Immunology 2 Flashcards
Describe the 4 types of hypersensitivity reactions
Type 1 – IgE mediated drug hypersensitivity
Type 2 – IgG mediated cytotoxicity
Type 3 – Immune complex deposition
Type 4 – T cell mediated
Describe the process Type 1 Hypersensitivity reaction
Needs prior exposure to antigen/drug
IgE antibodies formed after exposure to molecule
IgE becomes attached to mast cells/leucocytes, expressed as cell surface receptors
Re-exposure cause mast-cell degranulation and releases inflammatory tings like histamine, prostaglandins, leukotrienes, platelet activating factor
Describe some signs/symptoms of Anaphylaxis
Rapid onset
Breathing difficulty, wheeze, cough, SOB
Hypotension
Circulation problems - low BP, high HR
Rash/Hives (itchiness)
Swelling of lips, tongue, throat
Loss of consciousness
Cyanosis
How common is it to have a biphasic response with anaphylaxis?
1-20% of people have biphasic response
Describe the process of a Type 2 Hypersensitivity reaction
Antibody dependent
Drug/Metabolite combines w/ protein
Body treats it as foreign and forms antibodies (IgG, IgM)
Antibodies combine w/ antigens
Complement system activates, damages cells
Describe the process of a Type 3 Hypersensitivity reaction
Immune complex mediated
Antigen/antibody forms large complex and activates complement system
Small blood vessels damaged/blocked
Leucocytes attracted to site of reaction
They release inflammatory substances
Example of a Type 3 Hypersensitivity reaction
Glomerulonephritis
Vasculitis
Example of Type 1 H reaction
Anaphylaxis
Example of Type 2 H reaction
Haemolytic anaemia
MS
Pemphigus
KEY symptoms of Anaphylaxis?
ABC PROBLEMS
AIRWAY
BREATHING
CIRCULATION
Describe the process of Type 4 Hypersensitivity reaction
Lymphocyte mediated
Antigen specific receptors develop on T lymphocytes
Leads to local/tissue allergic reaction
Example of Type 4 H reaction
Contact dermatitis
Stevens Johnson syndrome
Treatment of Anaphylaxis
Basic life support (ABCDE!!)
Stop drug if infusion
IM ADRENALINE 500MG
(300mg in epipen)
High flow O2
IV fluids - to ↑ BP
If no response after 5 mins, do IM again
What blood test can you do to confirm anaphylaxis?
When would this test be done?
Mast cell tryptase
AFTER treatment, otherwise Px will die
Difference between Immune and Non-immune anaphylaxis
NON-immune is due to direct mast cell degranulatin
No prior exposure
but clinically identical
What does adrenaline do?
Vasoconstriction - ↑ Peripheral vascular resistance, ↑ BP, ↑ Coronary perfusion
VIA alpha-1
Stimulates Beta-1 positive ionotropic and chronotropic effects on heart
↓ Oedema and bronchodilates VIA beta-2
Releases further mediators from mast cells and basophils by ↑ Intracellular c-AMP
∴ ↓ Release of inflammatory mediators
RF for hypersensitivity reaction
F
EBV, HIV
Prev drug reactions
Uncontrolled asthma
Medication (w/ macro molecules)
Certain HLA groups
Acetylator status
What are the clinical criteria for an allergy to drug
No correlation with pharmacological properties of drug
No linear relation w/ dose (Even a tiny amount will cause anaphylaxis)
Has a primary exposure
Small number of patients
Happens on re-exposure
Give examples of polymorphonuclear leukocytes
Neutrophils
Eosinophils
Basophils
Give examples of mononuclear leukocytes
Monocytes
T-cells
B-cells
What is the key role of monocytes?
Plays important role in innate and adaptive immunity (phago and Ag presentation)
Removes foreign or dead bodies
What are the 2 main intracellular granules in neutrophils?
Primary - kills microbes by secreting toxic substances
&
Secondary
What are neutrophils involved in?
Play important role in innate immunity (phagocytosis)
Where do macrophages reside?
Reside in tissues
e.g. Kupffer cells in liver, microglia in brain
What is the approx lifespan of macrophages?
Months/years
Main role of macrophages?
Remove foreign bodies and self (dead/tumour cells)
Presents Ag to T-cells
Approx lifespan of eosinophils
8-12 days
What dye is used to stain eosinophil granules?
Acidic dyes (eosin)
Main role of eosinophils?
Activates neutrophils
Induces histamine release from mast cells and provokes bronchospasms
Mainly associated with parasitic infections and allergic reactions
Lifespan of basophils?
~2 days
How are basophils involved in allergic reactions?
IgE binds to receptors
Causes de-granulation releasing histamine
What type of dye is used to stain basophil?
Basophil granules stain with basic dyes
Basophils are very similar to?
Mast cells
Where are mast cells found?
Where is their precursor found?
Only in tissues
Precursor in blood
How are mast cells involved in allergic reactions?
IgE binds to receptors
Causes de-granulation releasing histamine
T-cells play a major role in
Adaptive immunity
Lifespan of T-cells
Hours-years
Where do T-cells mature?
Thymus
Where can T-cells be found?
Blood, lymph nodes and spleen
What are the 4 types of T-cells?
Brief description of their function
T helper 1 - CD4 - helps immune response for intracellular pathogens
T helper 2 - CD4 - helps produce antibodies against extracellular pathogens
Cytotoxic T cell - CD8 - kills cells directly
T regulator - regulates immune response
Lifespan of B-cells?
Hours-years
Where do B-cells mature?
Bone marrow
B-cells recognise
Antigens presented by antigen presenting cells (APC)
B-cells differentiate into
Plasma cells that make antibodies
Where are B-cells found?
Blood, lymph nodes and spleen
Natural killer cells account for ___ of __
15% of lymphocytes
Where are Natural killer cells found?
Spleen, Tissues
How do natural killer cells kill?
Via apoptosis
What do natural killer cells kill?
Virus infected cells
Tumour cells
Are Immunoglobulin’s soluble?
Yes
Name the 5 classes of Igs
IgG
IgA
IgM
IgD
IgE
Describe the characteristics of IgG
Predominant in human serum
70-75% of IgG in serum
Crosses placenta
Difference between mast cells and basophils
Mast cells are fixed in tissue
Basophils can circulate in blood around body
Mast cells express ____
High affinity IgE receptors
Describe the characteristics of IgA
15% of Ig in serum
Predominant in mucous secretions e.g. saliva, milk, bronchiolar secretions
Describe the characteristics of IgM
10% of Ig in serum
Mainly found in blood
Mainly primary response, initial contact w Ag
Why can’t IgM cross the endothelium?
Too big
Describe the characteristics of IgD
1% of Ig in serum
Transmembrane monomeric form present on mature B cells
What is IgE associated with?
Allergic response and defence against parasitic infections
Define epitope
The part of antigen that binds to antibody/receptor binding site
Define affinity
Measure of binding strength between an epitope and an antibody binding site.
Higher the affinity, the better
What do interferons (IFN) do?
Induce a state of antiviral resistance in uninfected cells and limits spread of viral infection
What do interleukins (IL) do?
Cause cells to divide, to differentiate and to secrete factors
Over 30 types
What do colony stimulating factors (CSF) do?
Involved in directing division and differentiation on bone marrow stem cells (precursors of leukocytes)
What does tumour necrosis factor do?
Mediate inflammation and cytotoxic reactions
Describe innate defence mechanisms
1st line of defence
Provides a barrier to antigens
Present from birth
No memory
DOES NOT require lymphocytes
Describe adaptive (specific) defence mechanisms
Response is specific to antigen
Quicker response
MEMORY to specific antigen
REQUIRES lymphocytes
Give some examples of physiological barriers
Temperature
Fever response (inhibits micro-organism growth)
pH
Gastric acidity
Why are neonates more susceptible to infection than adults? (gastric acidity)
Neonates have a less acidic stomach
∴ more susceptible