Immunology Flashcards

1
Q

Innate immune system

A

First line of defence
Non-specific (antigen independent)
Unchanged over time - no memory
Fast to develop, within hours

SOLUBLE MEDIATORS - complement system, coagulation system, lactoferrin and transferrin, interferon, cytokines and chemokines (interleukins), acute phase proteins (CRP)

CELLULAR MEDIATORS - monocyte, dendritic cells, neutrophils, eosinophils, mast cells, basophils, NK cells

ANATOMICAL BARRIERS - skin and epithelial layers

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2
Q

Adaptive immune system

A

Specific lymphocyte activity
Develops slowly over days
Has memory and augments with time
Immune tolerance to self
2 arms - humoral (antibody production) and cellular immunity

SOLUBLE MEDIATORS - complement system components, antibodies, cytokines
CELLULAR MEDIATORS - T-cell, B-cell, antigen-presenting cells

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3
Q

Immune tolerance

A

Process where immune response to self-antigens is prevented
Central (in thymus and bone marrow, begins in fetal life), peripheral and acquired (includes that which occurs in pregnancy) tolerance
Prevents development of autoimmunity

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4
Q

Hypersensitivity

A

TYPE 1 - mast cell mediated
- mast cell degranulation, assoc with IgE
- eg hayfever, allergy

TYPE 2 - complement mediated
- antibody dependent, activation of complement via classical pathway via IgM and IgG
- eg haem disease of newborn, pernicious anaemia, transfusion, Graves’ disease, MG, autoimmune disease, food allergies

TYPE 3 - antibody-antigen complex mediated, IgG
- immune complex deposition, develops in 10 days
- eg RA, SLE, glomerulonephritis

TYPE 4 - T-cell mediated
- cell-mediated reaction, delayed response (48hrs) involving T-cells
- eg graft rejection, contact sensitivity, mantoux test

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5
Q

Transplantation

A

Grafts:
Autograft - from same person
Allograft - from different individual of same species
Xenograft - from different species

Rejection:
Hyperacute = severe immunological response to graft, within minutes-hours (due to pre-formed host antibodies)
Acute = primary immune response to graft, within days-weeks (due to donor leukocytes)
Chronic = months-years

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6
Q

Types of vaccine

A

Attenuated (live)
- mumps, measles, rubella, BCG, polio PO, yellow fever, VZV

Killed
- cholera, polio IM, rabies, hepA

Acellular toxoid - tetanus, diphtheria
Acellular organism subunits - pertussis, hepB, influenza, recombinant vaccine of virus-like particles (VLPs) eg HPV vaccine Gardasilµ

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7
Q

Complement system

A

30 proteins synthesized in liver, inactive form in plasma
Part of innate and adaptive immune systems
10% of total body protein

All 3 pathways produce protease C3 convertase, to cleave C3 to C3a and C3b:
CLASSICAL
- requires antibody as trigger, fixation of C1 to IgG/M
ALTERNATIVE
- requires antigen as trigger
MANNOSE-BINDING LECTIN

Overall functions - opsonization (via C3b), leukocyte adhesion, chemotaxis and activation (via C5a), cell lysis via membrane attack complex (MAC), inflammatory mediator (by activation of lipoxygenase pathway of arachidonic acid metabolism by C5a), increase in vascular permeability (via C3a and C5a)

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8
Q

Specific complement component functions

A

C3b - opsonization

C3a and C5a - anaphylatoxin activity, stimulate histamine release

C5a - chemotaxis, activates lipoxygenase pathway

C5b and C6-9 - cell lysis via MAC

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9
Q

Interferons

A

Glycoproteins, class of cytokines
Production induced by microorganisms (via infected host cells) and cytokines
3 major classes of IFN - IFN-1 (α), IFN-2 (β and γ), IFN-3

Functions:
- anti-viral (inhibits replication)
- anti-oncogenic
- activates NK cells and macrophages
- upregulation of major histocompatibility complex class 1
- increased p53 activity (promotes apoptosis)

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10
Q

C reactive protein

A

Acute phase serum protein
Coats pathogens to promote opsonisation
Produced by liver
Gene on chrom1

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11
Q

ESR

A

Non-specific measure of inflammation
Basal ESR higher in females

Increased in inflammation
Decreased in sickle cell, polycythaemia, heart failure

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12
Q

Cytokines

A

Group of proteins responsible for cellular signalling
Produced by leukocytes
Water soluble, glycoproteins

Classification of cytokines:
- promoters of Th-1 helper cells (IFN-γ and Il-2)
- promoters of Th-2 helper cells (IL-4/5/6 and TGF-β)
- non-immunological cytokines (EPO and thrombopoietin)
- chemokines
- colony-stimulating factor

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13
Q

IL-1 and TNF

A

2 major cytokines mediating inflammation
Act on endothelium, leukocytes, fibroblasts

Induce systemic acute phase reactions - fever, increased sleep, decreased appetite, increased acute phase proteins, neutrophilia, shock

Effects on endothelium - ↑leukocyte adherence, ↑prostacyclin synthesis, ↑procoagulant activity, ↑anticoagulant activity, ↑IL-1/6/8 and ↑PDGF, ↑synthesis of NO

Effects on fibroblasts - ↑proliferation, ↑collagen synthesis, ↑collagenase secretion, ↑protease secretion, ↑prostaglandin E synthesis

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14
Q

EPO

A

Glycoprotein produced by kidney
Regulates RBC production

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15
Q

Thrombopoietin

A

Glycoprotein produced by kidney, liver, striated muscle, stromal cells in bone marrow
Regulates production of platelets (megakaryocytes)

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16
Q

Cellular mediators

A

Originate from bone marrow
eg myeloid cells (leukocytes), lymphoid cells (B-cells, T-cells, NK cells)
Myeloid progenitor cells give rise to erythrocytes, platelets, leukocytes, dendritic

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17
Q

Leukocytes

A

GRANULOCYTES - neutrophils, eosinophils, basophils
- granules store antibiotic compounds and enzymes, utilised in digestion of endocytosed particles
- neutrophils cannot replicate
- eosinophils combat parasitic infections, assoc with atopy/allergy, stain pink with eosin (red dye, acid loving), have bilobed nuclei, induce mast cell degeneration, contain histamine, plasminogen, lipase, major basic protein
- basophils 0.5% of circulating, respond to inflammatory immune response and in formation of acute and chronic allergic diseases, including anaphylaxis, asthma, atopic dermatitis and hay fever, produce histamine and serotonin that induce inflammation, and also heparin

AGRANULOCYTES - monocytes, macrophages (monocyte outside blood vessels), lymphocytes
- only macrophages can form giant cells

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18
Q

Lymphocytes

A

80% T-cells
15% B-cells
10% NK cells - specific for MHC class 1, have CD16 receptors. Decidual NK cells (present in pregnancy) stain positive for CD56 but negative for CD16.

19
Q

T-cells

A

Principal mediators of adaptive immune system
Do not recognise free antigens, recognise antigens bound to MHC molecules

  1. Th-1 and Th-2 express CD4 surface protein
    - MHC class 2 restricted
    - express α or β T-cell receptors
  2. T cytotoxic and suppressor express CD8 surface protein
    - MHC class 1
    - express α or β T-cell receptors
  3. T-cells expressing both CD4 and CD8
    - MHC unrestricted
    - express γ or δ T-cell receptors
20
Q

T-cell development

A

Originate in bone marrow, mature in thymus
Undergo clonal deletion - where T and B cells expressing receptors for self-antigens are deactivated

21
Q

Th-1 and Th-2 cells

A

Th-1
- mediate cellular response
- interact with monocytes, macrophages, CD8 positive T cells
- produce pro-inflammatory cytokines INF-γ, TNF-α, IL-2 and IL-12
- decrease in pregnancy

Th-2
- mediate humoral response
- interact with B cells
- produce anti-inflammatory cytokines IL-4, IL-5, IL-10 and IL-13
- increase in pregnancy

22
Q

B-cells

A

Originate in bone marrow, differentiation induced by Th cells and antigens
Differentiate into - plasma cells (secreting antibodies) and memory cells
On surface - Fc receptors, complement receptors, MHC class 2
Produce immunoglobulin IgG/A/M/E/D

23
Q

Lymph nodes

A

Cortex
- outer (nodular) contains B cells
- inner (juxtamedullary) contains T cells

Medulla
- medullary cord contains plasma and T cells
- medullary sinuses contains histiocytes (immobile macrophages) and reticular cells

24
Q

MHC

A

= major histocompatibility complex
Gene on short arm of chrom6

Class 1
- expressed on all nucleated cells
- 3 major sub-loci genes HLA- (ABC) and 3 minor sub-loci genes (EFG)
- presents intracellular antigens

Class 2
- expressed on antigen-presenting cells
- 3 major sub-loci genes, 3 minor, all HLA-D
- presents extracellular antigens to T-lymphocytes

25
Q

Antigen presenting cells

A

B-cells
Dendritic cells
Macrophages

26
Q

Immunoglobulins

A

= antibodies

Double stranded Y shaped structure - 2 heavy chains at the stalk (constant region), 2 light chains bound by disulfide bonds
- Variable region that forms antigen-binding site (Fab - fragment antigen binding) region, light and heavy chain portions
- Constant region (Fc - fragment crystallizable region) receptor binding site, made of 2 heavy chains only

5 classes of immunoglobulin - IgG, IgA, IgM, IgE, IgD

27
Q

5 classes of immunoglobulins

A

IgG - 75% of total Ig pool
- monomer
- 4 subtypes
- in RhD treatment

IgA - 20% total Ig pool
- dimer
- 2 isoforms
- found in mucosal epithelium (GI, resp, urinary tracts)
- secreted in breast milk so key for neonatal immunity

IgM - 5% total Ig pool
- 1st to be produced in infection
- pentamer, heaviest molecular weight
- intravascular only

IgE - binds to basophil and mast cells
- monomer
- involved in allergy and parasitic infections

IgD - <1% total Ig pool
- monomer

28
Q

Immunohistochemistry

A

Process of identifying antigens in cells by using antibodies
- 2 methods - direct (using only one antibody), indirect (using two antibodies)
- widely to diagnose abnormal cells
- diagnostic markers are CK7/20/Ca199/Ca125 etc

29
Q

Diagnostic IHC markers

A

CK 7 +ve in lung, breast, ovarian, cervical, bladder adenocarcinomas

CK20 +ve in GI epithelium, urothelium, CRC, pancreatic duct, mucinous ovarian

Ca19-9 +ve in GIT carcinomas, pancreaticobiliary, mucinous ovarian

Ca 125 +ve in ovary, cervical, endometrial, GIT, breast, thyroid adenocarcinomas

Ca15.3 +ve recurrent breast carcinoma

Calretinin and inhibin +ve in ovarian sex cord stromal tumour

CEA (oncofetal glycoprotein) +ve in GIT, lung, medullary carcinoma of thyroid

Epithelial membrane antigen +ve in mesotheliomas

30
Q

SLE

A

Systemic lupus erythematosus
1/1000 women (9x more in women)

Features - joint arthritis, skin (macular rash, photosensitivity, Raynaud’s), haematological (anaemia, thrombocytopenia, leucopenia), renal, neurological

Autoantibodies - ANA, Anti-DSDNA, Anti-Ro, Anti-La, anticardiolipin antibodies

31
Q

SLE in pregnancy

A

Pregnancy increases risk of SLE relapse

Complications of SLE during pregnancy - miscarriage, PET, FGR, fetal death, pre-term, congenital heart block (high perinatal mortality rate), cutaneous neonatal lupus (transient, in 5% of anti Ro/La +ve mothers)
- but complications reduced if SLE in remission at time of conception, and no renal disease

32
Q

Multiple sclerosis

A

Autoimmune disorder of CNS, autoantibodies directed against myelin-producing oligodendrocytes
Destruction of myelin due to cell-mediated immunity by Th-1 cells
Diagnosis needs two demyelinating lesions in brain or spinal cord disseminated in time or space - MRI, CSF (raised IgG and oligoclonal bands), visual evoked potential
Relapsing-remitting (85%) or primary progressive
- relapse rate decreases in pregnancy due to decreased cell-mediated immunity and increased humoral immunity. But then increases by 50% in first 3mo PP.
0.1% prevalence in UK, higher risk in family
Treatments - corticosteroids, IFN beta, plasma exchange, glatiramer acetate

33
Q

Myasthenia gravis

A

1/10,000-1/50,000
Due to IgG antibodies against nicotinic acetylcholine receptor on motor endplate
Only affects skeletal muscles
Tensilon test to diagnose

Pregnancy complications - arthrogyposis multiplex congenital (fetal contractures due to lack of movement, as transplacental myasthenic antibodies) in 20%, pre-term, FGR
- 40% have exacerbation, 30% remission, 30% no change in disease progress

34
Q

Fetus immunology

A

Semi-allograft

Antigenically competent - IgM produced at 11weeks, T-cell slower, NK cell activity 50% that of adults, cytotoxic T cell 1/3 that of adults

Maternal Ig transfer to fetus - only IgG can cross placenta, starts at 12w and peaks at 32w, passive

35
Q

Uterine immune system cells

A

Lymphocytes - 70% NK cells, 10% T-cells, virtually no B-cells
Uterine large granulolymphocytes
Macrophages
Dendritic cells

1:1 T-cells to B-cells
CD8 T cells>CD4 T cells

36
Q

Maternal immunology

A

Humoral and cellular responses
- humoral tends to dominate (Th-2 cell mediated) hence SLE worsening
- progesterone suppresses Th-1 cells hence RA (Th-1 dependent) improves in pregnancy
Increased complement activation
Increased acute phase protein levels
Decreased NK cell activity
Increased endothelial cell activation mediated via VEGF and PAI-1
Decreased IgG, IgA, IgM

37
Q

Fetal cells

A

2 immunological interfaces:

Extra-villous cytotrophoblast/decidua in early pregnancy
- expresses MHC1 but not MHC2 antigens

Syncitiotrophoblast/maternal blood in late pregnancy
- direct contact with maternal cells
- does not express MHC1 or MHC2 antigens, so does not stimulate cytotoxic activity
- inhibits NK cell activity

= HLA-A and HLA-B are downregulated
HLA-E and HLA-G are upregulated

38
Q

Immuno-contraception

A

Not in humans but in animals, birth control using body’s immune response to avert pregnancy
- antibodies act on sperm surface, zona pellucida or inplantation-associated antigens eg hCG

39
Q

IgA

A

Two subtypes (1&2)
Plasma IgA is mainly monomeric
10-15% of total immunoglobulins
Activates complement via the alternative (not classical) pathway.
Does not cross the placenta and does not sensitize mast cells
Not absorbed from the GI tract in neonates (IgG is absorbed)

IgA is the major class of Ig in secretions - tears, saliva, colostrum, mucus - so important in local (mucosal) immunity
- in secretions is dimeric

40
Q

IgD

A

Main function is as receptor on naive B-cells
Makes up to 1% of serum immunoglobulin, is not secreted in epithelia and does not activate complement or sensitize mast cells
Does not cross the placenta

41
Q

IgE

A

Monomer
Important in immediate hypersensitivity reactions including anaphylaxis
Sensitizes mast cells and binds to macrophages and polymorphs
Does not activate complement
Raised in parasitic infections and responsible for atopic allergy

42
Q

IgG

A

Monomer with 4 subtypes
Crosses the placenta - actively transported - concentration in cord blood slightly higher than that in maternal blood at term
Causes Rhesus disease
Feed-back inhibition of B-cells, activates antibody-dependent cell mediated cytotoxicity, activates complement
75% of Igs

43
Q

IgM

A

Pentamer
Primary activator of complement and serves as naive B-cell receptor
First immunoglobulin to be synthesised during B-cell maturation
Does NOT bind to mast cells, neutrophils or macrophages
Expressed on the surface of B cells (monomer) or secreted (pentamer)
Does not cross the placenta - the presence of IgM in fetal blood indicates fetal infection and fetal antibody production

44
Q

Phagocytic cells

A

Monocytes in circulation, macrophages out
Neutrophils
Dendritic cells
(less powerfully - basophils and eosinophils)