Immune recognition and immune tolerance Flashcards

1
Q

Main cellular players in immune response

A

Innate:
-Dendritic cells
-Macrophages
-Neutrophils

Adaptive:
-CD4+ helper T cells
-CD8+ cytotoxic T cells
-B cells

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2
Q

Downside of random T cell receptor diversity

A

-Self reactivity is possible
-Autoimmune conditions

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3
Q

What does immune tolerance allow?

A

-Prevents autoreactivity but permits appropriate anti-pathogen responses

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4
Q

How do T cells develop

A

-Develop in the thymus gland
-T cell precursors are seeded from bone marrow into thymus
-Multi-lobular organ containing
organised zones with several specialized cell types

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5
Q

What is thymic education of T cells?

A

-Thymocytes from bone marrow are seeded into thymus, where they express functional T cell receptor
-Learn which accessory molecule (CD4+ or CD8+) is more appropriate for that T cell
-Learn how to use them safely & within the laws of MHC restriction

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6
Q

What happens to T cells that can’t express a functional T cell receptor

A

-Only T cells capable of forming alpha beta T cell receptor survive
-Cells with non-functional T cell receptor die by apoptosis

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7
Q

How do T cells positively select for self MHC

A

-Thymic cortex presents MHC I and II
-If T cell has affinity for MHC II, it stops expressing CD8+ and will graduate as a CD4+ receptor
-If T cell has affinity for MHC I, it stops expressing CD4+ and will graduate as a CD8+ receptor
-Some T cells don’t have affinity for MHC I or II - they apoptose and die

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8
Q

What is negative selection of T cells

A

-Eliminates high affinity self-reactive T cells
-T cells with high affinity for self peptide and self MHC are eliminated
-T cells with low/moderate affinity are allowed to graduate
-Takes place in Thymic Medullary Epithelial cells (TMECs)

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9
Q

What Tissue Restricted Antigens (TRAs) do Thymic Medullary Epithelial Cells (TMECs) express?

A
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10
Q

What can failure of TRA expression lead to?

A

-Failure of Thymic Medullary Epithelial Cells (TMECs) to express tissue restricted antigens leads to
autoimmune diseases
E.g. Autoimmune Polyglandular Syndrome type 1

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11
Q

Thymic education flow chart

A
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12
Q

What are the 2 peripheral mechanisms of immune tolerance

A

-Anergy
-Regulatory T cells

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13
Q

What is anergy?

A

-Signal 1 without signal 2 causes anergy
-Anergy is when T cells remain in circulation but are unresponsive to future stimulation
-Anergy occurs under steady state conditions: when not activated by infection/inflammation, APC do not express co-stimulatory molecules

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14
Q

3 reasons why anergy is important?

A

-Important for tolerance to antigens
not expressed in thymus
-Important for tolerance to food antigens
-Important for tolerance to commensal bacteria

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15
Q

What are regulatory T cells and how do they work?

A

-T cells dedicated to controlling or suppressing effector T cells
-Directly alter function of effector T cells to stop them proliferating/secreting cytokines
-Reduce costimulation and alter cytokine production by APCs to stop messages getting to effector T cells

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16
Q

What are the 2 main types of regulatory T cells?

A

nTreg:
-‘naturally occurring’
-Produced in thymus
-Respond to self antigens
-Protection for autoimmunity

aTreg:
-‘adaptive, i.e. induced’
-Develop in periphery
-Constant low level exposure to antigen
-Protection from autoimmunity
-Regulation of responses to food antigens

17
Q

T regs and autoimmune diseases

A

-Individuals lacking nTreg develop multiple autoimmune diseases
-Individuals with autoimmune diseases often have impaired Treg function
-Tregs are targeted in immunotherapy of autoimmune diseases

18
Q

2 methods to prevent function of Tregs?

A

-anti- tumour responses
-vaccination

19
Q

PAMPs and PRRs

A

-Tissue dwelling APC recognise bacterial/viral products as
‘foreign’ via pathogen associated molecular patterns (PAMPs)
-PAMPs are conserved products of microbial metabolism which are:
-unique to microbes
-invariant between members of a given class
-vital for microbial fitness
-Immune system has a range of pattern recognition receptors (PRRs) which recognise PAMPs

20
Q

Where and how does activation of naive lymphocytes occur?

A

-Lymphoid organs
-Here they secrete combination of cytokines and chemokines which lead to upregulation of adhesion molecules on the high endothelial venules that line the arterioles going into the lymph node
-This, along with the chemokines leads to increase of naive T cell migration into lymph node
-Signals which allow T cells to leave lymph node are blocked
-Causing increase in size and cellularity of lymph node -inflammation

21
Q

What is signal 3 in this image?

A

-Cytokine production by dendritic cell that instructs T cell to polarise into the type of T cell that is good at clearing the bacterial infection

22
Q

Differentiation of CD4+ T helper cells

23
Q

What happens when T cells encounter inflamed tissue?

A

-Cross over from bloodstream into tissue
-CD4+ T cells will secrete cytokines (IFN-y, TNF-A) which help neutrophils and macrophages clear pathogens
-CD8+ T cells will kill cells that present peptide on MHC I
-Some T cells migrate out of tissue and become memory cells

24
Q

What happens when infection is removed?

A

-the innate system is no longer activated - inflammation subsides
-antigen is cleared - the stimulus for T cells is removed
-most effector T and B are removed - death by neglect/cytokine
starvation
-apoptotic cells are removed by macrophages

25
Q

Where are immunological memory cells stored?

A

Secondary lymphoid organs:
-bone marrow
-lymph node
-spleen

Plasma cells:
-Secrete high affinity antibodies
-Live for years
-Protective immunity

Memory B cells:
-High frequency
-Develop into plasma cells

Memory T cells:
-High frequency
-Immediate effector function