoneum/pleura-> have commensal flora that line the tracts and act to destroy pathogens
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2
Q

Why does the MALT component only exist in certain parts of the body

A

MALT exists at areas that are vulnerable to infection due to their once cell thick layer of epithelium, and their activity in; gas exchange (BALT), food absorption (GALT), reproduction (genitourinary) and Sensory activities (NALT)

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3
Q

What Ig is the most dominant in the MALT

A

IgA-> produced by plasma cells in sub-epithelial tissues

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4
Q

What is the common mucosal immune system

A

Describes how priming of lymphocytes in one mucosal tissues can induce protective immunity at other mucosal surfaces-> Ig produced at one mucosal site will be produced at all mucosal sites

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5
Q

How can the common mucosal immune system occur?

A

Circulation of lymphocytes within the mucosal immune system is controlled by tissue specific adhesion molecules and chemokine receptors (tissues have receptors that will attract gut-primed IgA producing B cells

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6
Q

What structures does the GALT consist of

A
  1. Tonsils and Adenoids-> rings of lymphoid tissue that surround the entrance to the GI and resp tracts
  2. Appendix
  3. Peyers Patches-> important site for induction of immune response in the SI
  4. Solitary lymph nodes/scattered lymph cells
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7
Q

What are some of the protective mechanisms displayed by the GALT (immune and non-immune)

A

Immune; IgA, cell mediated immunity, T cells, DC, Macrophges, NK cells
Non-Immune: mucous, microflora, motility, gastric acid, epithelial cell barrier

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8
Q

What are intra-epithelial lymphocytes and where are the found

A

Cells found within the epithelium of mucosal tissues and act like innate immune cells-> include alpha-beta T ells and gamma-delta T cells

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9
Q

What other cells (apart from IEL) are found within the GALT

A

Spread throughout the lamina propria are activated B cells (secrete IgA), T cells (innate), mast cells, DC, NKC

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10
Q

What are isolated lymphoid follicles

A

Known as effector structures- contain lots of plasma cells and B cells

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11
Q

What is Peyers Patches

A

Patches of masses of lymphocytes arranged in follicles covered by specialised epithelium that line the SI

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12
Q

What are the specialised cells that line the epithelium of peyers patches

A

Microfold/M cells: take up antigen by endo/phagocytosis-> antigen is then transported across the M cell in vesicles and released at basal surface–> antigen is then bound by D which then activate T cell and immune response

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13
Q

What are the 6 ways in which antigens are able to be captured by APC in mucosal tissue

A
  1. Nonspecific transport across the epithelium (ie. diffusion or by M cells)
  2. Enterocytes-> capture and internalise the antigen:antibody complex and transport across the epithelium though the FeRn (receptor) on their surface-> at basal membrane the DC cells expressing FeRn pick up the complex and present to T cells
  3. Enterocyte infected wit pathogen ill undergo phagocytosis by DC and pathogen will move across boundary
  4. DC/NK cells send out projections into the epthelium and pick up/internalize antigen form the lumen
  5. Goblet cells will uptake the antigen
  6. Capture of antigen by intraepithelial DC
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14
Q

How are lymphocytes lured back to their place of activation

A

-Chemokines CCL21 and CCL19, which are released from the lymphoid tissues and bind the receptor CCR7 on naïve lymphocytes→ If the naive lymphocytes do not see their antigen, they exit from the lymphoid organ via the lymphatics and return to the bloodstream
-Gut specific homing of antigen-stimulated T and B cells is by expression of homing molecules CCR9 and integrin alpha4:beta7→ This binds to the mucosal vascular addressin MAdCAM-1
which is found mainly on the endothelial cells that line the blood vessels within the gut wall

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15
Q

What are the 4 steps in the movement of lymphocytes from site of activation to delivery at effector site

A
  1. M cells bring in antigens and display them to DC
  2. DC present antigen to T and B cells which then become activated
  3. Activated cells move via the lymphatics into the mesenteric lymph node
  4. From here they exit via lymph and move into the thoracic duct and travel throughout the body via blood
  5. When cell arrives back at activation site it will leave blood via BV and move into the lamina propria where it will sit as an effector cell
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16
Q

What common feature to IgM and IgA have in common

A

Both have a J-chain attached to the poly Ig receptor that allows it to be transported across the epithelial surface into the lumen

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17
Q

What are the actions of IgA

A

Neutralises viruses and bacterial enzymes, activates complement by the alternative pathway, binds antigens, binds to Fc-alphaR to opsonise antigens, initiates inflamm cytokine release

18
Q

Where is IgA secretion most concentrated

A

Gut secretions

19
Q

What is oral tolerance

A

Refers to a state of systemic hyporesponsiveness (unresponsiveness) induced by food antigen (doesn’t react to presence of food antigens-this is the normal state of the GIT)

20
Q

What causes oral tolerance

A

May involve: T cell anergy (no co-stimulation), Deletion of antigen specific T cell by apoptosis (due to overwhelming presence of antigen) or development of reg T cells that suppress Ag-specific responses

21
Q

What occurs if an antigen has a PAMP and induces and inflammatory response?

A

Most antigens induce tolerance, but if an antigen induces inflammation, protective immunity will develop instead of tolerance

22
Q

Why is oral tolerance important

A

Do not want to trigger an immune response everytime you eat-> oral tolerance allows the mucosal system to focus on pathogens/Ag’s that could cause harm to the host

23
Q

What causes food allergies

A

Off balance of Treg and T effector cells-> more effector cells/lack of Treg will cause developement of food allergy
-the reaction is driven by IgE -> when person is exposed to allergen, will trigger Th2 cells to release IL-4 and produce IgE-> IgE will crosslink and cause released of cytokines/granules from mast cells and basophils

24
Q

Why are children more likely to have allergies? Why are they able to grow out of them?

A

When baby is developing in utero it is not exposed to a range of antigens and has no commensal flora therefore is more sensitive to antigens-> as the child grows and the immune system develops/increase in commensal flora- the allergy can disappear

25
Q

What are the 2 immunostimulatory hormones

A

Prolactin and Growth hormone

26
Q

What are the 2 immunosuppressive hormones

A

Adrenocorticoids, glucocorticoids

27
Q

How do immune cells interact with the nervous tissue to produce feelings/behaviour associated with sickness

A
  1. Systemic cytokines cause release of local cytokines (from APC)
  2. Local cytokines act on peripheral nerves that then stimulate the vagus nerve
  3. The vagus nerve triggers release of cytokines in the CNS
  4. Cytokines in the CNS act on the hypothalamus and trigger behaviour associated with sickness
28
Q

How can stress impact on the immune system

A
  1. stress will trigger the release of ACTH fro the hypothalamus-> 2. ACTH acts on the adrenal cortex to cause release of IL-4 that increases differentiation of Th2 cells but will then suppress differentation of Th1 cells and APC–> by depressing Th1 and APC activity there will be re-emergence of dormant disease/increased susceptibility to infection, and by increase Th2 you get increased degranulation of immune cells creating ‘sick’ symptomsq
29
Q

What are the 3 types of leukocytes in the endometrium

A

Marcophages, T lymphocytes and IEL (and Nk cells)

30
Q

What are the effects of progesterone and oestrogen on the immune capability of female repro tract

A

Oestrogen and progesterone increase the capacity to eliminate bacteria through increasing neutrophils (highest in late secretory stage)

31
Q

If a woman is infertile, what kind of antibodies are most likely in her cervical mucous- what kind of Ig are they most likely to be

A

Anti-sperm antibodies- IgA and IgG

32
Q

True or false- seminal fluid is immunosuppressive

A

True- needs to be able to suppress the immune response against sperm/seminal protein whilst in the female repro tract in order for conception to take place

33
Q

What occurs if the blood testes barrier is destroyed

A

The testes are an immune privileged area-> as sperm antigens are not presented to developing T cells, they are seen as foreign and will be attacked by the immune system-> the epididymis epithelial (Blood testes) barrier prevents sperm antigens from getting into the blood and from antibodies getting into the testes. If this barrier is disturbed, the immune system will develop antibodies against the sperm, which may lead to infertility

34
Q

What is an immune privileged area

A

Areas that are able to tolerate the introduction of antigens without eliciting an inflammatory immune response-> eg testes, eye and brain

35
Q

Theoretically, should a developing fetus be able to survive in the mothers body? If not, why

A

Theoretically, as the fetus will inherit 50% of genetic material from the father, a maternal immune response should result soon after blastocyst implantation in uterus (as the fathers genetic material is foreign)-> but this does not occur

36
Q

How do trophoblastic cells avoid destruction by the immune system-> 3 mechanisms

A
  1. Reduced or modified transplantation antigen expression of the trophoblast- don’t express MHC 1 so can’t be viewed as foreign
  2. Modulation of the maternal immune system to protect the foetus from recognition and attack
  3. Placenta acts as a barrier that maternal lymphocytes can not penetrate
37
Q

True or false: innate immunity is enhanced during pregnancy

A

True- uterine and placental cells express cytokines that cause increased activity of local maternal T cells

38
Q

What HLA classes do trophoblast cells NOT express

A

HLA-A and HLA-B

39
Q

What HLA classes are expressed by trophoblast cells

A

HLA-G-> non classical MHC1

AND HLA-E (role in preventing attack by NK cells)

40
Q

What is the function of HLA-G in preventing attack of trophoblast cells

A

Not clear- but could be preventing natural killer cell attack by acting on inhibitory sensors, preventing CTL (CD8) and activation of Th2 cells

41
Q

What hormones does the trophoblast secrete that are immunosuppressive

A

HCG= human chorionic gonadotrophin hormone

Progesterone

42
Q

In pregnancy what immune cells are increased and which are suppressed

A

Increased= Th2, peripheral blood monocytes and granulocytes, increased FcR in macrophages (increased phagocytosis)
Suppressed; Th1, IFN-g production, NK cells

III (13 decks)

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