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OPTM5101/5102 > Week 7 - Immunity, ocular surface immunology > Flashcards

Week 7 - Immunity, ocular surface immunology Flashcards

1
Q

What are the functions of monocytes and macrophages?

A
  • Generally the 1st phagocytic cell to sense an invading microbe
  • Orchestrate the response to infection. Recruit neutrophils and other leukocytes to area
  • the major cells in chronic inflammation
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2
Q

What are neutrophils?

A

WBC - 70% - involved in killing pyogenic bacteria and fungi
No mitochondria
Granules - myeloperoxidase, lysozyme, acid hydrolases
Major cells in acute inflammation

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3
Q

How does phagocytosis occur?

A
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4
Q

What is the role of eosinophils?

A

Eosinophils release granule content to kill large pathogens that cannot be engulfed by phagocytes.
Also play a role in allergic disease - release histamines

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5
Q

Basophils and Mast cells

A

Stimulated to release granule contents upon
- when allergens cross-link IgE molecules on surface (i.e. specific immunity)
- binding to complement factors C3a and C5a

Granules contain hisamine and heparin
- cause adverse symptoms of allergy
- Immunity against parasites by enhancing acute inflammation: attraction of neutrophils and eosinophils

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6
Q

Natural killer cells

A

non-phagocytic
Target virally infected and tumour cells

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7
Q

Secreted products include?

A

1) complement
2) opsonins - complement (and antibody for adaptive)
3) acute phase proteins
4) cytokines - interferons, cytokines

Mediating protection before the development of adaptive immunity

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8
Q

What are complement?

A
  • Synthesised by hepatocytes
  • Circulate in plasma and place of activation to set up an enzymatic cascade
  • system is controlled to protect the host
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9
Q

Functions of complement system

A

Initiate acute inflammation - by direct activation of mast cells
Chemotaxis - attraction of neutrophils
Opsonisation - enhancement of attachment of the microbe to the phagocyte
Killing - of the microbe by activating the membrane attack complex

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10
Q

Acute phase proteins

A

Produced in liver
macrophages and neutrophils produce cytokines in response to tissue injury/infection, which leads to stimulus to produce more APP.
Maximise activation of the complement system

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11
Q

Cytokines

A

Small molecules secreted by cells in response to a stimulus
Induce growth, differentiation, chemotaxis, activation, enhanced cytotoxicity
Same cytokine can be produced by different cell populations, or can induce different functions in different cell types

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12
Q

Other proteins of the Innate System

A

Fibronectin
Lysozome
Lactoferrin

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13
Q

Signs of inflammation

A

Redness
Swelling
Heat
Pain

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14
Q

Acute inflammation

A

Onset is rapid and short duration
Characterised by presence of oedema and neutrophils

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15
Q

Chronic inflmmation

A

Prolonged duration
Associated with the presence of lymphocytes and macrophages
Process in which acute inflmmation, tissue destruction and attempts to repair are all occuring at the same time
e.g.
TB, RA, chronic lung disease,

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16
Q

The 3 step process for acute inflammation

A

1) Alterations in vascular calibre
- increase blood flow to affected area

2) Increased vascular permeability
- enables plasma proteins and leukocytes to leave circulation

3) Leukocytes accumulate at injury site and become activated
- enables the offending agent to be eliminated

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17
Q

Vascular change - Acute inflammation

A

Transient vasoconstriction

Vasodilation
Increased blood flow causes heat and redness and oedema
Maximise movement of plasma proteins and cells to site of injury
Mediators include:
- histamine
- nitric oxide (NO) on smooth muscle

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18
Q

Increased vascular permeability - Acute Inflammation

A

Caused by:
1) formation of endothelial gaps in post-capillary venules by contraction of the cells and separation of inercellular junctions
2) Direct endothelial injury
3) Leukocytes - dependent injury
4) leakage from new blood vessels
- Decreased intravascular osmotic pressure
- increased fluid osmotic pressure
therefore –> oedema

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19
Q

Leukocyte extravasation - acute inflammation

A

Leukocytes at site of injury -
- kill microbes
- Get rid of necrotic tissue
- ingest offensive agents

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20
Q

What leukocytes are involved?

A

Neutrophils
- first 6-24 hours
Monocytes/macrophages
- recruited later 24-48 hours

21
Q

Chemotaxis

A

Leukocytes migrate to site of injury along a chemotactic gradient
Chemoattractants
- exogenous bacterial products
- endogenous chemical mediators

22
Q

Leukocyte activation

A

Leukocytes express a number of receptors that are involved in their activation

  • toll-like recceptors
  • 7-transmembrane G-protein coupled receptors
  • Cytokine receptos
  • opsonin receptors
23
Q

effects of mediators

A
24
Q

Role of mediators in inflammation

A
25
Q

Outcomes of Acute inflammation

A
26
Q

Features of chronic inflammation

A

1) infiltration of monocellular cells
- macrophages, lymphocytes and plasma cells

2) tissue destruction: induced by persistent agent or by inflammatory cells

27
Q

Granulomatous inflammation

A

A special type of chronic inflammation
Collection of macrophages, epitheloid cells and giant cells
- Uveitis

28
Q

Innate vs adaptive immunity

A
28
Q

What are the two branches of the adaptive immune response?

A

1) Humoral (antibody M mediated) immune responses
- a specific defense provided by B cells secreting antibodies
- targets bacteria, viruses, parasites and fungi

2) Cell mediated immune response
- Response mounted by T cells
- Targets pathogens infected cells and cancers

29
Q

Monocytes/macrophages

A

Monocytes leave the blood and become macrophages

Macrophages are large phagocytic cells that engulf:
- Antigens
- remove dead and dying cells

30
Q

Dendritic cells are?

A

Dendritic cells are sentinel cells: present antigen to T cells
Activate naive T cells

31
Q

Mature dendritic cells

A

Antigen presenting cells

Reduced capacity for antigen uptake
increased antigen presentation and T cell stimulation
Redistribution of MHC II from intracellular compartments to cell surface

32
Q

MHC I (endogenous antigen) versus MHC II (exogenous antigen)

A

The MHCEI and MHCEII molecules show preferential restriction to T cells bearing CD8 or CD4 respectively

This is related to the observation that CD8 binds to the polymorphic a3 domain of MHCEI,
whilst CD4 interacts with the b2 domain of MHCEII

33
Q

Lymphocytes

A

The most common types of lymphocytes are
B lymphocytes (B cells): responsible for making antibodies
Differentiate into plasma cells
Present antigen

34
Q

Lymphocyte - T cells

A

Helper T cells enhance the production of antibodies by B cells

Cytotoxic T lymphocyte (CTL) that kill virus and tumour cells

Regulatory T cells - required for immunological tolerance, they shut down T cell mediated immunity towards the end of a reaction to restore homeostasis

35
Q

Residence of B and T cells

A

Both B and T cells also take up residence in lymph nodes, the spleen and other tissues where they:
- encounter antigens
- continue to divide
- mature into fully functional cells

36
Q

Adaptive immunity in the eye - HSV keratitis

A

Herpes simplex virus keratitis
- vision loss due to corneal scarring and neovascularisation caused by inflammation

Virus can replicate in the corneal epithelium, stroma and endothelium and can result in inflammation, ulceration, vascularisation and oedema

37
Q

Overview of the innate and the adaptive immunity system

A
38
Q

Overview of the B and T cells

A
39
Q

Eye Associated Lymphoid Tissue

A

IgA positive lymphoid tissue in lacrimal gland

Includes conjunctival ALT — diffuse and follocular lymphocyte accumulations (B and T cells)

Lacrimal drainage ALTs — canaliculae and lacrimal mucosa – diffuse and follocular accumulation (T and B cells)

40
Q

CALT clinical distribution

A

CALT concentrated across cornea during eyelid closure

Cornea has relatively low concentration of immune cells in structure

CALTS situated to support corneal immune protection

41
Q

CALTs - clinical manifestations

A
42
Q

Process of CALT movement

A
43
Q

LDALTS

A

Demonstrate diffuse and follicular accumulations of immune cells

Secretory form of IgA throughout mucosal epithelium

Diffuse layer of sub-epithelial igA-positive plasma cells

44
Q

LDALTs - follicular accumulations

A

follicular lymphocyte accumulations probably larger in drainage system than conjunctiva

Central mass of B-cells, surrounded and infiltrated by T cells, germinal centre apparently less dense

45
Q

What is the function of the corneal barrier function

A

Squamous epithelial cells a very effective, renewable barrier, tight junctions form barrier

Effective secondary protection through tight packing of basal epithelium

46
Q

Other protective biological agents

A

Antimicrobial - lysozyme, lactoferrin, mucin, small antimicrobial proteins

Immune modulators – complement, interleukins, surfactant protein

Some produced and secreted in lacrimal gland, others by conjunctiva and lacrimal mucosa

Immune and pro-inflammatory mediators - higher concentrations in closed eye

47
Q

Summary of tear movement and immunity

A

OPTM5101/5102 (17 decks)

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