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Introduction to Clinical Immunology > Major cells of the Immune System > Flashcards

Major cells of the Immune System Flashcards

1
Q

what is the functions of neutrophils?

A

circulate in blood (~10 hours) then migrate into tissues
accumulate in sites of tissue injury and bacterial infection via chemotaxis
major role in phagocytes, produce reactive oxygen and nitrogen species in process called respiratory burst, produce antimicrobial peptides, produce NETs

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2
Q

how are neutrophils identified?

A

multi-lobed nucleus and granular cytoplasm
CD10, CD13, CD15, CD16, CD33, CD141, CD178, CD200R
12-17um; 40-95% of total WBCs; 1.6-7.5x10^9/L

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3
Q

disease associations with neutrophils?

A

increase in bacterial infection, neutrophilic malignancies.
decreased function in chronic granulomatous disease and chediak-higashi syndrome

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4
Q

what type of cells are neutrophils?

A

granulocytes

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5
Q

what is the function of eosinophils?

A

activated by IgE cross-linkage of FceRI
release pro-inflammatory mediators (peroxidase, major basic protein, cationic protein)
granule proteins are capable of killing larger parasites
short lived in peripheral, blood lasting (up tp 12h); remain in tissues up to 12 days when unstimulated

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5
Q

what type of cells are eosinophils?

A

granulocytes

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6
Q

eosinophil identification

A

Bi-lobed nucleus and eosin-stained granules
1-5% of blood leucocytes; 0.1-0.5x10^9/L
CD9, CD23, CD32, Siglec-8, FcERIII

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7
Q

Disease associations with eosinophils

A

inappropriate activation in allergic response
eosinophilia usually as a result of a parasitic infection, allergic or autoimmune disease

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8
Q

what type of immune cells are basophils?

A

granulocytes

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9
Q

function of basophils

A

activated when antigen binds and cross-links FceR1 and IgE
toxic degranulation releases vasoamines and eicosanoids such as histamine and leukotriene C4, which increase vascular permeability

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10
Q

identification of basophils

A

large cytoplasmic granules stained by basic dyes and a bi-lobed nucleus
up to 0.5% leukocytes in peripheral blood
CD69, CD123, FceRI

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11
Q

disease asscoiations with basophils

A

inappropriate activation in allergy
basophilia can be a sign of chronic inflammation

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12
Q

what is the function of mast cells?

A

tissue-resident cells (skin, connective tissue, respiratory / digestive / genitourinary mucosal epithelium )
degranulation occurs when an antigen binds to the IgE/FceRI complex present on the surface of mast cells
toxic mediators released include: histamine, tryptase, peroxidase, serotonin, heparin
main role in multicellular parasitic infections

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13
Q

identification of mast cells

A

round nucleus and large dense cytoplasmic granules
FceRI, CD117/c-Kit, CD23, CD203c

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14
Q

disease associations with mast cells

A

allergic diseases including asthma, eczema and life-threatening anaphylaxis; IgE binds to FceRI at rest, then cross-linked by allergen
mastocytosis-skin lesions, nausea / vomiting / diarrhoea / flushing / palpitations

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15
Q

what type of cells are tissue-resident macrophages?

A

myeloid cells

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16
Q

function of tissue-resident macrophages

A

typically first response to pathogens in tissue; therefore stimulate recruitment of further immune cells
phagocytosis and antigen presentation
tissue-specific macrophages are foetally derived and self renew in their specific tissue (not from blood monocytes)
derived from embryonic cells during development
specific types are resident throughout the bodys tissues
Kuppfer (liver) / Langerhans (skin) / microglial (neural) cells

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17
Q

identification of tissue-resident macrophages

A

CD14, CD16. MHCII
large cells in tissues, 25-80um diameter

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18
Q

disease associations with tissue-resident macrophages

A

hyper-activation can lead to histiocytosis (excessive breakdown of host tissue)

19
Q

what kind of cells are monocyte-derived macrophages

A

myeloid cells

20
Q

what is the function of monocyte-derived macrophages

A

inflammatory M1 macrophages are derived from monocytes in the peripheral blood
activated by IFNy and GM-CSF, recognition of microbial PAMPs, inflammatory mediators, complement proteins
main function is phagocytosis
secrete inflammatory cytokines: TNFa, IL-6, IL-8, IL-1B
Antigen presentation via MHC class II; activates T lymphocytes
alternatively activates M2 macrophages have a role in tissue repair and wound healing

21
Q

identification of monocyte-derived macrophages

A

CD14, CD16, MHCII
Irregular morphology, ‘kidney-bean’ nucleus (monocyte), phagosomes visible

22
Q

disease associations with monocyte-derived macrophages

A

chronic myeloid leukaemia

23
Q

what type of cells are dendritic cells?

A

myeloid / lymphoid cells

24
Q

what is the function of dendritic cells

A

potent/professional antigen-presenting cell; migrate to lymphoid organs to active and polarise adaptive immune response
capture antigen by phagocytosis and pinocytosis
act as sentinels continuously sampling the local tissue microenvironment
recognise danger through expression of various receptors (e.g. TLR)
activated by microbial products and inflammatory cytokines
subtypes; may be conventional (myeloid-derived) or plasmacytoid (lymphocyte-derived)

25
Q

identification of dendritic cells

A

constitutively express MHC class II
extensive network of dendrites
cDC, CD11b, CD11c

26
Q

disease associations with dendritic cells

A

can act as a reservoir of antigen, including viruses (ongoing viral infection)

27
Q

what type of cells are NK cells?

A

innate lymphoid cells

28
Q

what is the function of natural killer cells

A

ILC Type 1 are cytotoxic - best characterised are natural killer cells (100-600 cells/ul in peripheral blood)
activated by IFNa, IFNB, TNFa
cytolytic action through granzyme and perforin release
perform antibody-dependent cell cytotoxicity via FcyRIII
contact-dependent cytotoxicity by targeting cells lacking expression of MHC Class I
MHC class I engages inhibitory receptors known as killer immunoglobulin receptors (KIRs) on the NK cell, to inhibit NK cell function

29
Q

identification of NK cells

A

classic lymphoid cell morphology but lack the expression of unique-cell surface molecules (lineage-negative)
express combination of CD16/CD56 (low or high)

30
Q

disease associations with NK cells

A

absent in some variants of severe combined immunodeficiency

31
Q

function of cytotoxic T lymphocytes

A

cytotoxic T cells primarily function to kill other target cells such as cancer cells or virus infected cells
kill infected host cells through release of perforin and granzymes; and stimulate apoptotic signalling via Fas/Fas ligand co-ligation on cell surface
activated by peptide antigens expressed by major histocompatibility class I molecules found on the surface of all nucleated cells
respond via antigen-specific T cell receptor and require co-stimulation by dendritic cells
200-900 cells/ul in peripheral blood

32
Q

identification of cytotoxic T lymphocytes

A

CD23, TCR, CD8

33
Q

disease associations with Cytotoxic T lymphocytes

A

increased in viral infections, where up to 10% of all circulating T lymphocytes can be clonally-derived ion response to infection
cellular mediators of cytotoxic effects in autoimmunity

34
Q

Helper T -lymphocytes Th1, Th2, Th17 function

A

naive helper T lymphocytes are activated antigenic peptides presented by antigen presenting cells on MHC class II, using their antigen-specific TCR
400-2100 cells/ul in peripheral blood (all CD4+ cells)
Th1 activated in response to intracellular pathogens (viruses, mycobacteria); secrete IFNY to activate cytotoxic T lymphocytes, NK cells and macrophages
Th2 activated in response to extracellular pathogens; promote immunoglobulin class-switching
th17 activated in response to fungi and extracellular bacteria; activate neutrophils

35
Q

identification of t helper lymphocytes th1/th2/th17

A

all express CD3, CD4, TCR
Th1 = T-bet, secrete IFNY/TNFa
Th2 = GATA-3, secrete IL-4/IL-5/IL-23
Th17 = RORyt, secrete IL-17A/IL-17F/IL-22

36
Q

Disease associations with T helper cells

A

decreased in HIV (secondary immune deficiency)
th1 - organ specific autoimmune disorders (e..g coeliac), graft vs host disease, transplant rejection
th2 - allergy (promotes class-switching to IgE)
th17 - inflammatory disorders (IBD, psoriasis)

37
Q

function of regulatory T cells

A

suppress immune responses to self antigens to protect against autoimmunity
regulate immune responses to commensal organisms and maintain tolerance in the gut

38
Q

identification of T regulatory cells

A

CD3, CD4, TCR, CD25, FOXP3
Secrete IL-10 and TGFB
typical lymphocyte morphology; small, agranular, large nucleus

39
Q

disease associations with T regulatory cells

A

IPEX syndrome - genetic variants in FOXP3 lead to Treg deficiency - causes severe immune dysregulation and systemic autoimmunity

40
Q

naive and memory B lymphocytes function

A

activated by the presence of antigen binding to BCR (surface immunoglobulin)
responsible for developing antigen-specific immunoglobulin
can present antigen to T lymphocytes via MHC class II
100-500 cells/ul in peripheral blood
some antigen-activated B lymphocytes develop into memory B cells in secondary lymphoid organs
memory B lymphocytes are responsible for rapid secondary immune responses

41
Q

identification of naive and memory B lymphocytes

A

CD19/CD20/ surface immunoglobulin (part of BCR)
CD27 on memory B lymphocytes

42
Q

disease associations with naive and memory B lymphocytes

A

immunoglobulin disorders (reduced/absent Igs) due to defects in B-cell development, either in the bone marrow or during activation by antigen (e.g. failure to class-switch from IgM)
B-lymphocyte malignancies due to high level of somatic mutations in an antigen-driven response

43
Q

function of plasma cells

A

differentiate from activated from B-lymphocytes
high-level immunoglobulin secretion in immune response
migrate to bone marrow where they provide long-lived low-level specific immunoglobulin secretion (e.g. vaccine responses)

44
Q

identification of plasma cells

A

CD38/CD138
Reduction in CD19 and CD20 compared to B lymphocytes
peripheral nucleus with halo (large golgi apparatus for immunoglobulin secretion)

45
Q

disease associations with plasma cells

A

multiple myeloma; clonal malignancy of plasma cells usually with high-level secretion of clonal immunoglobulin
autoantibody secretion in autoimmune disease

Introduction to Clinical Immunology (7 decks)

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