Immunology Flashcards
(44 cards)
Innate immune system
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
Adaptive immune system
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
Immune tolerance
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
Hypersensitivity
TYPE 1 - IMMEDIATE mast cell mediated
- mast cell degranulation, assoc with IgE
- eg hayfever, atopy, anaphylaxis
TYPE 2 - CY’TWO’TOXIC complement mediated
- antibody dependent, activation of complement via classical pathway via IgM and IgG on cell surface
- eg Graves’ disease, myasthenia gravis
TYPE 3 - FREE (serum immune complex) antibody-antigen complex mediated, IgG
- can lead to immune complex deposition, develops in 10 days
- eg RA, SLE, glomerulonephritis, vasculitis
TYPE 4 - DELAYED T-cell mediated (no antibodies, not part of humoral)
- cell-mediated reaction, delayed response (48hrs) involving T-cells
- eg granuloma TB or sarcoidosis
Transplantation
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
Types of vaccine
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
Complement system
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)
Specific complement component functions
C3b - opsonization
C3a and C5a - anaphylatoxin activity, stimulate histamine release
C5a - chemotaxis, activates lipoxygenase pathway
C5b and C6-9 - cell lysis via MAC
Interferons
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)
C reactive protein
Acute phase serum protein
Coats pathogens to promote opsonisation
Produced by liver
Gene on chrom1
ESR
Non-specific measure of inflammation
Basal ESR higher in females
Increased in inflammation
Decreased in sickle cell, polycythaemia, heart failure
Cytokines
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
IL-1 and TNF
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
EPO
Glycoprotein produced by kidney
Regulates RBC production
Thrombopoietin
Glycoprotein produced by kidney, liver, striated muscle, stromal cells in bone marrow
Regulates production of platelets (megakaryocytes)
Cellular mediators
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
Leukocytes
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
Lymphocytes
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.
T-cells
Principal mediators of adaptive immune system
Do not recognise free antigens, recognise antigens bound to MHC molecules
- Th-1 and Th-2 express CD4 surface protein
- MHC class 2 restricted
- express α or β T-cell receptors - T cytotoxic and suppressor express CD8 surface protein
- MHC class 1
- express α or β T-cell receptors - T-cells expressing both CD4 and CD8
- MHC unrestricted
- express γ or δ T-cell receptors
T-cell development
Originate in bone marrow, mature in thymus
Undergo clonal deletion - where T and B cells expressing receptors for self-antigens are deactivated
Th-1 and Th-2 cells
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
B-cells
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
Lymph nodes
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
MHC
= 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
