Introduction to Immunology Flashcards
what are the physical barriers to infection?
skin and epithelial mucosa
Secretions
normal flora
how does the resp/GI/GU systems prevent infection?
Antimicrobial peptides secreted by epithelial cells in resp/ GI/ GU tracts (also secreted by phagocytic cells) – have anti-bacterial properties – inc cecropins, magainins, defensins
how do secretions prevent infection?
o Sweat, tears, saliva, gastric acid, sebaceous glands, mucus, breast milk
o Saliva – lysozyme (digests proteoglycan in bacterial cell walls), IgA, IgG and lactoferrin
IgA prevents attachment of microbes and may neutralise microbes insitu
Lactoferrin sequesters free iron (used my microbes) and has direct antimicrobial effects – bind to lipopolysaccharide part of bacterial membrane, causes oxidative damage of the membrane, which results in cell lysis.
how does normal flora prevent infection?
o Commensal bacteria – compete for nutrients, prevent attachment, release fatty acids, and antibacterial proteins, prevent invasion
o Lactobacilli in vagina – cause acidic pH (4.0-4.5)
what are the physiological defences agains infection?
o Temperature (fever), pH, location of immune cells within the bloodstream (can readily attack when and wherever microbes invade)
how do burns allow infection?
and dry mouth
allow access and more optimal growing conditions
how does cystic fibrosis lead to increased infection?
The increased viscosity of secretions in cystic fibrosis reduce the ability of the cilia to clear infections effectively, leading to repeated infections, and allows damage to the lungs to occur.
how does normal gut bacteria contribute to infection?
without normal gut flora keeping gut pathogens under control, other bacteria can increase in number and cause problems, such as a toxic megacolon here as a result of clostridium difficile infection.
name the molecules of the innate immune system
complement
interferon
cytokines
acute phase reactants
name the receptors of the innate immune system
pattern recognition receptors: toll-like receptors, mannan binding like lectin
name the molecules of the adaptive immune system
immunoglobulins
cytokines
name the receptors of the adaptive immune system
TCR - t cell receptor
BCR - b cell receptor
MHC/HLA
discuss the innate immune system
• First line of defence • Rapid • Already present at birth • Some specificity • No memory – same response with re-exposure • Detects alteration from haemostasis o Damage recognition – host o Pathogen recognition – pathogen
name the 5 activators of inflammation in the innate system
damage to tissues e.g. burns microbial infection complement activation autoimmunity allergens
name the mechanism involved in inflammation in the innate immune system: damage to tissues
prostaglandin
leukotriene
name the mechanism involved in inflammation in the innate immune system: microbial infection
exotoxins, endotoxins
TLRs - macrophages, mase cells
IL-1, IL-6, IL-12, TNF-a
NO
name the mechanism involved in inflammation in the innate immune system: complement activation
C3a
C5a
name the mechanism involved in inflammation in the innate immune system: autoimmunity
immune complexes
complement
T-cel
name the mechanism involved in inflammation in the innate immune system: allergens
mast cell degranulation
histamine
name the stages in the innate immune system
inflammation recruitment of immune cells activation of complement opsonisation phagocytosis
what happens as a result of inflammation in the innate immune response?
vasodilation loosening of endothelial tight junctions increased cell adhesion molecules chemotaxis smooth muscle contraction
with a diagram describe the recruitment of immune cells in the innate response
see notes
draw a series of diagrams to show the activation of complement in the innate response
see notes
what is opsonisation?
to prepare for eating
reduced repellent negative charge of cell membrane to allow phagocyte to come closer
give examples of opsonins
complement
antibodies
plasma proteins
use a diagram to describe phagocytosis
- phagocyte moves towards microbe
- phagocyte attaches to microbe via opsonin
- endocytosis of microbe within phagosome
- phagosome fuses with lysosome
- oxygen dependent species result in microbe death
- release of microbe products
what is the life span of neutrophils?
few days
what are the main functions of neutrophills?
phagocytosis
degranulation
what are the degranulation products in neutrophils?
peroxidase
defensins
acid and alkaline phsophatases
what are the main tagetts of neutrophils?
bacteria
fungi
name the receptors found on neutrophils
o Toll like receptors o Complement o IgG o Chemokine IL-8 o Chemoattractant C5a o ICAM + VCAM – adhesion to endothelium
life span of eosinophils
8-12 days
function of eosinophils
extracellular killing via degranulation
what are the components of eosinophil degranulation?
peroxidase
major basic protein
IL-8, cytokine
what induces degranulation of mast cels and basophils?
major basic protein
main target for eosinophils
parasites
what do IL-5 and IL-3 stimulate?
production and release of eosinophils from BM
expression of IgE receptors on eosinophils
life span of basophils
few days
where are basophils predominately found?
within circulation
main fuction of basophil
degranulation
degranulation products of basophils
histamine
prostaglandins and leukotrienes
cytokines: IL-4, IL-3
main target of basophils
parasites
receptors found on basophils
o Surface bound IgE
o C3a, C5a anaphylatoxins
o Toll-like receptors
draw: neutrophil
see notes
draw: eosinophil
see notes
draw: basophil
see notes
draw: mast cell
see notes
draw: macrophage
see notes
life span of mast cells
long
where are mast cells found?
present in tissues exposed o external environment e/g/ skin, lung, gut
what is the function of mast cells?
degranulation through cross linking of IgE receptors
degranulation products of mast cells
o Histamine o Proteases o Reactive oxygen species o Cytokines – TNF alpha, IL-4, IL-3 o Leukotrienes and prostaglandins
main targets for mast cells
parasites
receptors found on mast cells
o Surface bound IgE o C3a and C5a o Damage associated molecular patterns o Toll like receptors o Complement o Others: that can bind drugs e.g. opioids and antibiotics
what are macrophages? give examples of where they are found
• Tissue-based monocytes o Kupffer (liver), microglial (brain), mesangial (kidney)
life span of macrophages
months to years
main functions of macrophages
phagocytosis
antigen presentation to T cells
release TNF-a, IL-2, IL=6
receptors found on macrophages
o Toll like receptors
o Fc for IgG and IgA
o C3b
o MHC class I and II
draw: dendtiric cell
see notes
draw: NK cell
see notes
where are dendritic cells found?
tissues exposed to external environment
once activated where do dendritic cells migrate to? how?
lymphoid tissues
binding to microbes via pattern recognition receptors
main functions of dendritic cells
o Phagocytosis
o Antigen presentation to CD4+ T cells via MHC II
Shape enhances activation
o Secrete TNF alpha, IL-12, IL-23
discuss follicular dendritic cells
o Mesenchymal origin
o Within follicles of lymphoid tissue
o Do not express MHC II but interact with B cells
what are NK cells activated by?
IFN and macrophage derived cytokines e.g. IL-2
main functions of NK cells
o Bind to and kill virus-infected and cancerous cells –reduced MHC I expression
o Release of perforin + granzymes from granules
Perforates cell, inserts proteolytic enzymes, induces apoptosis
o Also induce apoptosis by binding to FasL molecules on virus
o Release IFN gamma and TNF alpha
what are NK cells inhibited by?
normal self signal via MHC I
receptors found on NK cells
o Killer activation receptors o Killer inhibitory receptors – recognise MHC class I o Toll-like receptors o Fc receptors o Adhesion molecules o FasL
name the common cytokines
IL-1, 2, 4, 5, 6, 8, 12
what produces IL-1
macrophages and epithelial cells
what produces IL-2
t cells
what produces IL-4
Th2 cells
mast cells
what produces IL-5
Th2 cells
mast cells
what produces IL-6
t cells
macrophages
what produces IL-8
macrophages
monocytes
keratinocytes
fibroblasts
what produces IL-12
b cells
macrophages
function of IL-1
fever lymphocyte activation acute phase proteins mobilisation of PMNs activates endothelium
function of IL-2
induces proliferation of T and NK cells
function of IL-4
induces B cell activation adn Th2 IgE production
inhibits Th1 response
function of IL-5
induces eosinophil growth and differentiation
B cell activation and IgA response
function of IL-6
lymphocte activation, fever, acute phase proteins
function of IL-8
chemotaxis of PMNs
function of IL-12
induces Th1 and activates NK cells
inhibits Th2 response
what produces TNF-alpha?
macrophages
T cells
what produces IFN-gamma
Th1 cells
NK cells
what produces prostaglandins and leukotrienes?
chemoattract t cells
eosinophils
mast cells
basophils
what produces nitric oxide
macrophages
PMNs
functions of TNF-a
increases vascular permeability
induces fever
functions of IFN-gamma
activated macrophages and PMNs
Induces Th1
Inhibits Th2
functions of histamine
increases vascular permeability
smooth muscle contraction
functions of prostaglandins and leukotrienes
increase vascular permeability
smooth muscle contraction
stimulate mucus secretion
functions of nitric oxide
vasodilation
smooth muscle relaxation
name 2 pattern recognition receptors
toll-like receptors
mannose receptor
what expresses toll-like receptors?
dendritic cells
macrophages
epithelial cells
function of toll-like receptors
bind lipopeptides, dsDNA, flagellin
what expresses mannose receptors
macrophages
epithelial cells
dendritic cells
function of mannose receptor
binds mannose-like carbohydrates (PAMPs) on bacteria, viruses, fungi
function of b-cell receptors
membrane bound immunoglobulin
recognise antigen directly
function of t-cell receptor
antigen needs to be processed and presented via MHC I or II before recognition by T cell
CRP is produced in the liver is response to what?
IL-1
IL-6
TNF
function of CRP
binds to bacteria
acts as an opsonin for phagocytosis
describe the adaptive immune response
- Specificity and memory
- Delayed response – days to weeks
- B-cell – antibody mediated
- T-cell
- Mucosa associated lymphoid tissues
what cells are found in the spleen?
lymphoid follicles - b-cells, follicular dendritic cells
macrophages
plasma cells
function of the spleen
filters blood
traps microbes and immune complexes
give 3 examples of mucosa associated lymphoid tissue
GALT
BALT - bronchus
NALT
what is GALT?
o Waldeyer’s ring
o Peyers patches in small intestine
o Appendix
o Lymphoid follicles in large intestine and rectum
describe b cell maturation and differentiation
see notes
draw an IgG, IgE, IgD molecule
y shaped
draw an IgM molecule
round
draw an IgA molecule
linear
when is IgM first produced?
as a foetus
when is IgG first produced?
birth
when is IgA first produced?
1-2 months after birth
what are the functions of antibodies?
free antigen neutralisation
opsonisation for phagocytosis
activation of complement
antigen presentation
where are antibodies usually cleared from circulation?
liver
spleen
another name for major histocompatibility complex
human leucocyte antigens
what is the function of MHC?
presentation of antigens to T cells
where are MHC I found?
all nucleated cells
what does MHC I bind to?
CD8+ T cells
where are MHCII found?
antigen presenting cells: dendritic cells, macrophages, B cells
what does MHC II bind to?
CD4+ T cells
using a diagram show the pathways of antigen processing for MHC
see notes
name the CD4+ T cells
Th1
Th2
Th17
T regs
draw a diagram to show T cell maturation
see notes
function of Th1 CD4+
protection against intracellular pathogens
autoimmunity
function of Th2 CD4+
protection against extracellular pathogens
allergy, asthma
function of Th17 CD4+
protection against extracellular pathogens
autoimmunity
with the help of a diagram show b cell activation by T helper cells
see notes
what does class switching between IgM and IgM require?
stimulaiton of the B cell by a t helper cell
with the help of a diagram show CD8+ T cell perforin induced apoptosis
see notes
describe Fas-Mediated apoptosis of CD8+ T cells
- Nucleated cells infected with some viruses upregulate fas expression (CD95)
- When fas antigens present with MHC I molecules to CD8+, this causes the CD8+ cell to express a fasL receptor on their cell membrane
- Binding of fas with fasL causes target cell apoptosis
name the intracellular pathogens invoking an immune response
mycobacterium
viruses
protozoa
name the surface pathogens invoking an immune response
helminths
arthropods
name the extracellular pathogens invoking an immune response
bacteria
fungi
name the innate molecules involved in the immune response in intracellular pathogens
IFN
macrophages
NK cells
dendritic cells
name the innate molecules involved in the immune response in surface pathogens
mast cells
eosinophils
name the innate molecules involved in the immune response in extracellular pathogens
neutrophils
name the adaptive molecules involved in the immune response in intracellular pathogens
Th1, CD4+
cytotoxic CD8+
IgM, IgG, IgA
name the adaptive molecules involved in the immune response in surface pathogens
Th2, CD4+
IgE
name the adaptive molecules involved in the immune response in extracellular pathogens
Th17, CD4+
describe how immune function varies in the elderly
Thymic involution
Fewer naïve T cells – dependent on memory T cells
Reduced ability for T cell expansion
Reduced B cell development and diversity
• Diminished response to vaccination
More dependent on innate immunity
• But reduced function of pattern recognition receptors and superoxide killing
how can gender affect immune function?
oestrogen vs progesterone and testosterone
what may cause immune deficiency?
genetic cause
other diseases
drugs
environment/iatrogenic insults
secondary causes of immune deficiency: environmental
malnutrition
trauma
burns
secondary causes of immune deficiency: disease
infection HIV diabetes renal failure asplenia malignancy - CLL, myeloma, lymphoma
secondary causes of immune deficiency: drugs
immunosuppressive
antirheumatic
antiepileptic
how does malnutrition cause immune deficiency? protein-calorie mal
immune defences require energy
proteins: cytokines, acute phase proteins, chemokines etc
how does malnutrition cause immune deficiency? zinc
essential for proliferating cells
deficiency: PMN, NK, monocyte, B and T cell impaired function
how does malnutrition cause immune deficiency? iron
enzymes within cellular function and metabolic pathways
deficiency = impaired innate immune function - toxic oxygen species
how do glucocorticoids cause immune deficiency?
o Anti-inflammatory –
Activate lipocortins: reduce phospholipase A2 and arachidonic acid release
Alter transcription of enzymes needed for inflammation
how does ciclosporin cause immune deficiency?
o Calcineurin inhibitor
o Reduced inflammatory cytokine release from T cells
how does rituximab cause immune deficiency?
o Binds to CD20 (B lymphocytes)
o Allows NK and complement mediated apoptosis
